Center for Gastrointestinal Cancers CME: Rectal Cancers
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Center for Gastrointestinal Cancers CME: Rectal Cancers
April 22, 2022April 21, 2022 | Presentations by: Drs. Michael Cecchini, Kimberly Johung, and Vikram Reddy
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- 7746
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Transcript
- 00:00I'm doctor Trikini, one of the
- 00:02medical oncologists at Yale and Co.
- 00:04Director of the electoral cancer program.
- 00:06Here I'm going to be talking about
- 00:08some of the medical oncology
- 00:10aspects of rectal cancer.
- 00:12This is a CME developed dedicated
- 00:14to coal colorectal cancer.
- 00:16But given our time that we've
- 00:19allowed it for this session,
- 00:21we've decided to focus on rectal
- 00:23cancer so that we can be focused.
- 00:25So I'll be speaking.
- 00:26We have doctor Kimberly Jihong
- 00:28from radiation oncology and and.
- 00:30After becoming ready from colorectal surgery
- 00:33and as we go through each presentation,
- 00:36so introduce themselves as well.
- 00:38So I'm going to start out again
- 00:40talking about the medical oncology
- 00:42aspects of of rectal cancer.
- 00:45And we'll we'll a lot about
- 00:4930 patients and 30 patients,
- 00:5130 minutes per per topic.
- 00:54Again, medical oncology,
- 00:56radiation oncology and
- 00:58and colorectal surgery,
- 01:00and they'll be time for questions that
- 01:02can be answered into the chat or could
- 01:05certainly be addressed directly to us.
- 01:09So first I'm going to talk about the role of
- 01:12total neoadjuvant therapy for rectal cancer.
- 01:15How does totally odgen therapy,
- 01:18sometimes abbreviated as TNT,
- 01:20compared to standard
- 01:22preoperative chemoradiotherapy,
- 01:23which has been done since 2004?
- 01:27And which chemotherapy regimen to choose?
- 01:29Potentially,
- 01:30if we're going to use a total
- 01:32neoadjuvant therapy approach,
- 01:33and also,
- 01:33we'll then spend a little bit of time
- 01:35talking about the role of immunotherapy
- 01:37for microsatellite instability,
- 01:38high rectal cancer,
- 01:39a small subset of patients, but that may.
- 01:43This may have important
- 01:45implications for for outcomes.
- 01:48So.
- 01:51Rectal cancer has been treated
- 01:54traditionally with chemoradiotherapy,
- 01:55followed by surgery,
- 01:57followed by adjuvant chemotherapy in the
- 02:00United States from from the early 2000s.
- 02:03This is based on the sour trial
- 02:06which firmly placed neoadjuvant
- 02:09chemoradiotherapy as a standard of care,
- 02:11and again we typically used in the
- 02:13United States at least chemotherapy
- 02:15as an adjuvant in the setting
- 02:16and in certain parts of Europe.
- 02:18Of course,
- 02:19adjuvant therapy is more controversial,
- 02:20but in the United States.
- 02:21Currently considered standard of care
- 02:24for any clinical T3 or N1 rectal cancer,
- 02:28but over the last several
- 02:30years for various reasons,
- 02:32which will which will cover total
- 02:35new advance therapy has become.
- 02:38A new approach, perhaps?
- 02:40And there's four contemporary studies,
- 02:435 perhaps before they've been published.
- 02:45Those four studies that have been
- 02:47in dark color here versus the Oprah
- 02:50study that offers study rather
- 02:52that is not yet published but has
- 02:55had some prelim data presented.
- 02:57I'm not going to focus on that study.
- 02:59That's a study focused on the
- 03:02potential organ.
- 03:04Well, the.
- 03:07Analyzing organ preservation,
- 03:08so analyzing a watchful way to approach.
- 03:11But so we have the protest 23
- 03:13study the RAPIDO study the seller
- 03:15studying the Polish two study.
- 03:17I'll focus on the first three and
- 03:19and Doctor Johann will talk about
- 03:20some of the radiation aspects
- 03:22of these studies and as well as
- 03:23the Polish two study.
- 03:24I don't have any slides about that.
- 03:27So the rapid study made a splash
- 03:31at ASCO last.
- 03:32We'll ask the 2020 so a couple of
- 03:35years ago now and this is a study
- 03:38that tried to tried to look at.
- 03:42The the benefit of totally adds in therapy.
- 03:45But it also tried to look at how short
- 03:47course ready up there he might play a
- 03:50role in the total nail agent approach.
- 03:52So it was a study that was sort of trying
- 03:54to answer 2 questions at the same time,
- 03:57which always makes it difficult to
- 04:00really interpret the the results.
- 04:02So patients were randomized to
- 04:04either the standard of care approach,
- 04:06so this would be long course close to six
- 04:09weeks of Chemoradiotherapy followed by a.
- 04:12One month period of recovery
- 04:14and and and surgical planning,
- 04:16surgery, and adjuvant chemotherapy.
- 04:19But important to note that the
- 04:23chemotherapy optional so this is a study,
- 04:26a Dutch study and again in Europe.
- 04:28Chemotherapy is not always done
- 04:30in the admin setting,
- 04:31so optional chemotherapy is optional,
- 04:33so we can also see another departure
- 04:34there from what we would do in
- 04:36the United States for the systemic
- 04:38therapy experimental arm.
- 04:39Short course radiotherapy, Dr.
- 04:41Johann will speak about.
- 04:42You know the the the the reasons
- 04:44for short parts versus long course
- 04:46and how to think about that,
- 04:48but short portrait there we followed
- 04:50by new adjuvants are totally
- 04:52adjuvant capox here or full Fox.
- 04:54The totally by the few platinum
- 04:56doublet followed by surgery.
- 04:57So we have.
- 05:00Several things that are going on
- 05:02different than maybe what we would do
- 05:04here and under normal circumstances.
- 05:05We have short course radiotherapy.
- 05:06We have total new adjuvant and then we
- 05:08have patients in the the control arm,
- 05:10not necessarily getting what we
- 05:11would normally give because some of
- 05:13them agreement optional therapy so
- 05:14that they ended up being about 40%
- 05:16of patients in the control group
- 05:18that did not get adjuvant therapy.
- 05:21So you know some people would argue.
- 05:23Maybe this isn't really a fair
- 05:24comparison group as a standard of
- 05:26care group for for our US patients.
- 05:28Maybe a more accurate control comparative
- 05:30group would be to restrict the
- 05:32comparison to patients that receive
- 05:34just received adjuvant chemotherapy,
- 05:36which perhaps will will be
- 05:38done in the future.
- 05:40Teacher really data for this study.
- 05:42So the initial that this has been presented
- 05:45and then now published in The Lancet.
- 05:47So what did what did we see from the outcomes
- 05:49for patients with total new adjuvant therapy?
- 05:51So in the blue line here we have the total
- 05:53new adjuvant therapy group and the red line.
- 05:56We have the standard of care
- 05:57group and what do we see here?
- 05:58And we saw that disease
- 06:00related treatment failure.
- 06:01So essentially an end point
- 06:03very similar to progression.
- 06:05Free survival is better,
- 06:06so less likely to relapse with total new.
- 06:10Therapy.
- 06:12Hazen ratio of about .75 that's significant.
- 06:15Also distant metastasis reduced
- 06:17with with totally original therapy.
- 06:20Again, it has a ratio of .69.
- 06:22This is significant,
- 06:23so we're seeing overall essentially
- 06:25PFS and and just a metaphysis.
- 06:27But then when we look at local regional
- 06:29results, so regional failure no really,
- 06:31no real difference here with doing
- 06:33this totally legitimate approach.
- 06:35So that tells us that the PFS
- 06:37benefit essentially starting with F
- 06:38benefits primarily being driven by
- 06:40affective systemic therapy doing what?
- 06:42Expanding it always does eliminating
- 06:45micrometastatic disease,
- 06:46but what does to really become
- 06:49the standard of care?
- 06:50We need to see something
- 06:52like a survival benefit.
- 06:53So did we see anything like that?
- 06:54No, we absolutely did not in the study,
- 06:56so this is overall survival and you can see
- 06:59these curves are very clearly negative.
- 07:01I think if there was maybe some
- 07:03more separation of these curves,
- 07:04one could argue with more follow
- 07:05up from the study.
- 07:06We see a PFS benefit.
- 07:08This is a disease that has can stay
- 07:10controlled for a long time when it's.
- 07:12Pathetic,
- 07:12maybe with more follow up
- 07:13we see a survival benefit,
- 07:15but in this case I think it's going
- 07:17to be pretty hard to show that even
- 07:19how overlapping these curves are.
- 07:20See this system has a ratio of .92
- 07:24with POS 0.59, so no survival benefit.
- 07:28What about the past year rate and
- 07:30I've just made a big splash as well.
- 07:32I think people get excited about the
- 07:34past CR rate and I don't think this
- 07:37is actually a truly an appropriate
- 07:39endpoint to really be be engaging.
- 07:42Too much of our.
- 07:44Decision making on for the majority
- 07:46of patients at least.
- 07:48You know,
- 07:48for example,
- 07:49if we were to delay delay treatment,
- 07:51surgical treatment even more after radiation,
- 07:53I'm sure we would see even more
- 07:55past CR rates,
- 07:55but if it's not improving overall
- 07:57survival and it's not an,
- 07:58it's not changing the type of
- 08:00surgery we do and any statistically
- 08:02significant chash and past the our
- 08:04rates are not really super important.
- 08:05At the end of the day,
- 08:07in my opinion and where we
- 08:09haven't seen that with most of
- 08:10the attribute studies the the the
- 08:12the different surgeries are.
- 08:14Same so for the most part,
- 08:16so that was the RAPIDO study.
- 08:19What about another short course study?
- 08:20So this was another study that
- 08:22was very similar.
- 08:23So and it's designed so I think helps
- 08:27make the case for or against you.
- 08:29Argument therapy.
- 08:30Having two studies that that are
- 08:32very similar in their design.
- 08:33So this is an experimental design
- 08:36with the short course radiotherapy
- 08:38on the left here.
- 08:39Neoadjuvant Kpop for four cycles
- 08:42surgery and then adjuvant K pops or two.
- 08:45So instead of total neoadjuvant,
- 08:47it's mostly newagen,
- 08:49mostly total neoadjuvant versus
- 08:52the standard of care again.
- 08:55Chemoradiotherapy surgery and
- 08:56then cabox for six cycles.
- 09:01And this is actually a noninferiority
- 09:04study and like the other,
- 09:07the study that I just showed not all
- 09:11patients got adjuvant chemotherapy.
- 09:13So actually 25% of both arms didn't
- 09:17get adjuvant chemotherapy and in the
- 09:19study but but all the patients in the
- 09:22experimental arm that the new therapies
- 09:24so that that tells you already as
- 09:26far as systemic therapy goes, the
- 09:28experimental group is receiving more of it.
- 09:30Because because both groups are not
- 09:32all receiving adjuvant chemotherapy.
- 09:34This study was done in China and
- 09:36it was not considered optional.
- 09:38We don't know all the reasons why
- 09:40patients in the control group,
- 09:41for example, didn't get.
- 09:44Adjuvant chemotherapy,
- 09:44So what are some of the survival outcomes?
- 09:47We see the disease free survival again.
- 09:51Essentially a progression pre survival
- 09:53end points for patients that are
- 09:56nonstatic and so we see a statistically
- 09:58significant technically hazard ratio,
- 10:00though only .88.
- 10:02Favoring total neoadjuvant for for
- 10:06this total neoadjuvant approach.
- 10:08So that's the same as the the prior study,
- 10:11right?
- 10:12Essentially, we're seeing less relapsed.
- 10:14I suddenly imagine,
- 10:15but in this we are seeing.
- 10:17In contrast,
- 10:17we are seeing an overall survival
- 10:19benefit here,
- 10:20so we're seeing a has a ratio of
- 10:22.67 P value of .033.
- 10:25So unlike the rabbit study,
- 10:28we are seeing a survival benefit
- 10:30with total neoadjuvant for mostly new
- 10:32adjuvant klopps short course radiotherapy
- 10:34compared to long course radiotherapy,
- 10:37surgery and adjuvant K Pops.
- 10:38With that big caveat that.
- 10:41Where comparing patients that
- 10:43essentially only 3/4 of the patients
- 10:45received effective systemic
- 10:47therapy in the control group,
- 10:49whereas the majority receive it in
- 10:52the experimental group and you know
- 10:54you can argue, well, it doesn't.
- 10:56You know it doesn't matter.
- 10:58Patients are are able to get it if
- 11:00you do the totally edging approach
- 11:01and only a portion of them are
- 11:03able to do it if if if you do
- 11:06the standard of care approach I,
- 11:08I think we need a little bit
- 11:10more information about who's
- 11:11not getting touch with therapy.
- 11:13Because we don't find that three
- 11:15out of four kind of trial eligible
- 11:18kind of patients are not able
- 11:20to tolerate adjuvant therapy.
- 11:22So a little bit more information
- 11:24I'd like from the the reasoning
- 11:26for lack of engagement therapy.
- 11:29But the other big study in this also.
