Rectal Radiotherapy Antipathy

[TheWallnerus]

Is this a thing? Not doing chemoRT for everyone preop in N+ or local advanced rectal? The data to support preop chemoRT has "little relevance to practice in 2020?"

Not on my 2022 RT Utilization Bingo Card.

NICE withdraws quality standard on colorectal cancer treatment after “lack of consensus”​

"The decision comes after an update to the NICE guideline for colorectal cancer, published in January, 2020, prompted concerns around the recommendations on the use of preoperative radiotherapy or chemoradiotherapy. The disagreement centres on the updated recommendation to offer preoperative radiotherapy or chemoradiotherapy to patients with cancer in stages cT1–T2, cN1–N2, M0, or cT3–T4, any cN, or M0, which some experts say is contrary to current best practice."

"The statement by NICE that “the evidence also showed that preoperative therapy gives a small improvement in overall survival and disease-free survival”, is based on old historical data with little relevance to practice in 2020. Data from the 2012 CR07 trial showed no statistical difference in disease-free survival and overall survival from preoperative radiotherapy at follow-up after 8 years compared with selective postoperative chemoradiation, but these data were excluded because they were presented in a conference abstract.
High locoregional recurrence rates after radical surgery were reported in trials in the 1990s, and were significantly reduced by the addition of short course preoperative radiotherapy. These results form the basis of the current NICE guidance. We have since learned that pelvic recurrence reflected poor surgical technique and inadequate resection of the mesorectum. Surgery as routinely practised in the 1960–90s did not use meticulous sharp dissection along mesorectal and levator planes, which are acknowledged as necessary nowadays. Additionally clinicians did not make use of laparoscopic techniques, which facilitate an R0 dissection in the low rectum. The field of rectal cancer in 2020 is very different."

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[RickyScott]

Dutch trial and others showed w/tme radiation had abt 5% absolute benefit and that was in pre folfix era.at best, we are one new drug away from being eliminate here and at worst, folfox proves that it is sufficient alone.

 

[TheWallnerus]

Dutch trial and others showed w/tme radiation had abt 5% absolute benefit and that was in pre folfix era.at best, we are one new drug away from being eliminate here and at worst, folfox proves that it is sufficient alone.

you have mentioned these things before I believe! Prescient?!

 

[deleted941485]

Dutch trial and others showed w/tme radiation had abt 5% absolute benefit and that was in pre folfix era.at best, we are one new drug away from being eliminate here and at worst, folfox proves that it is sufficient alone.

Apparently not even a drug just one decision from the central planners at NICE.

 

[theradiator]

It's sad to let this go but the bleak future is inoperable gross disease not adjuvant? Like adjuvant prostate and brain metastases, let it recur and then salvage?

 

[thesauce]

I'm confused: why are we not focused on definitive chemoRT and the elimination of surgery? I thought that was the overall direction of rectal CA treatment?

 

[jondunn]

I'm confused: why are we not focused on definitive chemoRT and the elimination of surgery? I thought that was the overall direction of rectal CA treatment?

These are different pools of patients. If a high T3N0 can get a TME and that’s it, that’s one thing. On the other hand trying watchful waiting in a T3N2 that needs an APR

 

[StIGMA]

Can't have non-operative management without RT. RT should retain some role.
Short-course RT also is an easy sell pre-op.

 

[deleted941485]

Can't have non-operative management without RT. RT should retain some role.
Short-course RT also is an easy sell pre-op.

Apparently not haha.

We used to
Pride ourselves on being true oncologists.
Seems we lost the plot on that one too.

 

[RickyScott]

Can't have non-operative management without RT. RT should retain some role.
Short-course RT also is an easy sell pre-op.

We will always retain some role, just diminished. same may be true of lung cancer someday. If this were a football team, radiation is in danger of becoming the longsnapper

 

[deleted941485]

We will always retain some role, just diminished. same may be true of lung cancer someday. If this were a football team, radiation is in danger of becoming the longsnapper

Plus add in the UK. There are no rad oncs. It’s just clinical oncologists whom I have always suspected that RT to them is a bother. They have more and more going on the inpatient and drug side and so getting rid of RT just means getting rid of something that’s more of a nuisance than anything else. They have no interest in developing it further and omission makes for good publications in a academia.

 

[TheWallnerus]

If this were a football team, radiation is in danger of becoming the longsnapper

I laugh because it is too early to shed a tear on Monday

I have always suspected that RT to them is a bother. They have more and more going on the inpatient and drug side and so getting rid of RT just means getting rid of something that’s more of a nuisance than anything else.

