Bladder Case

[xrt123]

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Patient with grossly positive node (2cm) at time of a partial cystectomy. Urologist isn't aggressive and since the margins were negative on the partial cystectomy specimen didn't feel the need to do any further resection or take out any more than the one node he saw that was enlarged. Imaging shows no other grossly involved nodes. He was sent to the MedOnc. MedOnc curbsides me and there is certainly plenty of retrospective data (and the Egyptian trial) to say there is increased risk of pelvic failure.

Would you treat pelvis after chemo and if so would you include the remaining bladder despite negative margins?

 

[medgator]

Yes, assuming pt had a negative PET at some point before/after surgery....

Btw, not sure about the data for "partial" cystectomy" as a form of bladder preservation in muscle-invasive disease

 

[KHE88]

What were margin size, histology, and T-stage? Surprised surgeon didn't abort and went ahead with partial cystectomy in setting of a gross node.

This is data post complete cystectomy...

Squamous cell carcinomas of the bladder have the worst prognosis but are extremely uncommon (<5%). But they are 70% of cases in Egypt. So you have to interpret the Egyptian trial in that context (mostly SCCa). Also there was 30% incidence of small bowel obstruction (pre-IMRT era) on that trial. NRG GU-001 currently open investigating post-op IMRT; however, requires radical cystectomy, not partial.

From Baumann publication, pelvic failures are more common for pT3-T4 disease and positive margins, usually sidewall, but also high rates of presacral or op-bed failures. Pelvic failures with negative margins are rare. Also <10 nodes removed. Your guy only had one?

For partial cystectomy, LRR up to 50% in first year.

Most bladder patients met out and die from distant mets.

I don't know. I strongly suspect this person has occult distant disease. Metastatic workup negative? Don't know if the toxicity is worth it. Would be interested in seeing any data for PORT in partial cystectomy patients. I'm not aware of any as typically the selection criteria for partial cystectomy is so strict. I would imagine the salvage for the half of patients who fail locally would just be removing the rest of the bladder then chemo. I'm not sure if you could go on GU-001 in that setting.

 

[Chartreuse Wombat]

Patient with grossly positive node (2cm) at time of a partial cystectomy. Urologist isn't aggressive and since the margins were negative on the partial cystectomy specimen didn't feel the need to do any further resection or take out any more than the one node he saw that was enlarged. Imaging shows no other grossly involved nodes. He was sent to the MedOnc. MedOnc curbsides me and there is certainly plenty of retrospective data (and the Egyptian trial) to say there is increased risk of pelvic failure.

Would you treat pelvis after chemo and if so would you include the remaining bladder despite negative margins?

"Remaining bladder?" for node positive prostate cancer. D'oh

 

[RadOncDoc21]

I find doing partial bladders very challenging with setup and targeting disease which is why I just do whole bladder (empty bladder) and try to dose escalate to 54-60 Gy depending on small bowel constraints. I usually do a mini-pelvis to 45 Gy and boost positive nodes to same dose. I have yet been able to go higher than 60 feeling confident I’m hitting my target.

 

[xrt123]

"What were margin size, histology, and T-stage? Surprised surgeon didn't abort and went ahead with partial cystectomy in setting of a gross node. "

It was high grade papillary urothelial. The reason it was a partial is that the invasive cancer was in a diverticulum. Surgery was done to go in and remove a presumed superficial malignancy. Muscle was involved so at least a T2 but the path report doesn't actually specifiy. Thanks.

 

[Palex80]

I would treat. A positive node and no pelvic dissection are good enoung reasons to me. The fact that the patient still has his bladder makes the whole issue easier, treating a patients with a neobladder is always an issue.

 

[mheat3]

I'd advocate for systemic therapy first (assuming he got nothing preop) then re-stage and if no DM proceed with RT.

 

[Radiator20]

the invasive cancer was in a diverticulum

Muscle was involved so at least a T2

If it's muscle-invasive and in a diverticulum, my understanding is it's T3 by definition (since the muscle in question is herniated through the perivesical tissue, that barrier is lost.) While he is certainly at risk for distant failure, the inadequacy of surgical management here (both primary and nodes) makes me think he is also at quite high risk for locoregional failure. I'd treat. And given that he didn't have neoadjuvant chemo, adjuvant chemo in addition seems appropriate to me.