- 11:32Was presented initially the
- 11:35same ASCO as RAPIDO study.
- 11:37Asked the 2020 yeah so the other big
- 11:40studies produced 23 which was looking
- 11:43at intensifying the chemotherapy
- 11:45to full Fox theory and as a rule,
- 11:47a toxic or expensive or given
- 11:50even convenient treatment might
- 11:51be justified if there's been
- 11:54improvement in overall so revival.
- 11:56On quality of life,
- 11:57but does these pre survival benefit alone?
- 11:58It's tough not considered sufficient.
- 12:00We're actually going to intensify therapy.
- 12:02So compared to the prior presentations
- 12:04where we're really kind of just
- 12:06talking about reordering the therapy
- 12:08and this we're talking about
- 12:10reordering and intensifying, right?
- 12:11So we better we better be able
- 12:13to show a survival benefit for us
- 12:15to to comfortably say that
- 12:17full Fox theory can
- 12:18become a standard of care.
- 12:19So what did they do in this study?
- 12:21They took patients that were
- 12:24randomized to the typical.
- 12:26Chemoradiotherapy followed by
- 12:29surgery followed by chemotherapy.
- 12:32Interestingly,
- 12:32six months of chemotherapy here, right?
- 12:36We would normally be four months
- 12:37in the United States and then in
- 12:40the the the experimental arm.
- 12:41Both fear and off for three months.
- 12:44Maria therapy long course.
- 12:45This time in that short course or and
- 12:48then followed by adjuvant chemotherapy.
- 12:51So again, that truly shows new adjuvant
- 12:55but mostly neoadjuvant or half new adjuvant.
- 12:58In this study, again,
- 13:00how many questions does this study?
- 13:02Kind of trying to answer.
- 13:03It's trying to answer.
- 13:04It's not.
- 13:05It's not asking a question of
- 13:07different types of radiation,
- 13:08so that that that simplifies
- 13:10the design a little bit,
- 13:11but it is.
- 13:12It is looking at slightly
- 13:13different chemotherapy schedule,
- 13:14even in the control group that would
- 13:16normally do more systemic therapy,
- 13:18but I think that's OK.
- 13:20So what do we see in the produce?
- 13:2123 study we saw a past CR rate just to
- 13:24I think everybody focuses on the number,
- 13:26so I want to highlight them as well.
- 13:28Pathologic complete response rate
- 13:3028% with triplet chemotherapy.
- 13:31Full Fox series and I have full
- 13:34Fox series here.
- 13:35That's what we call it a lot in the United
- 13:36States is technically a different regimen.
- 13:38This was actually a full fear or not,
- 13:39but.
- 13:41Very obviously the same drugs,
- 13:43just very similar, slightly modified dosing,
- 13:47so the pathologic complete
- 13:49response was 28% versus 12%,
- 13:51so full Fox full Fox theory
- 13:54short course, long course.
- 13:55It seems like with the total the edge
- 13:58and approaches are are complete response
- 14:00that Pathologic complete response rates
- 14:02are pretty consistent at the 20 to 25,
- 14:04maybe to to 30% range.
- 14:06So what do we see in survival
- 14:08outcomes for these patients?
- 14:09So if we look at disease free survival?
- 14:12Three year disease free survival benefit
- 14:14that favors will total new agent.
- 14:16The Fox theory 59% of 76 versus 69%
- 14:21when we look at overall survival.
- 14:22This says that this is not
- 14:24statistically significant,
- 14:24but you can see the cursor separated there.
- 14:27That may change over time for
- 14:29seeing the disease free survival
- 14:31benefit as more time elapses,
- 14:33we may see a survival benefit,
- 14:35but at this time there's clearly not
- 14:38statistically significant survival benefit.
- 14:40But what about?
- 14:43The metastasis free survival,
- 14:45so again 79% versus 72%,
- 14:46so we are doing a better job
- 14:48controlling systemic disease,
- 14:50just like we saw in the rapid of the trial.
- 14:52With this this early use and increased
- 14:55intensity full Fox area and I think
- 14:57that's where the the the hope of using a
- 15:00more intensive treatment like this is,
- 15:02is is the hopefully increase
- 15:04control of micrometastatic disease
- 15:05and care more of those patients.
- 15:07But we did not see that yet in this study.
- 15:09So so.
- 15:12When we talk about intensifying therapy,
- 15:13we want to be really sure that we are.
- 15:17We are being safe about it,
- 15:20right?
- 15:21So how tolerable as whole thought series?
- 15:23So I think about this and kind
- 15:24of four periods of its use here.
- 15:26The neoadjuvant period chemoradiotherapy
- 15:28period,
- 15:29the perioperative period and the
- 15:31adjuvant chemotherapy period.
- 15:32So we look at the neoadjuvant period.
- 15:34Most people got through the six cycles of
- 15:37folks aren't the full without an issue,
- 15:40no new safety signals.
- 15:42Emma radiotherapy period 95% of
- 15:44patients with teams made it through
- 15:46the chemoradiotherapy period.
- 15:48First is 99% of the standard of
- 15:50care who went straight to it.
- 15:5280s through period were similar
- 15:53in both groups,
- 15:54so I think they checked those
- 15:56boxes in the perioperative period,
- 15:58so 92% of the patients that received
- 16:00full box period induction Underwood
- 16:01surgery versus 95 with standard of care.
- 16:04So there is small difference.
- 16:06Postoperative morbidity was
- 16:07similar between the groups,
- 16:08so we're not seeing an
- 16:10increase in complications.
- 16:10We're also not seeing a difference,
- 16:13by the way,
- 16:14in the type of surgery people needed.
- 16:16So if we had hoped that this surgery
- 16:18was going to reduce the rate of APR,
- 16:21etcetera, we were a little bit.
- 16:22Let down,
- 16:23so I think that is important to
- 16:25notice to note even that higher
- 16:27path the rate didn't translate into
- 16:29necessary significant reductions
- 16:31in morbidity from from surgery,
- 16:33at least in the entire study population.
- 16:35What about adding chemotherapy?
- 16:37If you get totally adjuvant,
- 16:39are you less likely to tolerate
- 16:41adjuvant chemotherapy at least
- 16:43to start the adjuvant?
- 16:44Chemotherapy? The answer was no.
- 16:46You know 77 versus 79% of patients
- 16:48were able to start the editing therapy,
- 16:50but TNT patients ended up
- 16:52receiving fewer adjuvants.
- 16:53Cycles, but overall we have cumulative
- 16:55amounts of chemotherapy patients
- 16:57received to the total neovagina
- 17:00from ARM still still received more
- 17:04chemotherapy cumulatively again.
- 17:07About 21% here are patients
- 17:08in the standard of care group
- 17:10did not receive chemotherapy,
- 17:11so you are comparing a group 100% of
- 17:14the whom at least got some systemic
- 17:16therapy and and a control group.
- 17:18Only 79% got effective systemic any
- 17:21level of affective systemic therapy.
- 17:25So if we kind of summarize what the
- 17:27difference is between these three,
- 17:29these three or four trials,
- 17:31so they all had slightly
- 17:34different eligibility.
- 17:35Rapido trial actually had the most
- 17:37advanced tumors and only allowing
- 17:39clinical test for and two disease.
- 17:41But they all have very consistent.
- 17:44Results,
- 17:45are fairly consistent results they used
- 17:48in addition to having different stages,
- 17:51essentially of eligibility.
- 17:53They all use different.
- 17:55Types of chemotherapy.
- 17:56Different durations of chemotherapy,
- 17:57and it's only in the new agent
- 17:59period and therefore different
- 18:01postoperative regiments as well.
- 18:03But they're they're three year
- 18:05overall survival and disease free.
- 18:08Survival are are all are
- 18:10all relatively similar,
- 18:11and comparisons to their control arms
- 18:14with the only overall survival benefit.
- 18:17The clearly demonstrated so far
- 18:19in the in the stellar trial.
- 18:22So.
- 18:24Umm?
- 18:24Is TNT a standard of care
- 18:27or the standard of care?
- 18:29And I I want to say that it's really hard
- 18:35to compare and these these these trials.
- 18:39How do you mix and match?
- 18:40You mix and match full thoughts
- 18:42with long Horse.
- 18:43Full fox theory with short course
- 18:46it becomes a little bit busy and
- 18:48to think about it and so it's
- 18:50hard to say that ordering truly
- 18:51matters for survival benefits when
- 18:53the TNT groups are getting more
- 18:55effective systemic therapy and all
- 18:56the studies because the rate of
- 18:58adjuvant therapy is underwhelming,
- 18:59at least for our US patients,
- 19:01one could argue,
- 19:02hey,
- 19:03that is real life and and people
- 19:06that get a surgery that maybe aren't
- 19:08as likely to be able to tolerate.
- 19:11Affective post of the post treatment
- 19:13surgery and so that it's easier
- 19:15to get into systemic therapy
- 19:16in the neoadjuvant pair period.
- 19:18I think that's one of the arguments
- 19:20in a more and more of the surgical
- 19:23disease pancreatic cancer,
- 19:24for example.
- 19:25But I I think it's a little bit
- 19:28more complex here,
- 19:29because that's not quite the case
- 19:30that we see in our patient population
- 19:32here in the United States that we
- 19:34aren't able to get in affective
- 19:36systemic therapy up to 3040% of the time.
- 19:38It seems a bit extreme,
- 19:39so I think that.
- 19:40One of the contenders here is that
- 19:42these guys are all done outside the US,
- 19:43where the less aggregate therapy
- 19:45is used for rectal cancer.
- 19:46So we may be seeing mainly an
- 19:48effect that one group of patients
- 19:49is getting systemic therapy and
- 19:51one isn't
- 19:52in 25% of the time, but in the end.
- 19:54For me, the positives outweigh that.
- 19:55The potential negatives here,
- 19:57and I'm using this,
- 19:58I'm using neoadjuvant therapy
- 19:59in the majority of patients,
- 20:01and certainly I think this is a
- 20:03finitive care, and if an OS benefit
- 20:05is shown kind of across the board,
- 20:06it will become the standard of care.
- 20:09So I think some of my.
- 20:11Panelists will focus especially
- 20:12Doctor Reddy talking about the
- 20:14surgical benefits of this we'll.
- 20:16We'll talk about the reduced time to often
- 20:18reserve reversal of the major advantage,
- 20:20the possibility of reduced surgical
- 20:23morbidity for low rectal cancer.
- 20:25Certainly in selected patients.
- 20:27Improve disease free survival.
- 20:29Possibility of OS benefit.
- 20:31There's longer follow-up.
- 20:32Certainly in some of these studies like the.
- 20:34Or just stay and we're not
- 20:36going to talk about well,
- 20:38I'm not going to talk about watching me much,
- 20:39but but the possibility of
- 20:43available for watching rate.
- 20:44Of course,
- 20:44with TNT that's not available
- 20:46with without it disadvantages,
- 20:47I think, for a lower rate of
- 20:51therapy completion compared to CRT.
- 20:53Even so, it just it's small.
- 20:55It's delaying tended defended his surgery,
- 20:57which can be important and many
- 20:59patients cannot tolerate the long
- 21:00duration of systemic therapy.
- 21:01For example, studies and produce 23.
- 21:03So I think that brings me to my next point,
- 21:06that which chemotherapy regimen to you this?
- 21:08I think full Cox Cable box
- 21:09for at least four months,
- 21:11and the majority of patients for the
- 21:13total nudging therapy is there's there's.
- 21:15There's the approach most widely adopted,
- 21:17and I support that.
- 21:20Thus can be used for select patients
- 21:22that are younger fit where local
- 21:24response is more meaningful for surgery,
- 21:26but I think there's insufficient evidence
- 21:28to recommend this over whole Fox.
- 21:31For for patients and shouldn't
- 21:33necessarily be broadly used yet.
- 21:35So just spend a few minutes
- 21:38talking about the.
- 21:40The role of checkpoint inhibitors for MSI
- 21:42high rectal cancer that is nonmetastatic.
- 21:45This was presented data
- 21:46presented at GIS this year,
- 21:47which I do ultimately think
- 21:49will be practice changing,
- 21:50but small numbers because these are patients,
- 21:53so mismatch repair deficient
- 21:55colorectal cancer in rectal cancer.
- 21:58Excuse me,
- 21:59is is 5 to 10% of of rectal cancer,
- 22:02mostly when syndrome patients.
- 22:04Important to note that these
- 22:06patients have chemo resistant
- 22:07disease and so the the group.
- 22:10Somewhere else when Kettering evaluated,
- 22:13giving these patients the checkpoint
- 22:15inhibitors to taking clinical stage
- 22:17two or three rectal cancer giving an
- 22:19anti PD one therapy and then following
- 22:21them by endoscopy and an MRI to see
- 22:24if they responded and had responded
- 22:26or had residual disease and then
- 22:29patients would go on to the standard.
