Survival of patients with stage IV high-grade serous ovarian cancer treated with intraperitoneal versus intravenous platinumbased chemotherapy (501)

Abstract

Objectives: Patients with advanced high-grade serous ovarian carcinoma (HGSOC) are often treated with a combination of surgery and chemotherapy. Patients with stage IV HGSOC can be treated with neoadjuvant chemotherapy (NACT) or with primary cytoreductive surgery (PCS) if the disease is resectable at presentation. The objective of this study was to compare survival outcomes in patients with stage IV HGSOC treated with PCS followed by either intravenous (IV) or intraperitoneal (IP) platinum-based chemotherapy. Methods: A retrospective cohort study was conducted among 74 women with stage IV HGSOC managed with PCS followed by adjuvant IV or IP chemotherapy between 2004 -2020 at a tertiary cancer center. Clinical-demographic details were collected, and progression-free (PFS) and overall survival (OS) rates were compared using Kaplan-Meier analysis. Cox regression analysis was conducted to assess whether the use of IP was associated with improved survival compared to IV chemotherapy after adjusting for important covariates. Results: Seventy-four women met our inclusion criteria, with 35 (47%) receiving IP chemotherapy and 39 (52%) receiving IV chemotherapy. There was no difference in stage distributions (stage IVB: 80% vs 80%), BRCA status, the median age at the time of the diagnosis, and CA-125 level before PCS between the two cohorts. The IP cohort was more likely to have aggressive surgery (cytoreduction that includes any of the following: large bowel resection, diaphragm stripping or resection, extensive peritonectomy, liver resection, splenectomy, disease removal of the porta hepatis, supra-clavicular lym- phadenectomy, and thoracic surgery) compared to IV cohort (82% vs 46.2%; p<0.001) with longer surgeries (414 vs 180 min, p <0.001) and more likely to have no residual disease at the end of the surgery (60% vs 36%; p <0.001). After median follow-up of 36 (7-200) months, 3-year PFS was 29% versus 25% (p=0.170) and OS was 74% versus 59% (p=0.580) in the IP versus IV arms, respectively. After adjusting for stage and residual disease on multivariable Cox regression analysis, the IP chemotherapy arm was not associated with better PFS or OS when compared to the IV arm. The presence of residual disease was the only significant variable predictive of worse PFS (1-9 mm: HR 2.05 (95% CI: 1.09-3.85; p=0.027) and >10mm: HR 3.5 (95% CI: 1.82-6.71; p<0.001)) when compared to patients with 0mm residual disease at the conclusion of PCS. In the entire cohort of stage IV patients, for those with 0mm, 1-9mm, and >10mm residual disease, the 3-year PFS was 50.4 %, 9.1 %, and 5.9% and 3-year OS was 86%, 62.6%, and 35.3%, respectively. Conclusions: In this cohort, patients with stage IV HGSOC who underwent PCS to no residual disease were more likely to be treated with IP chemotherapy as compared to IV chemotherapy. Patients in the IP arm were more likely to have undergone more aggressive cytoreductive surgery with a longer surgical time as compared to patients in the IV arm. Residual disease was inversely associated with survival in both IV and IP arms. IP chemotherapy was associated with a trend of improved survival; however, this did not reach statistical significance. A larger cohort is needed in order to understand the true impact of IP chemotherapy following PCS in patients with stage IV HGSOC. Objectives: Patients with advanced high-grade serous ovarian carcinoma (HGSOC) are often treated with a combination of surgery and chemotherapy. Patients with stage IV HGSOC can be treated with neoadjuvant chemotherapy (NACT) or with primary cytoreductive surgery (PCS) if the disease is resectable at presentation. The objective of this study was to compare survival outcomes in patients with stage IV HGSOC treated with PCS followed by either intravenous (IV) or intraperitoneal (IP) platinum-based chemotherapy. Methods: A retrospective cohort study was conducted among 74 women with stage IV HGSOC managed with PCS followed by adjuvant IV or IP chemotherapy between 2004 -2020 at a tertiary cancer center. Clinical-demographic details were collected, and progression-free (PFS) and overall survival (OS) rates were compared using Kaplan-Meier analysis. Cox regression analysis was conducted to assess whether the use of IP was associated with improved survival compared to IV chemotherapy after adjusting for important covariates. Results: Seventy-four women met our inclusion criteria, with 35 (47%) receiving IP chemotherapy and 39 (52%) receiving IV chemotherapy. There was no difference in stage distributions (stage IVB: 80% vs 80%), BRCA status, the median age at the time of the diagnosis, and CA-125 level before PCS between the two cohorts. The IP cohort was more likely to have aggressive surgery (cytoreduction that includes any of the following: large bowel resection, diaphragm stripping or resection, extensive peritonectomy, liver resection, splenectomy, disease removal of the porta hepatis, supra-clavicular lym- phadenectomy, and thoracic surgery) compared to IV cohort (82% vs 46.2%; p<0.001) with longer surgeries (414 vs 180 min, p <0.001) and more likely to have no residual disease at the end of the surgery (60% vs 36%; p <0.001). After median follow-up of 36 (7-200) months, 3-year PFS was 29% versus 25% (p=0.170) and OS was 74% versus 59% (p=0.580) in the IP versus IV arms, respectively. After adjusting for stage and residual disease on multivariable Cox regression analysis, the IP chemotherapy arm was not associated with better PFS or OS when compared to the IV arm. The presence of residual disease was the only significant variable predictive of worse PFS (1-9 mm: HR 2.05 (95% CI: 1.09-3.85; p=0.027) and >10mm: HR 3.5 (95% CI: 1.82-6.71; p<0.001)) when compared to patients with 0mm residual disease at the conclusion of PCS. In the entire cohort of stage IV patients, for those with 0mm, 1-9mm, and >10mm residual disease, the 3-year PFS was 50.4 %, 9.1 %, and 5.9% and 3-year OS was 86%, 62.6%, and 35.3%, respectively. Conclusions: In this cohort, patients with stage IV HGSOC who underwent PCS to no residual disease were more likely to be treated with IP chemotherapy as compared to IV chemotherapy. Patients in the IP arm were more likely to have undergone more aggressive cytoreductive surgery with a longer surgical time as compared to patients in the IV arm. Residual disease was inversely associated with survival in both IV and IP arms. IP chemotherapy was associated with a trend of improved survival; however, this did not reach statistical significance. A larger cohort is needed in order to understand the true impact of IP chemotherapy following PCS in patients with stage IV HGSOC.