 

[evilbooyaa]

Treat like a definitive bladder case that basically got the equivalent of a biopsy IMO. Idk how the surgeon is benefiting the patient with a partial cystectomy in a case like this.

 

[Radiator20]

Treat like a definitive bladder case that basically got the equivalent of a biopsy IMO. Idk how the surgeon is benefiting the patient with a partial cystectomy in a case like this.

So would you do concurrent CRT? Considering this like definitive trimodality treatment was my first thought as well (essentially, pt got a really aggressive TURBT), but on the one hand, T3N1 is more advanced than most of the bladder preservation experience I'm aware of... OTOH, all the gross disease is gone...

 

[evilbooyaa]

Honestly we're in a space without data. But if I was radiating this patient (and not sending him for something like neoadjuvant CT + completion cystectomy with lymph node dissection), I would do it with concurrent chemotherapy, yes, per BC2001. You could make an argument to omit the boost given no gross disease, I suppose, but I'm wary of partial bladder boosts in general anyways given how rarely I see/treat bladder cancer.

You could treat by the RTOG trial as well with a second look prior to finishing out the treatment.

N1 is stage III disease, so this is not a scenario to just leave him be for chemo/systemic therapy alone. He needs definitive treatment. He has thus far not received definitive treatment.

 

[Radiator20]

Honestly we're in a space without data. But if I was radiating this patient (and not sending him for something like neoadjuvant CT + completion cystectomy with lymph node dissection), I would do it with concurrent chemotherapy, yes, per BC2001. You could make an argument to omit the boost given no gross disease, I suppose, but I'm wary of partial bladder boosts in general anyways given how rarely I see/treat bladder cancer.

You could treat by the RTOG trial as well with a second look prior to finishing out the treatment.

N1 is stage III disease, so this is not a scenario to just leave him be for chemo/systemic therapy alone. He needs definitive treatment. He has thus far not received definitive treatment.

The more I’m thinking about this, the more I agree with you that concurrent CRT is absolutely the right answer. While he has no gross disease currently, that’s also the starting point CRT for, eg, a T2N0 after maximal TURBT. Thanks!

 

[DoctwoB]

If it's muscle-invasive and in a diverticulum, my understanding is it's T3 by definition (since the muscle in question is herniated through the perivesical tissue, that barrier is lost.) While he is certainly at risk for distant failure, the inadequacy of surgical management here (both primary and nodes) makes me think he is also at quite high risk for locoregional failure. I'd treat. And given that he didn't have neoadjuvant chemo, adjuvant chemo in addition seems appropriate to me.

Urologist weighing in. These can be tricky, since bladder tics are false diverticula I.e no muscle backing meaning you can’t diagnose muscle invasive disease on TURBT. As such if you see evidence of cT3 or greater (N1 in this case) on imaging my ideal initial management would be radical cystectomy with LND after neoadjuvant Chemo. If node was visible on imaging probably should have been done though.

Sometimes you’ll do a partial cystectomy, however for presumed T1 disease that actually is T3 on final path, which is a somewhat tricky situation as there is no good data to guide. Do you do completion cystectomy + LND + chemo? That would be gold standard IMO. Adjuvant chemo and observation also reasonable in sicker patients.

In this case with pN+ disease would recommend completion cystectomy with LND and neoadjuvant chemo. If unable to get that for some reason would do chemo +\- xrt. Would push for surgery in this setting though.

 

[medgator]

Urologist weighing in. These can be tricky, since bladder tics are false diverticula I.e no muscle backing meaning you can’t diagnose muscle invasive disease on TURBT. As such if you see evidence of cT3 or greater (N1 in this case) on imaging my ideal initial management would be radical cystectomy with LND after neoadjuvant Chemo. If node was visible on imaging probably should have been done though.

Sometimes you’ll do a partial cystectomy, however for presumed T1 disease that actually is T3 on final path, which is a somewhat tricky situation as there is no good data to guide. Do you do completion cystectomy + LND + chemo? That would be gold standard IMO. Adjuvant chemo and observation also reasonable in sicker patients.

In this case with pN+ disease would recommend completion cystectomy with LND and neoadjuvant chemo. If unable to get that for some reason would do chemo +\- xrt. Would push for surgery in this setting though.

