SUO 2017: Refining Selection Criteria for Neoadjuvant Chemotherapy

Washington, DC (UroToday.com) Dr. Duplisea and colleagues presented refining selection criteria for neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer (MIBC) prior to radical cystectomy (RC), combining clinical and molecular subtype risk factors. Recently, genomic studies have identified intrinsic basal, p53-like, and luminal molecular subtypes of MIBC. The basal subtype is associated with a worse prognosis when treated by RC alone, but has a favorable response to NAC [1]. As such, the objective of this study was to assess the value of NAC in patients with basal tumors, and to confirm subtype predicted response to chemotherapy irrespective of clinical risk grouping.

The authors identified patients with MIBC who underwent RC with or without NAC at two institutions. Patients were considered high-risk based on the presence of hydroureteronephrosis, cT3b-T4a disease, and/or histological evidence of lymphovascular invasion, micropapillary or neuroendocrine features on transurethral resection. Whole-genome analysis was performed on transurethral resected specimens classifying them into basal, luminal or p53-like subtypes. Overall survival (OS) outcomes were compared for each subtype and clinical risk criteria. There were 165 patients that were included in the analysis, including 52 (32%) patients who were low-risk, 113 (68%) patients who were high-risk; 49 (30%) of patients had basal tumors. Furthermore, 99 (60%) patients received NAC and of these, 82 (83%) were high-risk and 17 (17%) were low-risk. A significant survival benefit with NAC was seen in patients with basal tumors in both high-risk and low-risk cohorts (p<0.0001). There was no statistically significant difference in benefit for NAC in patients with either luminal (p=0.23), or p53-like subtype tumors (p=0.41).

Dr. Duplisea concluded that neoadjuvant chemotherapy seems to benefit patients with basal tumors regardless of whether they fall into the high-risk or low-risk group, confirming initial studies suggesting a response benefit for patients with basal tumors. Once validated, the risk criteria to identify high-risk tumors may include basal tumors, specifically because OS is this subtype is prolonged after NAC.

References:

1. Seiler R, Ashab HAD, Erho N, et al. Impact of molecular subtypes in muscle-invasive bladder cancer on predicting response and survival after neoadjuvant chemotherapy. Eur Urol 2017;72(4):544-554.

Presented by: Jonathan Duplisea, MD Anderson Cancer Center, Houston, TX

Co-Authors: Michael Metcalfe MD², Debasish Sundi MD², Roger Li MD², James Ferguson MD PhD², Shanna Pretzsch PhD², Jolanta Bondaruk PhD², Bogdan Czerniak MD², Ashish Kamat MD², Neema Nevai MD², Jay Shah MD², Woonyoung Choi PhD², David McConkey PhD², Peter Black MD³ and Colin Dinney MD²
¹MD Anderson Cancer Center Houston, Texas; ²MD Anderson Cancer Center Houston Texas; ³University of British Columbia Department of Urologic Sciences Vancouver BC Canada

Written by: Zachary Klaassen, MD, Society of Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre @zklaassen_md at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC

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