OBJECTIVE: Although trials of neoadjuvant chemotherapy for ovarian cancer use 3 cycles, real world practice varies. We evaluated the effect of higher order cycles of chemotherapy, followed by cytoreduction surgery or no surgery on survival, tumor resectability, and post-operative morbidity. METHODS: For our international, retrospective cohort study, the inclusion criteria were women with stage III to IV ovarian cancer undergoing interval (after 3-4 cycles of chemotherapy) or delayed (≥5 cycles) cytoreduction surgery or no cytoreduction surgery with chemotherapy alone (≥5 cycles). Multivariate regression analyses were used to model the effect of impact variables on overall survival and tumor resectability. RESULTS: Data were collected from 2498 patients from 22 centers across 12 countries. In total, 60.2% (n = 1504) underwent interval cytoreduction surgery, 30.4% (n = 760) underwent delayed cytoreduction surgery, and 9.4% (n = 234) did not undergo surgery. In the interval, delayed, and no-surgery groups, the mean follow-up periods were 57, 69, and 39 months, respectively. Patients undergoing interval versus delayed cytoreduction were more likely to achieve no residual tumor mass (no macroscopic residual disease [R0] = 72.2%, 1072/1484
64.6%, 490/758). Patients who underwent interval versus delayed cytoreduction surgery had a greater proportion of minor (Clavien-Dindo 1-2, 32%, 471/1473
28%, 212/756) and major (Clavien-Dindo 3-5, 9.6%, 141/1473
8.6%, 65/756) morbidities. Interval cytoreduction surgery was associated with statistically significant greater overall survival than delayed cytoreduction surgery (HR 0.81, p = .01). R0 at the time of delayed cytoreduction was not equivalent to R0 at the time of cytoreductive surgery. R0 in the interval setting was associated with better overall survival (HR 0.77, p = .01). Patients who did not undergo surgery had twice as poor overall survival compared with patients who underwent delayed cytoreduction surgery (HR 2.01, p <
.001). CONCLUSIONS: Women receiving >
4 neoadjuvant chemotherapy cycles had poorer overall survival, despite achieving R0 at surgery. Early maximum effort cytoreduction surgery with R0 in high volume centers and appropriate surgical resources are critical for increasing overall survival.