- 22:31Emma radiotherapy and surgery,
- 22:33and we know that the immune checkpoint
- 22:36behaviors are very effective in
- 22:38systemic disease and for various for
- 22:41various reasons that it's certainly
- 22:43been hypothesized for a while that
- 22:45would be even more effective than
- 22:47localized disease because they feel
- 22:49like immune escape and and they'll go,
- 22:52and they certainly went on to show
- 22:53that so that. I just put this slide up
- 22:57to to to mention that they they actually
- 22:59enroll pretty advanced patients too,
- 23:01and they still showed great outcomes here,
- 23:03so almost all the patients were no positive
- 23:05and certainly higher key stage tumors.
- 23:07What did they show when they
- 23:09did endoscopic following?
- 23:09Essentially all these patients,
- 23:11essentially the either got a New York
- 23:14complete or complete response within roughly,
- 23:17you know, six months of starting
- 23:20immune checkpoint diggers.
- 23:21What about looking at these these
- 23:24this radiographically by MRI again?
- 23:26Almost all of these patients
- 23:28and this this patient you know,
- 23:30subsided from analysis that wasn't
- 23:32on far enough, but all of this.
- 23:34All the patients analyzed actually got
- 23:36again a complete clinical response.
- 23:37So all 11 patients that have been
- 23:40followed for adequate duration
- 23:42to be together data analyzed had
- 23:44a complete clinical response.
- 23:47Again, this is an 11 patient study,
- 23:49but I think there will be perhaps
- 23:51more data looking at this patient
- 23:53population from other investigators
- 23:54and released from perhaps this team.
- 23:57Well,
- 23:57it may ultimately result in this becoming
- 24:00practice changing in the future,
- 24:01so I think stay tuned.
- 24:03I this is not approved yet for
- 24:05localized colorectal cancer.
- 24:06These patients need to watch very
- 24:08closely for progression because
- 24:09they're chemoresistant.
- 24:10I do think it will probably be
- 24:13incorporated into guidelines in the future.
- 24:14So in summary,
- 24:15total new agent therapy can be
- 24:17considered standard for most patients
- 24:19where systemic therapy is planned,
- 24:20which is most clinical teeth region
- 24:221 disease in the United States?
- 24:23Both Foxrock Fox can be used
- 24:25for most patients and full Fox,
- 24:26full, fair and ox.
- 24:28For select patients,
- 24:28immune checkpoint inhibitors will
- 24:30become a treatment option for localized
- 24:32disease in the future but are not
- 24:33yet in the treatment guidelines.
- 24:45Umm? I think if anyone has any
- 24:50questions we can take one question now.
- 24:54Although I am not entirely sure.
- 24:57Since I cannot see anybody but the panelists.
- 25:01Whether a question can get to me,
- 25:03I can't see anybody either.
- 25:15OK, on the chat, so certainly I'll answer
- 25:20this one question and then I'll I'll.
- 25:22I'll watch the chat a little
- 25:23bit closer after this.
- 25:24What is your current approach?
- 25:25My current approach is typically full
- 25:28fox for for four months cycles and
- 25:31long course radiotherapy for the most
- 25:33patients with John will talk about
- 25:36the radiation selection and planning,
- 25:37but usually starting with systemic
- 25:39therapy for logistical purposes.
- 25:41The fox, or for a cycles well Fox series,
- 25:46certainly unused in those select
- 25:48younger 5th patients where I think
- 25:50they have more aggressive disease,
- 25:51but that is not my normal practice.
- 25:55Right, I think our practice has
- 25:56been long course and you know,
- 25:58we'll talk about. I think Mike.
- 26:01You talked a lot about TNT will
- 26:03probably skip over my stellar trial and
- 26:05rapidough that I have in my slide set,
- 26:08so there were not redundant.
- 26:09Try to focus more on short
- 26:11course versus long course.
- 26:12We probably could incorporate short
- 26:14course more into our practice,
- 26:16but you know,
- 26:17I think everyone's just more comfortable
- 26:19with long course and the patients do well,
- 26:22so I'm going to dig in a little
- 26:24into the nitty gritty of radiation.
- 26:26So you guys have a sense of what
- 26:28we do for rectal cancer when
- 26:30we live down in the basement,
- 26:32so have a little bit of the
- 26:34technique and then we'll talk about
- 26:35short course versus long course.
- 26:37I'll touch on TNT,
- 26:38but I'm going to breeze over that
- 26:40fast because Doctor Shakini covered
- 26:42it quite well and then we'll leave
- 26:45watchful waiting to Doctor Reddy.
- 26:47So Kim, Johann, I treat you.
- 26:49I cancers here in New Haven and I
- 26:50think one of the things we need to
- 26:52emphasize is that the treatment of
- 26:54rectal cancer is a team based approach.
- 26:56So I'm lucky to work with these
- 26:58folks and a handful of others,
- 27:00and we really need to work together
- 27:02to get these patients treated and
- 27:04it's a collaborative approach and I
- 27:06think that's important to recognize.
- 27:09So with that I'll get started.
- 27:10So plan for today is I was going to
- 27:13talk about what is the benefit of
- 27:16radiation therapy for rectal cancer?
- 27:17So local control benefit prior to
- 27:19surgery that's quick doctor Chikani
- 27:21already touched on the sour trial.
- 27:23We'll talk about different
- 27:24radiation techniques,
- 27:25so when you see in my note,
- 27:26should we do 3D conformal should be the IRT.
- 27:29What does SBRT so that everyone has a
- 27:31sense of what those techniques are and
- 27:34how they're helpful for different scenarios?
- 27:36Then I'll touch on the standard long.
- 27:39Of course,
- 27:40chemoradiation versus short course
- 27:41radiation and then do a quick review of
- 27:45TNT because I think we we got a great
- 27:48review of that from Doctor Dakini,
- 27:50so I'm just showing some
- 27:51rectal plans down here.
- 27:52This is a 3D conformal plan and
- 27:54the one to the right is a IRT
- 27:56plan and we'll talk about the
- 27:58benefits of those two approaches.
- 28:02OK, so why do we use preop chemo radiation
- 28:06prior to surgery for rectal cancer patients?
- 28:09Michael talked about this already a bit,
- 28:12but the benefit is local control.
- 28:13We don't see the overall survival benefit,
- 28:16so this is the classic
- 28:18German rectal trial rate,
- 28:19which I think we all know about that
- 28:22compares pre-op versus post-op radiation in
- 28:25patients with locally advanced rectal cancer.
- 28:28And what we see is that patients who
- 28:31have locally advanced disease so T3T4
- 28:34or node positive, who had preop radiation.
- 28:37And this is long course with
- 28:38concurrent 5 of you.
- 28:39Now we more commonly used alotta
- 28:42compared to post op radiation.
- 28:44The local control was improved
- 28:45in the pre OP setting.
- 28:47And really it's you know if you
- 28:49contour these cases is that I can
- 28:51see the tumor in the preop setting
- 28:53in the post op setting I'm merging
- 28:55in the pre OP imaging and kind of
- 28:57treating where the tumor used to be.
- 28:59So I think that helps people understand
- 29:01why the local control benefit
- 29:03really exists in the preop setting.
- 29:05The other benefit of preop radiation is
- 29:07for those patients with distal tumors, right?
- 29:09We see an increased improvement in.
- 29:14Sphincter sparing surgeries or lack of need.
- 29:18Sorry my leg is going off for an
- 29:21APR and permanent colostomy so you
- 29:23know there are some patients where
- 29:25the tumor is so distal and involving
- 29:26this finger that we know that it's
- 29:28not going to benefit them.
- 29:29But you know,
- 29:30for patients who kind of have that
- 29:32distal tumor where they're on the brink
- 29:34of needing an APR versus and LAR,
- 29:36I think that that is another benefit
- 29:38of pre OP therapy.
- 29:40Toxicities are less in the Preop
- 29:43sitting as well.
- 29:45And but though,
- 29:46as I mentioned,
- 29:47no difference in overall survival.
- 29:50So that's that's why we employ
- 29:52radiation prior to surgery.
- 29:54So now I'm going to dig into a
- 29:55little bit of nitty gritty,
- 29:56dorky radiation therapy techniques.
- 29:58But I think it hopefully is of interest.
- 30:03So what?
- 30:03What are these different things
- 30:04that we're talking about,
- 30:05and what are the techniques and what are
- 30:07the benefits of using one versus another
- 30:09right in the setting of rectal cancer?
- 30:12So how we shape our radiation
- 30:14fields are with what we call
- 30:16these multileaf collimators,
- 30:17so these are.
- 30:20Tungsten leaves that are two millimeters
- 30:23or less and they move in and out of the
- 30:26beam so we can use them to shape the beam.
- 30:29But we also can use them to modulate
- 30:31the intensity of of the beam.
- 30:33So if you turn the beat Mom and they
- 30:35come in and out during treatment
- 30:37right then at different times,
- 30:38each portion of the tumor target can be
- 30:41getting different intensity of radiation,
- 30:43which allows us to conform the
- 30:45radiation dose to our tumor target
- 30:47and the goal here is dose of
- 30:49the tumor reduced side effects.
- 30:51So when we're talking about 3D
- 30:53conformal radiation, this is basically,
- 30:55you know,
- 30:56in the old days we would use an X ray
- 30:58and use Bony anatomy to set our fields.
- 31:003D conformal radiation just means
- 31:02that we're using a CAT scan and
- 31:05I sit for a couple of hours and
- 31:08contour my targets and contour.
- 31:10The normal tissues around those
- 31:12tumor targets every 2 millimeters
- 31:14through the slice of the skin,
- 31:15so that we can use those contours
- 31:18to shape the beams to fit the
- 31:21tumor target and avoid the normal
- 31:23structures as much as possible.
- 31:24But you can see that when we do
- 31:26that for a rectal plan, right,
- 31:27we're shaped around the muzzle ******
- 31:30but we're still treating quite a bit of
- 31:32normal tissue around the rectal tumor,
- 31:34so that would be the downside
- 31:37of a 3D conformal plan.
- 31:41Intensity modulated radiation or IRT that
- 31:43you'll hear us throwing around in the charts?
- 31:47It's something that's a little harder
- 31:48to get approved by the insurance
- 31:50companies for rectal cancer,
- 31:51but I'm seeing it approved more
- 31:53commonly nowadays.
- 31:54So this I would think about as
- 31:56your radiation beam is divided into
- 31:58like these tiny little beamlet.
- 32:00So if you're thinking about a flashlight,
- 32:02each portion of the flashlight
- 32:04has different intensity and then
- 32:06basically we're using a computer
- 32:09to optimize these intensities.
- 32:10And the shape of the beam so
- 32:12that we can create concave dose
- 32:14distributions that really conform
- 32:16to the shape of our tumor target
- 32:19and try to decrease toxicity.
- 32:21I have more luck getting this approved
- 32:23for postoperative cases because
- 32:25there's more normal bowel that falls
- 32:27into the field after surgery and I
- 32:30think it is more helpful for patients
- 32:32with T4 disease where we're treating
- 32:35external iliac nodes because the
- 32:37volume comes more anterior and there's
- 32:39more bowel that's in your field.
- 32:42But for T3 case,
- 32:43probably a 3D conformal plan is adequate.
- 32:48So I think this is just a good
- 32:50pictorial of what an intensity
- 32:51modulated plan looks like.
- 32:53This is a head neck case,
- 32:54but it can give you the sense that
- 32:56you have multiple beams targeted at
- 32:58your tumor with intensity of the beam.
- 33:01You know different across the entire area.
- 33:08And the other thing that IRT allows
- 33:10us to do is differentially dose
- 33:13different areas of the tumor target.
- 33:16So, for example, you can give.
- 33:20Gross disease, a high dose
- 33:23and simultaneously elective
- 33:25nodes can get a lower dose.
- 33:28You know which is.
- 33:29It's a convenient way to plan.
- 33:32So this is an example of an IRT
- 33:34plan for a postop rectal case,
- 33:36and you can see right compared to
- 33:38that 3D conformal plan that I showed
- 33:40you that was like a box coming
- 33:41across this whole area, right?
- 33:43We're really able to carve the
- 33:45dose out of this anterior small
- 33:47bell and try to spare toxicity,
- 33:49so I think this is where we're moving.
- 33:51If we can get insurance to
- 33:53play along with us.
- 33:57So then last as radiation technique
- 33:59that I wanted to mention was SBRT.
- 34:03So this is stereotactic radiation therapy
- 34:06which is really delivery of a blade of doses
- 34:09of radiation in five or fewer fractions.
- 34:12So we use this in the brain or
- 34:14outside of the brain in the body.
- 34:16And where are we using this in the
- 34:18context of rectal cancer, right?
- 34:19Because that's what we're
- 34:21talking about tonight.
- 34:22So as I said, multiple conformal beams are
- 34:24arcs to deliver high doses of radiation.
- 34:26With rapid falloff beyond the target volume.
- 34:29So if we use technology to be very tight
- 34:32with our dose distribution then we can
- 34:34get away with giving high doses of radiation.
- 34:38And protect the normal tissues so you
- 34:41know the technology outside of the
- 34:43brain really started in early stage.
- 34:45Lung cancers were using it in liver cancers,
- 34:47pancreas cancers,
- 34:48prostate cancers,
- 34:48but where we use it for rectal
- 34:51cancer is really in the setting
- 34:53of oligo metastatic disease,
- 34:54so I wanted to touch on that briefly.
