SUO 2015 - New approaches to adjuvant therapy for muscle-invasive bladder cancer - Session Highlights

Washington, DC USA (UroToday.com)  Bladder urothelial carcinoma is the fourth most common non-cutaneous solid malignancy in men and the ninth most common in women. Muscle invasive bladder cancer (MIBC) accounts for 25% of total bladder cancer patients at presentation with a 5-year mortality rate of 50-75% after cystectomy.

Neoadjuvant chemotherapy has been a widely accepted part of the treatment algorithm and has level 1 support (Grossman et al, NEJM 2003). However, up to 40% of patients are not eligible for neoadjuvant therapies for a variety of reasons. Thus, new treatment options are needed. In this session, Dr. Andrea Apolo (National Cancer Institute) presented the current state-of-the-art in adjuvant therapy for MIBC. Several randomized trials have been attempted in this setting, however almost all of them suffered from poor accrual. Stadler and colleagues attempted to randomize patients with p53+ bladder urothelial carcinomas to observation versus MVAC post cystectomy (JCO 2011). Almost 60% of patients refused randomization and the study was closed due to futility. A Spanish study randomized patients to gemcitabine/cisplatin plus paclitaxel versus observation after cystectomy (Paz-Ares et al, JCO 2010). For 142 randomized patients, an apparent survival benefit was noted in the adjuvant group (HR 0.44, p<0.001). However, for patients who progressed, those in the intervention arm received more salvage chemotherapy than patients who did not originally receive adjuvant therapy. Thus, the trial has been criticized as not representing a fair comparison. Finally, a recent metaanalysis suggested a benefit in OS and PFS for patient undergoing adjuvant therapy (Leow et al, Eur Urol 2014). Unfortunately, the heterogeneity in patient populations and outcome measures across the studies utilized limits the strength of these conclusions. In part due to the rapid adoption of chemotherapy in the neoadjuvant setting, the concept adjuvant chemotherapy has been somewhat abandoned and there are no ongoing adjuvant chemotherapy trials. This is not to say that the future of adjuvant therapy in MIBC is bleak.

In contrast, several exciting clinical trials are ongoing (clinicaltrials.gov) and seek to examine the role of radiotherapy, targeted agents (e.g. traztuzumab), and immune checkpoint inhibitors (e.g. PD-L1/PD-1) in the adjuvant setting. The data from these trials are eagerly anticipated to improve the outcomes for our patients with MIBC.

Presented by:

Andrea Apolo, MD,

National Cancer institute 

Written By:

Benjamin T. Ristau, MD. from the 2015 Winter Meeting of the Society of Urologic Oncology (SUO) "Defining Excellence in Urologic Oncology" -

December 2 - 4  Washington, DC USA

Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA.

 

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