The 5 year survival rates between radical cystectomy and bladder preservation are pretty comparable in single arm studies.

Why so anti radiation (seems to be the case with many urologists, not you specifically).

Where's the data for partial cystectomy at all in muscle invasive disease?

Adjuvant chemo won't be enough if you leave disease behind with partial surgery

 

[scarbrtj]

Sometimes you’ll do a partial cystectomy, however for presumed T1 disease that actually is T3 on final path, which is a somewhat tricky situation as there is no good data to guide. Do you do completion cystectomy + LND + chemo? That would be gold standard IMO.

For a T3N1 patient (not that we knew he was N1 pre-op, but now we do), it's not the gold standard; it's a gold standard.

Why so anti radiation (seems to be the case with many urologists, not you specifically).

It seems pretty likely we (we=the bladder guys & the XRT guys) will never come to consensus on this issue.

 

[RadOncDoc21]

For a T3N1 patient (not that we knew he was N1 pre-op, but now we do), it's not the gold standard; it's a gold standard.

It seems pretty likely we (we=the bladder guys & the XRT guys) will never come to consensus on this issue.

I get the same pushback from most old school surg oncs regarding RT with most adamant they can “get it all out” or “spare the patient from getting radiation.” It’s exhausting having to present data they really could care less about at tumor boards.

There is definitely a turf war. Why should a urologist give the patient the option for an equally effective alternative treatment with less side effects? This goes for both prostates and bladder... urologists

 

[medgator]

I get the same pushback from most old school surg oncs regarding RT with most adamant they can “get it all out” or “spare the patient from getting radiation.” It’s exhausting having to present data they really could care less about at tumor boards.

There is definitely a turf war. Why should a urologist give the patient the option for an equally effective alternative treatment with less side effects? This goes for both prostates and bladder... urologists

"A chance to cut is a chance to cure"

"Cold steel is the best deal"

 

[DoctwoB]

For a T3N1 patient (not that we knew he was N1 pre-op, but now we do), it's not the gold standard; it's a gold standard.

It seems pretty likely we (we=the bladder guys & the XRT guys) will never come to consensus on this issue.

Maybe getting into semantics but based on historical management I’d call it the gold standard because that is what has been SOC for basically forever. Obviously there is no great data saying it’s better (or worse) then trimodal therapy, and I’m not anti bladder preserving therapy in appropriate patients (ideally not multifocal disease, completely resectable via TUR, poor PS, patient preference)

Small N, but of the 12 ish Trimodal therapy patients I’ve followed 4 still ended up with cystectomy for local failure or refractory hemorrhagic cystitis.

For node positive disease we have pretty good data that ~20% N+ disease can have durable cure with surgery. Don’t know of any similar data for XRT, so in this setting would favor surgery.

 

[medgator]

Small N, but of the 12 ish Trimodal therapy patients I’ve followed 4 still ended up with cystectomy for local failure or refractory hemorrhagic cystitis.

It all comes down to patient selection imo and consenting them. I think many would still jump at the chance of bladder preservation

 

[scarbrtj]

Maybe getting into semantics but based on historical management I’d call it the gold standard because that is what has been SOC for basically forever.

One has to be skeptical of this logic.

Small N, but of the 12 ish Trimodal therapy patients I’ve followed 4 still ended up with cystectomy for local failure or refractory hemorrhagic cystitis.

Anecdotal doesn't trump data...
(EDIT: please note, we will not see eye-to-eye on this issue. Ever.)
(EDIT 2: One has to remember that it's a relatively recent modern development that N1 bladder cancer is not Stage IV. In other words, "everyone" used to think that N1 bladder cancer was incurable. There might have been some "traditional" 🙂 wisdom in that.)

 

[nkmiami]

I call bs. I have treated a lot of bladder, and not had a case requiring cystectomy for refractory hemhorage. 33% is total bs. large trial like the james nejm trial with old 2d radiation techniques had nothing like this- I am not sure even one case, but I dont even feel like looking in response to this kind of nonsense.

 

[DoctwoB]

I call bs. I have treated a lot of bladder, and not had a case requiring cystectomy for refractory hemhorage. 33% is total bs. large trial like the james nejm trial with old 2d radiation techniques had nothing like this- I am not sure even one case, but I dont even feel like looking in response to this kind of nonsense.

