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JU Insight: Patients with Muscle-Invasive Bladder Cancer with Nonluminal Subtype Derive Greatest Benefit from Platinum-Based Neoadjuvant Chemotherapy
By: Yair Lotan, MD; Joep J. de Jong, BSc; Vinnie Y. T. Liu, MSc; Tarek A. Bismar, MD; Stephen A. Boorjian, MD; Huei-Chung Huang, MA; Elai Davicioni, PhD; Omar Y. Mian, MD, PhD; Jonathan L. Wright, MD; Andrea Necchi, MD; Marc A. Dall’Era, MD; Hristos Z. Kaimakliotis, MD; Peter C. Black, MD; Ewan A. Gibb, PhD; Joost L. Boormans, MD, PhD | Posted on: 01 Mar 2022
Lotan Y, de Jong JJ, Liu VTT et al: Patients with Muscle-Invasive Bladder Cancer with Nonluminal Subtype Derive Greatest Benefit from Platinum Based Neoadjuvant Chemotherapy. J Urol 2021; 207:67. https://doi.org/10.1097/JU.0000000000002261.
Study Need and Importance: Neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) in patients with nonmetastatic muscle-invasive bladder cancer (MIBC) confers an overall survival (OS) benefit of 5%–10%, but use is inconsistent and nonselective. Molecular differences between tumors may impact response to therapy. Selection of patients based on likely response may improve utilization of NAC. This highlights the need for clinically validated biomarkers to be used at diagnosis to predict response to NAC.
What We Found: A total of 601 patients with MIBC were included, of whom 247 had been treated with NAC and RC, and 354 underwent RC without NAC. With NAC, the overall net benefit to OS and cancer-specific survival at 3 years was 7% and 5%, respectively. After controlling for clinicopathological variables, nonluminal tumors had the greatest benefit from NAC, with 10% greater OS at 3 years (71% vs 61%), while luminal tumors had minimal benefit (63% vs 65%) for NAC vs non-NAC.
Limitations: Limitations of this study include the retrospective study design, with a risk of selection bias, the combining of multiple cohorts, which introduces a risk of cohort-level batch effects, and possible treatment selection biases. Finally, these types of analyses are not a replacement for randomized trials.
Interpretation for Patient Care: In patients with MIBC, molecular subtyping revealed nonluminal tumors received the greatest benefit from NAC, while patients with luminal tumors experienced a minimal survival benefit. A genomic classifier may help identify patients with MIBC who would benefit most from NAC.
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