T4 Sigmoid Rectal Case

[Haybrant]

Tough case, 57 yo man with T4aN1M0 Stage III colorectal adenocarcinoma was taken for surgical resection up front bc colonoscopy report showed that his lesion was at 20cm. During surgery they found that it invaded further down and there the lesion was adherent to the posterior bladder wall. They did a diverting loop ileostomy and sent him to med onc.

Med onc offered FOLFOX alone. The med onc gave 7 cycles of FOLFOX, didn't get an interim image to see if he was responding. Gets follow up imaging and looks like he has progressed locally and there is a fistula to his rectal stump and invasive further into bladder. How to manage this now? Looks like his full bladder will get high dose. Is the fistula an issue or just start chemo/RT now and hope for the best when it comes to shrinkage? Thanks

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[OTN]

Tough case, 57 yo man with T4aN1M0 Stage III colorectal adenocarcinoma was taken for surgical resection up front bc colonoscopy report showed that his lesion was at 20cm. During surgery they found that it invaded further down and there the lesion was adherent to the posterior bladder wall. They did a diverting loop ileostomy and sent him to med onc.

Med onc offered FOLFOX alone. The med onc gave 7 cycles of FOLFOX, didn't get an interim image to see if he was responding. Gets follow up imaging and looks like he has progressed locally and there is a fistula to his rectal stump and invasive further into bladder. How to manage this now? Looks like his full bladder will get high dose. Is the fistula an issue or just start chemo/RT now and hope for the best when it comes to shrinkage? Thanks

Did he have a preop MRI? It certainly would have shown bladder invasion.

FOLFOX should have been offered after chemoRT, as his chance of local recurrence was always very, very high. I have serious doubts about the abilities of the medonc who offered FOLFOX alone.

If the colorectal surgeons along with urology can take down the fistula with a partial bladder resection I’d say do that first, but if it’s not possible I would proceed to chemoRT. I wouldn’t worry about full dose to the bladder necessarily. It will be toxic, but full-dose chemoRT to the pelvis is his only chance at cure now.

 

[Haybrant]

Did he have a preop MRI? It certainly would have shown bladder invasion.

FOLFOX should have been offered after chemoRT, as his chance of local recurrence was always very, very high. I have serious doubts about the abilities of the medonc who offered FOLFOX alone.

If the colorectal surgeons along with urology can take down the fistula with a partial bladder resection I’d say do that first, but if it’s not possible I would proceed to chemoRT. I wouldn’t worry about full dose to the bladder necessarily. It will be toxic, but full-dose chemoRT to the pelvis is his only chance at cure now.

Yes things have been quite solid for the most part with the parties involved but this isn't ideal. What do you consent him for if treating him w fistula - fistula will just worsen?

 

[OTN]

If the fistulous tract is due to cancer involvement/recurrence, which is sounds like it is, and they're not going to be able to operate prior to chemoRT, which it sounds like they're not, that tract will never heal until the malignancy is eradicated in the area. So, radiation might actually help with the fistula long-term, but usually they have to be fixed surgically after chemoRT. Might heal on its own if you can get a pCR from ChemoRT, though. Bladder/upper urinary tract infection shouldn't be as much of a concern with a fistula from the rectal stump to the bladder, rather than the intact bowel.

 

[seper]

I would do a cystoscopy or a retrograde contrast study to make sure there is no bladder fistula before XRT. If there is, he needs urinary diversion too.

 

[Haybrant]

If the fistulous tract is due to cancer involvement/recurrence, which is sounds like it is, and they're not going to be able to operate prior to chemoRT, which it sounds like they're not, that tract will never heal until the malignancy is eradicated in the area. So, radiation might actually help with the fistula long-term, but usually they have to be fixed surgically after chemoRT. Might heal on its own if you can get a pCR from ChemoRT, though. Bladder/upper urinary tract infection shouldn't be as much of a concern with a fistula from the rectal stump to the bladder, rather than the intact bowel.

take it to 5040 w 5FU?

as an aside ive seen a lot of people start with chemo when there is a liver met for example. They do restage after 2-3 cycles to assess response

 

[evilbooyaa]

Patient has a fistula now or may develop one in the future. Divert when patient has a documented fistula (do study to document presence or lack of one prior to RT) with bilateral nephrostomies. 1-year after RT if disease free patient can go to urologic reconstructive surgeon for takedown and repair of fistula. Would not attempt primary fistula takedown afer neoadjuvant chemoRT but the surgeons will likely try it anyways.