- 34:56So in order to deliver these high
- 35:00doses of radiation where quite
- 35:01precise with our patient set up.
- 35:03So this is what your patient
- 35:05is going to look like,
- 35:06if you send them to me for.
- 35:08SBRT, so we build something called VAC Lock,
- 35:12which is a mold underneath them
- 35:13that holds them in position.
- 35:15I often put abdominal compression
- 35:18so that they're breathing more
- 35:20shallow so we're really looks
- 35:21like a blood pressure cuff,
- 35:23shown here,
- 35:24but it's placed over their belly and
- 35:25if they're breathing more shallow
- 35:27then there's less respiratory
- 35:28motion of my tumor target.
- 35:30So my tumor volume is smaller.
- 35:32We then obtain usually an Ivy contrast
- 35:34CT scan from planning and then what
- 35:37we call a four dimensional scan.
- 35:40Which is really a video and it shows
- 35:42me how the tumor moves right if we
- 35:44have an oligo metastasis in the liver,
- 35:46it would show me how that moves as
- 35:49the patient breathes so that I can
- 35:51focus my radiation on that path and
- 35:53tighten up the dose distribution.
- 35:55We always use image guidance and
- 35:57I have a slide on that in I think
- 35:59the next slide to help us align
- 36:01the patient appropriately.
- 36:02For treatment we often put markers in
- 36:05the tumor so that we can use those
- 36:07as surrogates to align the patient.
- 36:09To be precise,
- 36:10with treatment and some places are used
- 36:13in what we call respiratory gating,
- 36:15where you can treat the patient only in
- 36:18certain phases of the respiratory cycle.
- 36:20So only in deep inspiration or
- 36:22exhalation in order to also reduce.
- 36:28Treatment volume.
- 36:28So basically the shape of the
- 36:31beam changes and the intensity
- 36:32across the beam changes as the
- 36:34beam arcs around the patient and
- 36:36that allows us to, you know,
- 36:38deliver this tight dose distribution.
- 36:44So this is just an example
- 36:46of our image guidance,
- 36:47so we usually obtain what we call
- 36:50it cone beam CT on the machine,
- 36:53and that is something that we fuse
- 36:55in with the planning CT so that
- 36:57we can scoot the patient around on
- 36:59the machine and make sure they're
- 37:01in the exact same position as they
- 37:04were for planning to be precise.
- 37:06So the purple,
- 37:07for example is planning CT and
- 37:09the green is what they look
- 37:11like on the day of treatment.
- 37:13And with that fusion we get
- 37:14them into the perfect position.
- 37:16So how do we use stereotactic radiation
- 37:19in the context of rectal cancer?
- 37:21So I wanted to bring up the Saber comment,
- 37:23trial touch on it briefly,
- 37:24because I think we're focusing more
- 37:26on locally advanced rectal cancer.
- 37:27But since I mentioned Asperity,
- 37:29I thought this was important to talk about.
- 37:31So the question is here in patients who
- 37:35have a controlled primary and only one
- 37:38to five sites of metastatic disease is
- 37:40what they looked at with all metastases.
- 37:43Amenable to stereotactic radiation,
- 37:45patients were randomized to just
- 37:48continuing on standard of care.
- 37:50Palliative chemotherapy versus
- 37:52that followed by ablating all
- 37:56sites of metastases with SBRT.
- 37:59Most patients had breast,
- 38:01lung,
- 38:02colorectal or prostate cancer so
- 38:04that's why I thought it was pertinent
- 38:07to our discussion tonight and overall
- 38:09survival was actually increased.
- 38:12When you.
- 38:16I distracted by Vicks. Screenshot there,
- 38:21so overall survival was increased.
- 38:24If if you use SBRT to ablate all lesions
- 38:27after standard of care chemotherapy,
- 38:30so increasingly we're seeing referrals for
- 38:33patients who finished chemotherapy and may
- 38:37have one to five liver metastases or one
- 38:40lung metastasis and one liver metastasis.
- 38:43And actually, I'll mention that
- 38:45we are getting a new linac called
- 38:48the reflection probably installed.
- 38:50Within the next year,
- 38:51we're going to be one of the first
- 38:54in the nation to get this installed,
- 38:56so Stanford has one now and I
- 39:00think we'll probably be third,
- 39:02but the benefit of this is you can treat
- 39:04multiple alignments at the same time.
- 39:06So now if I put a patient on the machine,
- 39:08I have to allot 30 minutes for each
- 39:11oligo metastatic site on the reflection
- 39:13I can treat 5 at the same time,
- 39:15so it really increases output
- 39:18and also decreases.
- 39:20You know patient burden.
- 39:21The other thing that the reflection
- 39:23does is tracks based on PET.
- 39:25So we'll be infusing pet tracer in
- 39:28our department and then the machine
- 39:31communicates with the pet tracer and
- 39:33we'll track the tumor based on pet
- 39:36and move with the tip tumor during
- 39:39treatment again to tighten radiation
- 39:41dose and the other exciting thing
- 39:43is right that we can create a lot
- 39:46of advances in new bio tracers.
- 39:49For patients who have molecular targets.
- 39:53Sorry my leg keeps hurting though.
- 39:55OK.
- 39:58So those are me going into the nitty
- 40:00gritty of radiation techniques and I
- 40:02hope I have not bored you to tears.
- 40:04I'm going to touch a little bit on
- 40:06short course versus long course,
- 40:08and then we'll we'll talk a little
- 40:11bit about T&T.
- 40:12So the data for short course
- 40:14versus long course,
- 40:15I think is really mixed and
- 40:17challenging to interpret,
- 40:18and I think the problem is is,
- 40:19as doctor Shakini touched on,
- 40:22a lot of the studies are comparing
- 40:25short course T&T versus standard.
- 40:27On course,
- 40:28so you don't know if it's the TNT or if it's
- 40:31the short course that's causing the benefit,
- 40:33right?
- 40:34So I always start back at
- 40:36this old Polish study,
- 40:38which is a classic study looking at
- 40:40advanced tumors randomized to short course,
- 40:42followed by surgery followed by
- 40:45chemo versus standard long course
- 40:47followed by surgery followed by chemo.
- 40:49No difference in outcomes.
- 40:50But what I in terms of local
- 40:53control or overall survival.
- 40:55But I will point out that.
- 40:59If you look at patients.
- 41:03Who have so in this Trog study,
- 41:06which asked a similar question
- 41:09for advanced patients.
- 41:10Again no difference in local
- 41:12controller overall survival,
- 41:13but I think the important thing
- 41:15to note is that for our patients
- 41:18with distal tumors there was not
- 41:20a statistically significant but
- 41:22an absolute numbers.
- 41:24Hard to ignore difference in terms
- 41:26of local control, so I think.
- 41:30For all of us, we're still a
- 41:32little bit weary about using
- 41:33short course for distal patients.
- 41:36Because of this data, and I can let
- 41:38Vick touch on that in his opinion,
- 41:40when he gets a chance to speak.
- 41:44I think this is interesting because
- 41:46so traditionally for short course
- 41:48radiation we were following by
- 41:50immediate surgery and so the question
- 41:52asked in the Stockholm three trial
- 41:54right was short course followed
- 41:56by immediate surgery versus short
- 41:58course followed by delayed surgery
- 42:00versus long course where strangely
- 42:02they did not use chemotherapy.
- 42:04So I think that's a hard comparison.
- 42:06So in my mind,
- 42:07I look at this trial and interpret
- 42:09it as should we doing short
- 42:12course followed by immediate.
- 42:14Surgery or should we be doing short
- 42:16course followed by delayed surgery?
- 42:18Everyone had a TM.
- 42:19There was no difference in the
- 42:20outcomes in terms of local control,
- 42:22Mets or overall survival.
- 42:26And so the final outcome was that short
- 42:28course with delay was noninferior to
- 42:31short course with immediate surgery.
- 42:33I think the important thing to note
- 42:35is that the past CR for patients who
- 42:37had immediate surgery right was a
- 42:39lot lower than the path CR rate for
- 42:41patients who had delayed surgery.
- 42:42So I think right when Vick and I share
- 42:45patience and we do give them short
- 42:46course therapy, we're increasingly
- 42:48doing that with delay to surgery.
- 42:51I guess the question Mike would be do
- 42:53we give chemotherapy in that interim?
- 42:54Or do we just?
- 42:56Relay them to surgery.
- 42:57The concern was that there would be more.
- 43:00Complications if you don't take
- 43:02the ****** out right away after
- 43:04high dose short course radiation,
- 43:06but in fact postop complications
- 43:07were lower in the patients who had
- 43:09a short course followed by delay.
- 43:15So finally T&T and I'll make this short,
- 43:19because I think Mike really covered
- 43:21this well, so I think this is an
- 43:24interesting study that sort of sets the
- 43:26groundwork for the TNT approach, right?
- 43:28It's only a phase two trial.
- 43:29It's a small trial.
- 43:31Well, 250 patients are not so small,
- 43:33but non randomized,
- 43:36and we're really looking at long course,
- 43:39followed by surgery or increasing cycles.
- 43:43Full Fox prior to surgery and you see that
- 43:46within each cycle of folfox prior to surgery,
- 43:49the past CR rate is increasing.
- 43:52So in my mind,
- 43:53this is sort of like the setup for
- 43:56thinking about the TNT approach
- 43:58and then Polish to Mike.
- 43:59I think you touched on this,
- 44:01so I'll also be quick,
- 44:03but really we're looking at patients who
- 44:06have again locally advanced disease,
- 44:08randomized to long course.
- 44:12Followed by surgery versus short
- 44:14course chemo and TMB.
- 44:15So now the problem is right.
- 44:16We're looking at two different questions.
- 44:18We're looking at short course and neoadjuvant
- 44:21chemo at the same time as we're looking
- 44:23at long course versus short course,
- 44:25but no difference in outcomes
- 44:28in terms of local control.
- 44:30Distant meds are zero resections.
- 44:32Past CR.
- 44:35And those three year overall survival
- 44:37was higher with short course.
- 44:39But the question is,
- 44:40is it higher because of the short
- 44:41course or it's probably higher?
- 44:43I would say because of the
- 44:45full Fox prior to surgery.
- 44:50And then if we look at long term follow-up,
- 44:53the overall survival difference was lost.
- 44:58For Polish two and then Stella,
- 45:02I think we we did discuss quite well,
- 45:05so I'll briefly talk about this,
- 45:08but again, this was looking at Preop
- 45:10short course radiation followed
- 45:11by chemo and whether it was not
- 45:13inferior to long course chemo,
- 45:15radiation and patient with
- 45:16locally advanced disease.
- 45:17So patients are getting short course
- 45:20followed by 4 cycles of chemo followed
- 45:22by surgery and randomized to either
- 45:25TNT or loan course chemoradiation.
- 45:29And there was no difference in
- 45:31survival or local regional recurrence.
- 45:32The TNT group actually had better three
- 45:35year overall survival and acute Grade
- 45:393 toxicities during preop treatment
- 45:42were slightly higher in the TNT group
- 45:45versus in the Chemo Radiation group.
- 45:47But I think we found this
- 45:49is tolerable for patients.
- 45:50So as Michael said, I think we're
- 45:52moving more and more towards T&T.
- 45:53For most of our patients.
- 45:55Based on these studies.
- 45:58Rapido I think Doctor Jacchini also.
- 46:06Four and two. Looking at
- 46:10standard long course treatment.
- 46:13Versus short course chemo TMDE.
- 46:18With past CR higher with T&T.
- 46:23And distant means lower with TNT,
- 46:27so again, I think supporting our our
- 46:30practice change more towards TNT.
- 46:33I've NCCN guidelines in here.
- 46:35I don't think we need to review
- 46:36them because we cannot look at them,
- 46:37but basically supporting more the use of TNT.
- 46:42So that's what I had.
- 46:43I'm happy to take questions.
- 46:45I went fast, but it's getting
- 46:46late so I don't want to keep
- 46:47everyone on the line too long.
- 46:55We hand it over to you.
- 47:04Oh, I need to stop my screen share right?
- 47:35Can you see my screen? Yes, looks perfect.
- 47:41So I'm back ready.
- 47:42I'm one of the colorectal surgeons here.
- 47:44I'm going to talk about the surgical
- 47:46management of rectal cancer.
- 47:47I want to echo what Kim said.
- 47:50This is truly a multidisciplinary approach,
- 47:52and if anything,
- 47:53I actually use more services than I think.
- 47:56Mike and Kim,
- 47:58with the Intrastromal therapy nurses we use.
- 48:01We use our anesthesiologist and without
- 48:04all of these people surgical management
- 48:08of rectal cancer will be impossible.
- 48:11Before we talk about the surgical.
- 48:13The management of surgery.
- 48:14I think it's it's important to look at the
- 48:17origins of of surgery for rectal cancer.
- 48:20Surgery was usually very limited,
- 48:22mainly because of the high
- 48:23morbidity and mortality.
- 48:24This is like in the pre 1900s.
- 48:29Most of the rectal cancers were
- 48:30treated by transient illusion.
