Neoadjuvant chemotherapy with interval debulking surgery versus chemotherapy alone for advanced epithelial ovarian cancer

Abstract

<h3>Objectives:</h3> The treatment of advanced epithelial ovarian cancer (EOC) involves a combination of cytoreductive surgery and chemotherapy. For patients with unresectable disease or extensive comorbidities at the time of diagnosis, administration of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) has been shown to be a non-inferior treatment approach compared with primary cytoreduction, and has gained wider acceptance in the past decade[i],[ii]. Additionally, GOG 213 showed that in patients with platinum-sensitive, recurrent ovarian cancer, secondary surgical cytoreduction followed by chemotherapy did not result in longer overall survival than chemotherapy alone[iii], The approach of chemotherapy without IDS has not been reassessed since the advent of VEG-F and PARP inhibitors and checkpoint blockade. This study aims to examine the survival outcomes of patients treated with chemotherapy alone versus those who underwent IDS. <h3>Methods:</h3> A retrospective cohort study was conducted at a single institution after IRB approval. Patients with Stage III or IV EOC diagnosed between 2005 and 2019 who received NACT due to unresectable disease or medical comorbidities were included. Patient demographics and clinical characteristics were collected. The primary outcome was the hazard of death in patients who underwent IDS (treated as a time-dependent covariate), compared to those who received chemotherapy alone. Age was categorized into groups: < 50 years, 50-64 years, and 65+ years. Kaplan-Meier curves stratified by IDS status were estimated using a landmark analysis conditional upon surviving at least 6 months post-diagnosis. <h3>Results:</h3> 81 patients met inclusion criteria, 50 (62%) received NACT + IDS, and 31 (38%) received chemotherapy alone. Four (5%) patients had <i>BRCA</i> mutations. Of the 50 patients who underwent IDS, 41 (82%) patients had an optimal debulking and 40 (80%) received additional adjuvant chemotherapy. The major surgical complication rate was 14% and the rate of upper abdominal surgery was 22%. The rate of chemotherapy toxicity was 29% in the chemotherapy alone group and 34% in the IDS group. The univariate estimate for the hazard of death in women who underwent IDS was 0.85, with a 95% CI: (.32, 2.3), p-value=.75. Adjusting for age, parity and BMI, the hazard ratio was estimated to be 1.03 with a 95% CI: (.35, 3.0), p-value=.96. There was no statistically significant difference in survival when comparing IDS status in patients who survived at least 6 months from diagnosis (p=0.45). <h3>Conclusions:</h3> While the observed hazard of death was lower in the patients who underwent IDS versus those who did not, the results were not statistically significant. While this study is underpowered to validate chemotherapy only as a treatment regimen for patients with EOC, the results warrant further large-scale investigation to assess the utility of treating advanced EOC with chemotherapy alone, particularly among the <i>BRCA</i> mutated/HRD population with chemosensitive tumors.