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First-Line Options in Muscle-Invasive Bladder Cancer

Panelists:Raoul S. Concepcion, MD, FACS, Urology Associates; Michael S. Cookson, MD, MMHC, University of Oklahoma Health Sciences Center; Daniel P. Petrylak, MD, Yale School of Medicine; Daniel I. Quinn, MBBS, PhD, FRACP, FACP, University of Southern California; Neal D. Shore, MD, FACS, Carolina Urologic Research Center; Charles J. Ryan, MD, UCSF Helen Diller Family Comprehensive Cancer Center
Published: Thursday, Aug 04, 2016


Transcript:

Raoul S. Concepcion, MD:
We’re going to switch gears a little bit now and go into a tumor type that we’ve never really discussed here on Peer Exchange, but there’s lots of great studies. There are more new drugs coming on to the market. And obviously for the urology team here, it’s something that we see a lot. I think there is a real potential here, again, as we see more and more patients that present with hematuria and, ultimately, bladder cancer. As we all know, there tends to be two basic types of bladder cancer: non–muscle-invasive and muscle-invasive bladder cancer.

This first case we’re going to go through is a 53-year-old white female who presents to her primary care physician with pelvic and flank pain, as well as microscopic hematuria. As is often times done in the community and elsewhere, she was treated with antibiotics by the PCP. She continued to have too-numerous-to-count red cells on high-powered field, has no history of kidney stones, is a nonsmoker, works at a local boot factory in middle Tennessee, is sexually active, and has no prior surgical history. After she failed therapy and continued to have blood in her urine, she was sent to urology. They got a CT scan of the abdomen and pelvis, which showed left hydroureteronephrosis—thickening of the left lateral wall of the bladder—and a questionable 2-cm lymph node to the left common iliac artery. She underwent cystoscopy under local anesthesia, and it showed a nonpapillary tumor to the left lateral wall and hemitrigone. Orifice invasion was not identified, and examination otherwise was unremarkable. She was then taken for general anesthesia, had a biopsy that showed high-grade urothelial carcinoma with invasion deep into the muscularis, and her EUA (examination under anesthesia) basically showed that her bladder was not fixed.

So, we’ve got a young woman. She’s healthy, a nonsmoker, and has left hydroureteronephrosis, thickening of the left bladder wall. Orifice invasion is not identified; nonpapillary tumor; broad-based, high-grade urothelial cancer with at least invasion into the superficial; and also probably deep muscularis. At least a T2, T3 disease. Dr. Cookson?

Michael S. Cookson, MD, MMHC: Well, there are a couple of things about her that are interesting. And I think it’s been reported in lung cancer, a higher incidence of nonsmoking-related disease. We’re seeing that in bladder, too. In this particular lady, she has hydronephrosis. That’s a harbinger of poor outcome, usually related too late in discovery, and also associated with lymphadenopathy. Most of the time, these patients have no obvious radiographic evidence. But this lady does. I think there are many things about her features that make us think she has systemic risk and may already have regional nodes. Even if she didn’t have the node, I would be in favor of suggesting platinum-based neoadjuvant chemotherapy up front for her. The challenge will be, what’s her renal function with an obstructed kidney? Because we can’t get in from below, she may need a nephrostomy tube to allow for her to get the renal function she needs to get the therapy that she needs.

Raoul S. Cookson, MD: So, let’s just say her creatinine is 1.1 mg/dL and they go ahead and put in a left percutaneous nephrostomy tube. Dan, I think this is an area where, historically, urologists are getting better, but we have not necessarily always embraced the concept of neoadjuvant chemotherapy for muscle-invasive bladder cancer.

Daniel P. Petrylak, MD: We have two randomized trials which have demonstrated a survival benefit for neoadjuvant platinum-based chemotherapy. The two regimens used in that study were MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) in the United States, or in Europe, it was CMV (cisplatin, methotrexate and vinblastine). This shows about a 10% overall difference, or improvement, in overall survival in favor of systemic chemotherapy. We recommend neoadjuvant cisplatin-based therapy routinely for those patients who have adequate renal function prior to cystectomy.

Raoul S. Concepcion, MD: What if they have poor renal function? How does carboplatin do in this setting?

