EAU 2019: The Pathologic and Clinical Response of Molecular Subtype of Muscle-Invasive Bladder to Neoadjuvant Chemotherapy

Barcelona, Spain (UroToday.com) Molecular subtyping in muscle-invasive bladder cancer remains a hot topic.  Approximately 10-20% of patients with muscle-invasive disease will have a complete response to chemotherapy and be pathologic T0 following cystectomy.  Researchers around the world look to identify molecular markers that may be utilized in prognostication and prediction of response of patients treated with neoadjuvant chemotherapy with muscle-invasive bladder cancer. 

In this multicentered, international study, an initial cohort of 363 patients with pT2-4aN0-3M0 bladder cancer was retrospectively reviewed.  Of which, 219 patients diagnosed with cT2-4aN0M0 bladder cancer.  Approximately half of those patients were treated with neoadjuvant chemotherapy and the other half directly with radical cystectomy.  Pathologic response and survival outcomes were analyzed utilized immunohistochemistry staining of formalin fixed slides based on CIT-basal and luminal subtypes.  CD5/6, CK20 CD44 were also performed in parallel to investigate the predictive value of a two subtyping system. 

The clinical prognosis of the CIT-Basal subtype was worse than the luminal cohort on retrospective review (p<0.001).  In the neoadjuvant cohort, the pathologic response rate was worse in the basal compared to the luminal subtype (65% vs 29%, p=0.001).  For a patient with the luminal subtype, neoadjuvant chemotherapy was associated with an improvement in overall survival compared to cystectomy alone (p=0.001).  In patients with the basal subtype, neoadjuvant chemotherapy was not associated with a statistically significant improvement in overall survival (p=0.541) compared to cystectomy alone.  Furthermore, ERBB2, FGFR3, PIK3CA mutations were presents in neoadjuvant responders(49%). 

In summary, this group demonstrated data that the luminal subtype demonstrates a greater survival benefit from neoadjuvant chemotherapy compared to the basal subtype.  This data is a follow up from their 2017 analysis, which continues to support analysis of molecular markers in bladder cancer.  Clinical predictors of pathologic response are critical to better assess which patients benefit from neoadjuvant chemotherapy, and which patients may successfully be able to avoid radical cystectomy.

Presented by: Ruiyun Zhang, Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China

Written by: David B. Cahn, DO, MBS, Fox Chase Cancer Center, Philadelphia, Pennsylvania, Twitter:@dbcahn at the 34th European Association of Urology (EAU 2019) #EAU19 conference in Barcelona, Spain, March 15-19, 2019.