Be honest. When’s the last time you saw one of these patients 5-10 years post XRT? Would you be consulted when they came in with clot retention? Just because you don’t see them (and trials often aren’t long enough to see them) doesn’t mean they don’t exist.

Once again I’m not saying this to rag on Trimodal. I also see the many complications that come from cystectomy. But bladder xrt is not benign.

 

[RadOncDoc21]

Maybe getting into semantics but based on historical management I’d call it the gold standard because that is what has been SOC for basically forever. Obviously there is no great data saying it’s better (or worse) then trimodal therapy, and I’m not anti bladder preserving therapy in appropriate patients (ideally not multifocal disease, completely resectable via TUR, poor PS, patient preference)

Small N, but of the 12 ish Trimodal therapy patients I’ve followed 4 still ended up with cystectomy for local failure or refractory hemorrhagic cystitis.

For node positive disease we have pretty good data that ~20% N+ disease can have durable cure with surgery. Don’t know of any similar data for XRT, so in this setting would favor surgery.

Historically, all women got mastectomies and a complete lymph node dissections for all stages of breast cancers. Historically, they would do radical hysterectomies for cervical cancers and patients underwent esophagectomies for esophageal cancers. All anal cancers were treated surgically and now we are starting to see less surgery for rectal cancers (still not SOC) but being investigated.

Just because we “historically” use to do do more surgery doesn’t mean we should keep doing it the same way we have been doing it.

Don’t worry, we won’t take all the patients from you, maybe we can even work together!

 

[scarbrtj]

Be honest. When’s the last time you saw one of these patients 5-10 years post XRT? Would you be consulted when they came in with clot retention? Just because you don’t see them (and trials often aren’t long enough to see them) doesn’t mean they don’t exist.

Once again I’m not saying this to rag on Trimodal. I also see the many complications that come from cystectomy. But bladder xrt is not benign.

4 out of 12 patients to need salvage cystectomy *OR* cystectomy due to hemorrhagic cystitis is in line with the literature IMHO. That experience is valid as phrased. I would say there is maybe a ~33% relapse rate and <1% incidence of XRT-related hemorrhagic cystitis... this is like that time Scottie Pippen said he'd never forget the night he and Michael Jordan combined to score 70 points. Michael scored 69 that nite and Scottie scored a point. (Having bladder CA re-grow in your bladder after XRT can cause blood in urine; probably "XRT-related hemorrhagic cystitis" and local recurrence symptoms overlap?) The rad oncs need to keep in mind that even though we follow patients long-term, we don't do cystoscopies. This will always limit our "true" insight into bladder XRT outcomes long-term I think. However, if you see a patient back 10 years later and they're peeing fine and have clear urine, a cystoscopy is moot then.

About 3 or 4 out of 12 patients will relapse after XRT long-term. About 3 or 4 out of 12 bladder patients will relapse after surgery long-term. Probably living without a bladder and having a stoma and changing urine out of a bag all day long for the rest of your life is not that bad. However, an irradiated bladder is a very useful, well-behaved bladder for the majority of patients. And when it is useful and well-behaved, it's much, much better than having no bladder at all. The QOL literature (it's weak and sparse) comparing cystectomy and chemoRT probably "overall" suggest better QOL w/ chemoRT.

 

[Radiator20]

I actually think we and DoctwoB are mostly on the same page, other than hemorrhagic cystitis rates...

For example, MGH experience: 475 pts, median 7 yr f/u:
-5 yr salvage cystectomy rate 30% (but only 16% in pts since 2005).
-one out of 475 pts required cystectomy for hemorrhagic cystitis.

Not saying DoctwoB's experience isn't real, but it doesn't seem reflective of the long-term experience at high-volume centers. That said, let's not, in accusing him of being anti-RT, ourselves be anti-urology... I think he is overall trying to be fair.

