The effect of neoadjuvant chemotherapy on survival outcomes in patients with variant histologies who underwent radical cystectomy with precystectomy diagnostic accuracy: A multicenter study of the Turkish Urooncology Association

Objectives: To evaluate the role of neoadjuvant chemotherapy in the final treatment plan and its impact on survival in bladder cancer patients who were diagnosed with variant histology in the radical cystectomy specimen and whose diagnostic accuracy was achieved with the previous transurethral resection of the bladder specimen.

Methods: In this retrospective multicenter study, data from 221 patients across 9 centers were analyzed between January 2012 and January 2022. The primary endpoint was overall, cancer-specific, recurrence-free, and metastasis-free survival rates among patients with and without neoadjuvant chemotherapy, and the secondary endpoint was to identify independent predictors of survival. The Kaplan-Meier method was used to estimate overall survival, cancer-specific survival, recurrence-free survival, and metastasis-free survival, and multivariate analyses were performed using the Cox-regression model.

Results: Kaplan-Meier estimates of overall, cancer-specific, recurrence-free, and metastasis-free survival demonstrated no significant difference between two groups. Cox multifactorial analysis revealed that the age (HR 1.030, 95% CI 1.003-1.057, p = 0.027), presence of pT4 tumor stage (HR 3.861, 95% CI 1.303-11.494, p = 0.015), and pN+ (HR 2.288, 95% CI 1.475-3.550, p < 0.001) at radical cystectomy histopathology were independent predictors of overall survival; presence of pT4 tumor stage and pN+ at radical cystectomy histopathology were independent predictors of cancer-specific survival (HR 8.245, 95% CI 1.873-36.292, p = 0.005 and HR 1.792, 95% CI 1.049-3.061, p = 0.033) and metastasis-free survival (HR 9.957, 95% CI 1.286-77.073, p = 0.028 and HR 2.949, 95% CI 1.674-5.197, p < 0.001); and the age (HR 1.047, 95% CI 1.006-1.090, p = 0.025) and pN+ at radical cystectomy histopathology (HR 4.150, 95% CI 1.917-8.981, p < 0.001) were independent predictors of recurrence-free survival.

Conclusion: Neoadjuvant chemotherapy does not provide any survival advantage in variant histology; therefore, considering the disadvantages, such as delaying radical cystectomy, which can lead to inadvertent disease progression and chemotherapy-related toxicities, cautious should be exercised when administering neoadjuvant chemotherapy.