Topic: Muscle Invasive Bladder Cancer

Neoadjuvant Cisplatin-Based Chemotherapy for Muscle-Invasive Bladder Cancer

Robert Dreicer, MD, MS, MACP, FASCO, Associate Director for Clinical Research and the Deputy Director of the University of Virginia Cancer Center, discusses phase 3 study evidence in support of cisplatin-based chemo which he argues is a secure alternative to immune-checkpoint inhibition, a more experimental treatment. He begins by paralleling support of immune-checkpoint inhibition to other oncological examples of physician claims of “I already know the answer.” Dr. Dreicer reflects on the 90s, specifically on the recommendation of high dose chemo for advanced breast cancer prior to the completion of studies. Once the studies were completed it became clear that high dose chemo did not demonstrate an improvement in treatment and may in fact have proved itself mostly harmful. He continues by reviewing a randomized trial comparing long-term survival results of patients treated with gemcitabine plus cisplatin against methotrexate, vinblastine, doxorubicin, and cisplatin in patients with bladder cancer. The trial found that cisplatin-based chemo had a 15.3% response rate. Dr. Dreicer overviews a phase 3 trial which found that cisplatin-based therapy reduced risk of death by 16%, corresponding to an increase in 10-year survival from 30% to 36%. He concludes with an argument for cisplatin-based treatment due to the availability of higher-quality evidence for its use than immune-checkpoint inhibition.

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Neoadjuvant Immune-Checkpoint Inhibition for Muscle-Invasive Bladder Cancer

Petros Grivas, MD, PhD, Associate Professor of Oncology at the University of Washington School of Medicine in Seattle, argues for the use of immune-checkpoint inhibition over cisplatin-based chemotherapy for muscle-invasive bladder cancer (MIBC) based on promising level 1 evidence. He begins with an overview of the PURE-01 trial, which found that single-agent pembrolizumab safely achieved a pTO of 42% and a down-staging rate of 54%. Dr. Grivas continues by discussing the possibility of imaging endpoint use, reaching the conclusion that more validation is necessary before progress can be made in this area. He then returns to the PURE-01 trial, reviewing the surgical safety data which demonstrate high-grade complications post-pembrolizumab in 34% of patients, a significant minority. Dr. Grivas follows this by looking at the wider landscape of phase 2 trials in MIBC beyond just PURE-01, noting that they have shown promising pathologic complete response rates and rates of pathologic downstaging to non-muscle invasive disease. He looks to the future, suggesting that with more data and validation physicians will be able to treat patients based on their individual biology. Dr. Grivas concludes by arguing that it may be possible to use immune-checkpoint inhibition in patients who are unfit for cisplatin or to even avoid using cisplatin altogether, but notes that there is a need for more high-quality studies to inform discussions.

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Bladder Cancer Journal Vol. 6, Issue 4

Upregulated FGFR3 signaling in NMIBC and MIBC, the diagnosis and management of checkpoint inhibitor side effects in bladder cancer patients, the etiology of treatment delays in patients receiving neoadjuvant chemotherapy for MIBC, and 25-year trends in stage-specific incidence rates for bladder cancer.

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Immunotherapy For Muscle Invasive Bladder Cancer

A. Edward Yen, MD, Assistant Professor of Medicine in the Hematology and Oncology Section at Baylor College of Medicine in Houston, Texas, discusses the findings of recent immunotherapy trials for muscle invasive bladder cancer (MIBC). He explains that cisplatin-based neoadjuvant chemotherapy combinations are the current standard of care for MIBC and can provide a significant overall survival benefit, but 40 to 50% of patients are not eligible for cisplatin to begin with, and only 20% of those eligible patients actually receive cisplatin, which suggests that there are major therapeutic gaps that immunotherapies could potentially fill. Dr. Yen goes into depth on the findings of the phase II PURE-01 study of pembrolizumab, the phase II ABACUS study of atezolizumab, and the phase I NABUCCO study of nivolumab/ipilimumab, observing that all three therapies produced good responses and appeared to be correlated to different biomarkers from one another. He concludes by predicting that neoadjuvant immunotherapy will become standard of care for cisplatin-ineligible patients, but he also stresses that future studies should include higher-risk patients and should focus on predictive biomarkers.

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Updates in Muscle Invasive Bladder Cancer

Sia Daneshmand, MD, Associate Professor of Urology and Director of Clinical Research at the University of Southern California, describes the current landscape of muscle invasive bladder cancer treatment, highlighting developments in radical cystectomy and chemotherapy. He observes that while radical cystectomy has long been the gold standard, efforts are being made to preserve reproductive organs in female patients who have low-stage disease. Dr. Daneshmand also notes the significant number of neoadjuvant chemotherapy phase II trials currently underway. While studies examining adjuvant chemotherapy have shown promise, the limitations of these trials necessitate further research. Similarly, research comparing super-extended lymph node dissection (LND) with extended LND have yielded insignificant p-values, but absolute numbers demonstrate a positive upward survival trend over 5 years. Dr. Daneshmand concludes that additional clinical trials will reveal the optimal combination and sequencing of treatment options.

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Robotic Cystectomy and ICUD for Muscle Invasive Bladder Cancer

Sanjay G. Patel, MD, Assistant Professor of Urology at the University of Oklahoma College of Medicine, evaluates oncologic evidence comparing open radical cystectomy to robotic cystectomy. This includes addressing morbidity rates detailed in a recent meta-analysis, and questioning whether open diversion could affect these results. Additionally, Dr. Patel analyzes the learning curve associated with performing a robotic cystectomy. Finally, he explains the cost differences between the two techniques, as well as why a more costly operation and/or hospital stay may still be more indirectly cost-effective down the road.

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Case-Based Panel Discussion: Muscle-Invasive Bladder Cancer

A. Edward Yen, MD; Jennifer M. Taylor, MD, MPH; Guilherme Godoy, MD, MPH; and Seth P. Lerner, MD, examine four unique case examples to elaborate on various treatment approaches for muscle-invasive bladder cancer (MIBC) based on individual patient needs. The panel discussion reviews current data on neoadjuvant chemotherapy, trimodal therapy, and checkpoint inhibitors in this setting.

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