Objectives To evaluate the effect of cancer program–level variations in use of neoadjuvant chemotherapy (NACT) on overall survival among patients with advanced ovarian cancer.

Methods We included women with advanced-stage epithelial ovarian cancer treated 2004–2015 in Commission on Cancer–accredited cancer programs that began administering NACT liberally or continued to restrict its use after the publication of a randomized trial in 2010. We used flexible parametric survival models to perform a difference-in-differences analysis evaluating the effect of liberal NACT administration on case-mix–standardized median overall survival and 1-year mortality rates.

Results We identified 19,562 patients treated in 332 cancer programs that increased use of NACT from 21.7% in 2004–2009 to 42.2% in 2010–2015 and 19,737 patients treated in 332 programs that marginally increased use of NACT (20.1% to 22.5%) over the same period. Standardized median overall survival improved by similar magnitudes in programs with liberal (from 31.6 to 37.9 months; 6.3-month difference; 95% CI, 4.2–8.3) and restrictive (from 31.4 to 36.8 months; 5.4-month difference, 95% CI, 3.5–7.3) use of NACT after 2010 (difference-in-differences, 0.9 months; 95% CI, −1.9 to 3.7). One-year mortality declined more in programs with liberal (from 25.6% to 19.3%; risk difference, −5.2%; 95% CI, −6.4 to −4.1) than with restrictive (from 24.9% to 21.8%; risk difference, −3.2%, 95% CI, −4.3 to −2.0) use of NACT (difference-in-differences, −2.1%; 95% CI, −3.7 to −0.5).

Conclusions Compared with cancer programs that administered NACT restrictively, those that administered it liberally achieved similar improvements in median overall survival and larger declines in short-term mortality.