Impact of delay in adjuvant chemotherapy administration for patients with advanced-stage epithelial ovarian carcinoma undergoing primary debulking surgery with bowel resection

Abstract

<h3>Objectives:</h3> Patients with epithelial ovarian carcinoma (EOC) undergoing primary debulking surgery (PDS) with small or large bowel resection have a higher risk of postoperative complications that could delay administration of adjuvant chemotherapy. The aim of the present study was to evaluate the impact of chemotherapy delay in the survival of patients with EOC undergoing bowel resection using a hospital-based database. <h3>Methods:</h3> The National Cancer Database (NCDB) was accessed and patients diagnosed between 2004-2015 with stage III-IV EOC without a history of another tumor who underwent PDS that included small or large bowel resection with known surgery-chemotherapy interval and at least one month of follow-up were identified. Overall survival (OS) was compared between patients who received multi-agent chemotherapy 2-6 week (group 1), 7-9 weeks (group 2) and 10-12 weeks (group 3) from surgery with the log-rank test. A Cox multivariate model was constructed to control for confounders. Impact of chemotherapy delay was also evaluated among patients who achieved complete gross resection (CGR) and those who had macroscopic disease. <h3>Results:</h3> A total of 9274 patients who met the inclusion criteria were identified; 69.8% received adjuvant chemotherapy 2-6 weeks from surgery while 24.5% and 5.7% received chemotherapy 7-9 weeks and 10-12 weeks respectively. Patients in group 2 (30.2%) and 3 (36.6%) were more likely to experience a prolonged hospital stay (>10 days) following PDS compared to those in group 1 (19.4%), p<0.001. Rates of unplanned re-admission within 30-days from surgery in group 1,2 and 3 were 7.7%, 9.2% and 11.3% respectively, p=0.002. Median OS for patients in group 1 was 44.78 months compared to 42.25 and 39.89 for those in groups 2 and 3 respectively, p=0.103. After controlling for patient age, race, presence of comorbidities insurance, tumor histology and stage, compared to patients in group 1 those in group 2 (HR: 1.04, 95% CI: 0.98, 1.10) and group 3 (HR 1.05, 95% CI: 0.94, 1.17) did not have worse survival. Status of residual disease was available for 3659 patients; 46% achieved CGR. For patients with CGR, median OS for those in group 1 and 2 was 55.46 and 52.70 months compared to 42.18 for those in group 3, p=0.015. After controlling for aforementioned variables those in group 3 had worse survival (HR: 1.37, 95% CI: 1.04, 1.82) compared to patients in group 1 while there was no difference in survival between group 2 and 1 (HR: 1.06, 95% CI: 0.90, 1.27). For patients with macroscopic residual disease, timing of chemotherapy administration was not associated with survival; median OS for patients in group 1, 2 and 3 was 41.3, 42.74 and 41.13 months respectively, p=0.82. <h3>Conclusions:</h3> For patients with advanced stage EOC undergoing PDS with bowel resection extreme delay in adjuvant chemotherapy administration over 10 weeks from surgery may be associated with a negative impact on the survival of those who achieve CGR.