Factors Predicting 30-Day Grade IIIa–V Clavien–Dindo Classification Complications and Delayed Chemotherapy Initiation after Cytoreductive Surgery for Advanced-Stage Ovarian Cancer: A Prospective Cohort Study

SIMPLE SUMMARY: Both surgical outcome and timely initiation of chemotherapy are essential endpoints after cytoreductive surgery for advanced-stage epithelial ovarian cancer (AEOC). This was a multicenter prospective study of 300 primary AEOC patients who underwent cytoreductive surgery. We aimed to evaluate factors associated with 30-day severe postoperative complication as according to Clavien–Dindo classification (CDC) grade ≥IIIa and delayed initiation of chemotherapy defined as time to chemotherapy (TTC) >42 days after cytoreductive surgery for primary AEOC. The understanding of these risk factors and their consequences offers an opportunity to improve future perioperative care for AEOC. Our study highlights that patient with CDC grade ≥IIIa had a significant longer median TTC compared to patients without CDC grade ≥IIIa. Intraoperative upper-abdominal visceral injury was the strongest factor associated with both CDC grade ≥IIIa and TTC >42 days. In our analysis, patient performance status was the only preoperative modifiable risk factor for TTC >42 days. ABSTRACT: Objective: The aim of this study was to evaluate factors associated with 30-day postoperative Clavien–Dindo classification (CDC) grade IIIa or greater complications and delayed initiation of chemotherapy after cytoreductive surgery (CRS) for primary advanced-stage epithelial ovarian cancer (AEOC). Methods: This was a prospective study involving 300 patients who underwent primary or interval CRS for AEOC between February 2018 and September 2020. Postoperative complications were graded according to the CDC. Logistic regression analysis was used to evaluate factors predicting CDC grade ≥IIIa and time to chemotherapy (TTC) >42 days. Results: Interval CRS was performed in 255 (85%) patients. CDC grade ≥IIIa occurred in 51 (17%) patients. In multivariable analysis, age (p = 0.036), cardiovascular comorbidity (p < 0.001), diaphragmatic surgery (p < 0.001), intraoperative urinary tract injury (p = 0.017), and upper-abdominal visceral injury (e.g., pancreas, stomach, liver, or spleen) (p = 0.012) were associated with CDC grade ≥IIIa. In 26% of cases, TTC was >42 days (median (IQR) 39 (29–50) days) in patients with CDC grade ≥IIIa versus 33 (25–41) days in patients without CDC grade ≥ IIIa (p = 0.008). The adjusted odds ratio of developing TTC >42 days was significantly higher in patients associated with WHO performance grade ≥2 (p = 0.045), intraoperative bowel injury (p = 0.043), upper-abdominal visceral injury (p = 0.008), and postoperative CDC grade ≥IIIa (p = 0.032). Conclusions: Patients with advanced age, with cardiovascular comorbidity, and who required diaphragmatic surgery had an increased adjusted odds ratio of developing CDC grade ≥IIIa complications. CDC grade ≥IIIa complications were independently associated with TTC >42 days. Proper patient selection and prevention of intraoperative injury are essential in order to prevent postoperative complications and delayed initiation of chemotherapy.