Clinical outcomes of cytoreductive surgery and HIPEC in advanced and recurrent epithelial ovarian cancers with peritoneal carcinomatosis

Abstract

Introduction: The role of surgery for Peritoneal carcinomatosis (PC) has slowly evolved from palliation to potential curative intent. Attempting to remove all visible tumor deposits, “surgical cytoreduction” (CRS) was reported in 1930s for ovarian cancer and eventually became an accepted therapy with proven survival benefit. The new approach of combining CRS and Hyperthermic intraperitoneal chemotherapy (HIPEC) to treat peritoneal metastasis offer hope for long term survival in this group of patients. The risk and benefit of this approach continued to be debated. A prospective study was conducted to understand the perioperative outcomes of CRS & HIPEC. Aim: To evaluate the perioperative outcomes associated with CRS & HIPEC in Advanced and Recurrent Epithelial Ovarian Cancer with PC. Methods: Prospective analysis of patients undergoing CRS & HIPEC from November 2014 to July 2015 was done. Inclusion criteria included localized disease in peritoneal cavity, no distant metastasis and PS <2. Grade 3/4 complications from day of surgery until 30 days postoperatively were recorded. Results: We performed CRS & HIPEC in 20 patients from Nov 2014 to June 2015. HIPEC Plus regimens included Cisplatin (50 mg/m2) and Lipodox (15 mg/m2) intraperitoneally and Ifosphamide (1300 mg/m2) & Mesna (260 mg/m2) Infusion time was 90 minutes with a temperature range of 41-43 °C. Out of 20 patients 6 (30%) underwent primary debulking surgery and 14(70%) underwent secondary debulking surgery. PCI score ranged from 2-26 (mean 13.65). Mean operating time was 6.42 hrs and average blood loss was 1046 ml. Average hospital stay was 8 days and SICU stay was 4.9 days (range 3-14 days). Total 26 adverse events were observed of which grade 1 were 11 (42%), grade 2 were 8 (30%), grade were 3 (11.5%) and grade4 were 2 (8%). Most common complication was hematological (8) followed by respiratory (6), sepsis (4) renal (2), GI (2). 4 patients (5 events) developed grade3 or 4 complications in the form of septicaemia, pulmonary embolism, GI fistula of which 2 patients expited and remaining recovered although required prolonged hospitalization. Increased morbidity were observed in cases with symptomatic relapse, higher PCI score and CA 125 level higher than 250 U/ml. Most of the adverse events were grade 1 and 2 and were managed by observation only or GCSF support, transfusions and other minor interventions. The combined grade 3-4 morbidity was 20% (4out of 20) which consisted of neutropenia, infection and respiratory complications. One patient required relaparotomy and two patients expired attributed to pulmonary embolism and septicaemia respectively. Conclusion: Enthusiasm associated with improvement in survival is often dampened by increased perioperative mortality and morbidity figures and therefore CRS & HIPEC has not yet been considered standard of care by many centres. HIPEC after extensive cytoreductive surgery for ovarian cancer is a procedure whth acceptable morbidity that patients can tolerate. More follow up is needed to determinr the effect of HIPEC on survival. Till such time more data are obtained by way of larger randomised trials, this approach remains investigational.