I would take it to higher dose than 5040 personally, at least 54Gy. Can consider 59Gy as well as we know the bladder can handle that dosing fine.

Agree that med-onc is extraordinarily dumb in this case. Patient had a chance to not require re-resection with post-op RT.

Patient needs chemoRT first at this point. I would not attempt to do post-op RT after two intraabdominal/pelvic surgeries.

 

[Haybrant]

Did he have a preop MRI? It certainly would have shown bladder invasion.

FOLFOX should have been offered after chemoRT, as his chance of local recurrence was always very, very high. I have serious doubts about the abilities of the medonc who offered FOLFOX alone.

If the colorectal surgeons along with urology can take down the fistula with a partial bladder resection I’d say do that first, but if it’s not possible I would proceed to chemoRT. I wouldn’t worry about full dose to the bladder necessarily. It will be toxic, but full-dose chemoRT to the pelvis is his only chance at cure now.

I wanted to come back to this comment since it is a bit out of line with what I have seen evolving in rectal cancer particularly the consensus here that a bulky tumor like this should without question go to CRT - that does not seem in line with practice right now. The bigger issue to me is not that he started w FOLFOX but that he was not reimaged after a short time period to see response. Here is a mednet response from MSKCC Abe Wu to the question: "When would you consider initial induction chemotherapy (e.g. FOLFOX) followed by neoadjuvant chemoradiation, over neoadjuvant chemoradiation alone, in patients with locally advanced rectal cancer?"

"At MSKCC, we now routinely recommend induction chemotherapy (8 cycles of FOLFOX) to any rectal cancer patient who requires preoperative chemoRT. Initially, we adopted this approach for patients with particularly bulky or node-positive disease (as per Dr. McRee's answer above) but now do it for everyone. The primary rationale was to address the concern for systemic dissemination upfront, rather than having to wait several months after chemoRT and surgery. We have published our initial results with this approach (Cercek A, et al., JNCCN 2014). Of course, we don't yet have prospective evidence proving that induction chemotherapy is superior to traditional sequencing of therapy, or of which groups may benefit the most from induction chemotherapy, but we've felt comfortable enough with this approach and its potential advantages to make it our institutional standard of care. The NCCN guidelines also now describe induction chemotherapy followed by preop CRT as an acceptable strategy for locally advanced rectal cancer."

Another Comment from UNC is below:
"I think about using induction chemotherapy for larger, bulkier tumors; extensive radiographic evidence of nodal involvement; or those with encroachment into other organs for which margins may be an issue at the time of surgery. This approach is being formally studied on the PROSPECT trial in which patients with T2N1, T3N0, or T3N1 rectal cancer are treated with 6 cycles of FOLFOX after which they are restaged with MRI or EUS. If interval decrease in size is documented, the patient proceeds to surgery; otherwise traditional CRT is given."

 

[OTN]

I wanted to come back to this comment since it is a bit out of line with what I have seen evolving in rectal cancer particularly the consensus here that a bulky tumor like this should without question go to CRT. The bigger issue to me is not that he started w FOLFOX but that he was not reimaged after a short time period to see response. Here is a mednet response from MSKCC Abe Wu to the question: "When would you consider initial induction chemotherapy (e.g. FOLFOX) followed by neoadjuvant chemoradiation, over neoadjuvant chemoradiation alone, in patients with locally advanced rectal cancer?"

"At MSKCC, we now routinely recommend induction chemotherapy (8 cycles of FOLFOX) to any rectal cancer patient who requires preoperative chemoRT. Initially, we adopted this approach for patients with particularly bulky or node-positive disease (as per Dr. McRee's answer above) but now do it for everyone. The primary rationale was to address the concern for systemic dissemination upfront, rather than having to wait several months after chemoRT and surgery. We have published our initial results with this approach (Cercek A, et al., JNCCN 2014). Of course, we don't yet have prospective evidence proving that induction chemotherapy is superior to traditional sequencing of therapy, or of which groups may benefit the most from induction chemotherapy, but we've felt comfortable enough with this approach and its potential advantages to make it our institutional standard of care. The NCCN guidelines also now describe induction chemotherapy followed by preop CRT as an acceptable strategy for locally advanced rectal cancer."

