Prognostic Factors for Overall Survival in the VESPER Trial: Basal Molecular Subtype Is a Relevant Key Factor

BACKGROUND AND OBJECTIVE: Our aim was to identify potential prognostic factors for overall survival (OS) for patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy (NAC) and cystectomy in the VESPER trial (NCT01812369). METHODS: We focused on the NAC VESPER population (n = 437), including 218 patients who received dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin, and 219 who received gemcitabine and cisplatin. Tumor slides and formalin-fixed, paraffin-embedded blocks were available for central review in 297 cases of urothelial carcinoma. We investigated the effect of clinical, biological, pathological, and molecular characteristics on OS. KEY FINDINGS AND LIMITATIONS: Univariate analysis identified creatinine clearance, lymphovascular invasion, perineural invasion, and molecular subtype as factors with prognostic relevance for OS. Basal/squamous molecular subtype was the only covariate with the entire confidence interval greater than 0.5 for the time-dependent area under the receiver operating characteristic curve at 1, 3, and 5 yr, which suggests high prognostic value. Multivariable analysis demonstrated that these four prognostic factors were complementary for OS prediction. We did not observe a major difference in the 5-yr OS rate between groups with none of these factors (72%, 95% confidence interval [CI] 63-82%) or only one factor (67%, 95% CI 59-76%). By contrast, the 5-yr OS rate was lower for the group with two or more factors (38%, 95% CI 28-53%). CONCLUSIONS AND CLINICAL IMPLICATIONS: We identified four factors prognostic for OS for patients with MIBC treated with NAC in VESPER. Basal molecular subtype was the most significant prognostic factor for OS, as it was independent of the treatment arm, and showed high prognostic value, in particular during the first year after randomization.