- 48:31It was described by Lisfranc initially.
- 48:35It wasn't until 1907 that the
- 48:37traditional proctectomy that we
- 48:39see nowadays was described this.
- 48:41This involves both an abdominal
- 48:43and perennial approach,
- 48:44and it was the abdominal perineal resection.
- 48:48And it wasn't until 75 years later that the
- 48:51holy plane of surgery that we currently
- 48:54use was described by Bill Hill in 1982.
- 48:57Now, in between 1907 and 1982 some
- 49:00surgeons were still doing PME,
- 49:02even though they didn't call it PME,
- 49:04but because they weren't doing tme.
- 49:06They were persistent,
- 49:07high local recurrence rates and because
- 49:09of this there was a lot of interest
- 49:12in both chemotherapy and radiation.
- 49:14In addition to surgery for the
- 49:16management of rectal cancer.
- 49:17So the role of chemotherapy and radiation
- 49:19was mainly to decrease local recurrence,
- 49:22improve surgical resection of non
- 49:24resectable lesions and sphincter
- 49:26preservation and low lying rectal tumors.
- 49:29We went through a phase of several trials.
- 49:31I'm not going to go through all the trials.
- 49:33Pretty much.
- 49:34They all showed that multimodality
- 49:36treatment decreased local recurrence.
- 49:39So one of the important trials
- 49:40that I'm going to mention is this.
- 49:42Dutch tme trial.
- 49:42Now if you look at all the studies
- 49:44where they did surgery alone,
- 49:46local recurrence was about 2825%.
- 49:48When they added radiation,
- 49:50it dropped it down to about 12 to 14%,
- 49:52but if you look at the Dutch TME
- 49:54trial surgery alone by just following
- 49:56good surgical principles at a local
- 49:58recurrence rate of about 10%,
- 50:00you throw in radiation.
- 50:02After that we dropped it down to 5%,
- 50:04so DME becomes the standard no.
- 50:07You know we just debated between
- 50:09short and long hours chemo,
- 50:11radiation versus radiation,
- 50:12and then we finally come to this study,
- 50:15which kind of established what we
- 50:16do right now or what we used to
- 50:18do about 10 years ago and that was
- 50:21preoperative chemotherapy and radiation,
- 50:23followed by surgery followed by chemotherapy.
- 50:25Local recurrence was about 6%.
- 50:28So the summary of the trials
- 50:30basically showed that PME surgery
- 50:31was important for all patients.
- 50:33It really brought the local countries.
- 50:36And then pre-op chemoradiation with
- 50:38surgery and chemotherapy was the way to go.
- 50:41So now in recent times this I'm
- 50:44talking about 5 plus years ago
- 50:46patients got endoscopy.
- 50:47They got transrectal ultrasound.
- 50:49And they have two options.
- 50:52One, if it was an early stage cancer,
- 50:54either P1 or two lesion,
- 50:56they went for up front surgery.
- 50:58If,
- 50:58on the other hand,
- 50:59if they have locally advanced cancers,
- 51:00which was any cancer P3 and higher
- 51:02or no positive disease,
- 51:04they got chemoradiation followed by
- 51:06surgery followed by chemotherapy.
- 51:09Now we went from local pelvic
- 51:12failure of more than 25% by
- 51:14changing the surgical technique
- 51:16and by adding chemoradiation.
- 51:17We changed our local recurrence
- 51:19for 25% to about 5 to 10%.
- 51:24How are about 30 to 40% still went
- 51:27down to develop distant disease?
- 51:30Now, none of the trials we looked
- 51:32at improved overall survival.
- 51:33They established rules for good surgery,
- 51:35radiation and chemotherapy.
- 51:37But they didn't address any micrometastatic
- 51:40disease with upfront chemotherapy.
- 51:45They did not increase patient compliance
- 51:47and they did not increase downstaging.
- 51:49Now with chemoradiation what we saw was that.
- 51:53Pathologic complete response was
- 51:54noted in anywhere from 10 to 15%,
- 51:56but the question was can we do more
- 51:58and this is where T&T comes in.
- 52:00There were a bunch of trials I'm not
- 52:02going to go through all the trials
- 52:04because Mike and Kim did a good job.
- 52:05And pretty much every trial talks about
- 52:08increase in Pathologic complete response.
- 52:10Now the reason I focus only on this and
- 52:12not the other stuff is this plays a role
- 52:15and should we do surgery for rectal cancer
- 52:18patients underwent total management therapy.
- 52:21So what are the surgical options?
- 52:23One TNT changed this so it should not
- 52:25be an option when we talk about local
- 52:28excision and more radical surgery like LARP.
- 52:31Or even exempt for that matter.
- 52:34So let's talk about watch and wait now.
- 52:36Now when we talk about watch and wait,
- 52:38some of the terminology is important.
- 52:40You know there's differences
- 52:41between induction, chemotherapy,
- 52:42consolidation, chemotherapy,
- 52:43and DNMT is basically induction
- 52:46or consolidation chemotherapy.
- 52:48Now, Pathologic complete response.
- 52:50You know the definition of that is important
- 52:53because it's no evidence on pathology
- 52:56after proctectomy or full thickness excision.
- 52:58Now some of these cancers if you
- 53:00do a full thickness excision,
- 53:01you could still have tumor behind
- 53:02the rectal wall,
- 53:03which can't be excised with
- 53:05the transanal excision.
- 53:06So sometimes,
- 53:07even though we may say on a
- 53:10transitional excision specimen,
- 53:11that there's pathologic complete
- 53:12response that may not really be
- 53:15pathologic complete response.
- 53:16A few other things.
- 53:18What is a complete clinical response?
- 53:20This basically includes 3 things.
- 53:22One,
- 53:23there's no evidence of tumor on clinical
- 53:25endoscopic and radiologic studies
- 53:27clinical this digital rectal exam endoscopic.
- 53:30You know with the camera radiologic
- 53:32is with an MRI and usually the
- 53:34lesion on endoscopy looks like this.
- 53:37Here was the rectal cancer.
- 53:38It's gone now.
- 53:39You have this whitish scar with
- 53:42some telangiectatic.
- 53:44Then there's near complete
- 53:46pathological response,
- 53:47so some tumor is present.
- 53:49But if you give it a little bit
- 53:50more time from radiation,
- 53:51potentially this area can disappear.
- 53:54Then there's incomplete pathologic response.
- 53:57And here you see the ulcer.
- 53:59You know there's like a bed.
- 54:00There's some necrotic tissue.
- 54:01Likely this thing is not going to be
- 54:04a complete neurological response.
- 54:06And these three things become important
- 54:08when we when we talk about watching ready.
- 54:12Now, how did we come to watching late?
- 54:15A lot of this started looking at
- 54:18anal cancer treatment so long
- 54:20time ago for anal cancer,
- 54:21so you have to have any PR,
- 54:23but then chemotherapy and radiation
- 54:26effectively melted away the cancer
- 54:27that now we do APR's for anal
- 54:31cancer just purely for salvage.
- 54:34And for rectal cancer also we
- 54:35saw kind of saw it accidentally,
- 54:38like patients who had advanced age
- 54:40that no surgeon wanted to touch,
- 54:41or patients who have high core
- 54:43morbidities when we gave them
- 54:44chemotherapy and radiation,
- 54:45we saw Pathologic complete response
- 54:47and as we waited there
- 54:49tumors did not progress.
- 54:51And then we have a second group
- 54:52of patients where you know they
- 54:54got chemotherapy and radiation.
- 54:55They didn't see anything inside and
- 54:57they said why am I doing surgery?
- 54:59So now we have tried to transition
- 55:02to more intentional watching weight
- 55:04where this is for less advanced
- 55:06disease and if you get the complete
- 55:08or clinical complete response,
- 55:10we follow them very closely and we see if
- 55:13we can get away without doing surgery.
- 55:15Now the important thing for
- 55:17this is the selection.
- 55:18So the baseline stage is important.
- 55:20So when we stage them, if I'm MRI,
- 55:23the circumferential resection
- 55:24margin is less than one millimeter.
- 55:27Likely this patient is not a
- 55:29good candidate for watching late.
- 55:30If they have extensive nodal disease,
- 55:32or if they have lateral pelvic nodal disease,
- 55:35they're not good candidates for watching,
- 55:36right?
- 55:38The other important thing is that
- 55:40the tumor should be profitable
- 55:41and digital rectal exam.
- 55:43So if you can't palpate the tumor,
- 55:46they may not be a good candidate
- 55:48for watching right now.
- 55:49We also look at some endoscopic features
- 55:51to see if they're good candidates
- 55:52for this watch and read approach.
- 55:54We've got to make sure the tumors are small,
- 55:56they're not circumferential,
- 55:56and if after you do the totally
- 55:58adjuvant therapy you got to make
- 56:00sure there are no strictures,
- 56:01because if there are strictures,
- 56:03it's kind of hard to assess that they're in.
- 56:07Now, once we have these selection criteria,
- 56:10if all three selection criteria are met,
- 56:13there's 98% accuracy in what we are
- 56:16doing with watching now digital rectal
- 56:18exam again is the most accurate.
- 56:20We need to get a baseline before treatment,
- 56:22usually after treatment.
- 56:23If you see a smooth and regular
- 56:26mucosal surface on palpation.
- 56:28Patients usually don't have are are
- 56:30good candidates for this watch and with
- 56:32and endoscopy like I mentioned before,
- 56:34if there's whitening of the mucosa
- 56:35and you just see calendar pacius,
- 56:37they're also good.
- 56:38But if you see any ulceration,
- 56:40stenosis or masked,
- 56:41they don't have a clinical complete response.
- 56:45Biopsies should not be done
- 56:47because sometimes you only biopsy
- 56:49the superficial surface.
- 56:50Cancer may be found deeper
- 56:52inside and sometimes this.
- 56:53This may yield false assurance
- 56:55location and if they if,
- 56:56let's say the MRI shows a deeper lesion,
- 56:58they may not pursue surgery
- 57:00because they feel that well.
- 57:01They found the cancer on colonoscopy.
- 57:03Now I see nothing.
- 57:05Why why should I go for surgery?
- 57:08Lastly, MRI is important.
- 57:09This is where the radiologist comes
- 57:11in for us on Tito restored images
- 57:13and diffusion weighted images.
- 57:14We can see if there's any residual to.
- 57:18Now,
- 57:19what kind of surveillance do we
- 57:21follow after you know the patient
- 57:24gets done with Mike and Kim,
- 57:26they come to us in about 6 to 8 weeks later.
- 57:28We start with digital rectal exam
- 57:30and they lost and we get an MRI.
- 57:33If there's an incomplete response.
- 57:34Meaning we see an All Star
- 57:36team or anything like that.
- 57:37They go for a radical surgery.
- 57:39They found the other hand.
- 57:39If there's a near complete response.
- 57:42It may be reasonable in some patients
- 57:44to wait another 6 to 8 weeks and
- 57:46repeat the digital rectal exam
- 57:47and endoscopy to see if they go
- 57:49from near complete response to.
- 57:53To complete clinical response now most of
- 57:55these patients if you wait long enough,
- 57:57sometimes you have to wait 28 to 34 weeks.
- 57:59They do become complete clinical
- 58:02responders now, if, on the other hand,
- 58:03there's no continued response or any growth,
- 58:06you've got to look at protecting.
- 58:10Now for clinical complete responders,
- 58:12we'll be doing is we do
- 58:15additional rectal exam,
- 58:15anoscopy and MRI every three to four months.
- 58:18I usually tend to go every three
- 58:21months for at least two years.
- 58:22After two years we decreased the frequency.
- 58:25We do it every six months
- 58:27for about three years.
- 58:28And then this is the key part is
- 58:29that you got to go for this yearly
- 58:31because we don't have long term data.
- 58:33So if you're going to go with
- 58:35the watch and wait approach,
- 58:36we gotta make sure our application is
- 58:38committed to doing this every three months
- 58:40for two years every six months after.
- 58:44Now, what what is local report?
- 58:45The risk of local regrowth is about 10%.
- 58:48If you have, you know clinical
- 58:51complete response for two years
- 58:53and the actual risk is only 25% of
- 58:56two years and then most of these
- 58:58patients have aluminum components,
- 58:59so we can pick them up on
- 59:01endoscopy or digital rectal exam.
- 59:03Rarely do they have mesorectal or
- 59:06lateral pelvic sidewall disease.
- 59:07And the risk factors are basically
- 59:10increasing 2 stage for every
- 59:12increase in T stage from T1 to T3.
- 59:14There's about a 10% increase increase in
- 59:17risk of local regrowth after two years.
- 59:20If they're complete clinical responder,
- 59:22there is no risk,
- 59:23and there you know just because
- 59:24they have a higher stage.
- 59:28Even if there's regrowth,
- 59:2990% of these patients are
- 59:31amenable to R0 sections.
- 59:33I usually say if there are clinically
- 59:372M0 because they've had told me,
- 59:38as you been therapy, some patients may
- 59:41be candidates for transient addition.
- 59:43Some patients do go for proctectomy.
- 59:44Anything higher than that.
- 59:46They should go for proctectomy.
