Partial response or stable disease after neoadjuvant chemotherapy for advanced ovarian cancer: time for surgery or more chemotherapy?

Abstract

<h3>Objectives:</h3> The association between number of neoadjuvant chemotherapy (NACT) cycles prior to interval tumor reductive surgery (iTRS) and survival is poorly defined. The question of whether to proceed with surgery or more chemotherapy in a patient who does not have a complete response after 3-4 cycles of NACT remains unanswered. We sought to assess survival outcomes stratified by number of chemotherapy cycles and residual disease following iTRS in a population of patients with partial response (PR) or stable disease (SD) following 3-4 cycles of NACT. <h3>Methods:</h3> We identified a retrospective cohort of patients diagnosed between 2/2013 and 2/2018 who received at least 3 cycles of NACT (based on laparoscopic triage and/or medical and disease criteria) underwent iTRS for advanced ovarian cancer. All patients had a PR or SD following 3-4 NACT cycles based on imaging and CA-125. The population was divided into 4 groups based on number of NACT cycles prior to iTRS and residual disease status after iTRS (R0, no gross residual or R1, any amount of residual disease): (1) 3-4 NACT cycles/R0; (2) 3-4 NACT cycles/R1; (3) >4 cycles/R0; (4) >4 cycles/R1. Overall-survival (OS) and progression-free survival (PFS) were estimated using Kaplan and Meier product-limit estimator and modeled via the Cox proportional-hazards model. <h3>Results:</h3> The cohort consisted of 279 patients with a median age of 64. Most of the cohort was White (86.9%) with high-grade serous histology (90.3%) and stage IV disease (56.0%). The majority of patients received 3-4 cycles (73.8%), had a PR to NACT (92.8% vs 7.2% SD), with an overall R0 rate of 79.3%. For the entire cohort, R0 status was associated with improved OS (median of 43 months vs. 26 months; p<0.001). Receipt of > 4 cycles with an R0 resection was not associated with worse OS (HR 1.22, 95% CI 0.76-1.95) when compared to those who received 3-4 cycles with an R0 resection after iTRS. In the presence of R1 resection, receipt of 3-4 cycles or >4 cycles was associated with decreased OS (HR 1.89, 95% CI 1.17-3.05; HR 3.00 95% CI 1.65-5.46 respectively) compared to 3-4 cycles with a R0 resection. Only receipt of >4 NACT cycles with a R1 resection was statistically associated with worse PFS (HR 2.21 95% CI 1.38-3.55) compared to receipt of 3-4 cycles with a R0 resection. <h3>Conclusions:</h3> Residual disease is significantly associated with OS regardless of number of NACT cycles in patients with PR or SD to NACT. These data suggest that the ability to achieve R0 should take precedence in decision making regarding timing of surgery in patients who do not have a complete response to NACT for advanced ovarian cancer and that surgery can still benefit patients who require additional chemotherapy in order to be considered resectable.