(UroToday.com) The 2024 Southeastern Section of the AUA (SESAUA) annual meeting featured a bladder cancer session and a presentation by Dr. Seth Teplitsky discussing the prognostic significance of pathologic response to neoadjuvant chemotherapy in muscle-invasive urothelial carcinoma of the bladder with variant histology. Bladder cancers with variant histology encompass ~25% of cases are largely treatment refractory and are associated with atypical metastases and higher rates of cancer-specific mortality compared to pure urothelial cancers. Additionally, patients with variant histology are often excluded or underrepresented in neoadjuvant chemotherapy clinical trials for muscle invasive bladder cancer. There exists conflicting data regarding inherent neoadjuvant chemotherapy sensitivity for individual histologic variants. The objective of this study presented at SESAUA was to assess prognostic significance of pathologic response to neoadjuvant chemotherapy in muscle invasive bladder cancer patients with variant histology and pure urothelial cancers.
The National Cancer Database (NCDB) was assessed for patients with cT2-4 N0 muscle invasive bladder cancer who received neoadjuvant chemotherapy followed by radical cystectomy between 2004-2022. Patients were stratified into pure urothelial cancers or variant histology, including squamous, glandular, micropapillary, small cell/neuroendocrine, and sarcomatoid variants. Pure squamous tumors and adenocarcinoma were excluded. Pathologic response to neoadjuvant chemotherapy was defined as complete (ypT0N0), partial (≤ypT2N0), and no response (≥ypT2 or N+), then results of pathologic response to neoadjuvant chemotherapy and overall survival were analyzed. Kaplan-Meier analysis and log-rank tests were performed for overall survival and Cox proportional hazard regressions were performed to test relationships between neoadjuvant chemotherapy response and the presence of a variant histology in predicting overall survival.
A total of 5,372 patients were included, with 345 (6.4%) having variant histology. Among the variant histology patients, 133 (39%) were neuroendocrine/small cell, 79 (23%) were micropapillary, 67 (19%) were sarcomatoid, 46 (13%) were squamous, and 20 (5.8%) were glandular. Non-response rates to neoadjuvant chemotherapy in variant histology patients were significantly higher than those with pure urothelial cancers (65.2% vs 55.8%, p = 0.003):
In unstratified analysis, patients with variant histology exhibited shorter overall survival (p < 0.0001):
The relationship between neoadjuvant chemotherapy response and overall survival was different between the variant histology and pure urothelial cancer groups (p = 0.013) with the greatest differences seen in patients achieving partial response to neoadjuvant chemotherapy (overall survival HR for variant histology 4.88 [95% CI 2.29-10.38], p < 0.001):
Dr. Teplitsky concluded his presentation by discussing the prognostic significance of pathologic response to neoadjuvant chemotherapy in muscle-invasive urothelial carcinoma of the bladder with variant histology with the following conclusions:
- Patients with variant histology muscle invasive bladder cancer exhibit poor survival when treated with neoadjuvant chemotherapy followed by radical cystectomy compared with pure urothelial cancers, even when controlling for complete, partial and no pathologic response strata – this is most notable in patients with neuroendocrine/small cell and squamous differentiation
- The presence of variant histology is a poor prognosticator, and these data suggest that pathologic response is an inappropriate surrogate endpoint in neoadjuvant trials including both variant histology and pure urothelial cancers patients
Presented by: Seth Teplitsky, MD, University of Kentucky, Lexington, KY
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 Southeastern Section of the American Urological Association (SESAUA) Annual Meeting, Austin, TX, Wed, Mar 20 – Sat, Mar 23, 2024.