- 59:49There is increased risk for
- 59:51metastatic disease, unfortunately,
- 59:52if there's local regrowth,
- 59:53we don't know if it's because of
- 59:55tumor biology, but I think there's
- 59:56going to be more work on that.
- 59:58In terms of functional outcome,
- 60:00I mean with watch and wait all
- 01:00:01they're getting this chemoradiation
- 01:00:02so they're quality of life is so much
- 01:00:05better than what surgery they have.
- 01:00:06Fewer defecation, urinary problems.
- 01:00:08They also have better sexual function.
- 01:00:11They have superior functional outcomes.
- 01:00:13Then even those patients
- 01:00:15have had local excision,
- 01:00:16but about a third of the patients do have
- 01:00:18this large syndrome which is low interior
- 01:00:21section syndrome where they have frequency,
- 01:00:24urgency, clustering,
- 01:00:25occasional incontinence.
- 01:00:26But it is manageable and it doesn't prove it.
- 01:00:30Now, what about the future?
- 01:00:31Because now we don't know which patients
- 01:00:34respond well and become complete responders.
- 01:00:36So some people are working on
- 01:00:38actually cultures of the rectal
- 01:00:40cancer derived from the patients,
- 01:00:42and we treat them.
- 01:00:45And then we also create the patient
- 01:00:46and we see if these organized
- 01:00:48cultures actually complete.
- 01:00:49They respond and they may give
- 01:00:51us an indication on what the
- 01:00:52patient completed respond.
- 01:00:55Now let's talk about some of the
- 01:00:57surgical options that for surgery,
- 01:00:59it depends on where the tumor is.
- 01:01:00So the anatomy of the ****** is important
- 01:01:03to any tumors lower down chances of
- 01:01:06having an ostomy are much higher.
- 01:01:08So let's talk 1st about local excision.
- 01:01:11So local excision was described
- 01:01:13in the 1800s for benign tumors.
- 01:01:16It was kind of refined and
- 01:01:17perfected by Alan Park.
- 01:01:19He designed a lot of instruments.
- 01:01:21The first real rectal cancer
- 01:01:23transanal excision was done in
- 01:01:251977 at Saint Marks Hospital.
- 01:01:28In the 1980s,
- 01:01:29this guy was way ahead of his time.
- 01:01:31Gerhard because he designed with the setup,
- 01:01:34which is essentially a laparoscopic setup
- 01:01:36that's transiently scopic microsurgery,
- 01:01:38where you can go through the ****.
- 01:01:40It was the first natural orifice
- 01:01:43device where you can go through
- 01:01:44the **** and resect tumors,
- 01:01:46even up to 20 centimeters higher.
- 01:01:48The problem with that is it's
- 01:01:50a very complex system and the
- 01:01:51training curve is very high,
- 01:01:52so it didn't get adopted.
- 01:01:55We do have it we we do do these
- 01:01:57stem surgeries.
- 01:01:58Then they came up with a more easier
- 01:02:00platform which is using the laptop
- 01:02:02with the equipment in the 20 Tens
- 01:02:04this is much cheaper whereas the
- 01:02:06temps equipment is probably close
- 01:02:08to I think 1/4 of $1,000,000.
- 01:02:11So this one is much more accessible
- 01:02:13to all the institutions.
- 01:02:16Now we do local excision for T1 lesions.
- 01:02:19They usually have to be
- 01:02:21histologically favorable.
- 01:02:22Usually we make sure they have
- 01:02:23no lymphovascular invasion,
- 01:02:24poor differentiation, or tumor planning.
- 01:02:26Unfortunately,
- 01:02:27we don't know a lot of this information
- 01:02:29until after we did the surgery,
- 01:02:30so if a patient undergoes.
- 01:02:33Transitional expression for T1 lesion
- 01:02:35and if they have any of these bad features,
- 01:02:38I mean literally region for
- 01:02:40differentiation or general budding.
- 01:02:41They may have to consider.
- 01:02:44Radiation or protecting?
- 01:02:48Now, how about for two lesions?
- 01:02:50The problem with the two lesions
- 01:02:52is that local recurrence rate.
- 01:02:53If you do a local excision is
- 01:02:55about 13 to 30%.
- 01:02:56Now the main reason is because
- 01:02:58they have nodal involvement in
- 01:03:0030 to 40% of the patients.
- 01:03:02Now,
- 01:03:02some patients are still candidates
- 01:03:05for local excision of two lesions.
- 01:03:07These are high risk patients.
- 01:03:08And then there are some patients who
- 01:03:11absolutely refuse to have a philosophy.
- 01:03:12And sometimes you don't have a choice.
- 01:03:14You do something that's better than nothing.
- 01:03:19And there's data to show that chemo
- 01:03:21radiation may decrease local recurrence
- 01:03:23and also create this occult nodal disease.
- 01:03:26And when we when we give chemoradiation
- 01:03:28we see that the local recurrence
- 01:03:30is 15% as opposed to about 7%
- 01:03:32when we do a formal practice.
- 01:03:34So it's lower than the 30%.
- 01:03:39Now, how about doing more radiation
- 01:03:41therapy 1st and then doing local exception?
- 01:03:44Now, there are several trials which looked
- 01:03:46at it and they showed that it's it's
- 01:03:48got to be equivalent local recurrence
- 01:03:50and overall survival to proctectomy.
- 01:03:52So in select patients it may be useful.
- 01:03:56The downside is that if you do
- 01:03:58chemo radiation or totally adjuvant
- 01:04:00therapy up front, is there really
- 01:04:02role even for two lesions?
- 01:04:04The surgery even necessary,
- 01:04:06especially if there are
- 01:04:08complete clinical response.
- 01:04:12Now the problem with local excision after
- 01:04:15radiation is the post hoc healing issues.
- 01:04:19Now let's talk about.
- 01:04:20Let's go on the task list.
- 01:04:21Anytime we do local excision,
- 01:04:22this is the biggest thing we worry about.
- 01:04:24It is directly correlated to the
- 01:04:26depth of invasion of the tumor.
- 01:04:27So for a tumor that's confined to
- 01:04:30the top 1/3 of the submucosa of the
- 01:04:33wall of the ****** there's only 3%
- 01:04:35risk of lower normal metastases.
- 01:04:37Now, these are T1 lesions.
- 01:04:38Now the same T1 lesions if they
- 01:04:41if they invade the lower third or
- 01:04:43the deeper third of the submucosa,
- 01:04:45there's a 23% risk of blood from the taxes.
- 01:04:48These numbers are almost close
- 01:04:50to the two regions.
- 01:04:52Also, if they have information or
- 01:04:54invasion and four differentiation,
- 01:04:56there's higher chance there were some
- 01:04:59nice studies done which showed that
- 01:05:01Lymphovascular invasion is associated
- 01:05:03with lymph node metastasis and also with
- 01:05:05the 2.5 X increase in systemic recounts.
- 01:05:07This is a nice study done by chain
- 01:05:10in 2012 where they looked at T1
- 01:05:12lesions and T2 lesions years,
- 01:05:14vascular and region and four differentiation.
- 01:05:17And if you look at it, if they have both,
- 01:05:19it's almost 100% chance of winning
- 01:05:20on the test disease.
- 01:05:21Same for T1 and T2.
- 01:05:23Obviously everything is worse
- 01:05:25for the two regions.
- 01:05:26Also 44 differentiation again,
- 01:05:28another study showed a 5X fold
- 01:05:30increased chance of lymphoma
- 01:05:32capacities and that's why you know
- 01:05:34if we have these risk factors we try
- 01:05:37not to do a local excision tumor.
- 01:05:39Budding was initially described by in 1993.
- 01:05:42The Japanese had a lot of literature
- 01:05:45on using it as a predictor,
- 01:05:47and prognostic indicator of low forecasts.
- 01:05:51So we tried to do a local excision
- 01:05:55for like the low risk patients.
- 01:05:56Now how do we do it?
- 01:05:59Usually you know we have these operating
- 01:06:02scopes and we identify the lesion,
- 01:06:04get about 1 centimeter margin,
- 01:06:06excise the lesion down to the parackal fact
- 01:06:09some people close it up and some don't.
- 01:06:12And here's how attempts approach
- 01:06:14with the transcend the transient
- 01:06:16landscape with microsurgery.
- 01:06:17You're you have the laparoscopic instruments,
- 01:06:19we actually use it and we can actually go
- 01:06:22even up to the sigmoid to recycle lesions.
- 01:06:24This is,
- 01:06:25this is how it looks for anyone who is in GI.
- 01:06:27It looks like an advanced ESD procedure.
- 01:06:31Yeah,
- 01:06:31and there's a huge training
- 01:06:32curve associated with it now,
- 01:06:34even though it's the smallest surgery we do,
- 01:06:35there are complications associated with it.
- 01:06:38The biggest one is urinary retention.
- 01:06:41We also see bleeding.
- 01:06:43We receive this in about 5% of the
- 01:06:46patients or patients were anticoagulated
- 01:06:48and then the big thing is you
- 01:06:49know you can see public accesses.
- 01:06:50These are a bigger issue for higher lesions,
- 01:06:53where interpersonal entry is gained,
- 01:06:56but these can be managed by easily.
- 01:06:59Now what about the outcomes?
- 01:07:01One of the worst things about local
- 01:07:03excision is that we cannot harvest
- 01:07:05or stage the mesorectal lymph nodes.
- 01:07:08For key one cancers,
- 01:07:10again there's
- 01:07:1165% risk of nodal metastasis,
- 01:07:13and if you don't do a good surgery
- 01:07:15and there's positive margins,
- 01:07:16it increases the local recurrence
- 01:07:18and decreases the five year old
- 01:07:20overall survival for two regions.
- 01:07:22Again, local recurrence you know it's
- 01:07:24not the local recurrence is pretty bad,
- 01:07:27and the overall survival is slightly lower,
- 01:07:30but some patients are good candidates
- 01:07:33for this. You're more outcomes.
- 01:07:35Risk of lymph nodes increase
- 01:07:37as the destaging increases.
- 01:07:39Also, local recurrence increases.
- 01:07:42There are several studies confirming these.
- 01:07:45So in summary, we do transitional
- 01:07:48transitional excisions for T1 regions.
- 01:07:50If it's a high risk one,
- 01:07:52you can add in chemoradiation
- 01:07:53or do more radical surgery.
- 01:07:55For T2 would prefer radical surgery,
- 01:07:58but in some select patients maybe transient
- 01:08:00decision keep more regulation T3 no local.
- 01:08:03Decision to go straight forward main
- 01:08:06surgery which we will talk about.
- 01:08:07So the radical surgery for rectal
- 01:08:09cancer is a proctectomy thought.
- 01:08:11It was initially described in 1907 by Miles.
- 01:08:14There was the abdominal pain reduction.
- 01:08:16We further defined what good
- 01:08:18surgery means in 1982 by the field.
- 01:08:22And why do we have to do timing?
- 01:08:24The reason is if you do,
- 01:08:26if you if you operate in the
- 01:08:28non teaming planes,
- 01:08:28local recurrence can be as high as
- 01:08:3130% and if if if you look at our
- 01:08:34circumferential resection margin,
- 01:08:35if you go right next to the tumor and
- 01:08:36get a margin of less than one millimeter,
- 01:08:38that's a 50% local recurrence rate.
- 01:08:41We don't have to do much better if you
- 01:08:43just go 1 millimeter to the other side.
- 01:08:45Local recurrence drops to 17% by
- 01:08:47staying in TME drops to less than 10%.
- 01:08:51There's embryological portions for the
- 01:08:53Cammy plan that will not go over this.
- 01:08:56There are different surgical approaches.
- 01:08:57Here's the we used to do.
- 01:08:59Additional open incision and then we
- 01:09:00started going with a smaller lifestyle that,
- 01:09:02or minimally invasive
- 01:09:04approaches with laparoscopy.
- 01:09:06The insufflate,
- 01:09:06the belly,
- 01:09:07use a camera and use a little
- 01:09:09instruments and do the surgery.
- 01:09:10Now we're using the robotic thing.
- 01:09:12It's ergonomically better.
- 01:09:14The surgeon sits here and the
- 01:09:16robot sits next to the patient and
- 01:09:18we control it to do the surgery.
- 01:09:20The visualization is phenomenal.
- 01:09:21This is how it looks.
- 01:09:23We identify the wrestlers we can see.
- 01:09:25You know,
- 01:09:26pretty much everything we need to see and.
- 01:09:30And still again,
- 01:09:31we're out for radical resection.
- 01:09:32DME is the standard local recurrence,
- 01:09:35can rock to less than 7%.
- 01:09:36The problem with rectal cancer is the
- 01:09:38lower the fuel mirrors to the ****
- 01:09:40the higher the chance of the leak.
- 01:09:42So the lower the tumor,
- 01:09:43the higher the chance of them
- 01:09:45having the temporary announcement.
- 01:09:46And when we stay in these planes,
- 01:09:48there's nerves which wrap around us
- 01:09:50which can cause erectile dysfunction
- 01:09:52in attempt to 30% of the patients.
- 01:09:54Some report even as high as 80%.