Daniel P. Petrylak, MD: The trouble is there are no data with carboplatin. And there are a lot of us who feel that carboplatin is an inferior drug to cisplatin. So, we’ll try to make every effort to manipulate the cisplatin dosage schedule to get that full treatment in. For example, you can split the platinum over 2 different days. You can do other little tricks to try to keep the creatinine clearance up, but cisplatin should be used at all costs. If a patient has creatinine of 2 mg/dL, for example, I would just go right to cystectomy. I would not even bother with carboplatin-based therapy.

Transcript Edited for Clarity
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Transcript:

Raoul S. Concepcion, MD:
We’re going to switch gears a little bit now and go into a tumor type that we’ve never really discussed here on Peer Exchange, but there’s lots of great studies. There are more new drugs coming on to the market. And obviously for the urology team here, it’s something that we see a lot. I think there is a real potential here, again, as we see more and more patients that present with hematuria and, ultimately, bladder cancer. As we all know, there tends to be two basic types of bladder cancer: non–muscle-invasive and muscle-invasive bladder cancer.

This first case we’re going to go through is a 53-year-old white female who presents to her primary care physician with pelvic and flank pain, as well as microscopic hematuria. As is often times done in the community and elsewhere, she was treated with antibiotics by the PCP. She continued to have too-numerous-to-count red cells on high-powered field, has no history of kidney stones, is a nonsmoker, works at a local boot factory in middle Tennessee, is sexually active, and has no prior surgical history. After she failed therapy and continued to have blood in her urine, she was sent to urology. They got a CT scan of the abdomen and pelvis, which showed left hydroureteronephrosis—thickening of the left lateral wall of the bladder—and a questionable 2-cm lymph node to the left common iliac artery. She underwent cystoscopy under local anesthesia, and it showed a nonpapillary tumor to the left lateral wall and hemitrigone. Orifice invasion was not identified, and examination otherwise was unremarkable. She was then taken for general anesthesia, had a biopsy that showed high-grade urothelial carcinoma with invasion deep into the muscularis, and her EUA (examination under anesthesia) basically showed that her bladder was not fixed.

So, we’ve got a young woman. She’s healthy, a nonsmoker, and has left hydroureteronephrosis, thickening of the left bladder wall. Orifice invasion is not identified; nonpapillary tumor; broad-based, high-grade urothelial cancer with at least invasion into the superficial; and also probably deep muscularis. At least a T2, T3 disease. Dr. Cookson?

Michael S. Cookson, MD, MMHC: Well, there are a couple of things about her that are interesting. And I think it’s been reported in lung cancer, a higher incidence of nonsmoking-related disease. We’re seeing that in bladder, too. In this particular lady, she has hydronephrosis. That’s a harbinger of poor outcome, usually related too late in discovery, and also associated with lymphadenopathy. Most of the time, these patients have no obvious radiographic evidence. But this lady does. I think there are many things about her features that make us think she has systemic risk and may already have regional nodes. Even if she didn’t have the node, I would be in favor of suggesting platinum-based neoadjuvant chemotherapy up front for her. The challenge will be, what’s her renal function with an obstructed kidney? Because we can’t get in from below, she may need a nephrostomy tube to allow for her to get the renal function she needs to get the therapy that she needs.

Raoul S. Cookson, MD: So, let’s just say her creatinine is 1.1 mg/dL and they go ahead and put in a left percutaneous nephrostomy tube. Dan, I think this is an area where, historically, urologists are getting better, but we have not necessarily always embraced the concept of neoadjuvant chemotherapy for muscle-invasive bladder cancer.

Daniel P. Petrylak, MD: We have two randomized trials which have demonstrated a survival benefit for neoadjuvant platinum-based chemotherapy. The two regimens used in that study were MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) in the United States, or in Europe, it was CMV (cisplatin, methotrexate and vinblastine). This shows about a 10% overall difference, or improvement, in overall survival in favor of systemic chemotherapy. We recommend neoadjuvant cisplatin-based therapy routinely for those patients who have adequate renal function prior to cystectomy.

Raoul S. Concepcion, MD: What if they have poor renal function? How does carboplatin do in this setting?

Daniel P. Petrylak, MD: The trouble is there are no data with carboplatin. And there are a lot of us who feel that carboplatin is an inferior drug to cisplatin. So, we’ll try to make every effort to manipulate the cisplatin dosage schedule to get that full treatment in. For example, you can split the platinum over 2 different days. You can do other little tricks to try to keep the creatinine clearance up, but cisplatin should be used at all costs. If a patient has creatinine of 2 mg/dL, for example, I would just go right to cystectomy. I would not even bother with carboplatin-based therapy.

Transcript Edited for Clarity
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