You talkin' 'bout UK clinical oncologists or US med oncs

 

[deleted941485]

I laugh because it is too early to shed a tear on Monday

You talkin' 'bout UK clinical oncologists or US med oncs

US med oncs can’t run omission without RO buy in in this country. If your in UK you don’t need buy in…you are the RO and the MO.

 

[ramsesthenice]

What’s really in trouble is trimodality therapy. In some circumstances it’s possible to cut out any one part. At the end of the day, it’s the surgery that causes the most notable long term complications for patients and the component many patients are most motivated to avoid. In areas with buy in for w/w, RT isn’t going anywhere.

 

[metallica81788]

I'm getting more requests by surgery for short course in non-T3 and node negative cases without systemic; people I would have never considered irradiating in training. At least my surgeons seem to like it.

There will always be a population that will try non-operative management. Our role in rectal ca will evolve but I don't see it vanishing completely. I don't like treating any GI, so it doesn't bother me either way.

 

[Palex80]

I'm getting more requests by surgery for short course in non-T3 and node negative cases without systemic; people I would have never considered irradiating in training. At least my surgeons seem to like it.

There will always be a population that will try non-operative management. Our role in rectal ca will evolve but I don't see it vanishing completely. I don't like treating any GI, so it doesn't bother me either way.

I don‘t get it…
You are treating T2 N0 cases without chemo with a short course (5x5Gy) schedule? What is the idea?

 

[metallica81788]

I don‘t get it…
You are treating T2 N0 cases without chemo with a short course (5x5Gy) schedule? What is the idea?

Not often - it's borderline T2/T3 or N0/1 on MRIs or where surgeon is worried about margin in mid to upper tumors.

These cases go through a site specific tumor board at the mothership so these decisions aren't being made in a vacuum. I'm not just beam on for any rectal patient that walks in the door.

 

[ramsesthenice]

Not often - it's borderline T2/T3 or N0/1 on MRIs or where surgeon is worried about margin in mid to upper tumors.

These cases go through a site specific tumor board at the mothership so these decisions aren't being made in a vacuum. I'm not just beam on for any rectal patient that walks in the door.

@Palex80 I am sure it is surgeon specific. We have one in our group who has had a few bad experiences with post-op who is inclined to recommend neoadjuvant therapy is they are suspicious the patient is being under staged. That said, I typically talk them out of it in these situations. I think the data is pretty good that patients fitting prospect criteria (T3N0 or T2N1) probably do just as well with chemo only. My inclination now for patients who are upstaged to T3N0 or T2N1 on post-op pathology is to just give FOLFOX.

I also appreciate that a couple of our Gyn Oncs follow similar principles. They are not inclined to operate on women with cervical cancer who already meet in their words 1 1/2 Sedlis criteria since they would have a high likelihood of needing RT anyway.

I don't love the idea of using selective post-op radiation. We are terrible at collecting meaningful QOL and PROs from patients. But what is the big difference between doing pre and post-op RT? Post-op everything that gets radiation just gets left behind. The toxicity profile is not the same. The idea that we should change standard of care supported by multiple RCTs because theoretically surgery has gotten better sans data is essentially the antithesis of EBM.

 

[RickyScott]

What’s really in trouble is trimodality therapy. In some circumstances it’s possible to cut out any one part. At the end of the day, it’s the surgery that causes the most notable long term complications for patients and the component many patients are most motivated to avoid. In areas with buy in for w/w, RT isn’t going anywhere.

Surgeons don’t give up surgery. Just look at bladder cancer.

 

[Palex80]

Not often - it's borderline T2/T3 or N0/1 on MRIs or where surgeon is worried about margin in mid to upper tumors.

These cases go through a site specific tumor board at the mothership so these decisions aren't being made in a vacuum. I'm not just beam on for any rectal patient that walks in the door.

Good points! All well understood, thank you for clarifying!
Do the surgeons operate immediately after 5x5 Gy or wait for X werks at your institution.
If they operate immediately it might be interesting to look at your patients (depending on the case load) to draw some conclusions. „How many of my cT2cN0 turned out to be pT3/pN1?“

 

[metallica81788]

Good points! All well understood, thank you for clarifying!
Do the surgeons operate immediately after 5x5 Gy or wait for X werks at your institution.
If they operate immediately it might be interesting to look at your patients (depending on the case load) to draw some conclusions. „How many of my cT2cN0 turned out to be pT3/pN1?“

Yes for those they do operate very soon after 5x5, usually the next week. Early enough to where I give them start/end date in enough advance to get an OR reserved.
I'd have to go back and look at each case individually but there are a few that were upstaged as you mentioned.

