Do Molecular Subtypes of Muscle-invasive Bladder Cancer Predict Response to Neoadjuvant Chemotherapy? - Expert Commentary

Neoadjuvant chemotherapy is a standard of care for muscle-invasive bladder cancer (MIBC). Recently, new molecular subtypes based on gene-expression were identified but their impact on response to neoadjuvant has been unclear.

A recent study by Sailer et al. published in the Journal European Urology addressed this question. In this study, the investigators used affymetrix arrays to perform whole transcriptome profiling of transurethral resection specimens from 343 patients with MIBC. The tumors were classified using a single-sample genomic subtyping classifier (GSC) to predict consensus molecular subtypes (claudin-low, basal, luminal-infiltrated and luminal).

The classifier developed by the investigator could predict four consensus molecular subtypes with high accuracy (73%). Interestingly, luminal tumors had the best OS independent of neoadjuvant chemotherapy suggesting that a luminal phenotype is a good prognostic indicator rather than a predictive marker of response to neoadjuvant chemotherapy. On the other hand, basal tumors derived the highest benefit of neoadjuvant chemotherapy compared with surgery alone.

This important study shows the utility of using molecular subtypes of bladder cancer to develop predictive biomarkers for response to neoadjuvant chemotherapy. There is also emerging evidence that these subtypes may also predict response to immune-checkpoint inhibition. Understanding the biological basis and oncogenic pathways that eventually lead to the development of these subtypes is of paramount importance for the advancement of the field. 

Written by: Bishoy Faltas, MD

Seiler R, Ashab HA, Erho N, van Rhijn BW, Winters B, Douglas J, Van Kessel KE, Fransen van de Putte EE, Sommerlad M, Wang NQ, Choeurng V, Gibb EA, Palmer-Aronsten B, Lam LL, Buerki C, Davicioni E, Sjödahl G, Kardos J, Hoadley KA, Lerner SP, McConkey DJ, Choi W, Kim WY, Kiss B, Thalmann GN, Todenhöfer T, Crabb SJ, North S, Zwarthoff EC, Boormans JL, Wright J, Dall'Era M, van der Heijden MS, Black PC.  Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy. Eur Urol. 2017 Apr 5. pii: S0302-2838(17)30251-8. doi: 10.1016/j.eururo.2017.03.030. [Epub ahead of print]

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