Seems to me that:

1. Existing data, while limited, suggest that for patients with good baseline bladder function (i.e., a bladder worth saving), bladder preserving trimodality therapy should be at least as much SOC as the historically dominant approach of neoadjuvant chemo f/b cystectomy (nice point//counterpoint recently about this in JAMA Onc - I think Tim Mitin, who trained at MGH, easily came out on top)
2. After TMT, an appreciable minority of patients will require salvage cystectomy for LR;
3. But the remainder of patients can successfully avoid cystectomy with good QOL (because, in Zietman's phrase, the best bladder you'll ever have is the one you were born with).
4. Bladder preservation does not take business from urologists. If anything, it generates more business from over the long term them due to need for ongoing surveillance cystoscopies. Bladder preservation is not just chemoRT - it is trimodality (TURBT, chemoRT) with ongoing cystoscopic survellance. It's an opportunity for collaboration, not competition. Rad onc wins, urologist wins, pt wins.
5. With respect to the original pt in this thread, N1 disease is beyond most of the literature I'm aware of for TMT (e.g., BC2001 and MGH experience were all N0 patients). That said, after his initial non-oncologic procedure, I think definitive oncologic management with either with (a) neoadjuvant chemo f/b completion cystectomy/LND, or (b) bladder-preserving chemoRT, would be reasonable.

 

[emt409]

Urologist weighing in. These can be tricky, since bladder tics are false diverticula I.e no muscle backing meaning you can’t diagnose muscle invasive disease on TURBT. As such if you see evidence of cT3 or greater (N1 in this case) on imaging my ideal initial management would be radical cystectomy with LND after neoadjuvant Chemo. If node was visible on imaging probably should have been done though.

Sometimes you’ll do a partial cystectomy, however for presumed T1 disease that actually is T3 on final path, which is a somewhat tricky situation as there is no good data to guide. Do you do completion cystectomy + LND + chemo? That would be gold standard IMO. Adjuvant chemo and observation also reasonable in sicker patients.

In this case with pN+ disease would recommend completion cystectomy with LND and neoadjuvant chemo. If unable to get that for some reason would do chemo +\- xrt. Would push for surgery in this setting though.

What's the data for adj chemo without XRT? As far as I know, there is none without prior induction.

 

[evilbooyaa]

Agree with Radiator20 and DoctwoB (besides the rates of hemorrhagic cystitis, the rate of salvage cystectomy is reasonably correct). Patient needs definitive oncologic management, whether that's completion total cystectomy + chemo (neoadjuvant or adjuvant) or definitive chemoRT.

Given lack of N1 patients on bladder preservation trials, I would favor a surgical approach if patient is agreeable. If he is not, I would offer bladder preservation treatment. Maybe the Europeans can run a phase III trial for surgery and RT (like they did in Prostate) b/c that **** will never accrue in the US.

 

[nkmiami]

Agree with Radiator20 and DoctwoB (besides the rates of hemorrhagic cystitis, the rate of salvage cystectomy is reasonably correct). Patient needs definitive oncologic management, whether that's completion total cystectomy + chemo (neoadjuvant or adjuvant) or definitive chemoRT.

Given lack of N1 patients on bladder preservation trials, I would favor a surgical approach if patient is agreeable. If he is not, I would offer bladder preservation treatment. Maybe the Europeans can run a phase III trial for surgery and RT (like they did in Prostate) b/c that **** will never accrue in the US.

Agree with Radiator20 and DoctwoB (besides the rates of hemorrhagic cystitis, the rate of salvage cystectomy is reasonably correct). Patient needs definitive oncologic management, whether that's completion total cystectomy + chemo (neoadjuvant or adjuvant) or definitive chemoRT.

Given lack of N1 patients on bladder preservation trials, I would favor a surgical approach if patient is agreeable. If he is not, I would offer bladder preservation treatment. Maybe the Europeans can run a phase III trial for surgery and RT (like they did in Prostate) b/c that **** will never accrue in the US.

Should we be offering surgery to known node positive patients? When there is such a high risk of metastatic disease- does that really justify something like a radical cystecomy. I think the burden of proof is on the surgeons in the setting of very high risk of distant disease , to prove that such an invasive/organ sacrificing procedure is warranted over chemo/xrt not visa-verse. The disease course will be set by response to systemic therapies. In a lot of the neoadjuvant chemo studies, survival was strongly correlated with a signifcant path repsonse to neoadjuvant chemo, so much so, that it left me questioning the role of surgery. If they have a great response, did they need the surgery and if they had no response, surgery wasnt really beneficial.