 

[TheWallnerus]

Yes for those they do operate very soon after 5x5, usually the next week.

In (radiobiological) theory you can't get a pCR if you operate a week after 5x5. Right? Which is one way of saying it would be difficult to know, unless you follow all these patients actuarially for LC (which is hard for an individual human's brain to do), if 5x5 radiotherapy does anything in T2N0 rectal.

 

[metallica81788]

Agreed. It's not something I do often (maybe 1-2x a year) and it's certainly debatable, but after careful thought I have chosen other hills to die on.

 

[TheWallnerus]

Agreed. It's not something I do often (maybe 1-2x a year) and it's certainly debatable, but after careful thought I have chosen other hills to die on.

Oh I would irradiate those referrals for sure. But if I had to argue about it in tumor board I would suddenly look down at my phone and go "Sorry guys an an emergency just came up" and hustle out the door.

 

[Bequerel]

I haven’t done short course RT for rectal yet. Do you take whole traditional volume including nodes to 5Gy or just rectum with margin? Seems high for bowel if nodes get that much. We eve did it jn training and I can’t find volumes on recent publication.

 

[deleted1111261]

Whole pelvis 25/5 including nodes

 

[ramsesthenice]

Oh I would irradiate those referrals for sure. But if I had to argue about it in tumor board I would suddenly look down at my phone and go "Sorry guys an an emergency just came up" and hustle out the door.

Good because you would probably lose. There is no data supporting RT for T2N0 tumors. Bringing it up de novo would be a great way of becoming the guy who sees radiation as an answer to everything and hence, someone to be ignored. No, the best approach here is to put it back on whoever suggested it. "There is no known benefit of RT in T2N0 patients. That said, if you are really concerned that we are understaging the patient and you want to avoid the toxicity of post-op radiation, it might be a very reasonable consideration in this case."

Surgeons don’t give up surgery. Just look at bladder cancer.

Correct me if I am wrong, but they did give up on Anal cancer right?

Time will tell what happens in the long run but this is already different from bladder. Major centers like MSKCC have already made TNT with w/w their go-to approach for LARC and they are not alone. Our surgeons get a decent number of second opinions from patients who read they might not need surgery and walked away from the fist surgeon who told them otherwise. Change has to come within and compared to most other anatomic sites, there is more momentum here than I can think for some other disease. Another important difference is we are not really a threat to their volume. Abdominal colon cancers >> rectal cancer (pretty much a 2.5/1 margin). So right now transitioning to w/w only affects a third of a third of their CRC volume. If we magically got the cCR over 90% somehow would they find more pushback. Maybe. I think the real redline would be if we took this new magical therapy with a crazy high CR and tried to apply it to true (abdominal) colon cancers. That would become more of an existential threat and would not be taken lightly.

 

[Palex80]

In (radiobiological) theory you can't get a pCR if you operate a week after 5x5. Right? Which is one way of saying it would be difficult to know, unless you follow all these patients actuarially for LC (which is hard for an individual human's brain to do), if 5x5 radiotherapy does anything in T2N0 rectal.

Absolutely correct. But if something like 20% of his cT2cN0 turned out to be pT3/pN1, then he should consider discussing it with the radiologists.

 

[Palex80]

Whole pelvis 25/5 including nodes

Which is debateable, however. 😂

 

[deleted1111261]

I think with the Dutch, the Poles and the good people at RAPIDO - this seems to be the target.

 

[salubalu]

are y’all boosting extramesorectal nodes that aren’t being resected? Covering inguinals in low lying tumors invading the anal canal?

 

[jondunn]

are y’all boosting extramesorectal nodes that aren’t being resected? Covering inguinals in low lying tumors invading the anal canal?

You mean with short course?

 

[ramsesthenice]

are y’all boosting extramesorectal nodes that aren’t being resected? Covering inguinals in low lying tumors invading the anal canal?

I don’t usually cover inguinals unless they are positive or there is nodular disease in the anal canal. Pretty uncommon for low rectal adenocarcinomas to spread to inguinals for unclear reasons.

 

[Mandelin Rain]

I don’t usually cover inguinals unless they are positive or there is nodular disease in the anal canal. Pretty uncommon for low rectal adenocarcinomas to spread to inguinals for unclear reasons.

Same.

 

[dieABRdie]

are y’all boosting extramesorectal nodes that aren’t being resected? Covering inguinals in low lying tumors invading the anal canal?

Currently boosting 2 external iliac lymph nodes that will not be resected, to 59.4

 

[ramsesthenice]

Currently boosting 2 external iliac lymph nodes that will not be resected, to 59.4

I’ll do the same. 54-60. But my preference is to get them to take them out. Gotta talk it out beforehand.

