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

• The neoadjuvant systemic treatment guarantees a reduction in the burden of the tumor, prevents metastasization might allow a less demolitive surgery • Some clinical variables (age at diagnosis, completion and timing of treatments ) seemed to allow a better prognosis compared to others • It is mandatory to identify characteristics leading to good results in order to guarantee the patients the best management and even to fully inform them about the treatment results. 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.