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Expert Discusses Impact of Muscle-Invasive Bladder Cancer Guidelines

Danielle Bucco
Published: Thursday, Aug 24, 2017

Jonathan E. Rosenberg, MD
Jonathan E. Rosenberg, MD
There are now interdisciplinary guidelines for the treatment of patients with muscle-invasive bladder cancer, following a collaboration with the American Urological Association (AUA) and other prominent groups, such as the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Urologic Oncology (SUO).

“These guidelines now incorporate cisplatin-based chemotherapy for patients who have adequate kidney function, no significant neuropathy, no significant hearing loss, and who are otherwise healthy enough to undergo this type of treatment,” explains Jonathan E. Rosenberg, MD.

The guidelines provide evidence-based recommendations on staging, neoadjuvant and adjuvant chemotherapy, radical cystectomy, urinary diversion, perioperative surgical management, and pelvic lymphadenectomy. For example, the organizations gave a strong grade B recommendation to clinicans offering cisplatin-based neoadjuvant chemotherapy to eligible radical cystectomy patients prior to cystectomy, when utilizing a multidisciplinary approach.

There are also a number of recommendations on bladder preserving approaches, which are an addition to the updated set of guidelines.

In an interview with OncLive, Rosenberg, a medical oncologist at Memorial Sloan Kettering Cancer Center, discussed the guidelines and their significance for the treatment of patients with muscle-invasive bladder cancer.

OncLive: Can you discuss these guidelines for bladder cancer and their significance?

Rosenberg: Traditionally, muscle-invasive bladder cancer has been managed purely by urologists in the United States with radical cystectomy being the only treatment often offered. However, there have been several large, randomized trials that show a benefit with cisplatin-based neoadjuvant chemotherapy prior to cystectomy.

There’s been a large educational effort over the years and this is an outgrowth of that effort to implement appropriate therapy for patients who are candidates for cisplatin-based neoadjuvant chemotherapy. We know that it reduces the risk of death from bladder cancer by one-third and improves the survival by 5% to 10%, depending on the clinical trial. 

We have worked on these guidelines to establish this as a standard of care in conjunction with other organizations, such as ASCO. These guidelines now incorporate cisplatin-based chemotherapy for patients who have adequate kidney function, no significant neuropathy, no significant hearing loss, and who are otherwise healthy enough to undergo this type of treatment. 

Is immunotherapy mentioned in these guidelines?

Not yet. Immunotherapy for these patients remains experimental, and there are multiple clinical trials that are testing this. There is a focus on adjuvant immunotherapy in large randomized phase III trials that are currently accruing patients. These trials are testing whether PD-1/PD-L1 inhibition versus observation or placebo—depending on the study—will improve survival for high-risk patients after cystectomy.

Postoperative treatment is generally adjuvant cisplatin-based chemotherapy for patients with high-risk disease who have not received neoadjuvant chemotherapy. In my opinion, if they have received neoadjuvant therapy, these patients should consider enrolling on one of these trials if their cancer was still high-risk after cystectomy. 

There are many patients who can't receive cisplatin-based chemotherapy for a variety of medical reasons, in which case they are not receiving neoadjuvant chemotherapy and could consider enrolling in one of the adjuvant therapy trials. To date, there are no results from these studies and we are looking for evidence that these patients would benefit from this approach.  

Have any recent advancements in the field impacted these guidelines?

One of the questions that always arises is whether there are any molecular or clinical predictors about who would benefit from neoadjuvant chemotherapy. There are multiple intriguing technologies that are investigating this. My own opinion is that none of them are ready for primetime. 

One methodology is looking at DNA damage-repair mutations that is essentially the mechanism of action for cisplatin-based chemotherapy. It damages the DNA; the cells that have defective DNA repair are unable to recover, and we see better outcomes in those patients. However, the data thus far have been retrospective—none of it has been prospective—and it requires prospective validation.


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