 

[radoncftw]

You mean with short course?

Can boost to 35Gy in 5 Fx as an SIB with IMRT.
WashU folks doing this

Immunogenicity after two/three doses of mRNA vaccine in cancer patients treated with radiotherapy

www.estro.org

 

[ramsesthenice]

Can boost to 35Gy in 5 Fx as an SIB with IMRT.
WashU folks doing this

Immunogenicity after two/three doses of mRNA vaccine in cancer patients treated with radiotherapy

www.estro.org

With the exception of higher external iliacs, pelvic nodes are among the easiest thing to treat with radiosurgery, which is essentially what they are doing here. It makes sense.

 

[evilbooyaa]

Can boost to 35Gy in 5 Fx as an SIB with IMRT.
WashU folks doing this

Immunogenicity after two/three doses of mRNA vaccine in cancer patients treated with radiotherapy

www.estro.org

Had a guy with oligometastatic disease with good anatomy and a EI LN that I took to 40/5 simultaneously with 25/5 to remainder of pelvis after induction chemotherapy. So yes, although goal is basically to remain safe and respect bowel how you would with 25/5. This is more worthwhile in patients with lateralized pelvic nodal disease and not an issue for anyone planned for TME with positive mesorectal LNs.

 

[RadOncMegatron]

Does anyone know if this recommendation was update back to recommend radiation?

From the same NICE link it now states:

Preoperative treatment for people with rectal cancer​

1.3.2Do not offer preoperative radiotherapy to people with early rectal cancer (cT1-T2 cN0, M0), unless as part of a clinical trial.
1.3.3Offer preoperative radiotherapy or chemoradiotherapy to people with rectal cancer that is cT1-T2, cN1-N2, M0, or cT3-T4, any cN, M0.

 

[TheWallnerus]

Does anyone know if this recommendation was update back to recommend radiation?

From the same NICE link it now states:

Preoperative treatment for people with rectal cancer​

1.3.2Do not offer preoperative radiotherapy to people with early rectal cancer (cT1-T2 cN0, M0), unless as part of a clinical trial.
1.3.3Offer preoperative radiotherapy or chemoradiotherapy to people with rectal cancer that is cT1-T2, cN1-N2, M0, or cT3-T4, any cN, M0.

I still believe the guidelines are old (from last year)... who knows when (if?) they will be updated.

 

[RadOncMegatron]

I still believe the guidelines are old (from last year)... who knows when (if?) they will be updated.

Thanks for the response. I do think radiation has a role b/c pelvic recurrences suck, although I agree that we prb don't improve OS.

Unfortunate, that though there are multiple trials showing radiation improves local control, one retrospective study and UK surgeons' gut instinct about MRI's can over rule those studies.

 

[RickyScott]

Thanks for the response. I do think radiation has a role b/c pelvic recurrences suck, although I agree that we prb don't improve OS.

Unfortunate, that though there are multiple trials showing radiation improves local control, one retrospective study and UK surgeons' gut instinct about MRI's can over rule those studies.

Just trying to play devils advocate. Do we have good evidence that xrt improves local control vs neoadjuvant folfox alone?

 

[Palex80]

Just trying to play devils advocate. Do we have good evidence that xrt improves local control vs neoadjuvant folfox alone?

Of course not.

 

[RadOncMegatron]

Just trying to play devils advocate. Do we have good evidence that xrt improves local control vs neoadjuvant folfox alone?

Agree with your overall point, but isn’t standard for the new kid on the block to knock off what is standard of care or is that just boomer style thinking lol

 

[RickyScott]

Agree with your overall point, but isn’t standard for the new kid on the block to knock off what is standard of care or is that just boomer style thinking lol

Agreed, but I see it coming. We will be out of gi by early 2030s

 

[Palex80]

Agree with your overall point, but isn’t standard for the new kid on the block to knock off what is standard of care or is that just boomer style thinking lol

With a good TME, the risk of local recurrence in stage IIA and most stage III rectal cancers is very low.
I am not talking about the "big, nasty" cT4 cN2 cancers. Those patients still have a considerable risk for locoregional recurrence.

But what we see in daily praxis is >50% cT3 cN0 or cT3 cN1 disease.
These patients likely do not benefit from neoadjuvant RT, especially if the end up getting FOLFOX/CAPOX before or after surgery. Their risk of local recurrence is <5%.

 

[TheWallnerus]

But what we see in daily praxis is >50% cT3 cN0 or cT3 cN1 disease.
These patients likely do not benefit from neoadjuvant RT, especially if the end up getting FOLFOX/CAPOX before or after surgery. Their risk of local recurrence is <5%.