 

[evilbooyaa]

Should we be offering surgery to known node positive patients? When there is such a high risk of metastatic disease- does that really justify something like a radical cystecomy. I think the burden of proof is on the surgeons in the setting of very high risk of distant disease , to prove that such an invasive procedure is warranted over chemo/xrt not visa-verse.

Per NCCN guidelines, cN1 patients (which this patient would be less than cN1 in terms of nodal burden) gets treated definitively (either NAC chemo + surgery or definitive chemoRT). For cN2-3 patients, they recommend neoadjuvant chemo first followed by evaluation of response and definitive treatment if no progression.

Off protocol, I think offering surgery (w/ neoadjuvant chemo) would be a reasonable option. As would definitive chemoRT or even induction chemo followed by chemoRT. I think the concept that anything that is N+ in the pelvis means patients shouldn't be offered any surgery is extreme.

 

[nkmiami]

Per NCCN guidelines, cN1 patients (which this patient would be less than cN1 in terms of nodal burden) gets treated definitively (either NAC chemo + surgery or definitive chemoRT). For cN2-3 patients, they recommend neoadjuvant chemo first followed by evaluation of response and definitive treatment if no progression.

Off protocol, I think offering surgery (w/ neoadjuvant chemo) would be a reasonable option. As would definitive chemoRT or even induction chemo followed by chemoRT. I think the concept that anything that is N+ in the pelvis means patients shouldn't be offered any surgery is extreme.

I know that is conventional thinking, I just disagree. Most pts with node positive bladder cancer do really badly, so should you be subjecting them to this kind of surgery, when it has no proven benefit over RT. We dont do it in prosate cancer, and a prostatectomy is a lot more benign

Outcome of patients with grossly node positive bladder cancer after pelvic lymph node dissection and radical cystectomy. - PubMed - NCBI

Pelvic lymph node metastases from bladder cancer: outcome in 83 patients after radical cystectomy and pelvic lymphadenectomy. - PubMed - NCBI

 

[scarbrtj]

I know that is conventional thinking, I just disagree. Most pts with node positive bladder cancer do really badly, so should you be subjecting them to this kind of surgery, when it has no proven benefit over RT. We dont do it in prosate cancer, and a prostatectomy is a lot more benign

Outcome of patients with grossly node positive bladder cancer after pelvic lymph node dissection and radical cystectomy. - PubMed - NCBI

Pelvic lymph node metastases from bladder cancer: outcome in 83 patients after radical cystectomy and pelvic lymphadenectomy. - PubMed - NCBI

Maybe this "not aggressive" urologist was "smart" when he saw an enlarged lymph node, determined it was cancerous, and didn't do a full cystectomy...

 

[medgator]

Wasn't node positive disease considered M1/stage IV in previous staging editions?

 

[evilbooyaa]

I know that is conventional thinking, I just disagree. Most pts with node positive bladder cancer do really badly, so should you be subjecting them to this kind of surgery, when it has no proven benefit over RT. We dont do it in prosate cancer, and a prostatectomy is a lot more benign

Outcome of patients with grossly node positive bladder cancer after pelvic lymph node dissection and radical cystectomy. - PubMed - NCBI

Pelvic lymph node metastases from bladder cancer: outcome in 83 patients after radical cystectomy and pelvic lymphadenectomy. - PubMed - NCBI

I was going to write a somewhat mocking, sarcastic reply to you for citing studies from 2001 in this scenario (even in patients who didn't get adjuvant chemo as per the studies you posted) but then I looked up more recent data and the outcomes haven't obviously improved since 2001 when looking at entire cohorts. Those who get nodal downstaging with neoadjuvant chemo do much better, but that's obviously a subset of the population. Maybe you're right and if the 5-year survival is < 20%, taking out everybody's bladder is maybe overkill.

 

[RadOncDoc21]

Hence my prior posts... just because we did something “historically” doesn’t always mean it’s the best option.

 

[scarbrtj]

I was going to write a somewhat mocking, sarcastic reply to you for citing studies from 2001 in this scenario (even in patients who didn't get adjuvant chemo as per the studies you posted) but then I looked up more recent data and the outcomes haven't obviously improved since 2001 when looking at entire cohorts. Those who get nodal downstaging with neoadjuvant chemo do much better, but that's obviously a subset of the population. Maybe you're right and if the 5-year survival is < 20%, taking out everybody's bladder is maybe overkill.

Do not mock me.