A delay ≥8 weeks to neoadjuvant chemotherapy before radical cystectomy increases the risk of upstaging

To investigate delays to neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) and their effect on outcomes in a large national registry of patients with localized muscle invasive bladder cancer.

Within the National Cancer Database (2004-2014), we identified 2,227 patients who underwent NAC and RC for cT2-T4aN0M0 urothelial carcinoma of the bladder. Times from diagnosis to treatments were tested for association with overall survival and pathologic outcomes, using Cox models, and restricted cubic splines regression.

Median times from diagnosis to NAC and RC were 39 days (interquartile range: 26-56) and 155 days (interquartile range: 131-185), respectively. Time to NAC and time to RC were not associated with overall survival in the complete cohort, as well as in subgroups of responders and nonresponders to NAC. Overall, 916 patients (41%) were upstaged after RC, including 485 patients (22%) with positive lymph nodes. We identified delay to NAC ≥8 weeks as a significant cut-off point to predict the risk of upstaging in multivariable analysis (odds ratio: 1.27; 95% confidence interval: 1.02-1.59; P = 0.031). Black race, Medicaid insurance, and academic facilities were associated with a higher risk of delayed treatment.

After diagnosis of muscle invasive bladder cancer, NAC should be initiated as soon as possible and no more than 8 weeks to prevent upstaging. There is no evidence to support avoiding NAC due to concerns of delayed RC that was generated from surgery alone studies, as long as RC is performed within 7 months from initial diagnosis.