Survival outcomes after delayed cytoreduction surgery following neoadjuvant chemotherapy in advanced epithelial ovarian cancer

ObjectiveInterval cytoreduction following neoadjuvant chemotherapy is a well-recognized treatment alternative to primary debulking surgery in the treatment of advanced epithelial ovarian cancer where patient and/or disease factors prevent complete macroscopic disease resection to be achieved. More recently, the strain of the global COVID-19 pandemic on hospital resources has forced many units to alter the timing of interval surgery and extend the number of neoadjuvant chemotherapy cycles. In order to support this paradigm shift and provide more accurate counseling during these unprecedented times, we investigated the survival outcomes in advanced epithelial ovarian cancer patients with the intent of maximal cytoreduction following neoadjuvant chemotherapy with respect to timing of surgery and degree of cytoreduction.MethodsA retrospective review of all patients aged 18 years and above with FIGO (2014) stage III/IV epithelial ovarian cancer treated with neoadjuvant chemotherapy and the intention of interval cytoreduction surgery between January 2008 and December 2017 was conducted. Overall and progression-free survival outcomes were analyzed and compared with patients who only received chemotherapy. Outcome measures were correlated with the number of neoadjuvant chemotherapy cycles and amount of residual disease following surgery.ResultsSix hundred and seventy-one patients (median age 67 (range 20–91) years) were included in the study with 572 patients treated with neoadjuvant chemotherapy and surgery and 99 patients with chemotherapy only. There was no difference in the proportion of patients in whom complete cytoreduction was achieved based on number of cycles of neoadjuvant chemotherapy (2–4 cycles: 67.7%, n=337/498); ≥5 cycles: 62.2%, n=46/74). Patients undergoing cytoreduction surgery after neoadjuvant chemotherapy had a median 5-year progression-free and overall survival of 24 and 38 months, respectively. No significant difference in overall survival between surgical groups was observed (interval cytoreduction: 41 months vs delayed cytoreduction: 43 months, p=0.52). Those who achieved complete cytoreduction to R0 (no macroscopic disease) had a significant median overall survival advantage compared with those with any macroscopic residual disease (R0: 49–51 months vs R<1: 22–39 months, p<0.001 vs R≥1: 23–26 months, p<0.001).ConclusionsSurvival outcomes do not appear to be worse for patients treated with neoadjuvant chemotherapy if cytoreduction surgery is delayed beyond three cycles. In advanced epithelial ovarian cancer patients the imperative to achieve complete surgical cytoreduction remains gold standard, irrespective of surgical timing, for best survival benefit.

Association of time interval from neoadjuvant chemotherapy to interval cytoreduction and interval cytoreduction to adjuvant chemotherapy with survival outcomes and risk of platinum resistance.

e18043 Background: Neoadjuvant chemotherapy (NACT), followed by interval debulking surgery (IDS), is a possible approach to patients with stages IIIC and IV epithelial ovarian cancer who are most likely to have suboptimal results with upfront surgery. Delay in initiation of adjuvant chemotherapy has been associated with worse outcomes. Our study aimed to evaluate whether time from NACT to surgery (TNS) and from surgery to adjuvant chemotherapy (TSA) were associated with survival outcomes and with platinum-resistant relapse. Methods: We did a retrospective analysis of medical records from 194 patients with EOC treated with IDS at a single institution from 2007 to 2018. We calculated the median TNS and TSA and evaluated its relation to progression free survival (PFS), overall survival (OS) and time to platinum-resistant relapse (TTPR) through Kaplan-Meier and Cox regression analysis. Results: After a median follow-up of 62 months, OS was 58 months and PFS was 18 months. Most patients received at least 3 cycles of NACT (21.1% 3 cycles, 16.0% 4 cycles and 39.7% 6 cycles); and the rate of optimal cytoreduction was 75,8%. Optimal surgery was associated with survival (p < 0.001). TNS over 8 weeks and TSA over 7 weeks were associated with worse PFS (HR 1.57, 95%CI 1.07-2.31; HR 1.52, 95%CI 1.00-2.32, respectively) and OS (HR 1.83, 95%CI 1.13-2.96; HR 1.57, 95%CI 0.93-2.65, respectively) in univariate analysis but not in a multivariate analysis including residual disease as a covariate. In the subgroup of patients with residual disease < 10mm a multivariate analysis showed shorter PFS (HR 2.06, CI95% 1.16-3.66, p = 0.014) and OS (HR 2.20, CI95% 1.05-4.59, p = 0.035) for patients with TSA longer than 7 weeks. Longer TNS was associated with PFS (HR 1.66, 95%CI 1.06-2.59, p = 0.026) in univariate analysis but not in multivariate analysis. Interestingly, longer TNS was associated with shorter TTPR (65.6 vs. 35.0 months, p = 0.049) and a higher frequency of platinum resistant relapse at first relapse (48.8% versus 26.5%, p = 0.012). Conclusions: Our study provides evidence that delayed TSA is an independent prognostic factor for worse PFS and OS only in the subgroup of patients with residual disease ≤ 10mm. Longer TNS was associated with higher risk of platinum resistant relapse. One possible explanation is that NACT may select chemoresistant clones, which would have more time to grow and spread with longer intervals until surgery. Further studies are necessary to corroborate this hypothesis.