I wonder what the utilization rate of neoadj chemoRT in the USA is for these patients. I would guess... 80%?

You will find in the US either rad oncs don't know what a "good TME" is or don't trust their local surgeon to do a good TME and thus want to push for neoadj chemoRT.

 

[Palex80]

Have a look at the ESMO guidelines.

Gastrointestinal Cancers | ESMO

Rectal Cancer: ESMO Clinical Practice Guidelines

www.esmo.org

Early rectal cancer not suitable for local excision [cT1–cT2; cT3a/ b if middle or high, N0 (or also cN1 if high), MRF clear, no EMVI].
More advanced tumours up to and including cT2c/T3a/b should be treated by radical TME surgery because of higher risks of recurrence and the higher risk of mesorectal lymph node involvement.
...
These early, favourable cases, which are not suitable for local excision, i.e. cT1-2 but with adverse pathological features (e.g. G3, V1, L1), and some cT3a/b without clear involvement of MRF (MRF-) according to MRI, when located above the levators, may be appropriate for surgery alone with TME [II, A], as the risk of local failure is very low. Although not prospectively assessed, EMVI on MRI, even in the case of cT3a/b tumours, confers a higher risk of local and distant recurrence.


Intermediate/more locally advanced rectal cancers [cT3a/b (very low, levators clear, MRF clear or (cT3a/b in mid- or high rectum, cN1-2 (not extranodal), no EMVI].
The routine delivery of preoperative RT, either CRT or short-course preoperative radiotherapy (SCPRT), to all patients with imaging predicted cN+ remains controversial in view of the poor accuracy if categorised by nodal size alone, and the lack of prognostic relevance of the preoperative MRI assessment of involved lymph nodes on the risk of local recurrence. This is particularly valid because data suggest a low risk of local recurrence if the surgeon routinely carries out good-quality TME and removes the mesorectal nodes en bloc. However, it is the responsibility of the surgeon to demonstrate that consistent, good-quality TME is being achieved.


Locally advanced rectal cancers (>cT3b, and EMVIþ).
For patients with LARC, treatment decisions regarding neoadjuvant therapy should be based on preoperative, MRI-predicted CRM
( 1 mm), EMVI and more advanced T3 substages (T3c/T3d), which define the risk of both local recurrence and/or synchronous and subsequent metastatic disease. MRI also allows risk stratification in terms of the predicted required extent of surgery, and the achievement of a clear CRM (>1 mm). For resectable cancers, where there is no indication on MRI that surgery is likely to be associated with either an R2 or an R1
resection, standard TME should achieve a curative resection, and downstaging/downsizing is not necessary to achieve this. The use of CRT or SCPRT aims to reduce local recurrence.
...
Previous recommendations aimed to reduce the overall risk of an involved CRM to < 3% and local recurrence to (preferably) < 5% in the population in whom curative treatment is intend. Evidence from the UK CR07 trial suggests that, without RT, a local recurrence rate of 5% (27/543) can be achieved if a complete mesorectal excision is carried out with a negative CRM. MDTs and surgeons are, therefore, required to audit their local recurrence rates. There are recognised long-term adverse consequences of surgery and RT. Symptoms such as chronic pain, faecal incontinence and sexual difficulties are reported in both sexes. Good communication between surgeons, clinicians and patients will optimise joint decision-making.


Tumours with threatened resection margin.
The terms ‘unresectable/borderline cancers’ (i.e. cT4, with the resection margin at risk, involved MRF or CRMþ) are imprecise, but MRI can predict rectal cancers that are unlikely to be amenable to a curative resection without multivisceral resection, either because the tumour abuts or breaches the MRF or there is macroscopic tumour outside the MRF with local extension to pelvic side wall and sacrum or in terms of tumour spread involvement into the lateral compartment. In these circumstances, preoperative treatment is necessary to shrink the cancer back away from the threatened margin i.e. the MRF/CRM. Without preoperative treatment or in the case of no response, surgery is likely to lead to either an
R1 or an R2 resection. For such patients, CRT has been shown to significantly increase the chance of performing an R0 resection compared with RT alone.



You see what the picture is over here?
We are left with "tumours with threatened resection margin" more or less...

 

[TheWallnerus]

Guideline mentions TME a lot too. Again I think US rad oncs (I could be wrong!) don't *fully* appreciate what good rectal surgery entails and don't have the surgical vocabulary to interrogate the surgeons with which they work to determine if the surgeons are doing good TMEs. I am more confident in younger surgeons than older surgeons in this regard. But even then, I, myself, am never able to "choose" the surgeon