SUO 2017: Impact of Variant Histology on Response to Neoadjuvant Chemotherapy for Bladder Cancer

Washington, DC ( Dr. Lin-Brande and colleagues presented their work assessing the impact of variant histology response to neoadjuvant chemotherapy (NAC) for patients with bladder cancer.  Based on randomized clinical trial data, NAC provides a survival benefit for patients with pure urothelial carcinoma1, however it is unclear if histologic variants receive the same benefit. The objective of this study was to assess the ability of NAC to downstage patients with variant histology prior to radical cystectomy (RC) and to quantify variant subtype, extravesicular involvement, and overall survival (OS) for histologic variants. 
The authors identified 1,440 patients who underwent RC with curative intent between 2003 and 2016 from their prospectively maintained institutional database. Patients with neuroendocrine variants were excluded. Clinical histology was identified at time of TURBT with final pathology following RC. Multivariable Cox proportional hazards regression analysis was used to assess effect of variant histology on OS. Among these patients, 1,171 (81.3%) had pure urothelial carcinoma and 269 (18.7%) had variant histology. Variants were classified as squamous cell carcinoma (n=121, 44.9%), glandular (n=54, 20.0%), micropapillary (n=30, 11.2%), sarcomatoid (n=14, 5.2%), nested (n=10, 3.7%), clear cell (n=5, 1.9%), rhabdoid (n=3, 1.1%), and plasmacytoid (n=2, 0.7%). There were 28 (10.4%) patients who had more than one variant histology. Specimens with variant histologic patterns had higher incidence of extravesicular involvement at time of clinical staging (20.8% vs 13.3%, p=0.003). There were 193 (16.5%) patients with pure urothelial carcinoma that received NAC, of which 105 (54.4%) were downstaged; 69 (25.6%) patients with variant histology received NAC resulting in pathologic downstaging for 43 (62.3%) patients. Patients with variant histology were more likely to be downstaged in response to NAC compared to pure urothelial carcinoma (p<0.0001). Variant histology identified either during TURBT (HR=1.04, 95%CI 0.81-1.34, p=0.760) or RC did not affect OS (HR=0.79, 95%CI 0.61-1.02, p=0.070). 
The authors concluded that histologic variants compared to pure urothelial carcinoma are more likely to have extravesicular involvement at time of diagnosis and have a greater pathologic response to NAC. As such, NAC should be offered to eligible patients regardless of the presence of histologic variants.

  1. Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003;349(9):859-866.

Presented by: Michael Lin-Brande, USC Institute of Urology, USC/Norris Comprehensive Cancer Center, Los Angeles, CA
Co-Authors: Daniel Zainfeld, Saum Ghodoussipour, Jie Cai, Gus Mirand, Hooman Djaladat, Anne Schuckman, Sarmad Sadeghi, Tanya Dorff, David Quinn, and Siamak Daneshmad

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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