A risk-stratified approach to neoadjuvant chemotherapy in muscle-invasive bladder cancer: implications for patients classified with low-risk disease

Purpose To validate published risk criteria for informing use of neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC), and to examine outcomes of low-risk (LR) patients treated with immediate radical cystectomy (RC). Methods We identified 1931 patients who underwent RC for MIBC from 1980 to 2016. Patients were considered high risk (HR) with hydronephrosis, lymphovascular invasion, variant histology and/or cT3/4 disease. Kaplan-Meier survival estimates were compared to patients classified as LR, and logistic regression was used to examine factors associated with pathologic downstaging. Results A total of 1025 LR and 906 HR patients were identified. Median follow-up was 6.3 years (IQR 2.6-12), during which time 1321 (68%) patients died, 753 (39%) from bladder cancer. HR patients had significantly lower 5-year CSS than LR patients (50% vs. 68%, p = 0.001). Of 561 cisplatin-eligible LR patients treated with RC without NAC, 293 (52%) had pathologic non-organ confined disease; of these, 81 (14%) received adjuvant chemotherapy; 78 (14%) did not due to a perioperative event, while 134 (24%) did not due to patient/provider choice. NAC in LR patients was associated with greater odds of pT0 (OR 3.05; p < 0.001) and < pT2 (OR 2.53; p < 0.001) disease, but was not significantly associated with CSS (p = 0.31). Conclusions Our results validate the proposed risk groups. Among LR patients treated without NAC, 52% experienced pathologic upstaging, and 14% were unable to receive adjuvant chemotherapy due to a perioperative event. These data support offering NAC to both HR and LR MIBC patients, and may be useful for patient counseling.