Another Comment from UNC is below:
"I think about using induction chemotherapy for larger, bulkier tumors; extensive radiographic evidence of nodal involvement; or those with encroachment into other organs for which margins may be an issue at the time of surgery. This approach is being formally studied on the PROSPECT trial in which patients with T2N1, T3N0, or T3N1 rectal cancer are treated with 6 cycles of FOLFOX after which they are restaged with MRI or EUS. If interval decrease in size is documented, the patient proceeds to surgery; otherwise traditional CRT is given."

I had the biggest beef with the fact it seemed the medonc wasn't going to offer chemoRT at all - maybe I misread that. I don't have any problem necessarily with FOLFOX neoadjuvantly, but to do it on everyone as per MSKCC without any prospective data seems premature.

 

[Haybrant]

I had the biggest beef with the fact it seemed the medonc wasn't going to offer chemoRT at all - maybe I misread that. I don't have any problem necessarily with FOLFOX neoadjuvantly, but to do it on everyone as per MSKCC without any prospective data seems premature.

Oh ok I hear you; it was discussed but like the UNC rad onc mentions it was an issue of the lesion being very large/bulky/encroaching bladder and a large amount of small bowel. But like you I am surprised to hear that everyone at MSK is being treated like this. At the same time you look at phase II for folfox alone and the response rates are actually quite good, not very different from RT + 5FU. I was surprised when I saw it too

 

[evilbooyaa]

The PROSPECT trial is an abomination. They're going to take people that have favorable biology (and respond to chemo) and do surgery, and then claim that it's better than the non-responders who required CRT and then had surgery.

They should have taken good responders and randomize them to CRT vs no CRT, and do the same with non-responders.

 

[ramsesthenice]

Oh ok I hear you; it was discussed but like the UNC rad onc mentions it was an issue of the lesion being very large/bulky/encroaching bladder and a large amount of small bowel. But like you I am surprised to hear that everyone at MSK is being treated like this. At the same time you look at phase II for folfox alone and the response rates are actually quite good, not very different from RT + 5FU. I was surprised when I saw it too

Our med oncs are doing it to. They want to treat anyone that is T4 or N2 with neoadjuvant chemo first (but not in place of CRT to be clear). I don't have an issue with it most of the time but their fundamental argument for doing so flies in the face of all existing data. They argue that really high risk patients need to get on chemo sooner to reduce systemic progression. Induction does not improve DMFS or OS. Doesn't work in H&N cancer, doesn't work in breast, or most any other solid tumor. The Spanish trial in rectal cancer was stone cold negative. Not even a hint of a benefit in terms of disease control, though the neoadjuvant appeared to be a little better tolerated.

I had a case go terribly wrong recently with induction chemo recently. Dude had a big low rectal tumor that was quite symptomatic. I offered upfront RT since he was symptomatic. But he was N2 and the med oncs convinced him to do neoadjuvant chemo first. He kept getting febrile so before cycle 3 they decided to do a full odentectomy (they thought his teeth were the most likely source of infection). He progressed on chemo and I had to step in after cycle 4. He kept having mouth issues and ended up on TPN after RT which delayed surgery for 3 months. Sigh...

 

[Palex80]

Unfortunately it's not going to end well for your patient.
Even you get the chance to cure him, his QoL is going to be bad.

I'd do full dose CRT to 54+ Gy and then send him to surgery. If he is lucky, he will get to keep his bladder... Since the disease seems to be chemotefractory, expect a high risk of systemic spread, so be certain he is well restaged before pushing the dose high or embarking on aggressive surgery.

 

[Haybrant]

Unfortunately it's not going to end well for your patient.
Even you get the chance to cure him, his QoL is going to be bad.

I'd do full dose CRT to 54+ Gy and then send him to surgery. If he is lucky, he will get to keep his bladder... Since the disease seems to be chemotefractory, expect a high risk of systemic spread, so be certain he is well restaged before pushing the dose high or embarking on aggressive surgery.

he's on treatment now, mentally prep'd him for the worst