Can we define the clinical variables predicting T0 after neoadjuvant systemic therapy in bladder cancer?

Neoadjuvant chemotherapy (NAC) followed by radical cystectomy is standard for muscle-invasive bladder cancer (MIBC), yet complete pathological response (ypT0) occurs in only a minority of patients. Its clinical and temporal predictors remain poorly defined, limiting optimized patient selection and treatment timing.

We retrospectively analyzed 35 consecutive patients with MIBC (≤cN1M0) who achieved ypT0 after NAC followed by robot-assisted radical cystectomy (RARC) and compared them with 70 consecutive patients with residual disease (≥ypT1) treated at the same institution. Descriptive analyses were performed, followed by multivariable multinomial logistic regression to identify independent clinical and treatment-timing predictors of ypT0.

Early initiation of NAC within one month of diagnosis (p=0.004), completion of chemotherapy within two months (p=0.003), completion of all planned cycles (p=0.02), favorable clinical restaging prior to RARC (p<0.001), and surgery within an optimal post-chemotherapy recovery window (p=0.01) were significantly associated with ypT0. On multivariable analysis, independent predictors of ypT0 included age <70 years (OR=10.5), early treatment initiation (OR=51.1), timely completion of NAC (OR=25.5), completion of all cycles (OR=44.4), surgery within the optimal recovery interval (OR=19.1), total treatment-to-surgery interval <6 months (OR=35.6), and lower tumor stage at restaging (OR=9.34).

This study identified independent clinical and temporal predictors of complete pathological response following NAC and RARC for MIBC. Modifiable timing-related factors-including early treatment initiation, chemotherapy completion, and optimized surgical scheduling-were key to achieving ypT0, supporting improved patient selection and coordinated perioperative care in future studies.