Delays to Neoadjuvant Chemotherapy Have Risks in Bladder Cancer

Several factors, including race, insurance, and type of facility, were associated with delays in neoadjuvant chemotherapy treatment for bladder cancer patients.

Delaying neoadjuvant chemotherapy 8 weeks or more after diagnosis of urothelial carcinoma increases the risk of upstaging after radical cystectomy, according to a new study. Several factors, including race, insurance, and type of facility, were associated with such delays in treatment.

Previous research showed that delaying radical cystectomy can decrease overall survival (OS). “One of the hesitations in recommending neoadjuvant chemotherapy is that it may delay definitive therapy with radical cystectomy, which may compromise patient outcomes,” wrote study authors led by François Audenet, MD, of the Icahn School of Medicine at Mount Sinai in New York. “However, it is unclear if the effect of delays on patient outcomes still holds true in the setting of neoadjuvant chemotherapy utilization.”

The researchers used the National Cancer Database (NCDB) to examine delays in treatment and the effect on outcomes in a cohort of 2,227 patients who underwent neoadjuvant chemotherapy and radical cystectomy for cT2-T4aN0M0 urothelial carcinoma of the bladder between 2004 and 2014. The results were published in Urologic Oncology: Seminars and Original Investigations.

The median time from diagnosis to initiation of neoadjuvant chemotherapy was 39 days, while the median time to radical cystectomy was 155 days; the median time between the start of neoadjuvant chemotherapy and radical cystectomy was 112 days. After a median follow-up period of 45.7 months, the OS rate at 2 years was 69%; at 5 years, the OS rate was 49%. Taken as continuous variables, the time to neoadjuvant chemotherapy and to radical cystectomy were not significantly associated with OS, and no cutoff point was found that could predict poorer OS.

However, the timing of treatment was associated with upstaging risk. A total of 916 patients (41%) were upstaged after radical cystectomy, including 485 patients (22%) with positive lymph nodes. On a univariate analysis, the time to neoadjuvant chemotherapy taken as a continuous variable was significantly associated with a higher risk of upstaging, with an odds ratio (OR) of 1.003 (95% CI, 1.00–1.005; P = .034). The researchers identified 8 weeks as a cutoff point: those whose neoadjuvant chemotherapy began at least 8 weeks from diagnosis had an OR for upstaging of 1.24 (95% CI, 1.03–1.50; P = .021). This held on a multivariable analysis, where the OR for upstaging was 1.27 (95% CI, 1.02–1.59; P = .031).

A total of 552 patients in the cohort (25%) started neoadjuvant chemotherapy at least 8 weeks after diagnosis. A multivariate analysis revealed that African-American race was significantly associated with such a delay, with an OR of 2.10 (95% CI, 1.37–3.19; P < .001). The same was true for having Medicaid or other government insurance, with an OR of 1.53 (95% CI, 1.00–2.30; P = .046), and for treatment in an academic facility, with an OR of 1.24 (95% CI, 1.00–1.54; P = .047).

“Given the aggressiveness of the disease, we should expedite referral of patients for neoadjuvant chemotherapy initiation as soon as possible and no more than 8 weeks after diagnosis,” the authors concluded. “There is no evidence to support avoiding neoadjuvant chemotherapy due to concerns of delayed treatment that was generated from surgery alone studies, as long as radical cystectomy is performed within 7 months from diagnosis.”