(UroToday.com) Although targeted approaches have become available in second and third line settings, platinum-based chemotherapy remains the standard first-line treatment for advanced muscle-invasive bladder cancer (MIBC). Therefore, the prediction of platinum resistance is of utmost clinical importance. In this study, they established a routine compatible method for the molecular classification of MIBC samples according to the most relevant classifiers and applied this method to evaluate the impact of subtypes on survival after adjuvant chemotherapy.
This retrospective study included 191 patients with advanced MIBC (pT≥3 or pN+) who underwent radical cystectomy, with or without adjuvant chemotherapy. A 48- gene panel and classifier rule set were established to determine molecular subtypes according to TCGA, MDA, LundTax, and Consensus classifications. Additionally, 12 single platinum-predictive candidate genes were assessed. The results were correlated with patients’ clinicopathological and follow-up data and were validated using independent datasets.
The final evaluation of 159 patients demonstrated better survival in the luminal groups for those who received chemotherapy compared to those who did not. In contrast, no such difference was observed in basal subtypes. The use of chemotherapy was associated with better survival in patients with high APOBEC3G expression (p<0.002). This association was confirmed using an independent dataset of patients who received neoadjuvant platinum therapy.
The proposed method robustly recapitulates the most commonly used transcriptome-based subtype classifications from paraffin-embedded tissue samples. The luminal, but not basal, molecular subtypes had the highest benefit from adjuvant platinum therapy. They identified and validated APOBEC3G as a novel predictive marker for platinum treated patients.
Presented by: Csilla Olah, University of Duisburg-Essen, Essen, Germany
Written by: Stephen B. Williams, MD, MBA, MS @SWilliams_MD on Twitter during the International Bladder Cancer Network Annual Meeting, September 28-October 1, 2022, Barcelona, Spain