Urinary protein semi-quantification in immunochemotherapy for bladder cancer: markers of clinical outcomes.

OBJECTIVE: PD-1 based immunochemotherapy has improved bladder cancer (BC) outcomes, yet individual responses remain heterogeneous. Low-cost, non-invasive predictive biomarkers are urgently needed. Urinary protein semi-quantification (UPSQ) correlates with BC tumor load, but its predictive value during PD-1 based immunochemotherapy remains unclear. We conducted a post-hoc analysis of the TRUCE-01 (NCT04730219) and TRUCE-02 (NCT04730232) trials to explore the association between UPSQ and clinical outcomes. METHODS: 104 patients received 3 cycles of tislelizumab plus nab-paclitaxel. UPSQ at baseline (UP-B) and 60 ± 7 days (UP-60) after treatment initiation, urinary red blood cell (URBC) and urinary white blood cell (UWBC) were dynamically detected. Dynamic indices (UPDV score, UPV risk stratification) were defined to evaluate UPSQ changes. The primary endpoint was clinical complete response (cCR), and the secondary endpoints included overall survival (OS), cancer-specific survival (CSS), and events-free survival (EFS). Bulk RNA-seq transcriptomic analysis was performed in 22 MIBC patients. RESULTS: UPSQ decreased significantly at 60 days in the overall cohort and subgroups (all p < 0.05). Baseline URBC and UWBC were positively correlated with UPSQ, while tumor size was positively associated with UPSQ in MIBC patients. In regression analyses, several indicators reached nominal significance (unadjusted p < 0.05), but failed to remain significant (adjusted p > 0.05) after Benjamini-Hochberg correction due to limited sample size. Low UPV risk was correlated with a significantly higher cCR rate in both MIBC (OR 12.5, unadjusted p = 0.003, adjusted p = 0.055) and VHR-NMIBC (OR 3.47, unadjusted p = 0.031, adjusted p = 0.177) subgroups. UP-B grade showed a trend toward an inverse association with cCR (OR 0.48, unadjusted p = 0.028, adjusted p = 0.085) and OS (HR 1.70, unadjusted p = 0.045, adjusted p = 0.181) in the MIBC subgroup after multivariate adjustment. Transcriptomic analysis suggested that MIBC patients with high UP-B grade may exhibit a more aggressive tumor phenotype. CONCLUSIONS: UPSQ was linked to the clinical outcomes of patients receiving PD-1-based immunochemotherapy for BC. In MIBC, lower baseline UPSQ grade may be associated with a tumor transcriptomic phenotype contributing to better cCR and OS. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov, identifier NCT04730219; https://clinicaltrials.gov, identifier NCT04730232.