- 01:09:57And for the distal margin,
- 01:09:58we need about 2 centimeters,
- 01:10:00and if there's any question of that,
- 01:10:01we can even do a frozen section even
- 01:10:031 centimeter after chemoradiation
- 01:10:04can be acceptable in certain
- 01:10:06patients where the tumors are very.
- 01:10:10No, the most patients want the LAR,
- 01:10:13which is a low interior section syndrome
- 01:10:15and this is a sphincter preserving surgery.
- 01:10:17There's different kinds if it's a high tumor,
- 01:10:19you can do a standard
- 01:10:21LAR for super low tumors.
- 01:10:22We do low, ultra low or colloidal.
- 01:10:25Usually it's acceptable even if the
- 01:10:28internal sphincter is involved.
- 01:10:30We got to make sure that this will feel
- 01:10:32more margin is about 1 centimeter for us
- 01:10:33to be able to renounce the most divinest.
- 01:10:36Most of them do get some kind
- 01:10:38of an artificial ******.
- 01:10:39Now when we look at their anatomy,
- 01:10:41patients always ask us well,
- 01:10:42why are you picking out my sigmoid?
- 01:10:43Also, when the cancer is here and the
- 01:10:45reason is it has to do with the blood supply.
- 01:10:47So we got the sigmoid colon, the ******.
- 01:10:51And this is an open surgery.
- 01:10:53Here we are dividing the semi
- 01:10:55colon descending colon junction.
- 01:10:57Staying in the theme plane,
- 01:10:58identifying the nerves,
- 01:10:59dissecting not off the sacrum,
- 01:11:01taking it off the anterior.
- 01:11:03In this case,
- 01:11:04it's the uterus dividing it off the
- 01:11:07uterus and then once we do this,
- 01:11:09we use it.
- 01:11:09The retractors and open fashion
- 01:11:11go all the way low and then we try
- 01:11:14to transact it as low as possible
- 01:11:16and then insert statement through
- 01:11:17the **** to perform it.
- 01:11:19And that's the most.
- 01:11:21Laparoscopically we use
- 01:11:22these little instruments,
- 01:11:24so here we are identifying the
- 01:11:25IMA that we need to divide.
- 01:11:27We isolated and divided divide
- 01:11:29the IV and then free up the left
- 01:11:31colon and then we take down all
- 01:11:34the attachments of the left colon,
- 01:11:36dissect the ****** off the presacral plane.
- 01:11:39Here's the hypogastric plexus that
- 01:11:40we identify and keep safe so that
- 01:11:42there's no sexual dysfunction.
- 01:11:46There's a video of what this is doing.
- 01:11:48The surgery robotically?
- 01:11:49So we're taking down the plane in
- 01:11:52a quick second. You'll even see
- 01:11:54that you're highlighting up here.
- 01:11:55And green, we have a specialized
- 01:11:57dye that we use when we use the.
- 01:11:59They're right there when
- 01:12:00we use the robotic surgery,
- 01:12:02we're opening up the planes.
- 01:12:03This is the Mesorectal plane,
- 01:12:04which is the loose areolar tissue.
- 01:12:06It's almost bloodless.
- 01:12:07If you look at it.
- 01:12:08We're just, you know,
- 01:12:10going through it for quite fast.
- 01:12:11Like here,
- 01:12:12we are identifying the hypogastric nerves,
- 01:12:14preserving them so there's no sexual
- 01:12:17dysfunction, and we keep doing this,
- 01:12:18so I'll skip over this.
- 01:12:21You're real isolated on both
- 01:12:22the right and the left side.
- 01:12:24Here is the ******.
- 01:12:25The tumor is somewhere here,
- 01:12:27so now we're doing the disco mobilization.
- 01:12:30So you know we're not counting down
- 01:12:32we're getting the entirety of me.
- 01:12:34We have identified the tumor here,
- 01:12:35so now we're marking it off
- 01:12:37and we're thinning it out.
- 01:12:38The margin needs to be about 2 centimeters.
- 01:12:42Once we do that here, we're basing it off
- 01:12:45the prostate and the Seminole vesicles.
- 01:12:49Once we have done that,
- 01:12:50we use the stapler to divide
- 01:12:51it and extract the specimen.
- 01:12:52So in this case you know the
- 01:12:55staple really comes in and you
- 01:12:57have cleaned out the rectal wall.
- 01:12:58You can see that.
- 01:13:00The muscles of the rectal
- 01:13:02wall were dividing it.
- 01:13:04Once it's divided,
- 01:13:04the specimen is extracted and
- 01:13:06then we do this anastomosis
- 01:13:08and the fresh colon from
- 01:13:09higher comes down and it's.
- 01:13:13This is how it looks in real life.
- 01:13:16There's a spike coming in from below,
- 01:13:18with Spike with stapler.
- 01:13:19The spike is standard
- 01:13:20deployed on our staple line.
- 01:13:21There's the proximal annual
- 01:13:23that gets hooked on to it.
- 01:13:25And then Atmos as a fraction in two
- 01:13:27layers with two rows of statements.
- 01:13:29And sometimes we actually oversaw it.
- 01:13:31Here on hold we're holding up the
- 01:13:33the the prostate and the what.
- 01:13:38This is just rearranging it.
- 01:13:39Moving the fat out of the way so
- 01:13:40none of these get incorporated.
- 01:13:46So there's different colonic
- 01:13:48resources in this procedure.
- 01:13:49I showed you this one,
- 01:13:50which is called the Baker anastomosis.
- 01:13:52There's a jpegs or coal plasty I'll talk
- 01:13:54about why we use the most of the time.
- 01:13:56We do diversifications,
- 01:13:57especially after team radiation,
- 01:13:58or if it's a little tumor.
- 01:13:59So this is a temporary diverting look.
- 01:14:01Really awesome,
- 01:14:01now the next most can be done,
- 01:14:04stapled, or handsome.
- 01:14:05We prefer the staple because it's easier and
- 01:14:07quicker and faster and safer for patient,
- 01:14:09but in some situations
- 01:14:10we have to do a hands on,
- 01:14:12and that's the message because
- 01:14:14the State Fair misfired.
- 01:14:15This is a staple anastomosis
- 01:14:16that I showed you.
- 01:14:17The answer is much more difficult.
- 01:14:18We get it, it's it's usually done open.
- 01:14:21Uh, takes a longer time,
- 01:14:23so we usually staple misfires.
- 01:14:25Here's the tumor that's been excised.
- 01:14:27We take off the cuff of rectal mucosa,
- 01:14:30pull the corn,
- 01:14:31and do a hands on anastomosis through the.
- 01:14:34This adds about an hour to the case.
- 01:14:35You know this is usually not done nowadays.
- 01:14:38Now these are for tumors which
- 01:14:39involve the internal sphincter.
- 01:14:41What we do is we go all the way down below
- 01:14:43the headline right by the inner drum,
- 01:14:44divide it,
- 01:14:45pull the colon from above and
- 01:14:47literally look it up for the intercom.
- 01:14:49The functional results from
- 01:14:50this are actually comparable.
- 01:14:51PR and patients have good functional outcome,
- 01:14:55meaning they don't have incontinence,
- 01:14:57even though they only have their sponsor.
- 01:15:00This is more of historic interest,
- 01:15:02but we have about two or three
- 01:15:04patients where we have done this
- 01:15:05because they were hostile abdomen.
- 01:15:06So we do a abdominal incision and
- 01:15:08then we go through the back and
- 01:15:10we open up the toxics and actually
- 01:15:12under direct visualization to
- 01:15:13then that's the most as if they
- 01:15:15have a hostile anterior abdomen.
- 01:15:17This is recently of interest.
- 01:15:19This is called a transitional
- 01:15:21PME where the distal portion of
- 01:15:23the TME is very difficult.
- 01:15:25So what they decided to do was why
- 01:15:27not go through the **** divide the
- 01:15:29****** go up a little higher and then
- 01:15:32pull the colon down and do that that's mosis.
- 01:15:36It helps with the distal mobilization
- 01:15:37of the last three to six centimeters of
- 01:15:39the ****** but there's some complications.
- 01:15:41Is that because you're kind
- 01:15:42of doing it blindly?
- 01:15:44People are transacted the Aretha,
- 01:15:45or cause rectovaginal fistula,
- 01:15:47and these are bad problems.
- 01:15:49With good luck,
- 01:15:50periscopic skills,
- 01:15:51you're able to do the distal 3
- 01:15:52to 6 centimeters,
- 01:15:53so you're not huge advocates for the kids.
- 01:15:55I mean,
- 01:15:56you're still in terms of functional
- 01:15:58outcome after anastomosis.
- 01:16:00It's conflicted because
- 01:16:01you're missing your ******.
- 01:16:02Some people do report good outcomes,
- 01:16:04but there's higher rates of
- 01:16:05incontinence and worse quality of life,
- 01:16:07especially in women.
- 01:16:09And patients experience this low
- 01:16:11interoception syndrome where they have
- 01:16:12origins through frequency clustering,
- 01:16:14incontinence.
- 01:16:14Most of these symptoms do improve after year,
- 01:16:17and quantifiers of wars instead of just
- 01:16:20hooking up the colon straight into
- 01:16:22the venous actually helps with this.
- 01:16:24These are the different options the
- 01:16:26cloning jpod was described in 1986.
- 01:16:28Technically, a little bit more difficult.
- 01:16:30Very hard to do it in patients who are
- 01:16:33obese patients are diverticulosis,
- 01:16:34where bulky colon have a shortened mesentery.
- 01:16:37This is how it kind of looks.
- 01:16:38It looks like there's capacity.
- 01:16:40It's supposed to have a small colon.
- 01:16:42Call pasty was defined as an
- 01:16:43easier approach where you know
- 01:16:45you can you get this reservoir,
- 01:16:46but the problem is now you run
- 01:16:48an atmosphere and another staple
- 01:16:50one which can potentially leak.
- 01:16:51So we try not to do do this because there's
- 01:16:54a higher leak rate of the colopy side.
- 01:16:56Then there's a much easier technique
- 01:16:57where we do and decide we do about 3
- 01:17:00centimeters of this and looked it up,
- 01:17:01and it has similar outcome
- 01:17:02through cloning Jacobs.
- 01:17:03So we have now all transitioned to this.
- 01:17:06So in summary,
- 01:17:07you can do it stapled or hand so on.
- 01:17:09We do use reservoirs.
- 01:17:10Patients do get a perspective of stoma,
- 01:17:13but one big downside is this.
- 01:17:14Lower anterior resection syndrome.
- 01:17:16Now this is the procedure described by miles,
- 01:17:20which is abdominal pain and other
- 01:17:22section the absolute indication for it
- 01:17:24is if any external sphincters involved
- 01:17:25or if the patient is incontinent even
- 01:17:28for the diagnosis of the rectal cancer,
- 01:17:30some relative indications.
- 01:17:32If you're tall big guy,
- 01:17:33you know it's sometimes very hard to
- 01:17:36reinforce the walls for low tumor.
- 01:17:38So sometimes APR is the only option.
- 01:17:42For APR we do the same surgery except
- 01:17:44they get an cost and we do the same
- 01:17:47surgery as the low anterior section.
- 01:17:48But we also detect the **** so there's
- 01:17:50an elliptical incision to core down.
- 01:17:53Divide the sprinklers and then reach
- 01:17:56from our dissection to the other
- 01:17:58side and then we close up things.
- 01:18:01So it's used for patients where
- 01:18:03they're sphincter involvement.
- 01:18:04It's also used in patients who have
- 01:18:06incontinence in obese or called
- 01:18:08patients with mid rectal humans.
- 01:18:09We do an impr.
- 01:18:10There's very good long term
- 01:18:12functional outcomes,
- 01:18:12but no one wants it because
- 01:18:14it's a permanent collection.
- 01:18:16Now these are for locally advanced diseases.
- 01:18:18This is the public separation.
- 01:18:20There's different forms of it.
- 01:18:21You have the posterior pelvic
- 01:18:23example or complete public extempore.
- 01:18:24Both bladder,
- 01:18:25uterus and ****** or removed
- 01:18:27or and then bladder,
- 01:18:29prostate and ****** removed.
- 01:18:30Here's an example and then we are
- 01:18:33mobilizing the bladder and identifying
- 01:18:35the dorsal venous plexus ligating it.
- 01:18:38Then you know once we ligate we
- 01:18:40divide the prostate and the urethra.
- 01:18:43Now it's fully unblocked removed.
- 01:18:45So here's. State, water and ******.
- 01:18:47We take it out and usually patients end
- 01:18:49up with two colossal and two Oxo makes 1.
- 01:18:51There's a colostomy for stool.
- 01:18:53One is a urinary conduit because they
- 01:18:55don't have a ladder anymore for your.
- 01:18:58The outcomes from these are great.
- 01:18:59Five year overall survival is 53%,
- 01:19:01so doing a good operation upfront
- 01:19:04is better for locally advanced
- 01:19:06tumors rather than doing the half
- 01:19:08you know half past reception
- 01:19:10and then doing surgery for recurrent cancer,
- 01:19:12survival drops to 20%.
