Association of renal function in non-hydronephrotic patients receiving PD-1 ICIs for bladder cancer with treatment response.

Abstract

767 Background: Renal insufficiency in bladder cancer (BC) patients is often attributed to hydronephrosis, yet it can also result from paraneoplastic nephropathy. In other malignancies, PD-1 immune checkpoint inhibitor (PD-1 ICIs) therapy has been associated with renal function improvement upon treatment response. Our retrospective study investigates whether a similar correlation exists in BC patients receiving PD-1 ICIs. Methods: Based on the populations from the TRUCE-01 (NCT04730219) and TRUCE-02 (NCT04730232) trials, which evaluated tislelizumab-based immunotherapy in bladder cancer (BC), this retrospective analysis included patients who received ≥3 treatment cycles followed by radical cystectomy (RC) or maximum TURBT (M-TURBT). Patients with hydronephrosis were excluded. Data collected included demographics and serum creatinine (SCr) at baseline and post-treatment; eGFR was calculated using the CKD-EPI formula. The primary endpoint was clinical complete response (cCR; no residual lesions found in the specimen from RC or m-TURBT). Secondary endpoints were overall survival (OS) and the rate of eGFR change (RΔeGFR). Statistical analyses included Wald-Wolfowitz test, Pearson correlation, ART-ANOVA, and propensity score matching (PSM). Results: A total of 90 non-hydronephrosis pts with BC were finally included in our study. The median age was 67 years (IQR 61-72), and 73 (81%) were male. Median SCr in baseline was 76.2 umol/L (IQR 65.5-84.2), while median eGFR was 87.9 (IQR 77.8-96.5) mL/min/1. 73m 2 in all pts. After 3 cycles of treatment, 54 (60%) pts achieved pCR, and the median RΔeGFR is +1.59% (IQR -3.09% to +7.03%). In subgroup analysis, we found that RΔeGFR of pts with renal insufficiency (baseline eGFR < 60) were significantly higher than pts without renal insufficiency (median RΔeGFR,+17.2% vs. +1.27%,p = 0.015). Further, Pearson correlation analysis indicated the statistical correlation between baseline eGFR and RΔeGFR (p = 0.023, Rs = -0.243). Moreover, we conducted ART-ANOVA to explore the association between the treatment response and RΔeGFR, suggesting that a significant difference in RΔeGFR between cCR and non-cCR pts is only present in the population with renal insufficiency (Interaction effect: p = 0.001, F value = 11.36). Interestingly, the cCR rate of pts with renal insufficiency at baseline was higher (72% vs. 58%), even though the difference didn’t reach statistical significance. To further validate our findings, we performed PSM in pts with muscle-invasive bladder cancer in our study, indicating that our initial findings remained robust (cCR rate: 86% vs 59%). Conclusions: In a word, our study suggested that for pts with non-hydronephrosis renal insufficiency, renal function improvement during immunotherapy for BC correlates with a better treatment response.