Determining the optimal time for radical cystectomy after neoadjuvant chemotherapy

Abstract

Objective: To determine whether the recovery window (RW) between neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) affects 90-day postoperative morbidity and incidence of lymph node metastasis.

Patients and methods: We reviewed patients treated with NAC and RC from 1995 to 2013 for ≤cT₄ N₀ M₀ bladder cancer. The association of the RW with 90-day perioperative morbidity and lymph node metastasis was determined. Generalised linear models were used to determine predictors of each endpoint. Patients were stratified into four RWs by 21-day intervals (18-42; 43-63; 64-84; and ≥85 days) from last day of NAC to RC.

Results: We evaluated 306 patients with RW information during the study period. The median (range) RW was 46 (18-199) days. There was no difference in overall morbidity, re-admission, or major complication rates amongst the four RWs. In the multivariable analysis extravesical disease was an independent predictor of overall morbidity (odds ratio [OR] 1.95, 95% confidence interval [CI] 1.16-3.26; P = 0.011). Age (OR 1.05, 95% CI: 1.02-1.09; P = 0.004), and surgical duration ≥7 h (OR 2.87, 95% CI: 1.52-5.42; P = 0.001) were independent predictors of major complications. Only surgical duration ≥7 h was a predictor of re-admission (OR 2.24; 95% CI: 1.26-3.98; P = 0.006). A RW of ≥85 days had the highest incidence of node-positive disease (pN+; 40%). In a separate multivariable model that included clinical predictors for pN+, a RW of ≥85 days was an independent predictor of nodal metastasis (OR 2.92, 95% CI: 1.20-7.09; P = 0.018).

Conclusion: Patients treated with NAC for bladder cancer can undergo RC between 18 and 84 days (2.5-12 weeks) after NAC with no difference in the risk of perioperative morbidity. Delaying surgery beyond 12 weeks was associated with a significant risk of lymph node metastasis.

Keywords: bladder cancer; complications; cystectomy; muscle-invasive; neoadjuvant chemotherapy.