- 01:19:15Now recurrent cancer because I mentioned
- 01:19:17that it's beyond the scope of this lecture,
- 01:19:20but it's very difficult because
- 01:19:22you're in extra mesorectal planes,
- 01:19:24which means there's a lot of bleeding,
- 01:19:25and it also goes into the
- 01:19:27lateral compartments,
- 01:19:27so you think about things like creator.
- 01:19:30And it's very complicated because one
- 01:19:32year recurrence you have prior surgery,
- 01:19:34radiation fibrosis.
- 01:19:34So these are usually miserable surgeries,
- 01:19:37but if done right,
- 01:19:38they can be life saving for the patient.
- 01:19:40So in conclusion,
- 01:19:41you know rectal surgery is evolving,
- 01:19:43especially with Tony adjuvant therapy.
- 01:19:45Staples have made our life easier.
- 01:19:47Functional outcomes are getting better.
- 01:19:50And the goals of treatment for us from
- 01:19:52a certain perspective is local control.
- 01:19:54Improve the survival.
- 01:19:55Try to preserve the sphincter
- 01:19:57bladder and sexual function and
- 01:19:59try to improve their quality.
- 01:20:01So if we start off with,
- 01:20:03there were no good surgeries and patient
- 01:20:05had bought bad outcomes then 1980s.
- 01:20:07We made a lot of improvement.
- 01:20:08We then did minimally invasive
- 01:20:10surgery and now we're going
- 01:20:12to going back to no surgery,
- 01:20:14but we're getting better outcomes thanks
- 01:20:16to Mike and Tim and everyone else.
- 01:20:19So any questions?
- 01:20:24Thanks Vicki, I'll pose one of the questions.
- 01:20:26I'll leave one of the
- 01:20:27questions posed in the chat.
- 01:20:29So for clinical low, low digital rectal
- 01:20:33cancers that are clinically tied to.
- 01:20:37Versus instead of just taking
- 01:20:38the station straight to TME and
- 01:20:41considering preoperative RTE
- 01:20:42followed by Transcendental Decision,
- 01:20:44what what kind of sway is you for referring
- 01:20:46this patient like this over to us?
- 01:20:49So for the I mean my personal preference,
- 01:20:51I like to do crazy and all excision see
- 01:20:52if they have any high risk features.
- 01:20:54Because once you do chemo radiation.
- 01:20:57You won't know if they have
- 01:20:58any any any of the high risk
- 01:20:59features like Lancaster invasion.
- 01:21:01Poor differentiation.
- 01:21:02So personally I think it's much easier and.
- 01:21:07No, it's better to do training
- 01:21:09decision followed by humiliation.
- 01:21:11But some patients do get chemoradiation,
- 01:21:13then come and see us and we are never
- 01:21:16certain if they had any good features
- 01:21:19because sometimes the tumor is gone.
- 01:21:21But in some patients it is an option.
- 01:21:27Thank you.
- 01:21:30I think all those questions have to
- 01:21:31go on the chat, so feel free to.
- 01:21:35Answered some of them by text, but.
- 01:21:38Feel free to put any questions in
- 01:21:41the chat. I don't think anybody
- 01:21:44can voice in that question
- 01:21:46Doctor really. I think one of the great
- 01:21:48points you brought up a few times during your
- 01:21:50talk is the question of survivorship, right?
- 01:21:52And I don't I can be the first person to say
- 01:21:56I'm guilty of not doing the best job in that,
- 01:21:59and should we be looking into, you know,
- 01:22:02building sort of more of a survivorship
- 01:22:04program for our rectal cancer patients
- 01:22:06in terms of sexual health,
- 01:22:08rectal symptoms, local symptoms,
- 01:22:10because they are struggling and
- 01:22:12they don't know that we provide
- 01:22:14them the support that they need?
- 01:22:16And they come to me and I say,
- 01:22:17go see Doctor Reddy.
- 01:22:18But that you know that's not helpful.
- 01:22:21No, so we actually believe it or not.
- 01:22:23After five years we still follow
- 01:22:25the patients mainly for all
- 01:22:27their other side effects. So
- 01:22:29do you feel like you're taking that
- 01:22:30on your plate, or can we do something
- 01:22:33more institutionally to sort of have
- 01:22:35a better colorectal survivorship,
- 01:22:37or even just GI in general, right program?
- 01:22:40Should we enhance that? I mean,
- 01:22:41I think we do a great job with breast,
- 01:22:43but not such a good job with GI.
- 01:22:45So we've started our app.
- 01:22:47Have started doing this more OK.
- 01:22:49Patient patients are happy about this.
- 01:22:52Before we used to say five
- 01:22:53years ago and see us and they,
- 01:22:55you know they had all kinds of symptoms
- 01:22:57and they didn't know what was going on.
- 01:22:58They would reach out to everyone.
- 01:22:59Used to go on support groups and
- 01:23:01they they would just complain,
- 01:23:02but now we have made it a point that
- 01:23:04even after five years we followed them.
- 01:23:06They they come and see us once a year.
- 01:23:09If they're you know,
- 01:23:10if they see no improvement then they
- 01:23:12kind of disappear on their own,
- 01:23:13but they still
- 01:23:14send them all to you. Is what you're saying.
- 01:23:17No, even for the annual cancer anal
- 01:23:19cancer with rectal cancer anyway.
- 01:23:22Of chronic symptoms and incontinence.
- 01:23:24For years, local symptoms,
- 01:23:27urinary symptoms, and I think
- 01:23:29they struggle on their own,
- 01:23:31so I think that's something
- 01:23:32we need to focus on more as a
- 01:23:33group. The Sack board is.
- 01:23:34We even have patients with cervical
- 01:23:36cancer and prostate cancer.
- 01:23:37After radiation that we're managing,
- 01:23:39right, right, right, right.
- 01:23:41OK, well, I'm glad for
- 01:23:43your collaboration on that.
- 01:23:45Do you routinely?
- 01:23:48Therapy for like 12 floor physical
- 01:23:50therapy? Uh, that's already.
- 01:23:53So that's a little bit more difficult because
- 01:23:55it has to be based on insurance companies.
- 01:23:58Pelvic floor therapy does help the patients.
- 01:24:02Sacral nerve modulation helps patients
- 01:24:04with low interior section syndrome.
- 01:24:05The problem with that is
- 01:24:07that you have to implant.
- 01:24:08This device and they can't get
- 01:24:10MRI's after so a lot of patients
- 01:24:11don't don't want to go for
- 01:24:13that at least for five years.
- 01:24:15We don't want to do it.
- 01:24:16A lot of times trouble
- 01:24:18with who does pelvic floor therapy here?
- 01:24:21We do. OK, I can't figure out how to
- 01:24:27put the referral in. Private world
- 01:24:29send them to us so we get manometry
- 01:24:32and everything with GI and then
- 01:24:35so they can come to colorectal.
- 01:24:36OK so that's great to know.
- 01:24:39One thing we're trying to do
- 01:24:41is actually and and mind you
- 01:24:43is trying to advocate for Cdr
- 01:24:46diagnosis code for a large so that.
- 01:24:48You know there's no
- 01:24:51official code.
- 01:24:52But I think that that's more directed
- 01:24:54pelvic floor therapy because there
- 01:24:56is someone like in YPB who does it.
- 01:24:58But then I send the patients and they
- 01:25:00don't understand the issues, right?
- 01:25:02So patient comes back and they're
- 01:25:03like what was that?
- 01:25:04It didn't help me at all,
- 01:25:06and not only that, some of the
- 01:25:07problems that they use are very
- 01:25:08uncomfortable for patients,
- 01:25:09especially had radiation treatment.
- 01:25:12That right they don't understand the
- 01:25:13concepts? OK, that's great to know.
- 01:25:17The one that the one of the
- 01:25:19questions in the chat doctor Reddy
- 01:25:20is have you started adopting a
- 01:25:22wait and weight watch approach?
- 01:25:24Wasn't waiting approach included
- 01:25:25patients who are surgical candidates?
- 01:25:29It's a it makes me very nervous, but we have.
- 01:25:35Sadly, I'm still if if someone who's
- 01:25:3840 comes in, chances are we don't
- 01:25:41follow away from watch approach.
- 01:25:43We do advocate for them even a
- 01:25:46couple of times we have gotten burned
- 01:25:47for some patients who have had
- 01:25:49treatment somewhere else and we have,
- 01:25:51you know they have seen local recurrences.
- 01:25:53And we have taken care of them.
- 01:25:54It's not that they did anything wrong.
- 01:25:56Sometimes patients,
- 01:25:57when they see a local recurrence,
- 01:25:58they kind of get upset with the with
- 01:26:00the people locally because they say oh,
- 01:26:02and that's why we didn't show
- 01:26:03it and you missed the cancer.
- 01:26:05What's
- 01:26:06been your experience with salvage?
- 01:26:07For those patients with?
- 01:26:09So if you get them in time so it's
- 01:26:12interesting to patients who have had
- 01:26:14endoscopy and the and the pathology
- 01:26:17has shown no tumor in the wall,
- 01:26:19those patients are more reticent
- 01:26:21to go for a radical surgery.
- 01:26:23So even if the MRI shows something
- 01:26:25because the MRI will always say
- 01:26:27it can't rule out tumor or they
- 01:26:29you know they're kind of nebulous,
- 01:26:31patients don't go for surgery,
- 01:26:33especially if it's an APR.
- 01:26:35But those patients,
- 01:26:37unfortunately they come with
- 01:26:38locally advanced disease,
- 01:26:40like they're circumferential
- 01:26:41resection margins.
- 01:26:42I mean, we had someone who had a
- 01:26:44complete who done it memorial,
- 01:26:45who almost had a near complete response.
- 01:26:49After about a year started having symptoms.
- 01:26:51Endoscopy biopsy didn't show anything.
- 01:26:53One of our endoscopies actually
- 01:26:55did a deeper biopsy because
- 01:26:57I couldn't convince the guy.
- 01:26:58Found cancer,
- 01:26:59he had a 10 centimeter lesion
- 01:27:01with all circumferential resection
- 01:27:02margins positive and he did not
- 01:27:05want the public's information.
- 01:27:07It was positive on the prostate
- 01:27:09so you know this this survival
- 01:27:11is going to be
- 01:27:13and what I found too is,
- 01:27:14I think promising a patient the
- 01:27:17option of watchful waiting up
- 01:27:19front is challenging because they
- 01:27:21say this was proposed to me as an
- 01:27:23option or read about it and I always
- 01:27:24tell them we need to wait to see
- 01:27:26what your response is to therapy.
- 01:27:28We cannot commit to this.
- 01:27:30Day one, right?
- 01:27:31So I think that needs to be
- 01:27:33made clear to patients.
- 01:27:35And all of that, I mean, how many pay?
- 01:27:37I mean, we have patients who.
- 01:27:38I mean you know this because they
- 01:27:41all complain to you because I do
- 01:27:43a rectal exam after radiation.
- 01:27:45And they're like, oh,
- 01:27:46I can't tolerate this.
- 01:27:47And if you can't do a rectal exam,
- 01:27:50I think watching weight is out
- 01:27:52of the out of the. It's not
- 01:27:53right? It's clear that there's
- 01:27:55residual disease, right?
- 01:27:56No even if there is not
- 01:27:58residual disease, it's
- 01:28:00that they're not that you're
- 01:28:02not able to surveil them.
- 01:28:03Is what you're saying right?
- 01:28:04Yeah, I got that.
- 01:28:06Yeah, I think you know my view is we'll
- 01:28:09we'll see the final results from the
- 01:28:12Oprah trial and offer trial and get
- 01:28:15different pronunciations before before.
- 01:28:18I think this gets more mainstream.
- 01:28:23Moving our program forward right?
- 01:28:25We should probably start to consider
- 01:28:27this more for select patients.
- 01:28:30And now I mean we're seeing
- 01:28:32complete response rates of close
- 01:28:34to like 30%, right, right?
- 01:28:36I mean, compared to 10 to 15%?
- 01:28:38I mean, back then I used to only feel bad
- 01:28:4010 to 15% of the time that I did an APR.
- 01:28:44And there's no cancer.
- 01:28:45Now I gotta feel worse 30% of the time.
- 01:28:48I feel worse, right?
- 01:28:54Other questions from the group.
- 01:28:59Got 21, you're still holding on.
- 01:29:03Oh, that we we did set this to go until 8:30,
- 01:29:06but I think the goal was about 30 minutes
- 01:29:09per presentation with questions so.
- 01:29:11So we are at around 8:00 o'clock.
- 01:29:14If anyone has any burning questions,
- 01:29:17you can either put it in the
- 01:29:18chat before I finish talking,
- 01:29:19really finish talking,
- 01:29:20or you can email us directly.
- 01:29:22Of course our emails are
- 01:29:25ourfirstname.lastname@yale.edu
- 01:29:26and on on the website.
- 01:29:28Happy to communicate. Parting words,
- 01:29:32thank you for organizing this.
- 01:29:34I think it was great.
- 01:29:36Thank you Mike.
- 01:29:40Thank you all. Have a great night.
- 01:29:45See you soon. Alright, take care bye bye.