Predictive Value of Prior Non-muscle-invasive Bladder Cancer for the Effectiveness of Neoadjuvant Chemotherapy in Localized Muscle-invasive Bladder Cancer: A Real-world Analysis of the BLADRAC Cohort.

BACKGROUND AND

OBJECTIVE

It remains currently unknown whether the effectiveness of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) is the same in patients with or without prior non-muscle invasive bladder cancer (NMIBC). This study aims to perform a real-world analysis of the predictive value of prior NMIBC for the effectiveness of NAC in patients undergoing RC for MIBC.

METHODS

We included 2378 patients from the BLADRAC cohort who received RC with (n = 870; 37%) or without (n = 1508; 63%) NAC for primary (n = 1825; 77%) or secondary (n = 553; 23%) MIBC at 15 French centers from 2001 to 2023. Multivariable logistic regression models were fitted to identify the predictors of NAC delivery as well as those of pathological complete (pCR = [y]pT0N0) and pathological objective (pOR ≤[y]pT1N0) responses, while we assessed the predictors of recurrence-free (RFS), cancer-specific (CSS), and overall (OS) survival using multivariable Cox regression models. The heterogeneity of treatment effect of NAC according to the occurrence of prior NMIBC was determined further by testing the interaction terms between the occurrence of prior NMIBC and the effect of NAC within the models evaluating pathological and survival outcomes.

KEY FINDINGS AND LIMITATIONS: Patients with secondary MIBC were significantly less likely to receive NAC (odds ratio [OR] = 0.63; 95% confidence interval [CI] = [0.5-0.79]; p < 0.001) than those with primary MIBC. The use of NAC was an independent predictor of better pCR (OR = 6.02; 95% CI = [4.63-7.83]; p < 0.001), pOR (OR = 5.08; 95% CI = [4.09-6.3]; p < 0.001), RFS (HR = 0.61; 95% CI = [0.53-0.71]; p < 0.001), CSS (HR = 0.57; 95% CI = [0.47-0.69]; p < 0.001), and OS (HR = 0.61; 95% CI = [0.51-0.72]; p < 0.001), while the occurrence of prior NMIBC was not significantly associated with any of these endpoints (all p > 0.05). There was no significant interaction between the occurrence of prior NMIBC and the impact of NAC on pCR, pOR, RFS, CSS, and OS (all pinteraction > 0.05). The study is limited by its retrospective design.

CONCLUSIONS AND CLINICAL IMPLICATIONS: Our real-world data suggest that the occurrence of prior NMIBC could limit the access to NAC, while not predicting its effectiveness in patients treated with RC for localized MIBC.