Survival After Hyperthermic Intraperitoneal Chemotherapy and Primary or Interval Cytoreductive Surgery in Ovarian Cancer
Authors: Myong Cheol Lim, Suk-Joon Chang, Boram Park, Heon Jong Yoo, Chong Woo Yoo, Byung Ho Nam, Sang-Yoon Park, Sang-Soo Seo, Sokbom Kang, Jung Yeon Yun, Dae-Soon Cho, Sun Ho Kim, Tae-Sung Kim, Sung Sil Park, Dong Woon Lee, Sung Chan Park, Hyeong Min Park, Sung-Sik Han, Seoung Hoon Kim, Hee Chul Yang, Moon Soo Kim, Jong Mog Lee, Bang Wool Eom, Young Il Kim, Hong Man Yoon, Il Ju Choi, Sung Han Kim, Jae Young Joung, Ho Kyung Seo, Jung Nam Joo, Yong Jung Song, Sae Hyun Park, Dae Chul Jung, Min Jung Kim, Ji Won Park, Seung-Yong Jeong, Young Ho Yun, Sohee Park, Robert E Bristow
Journal: JAMA Surgery (2022)

<h3>Importance</h3> Ovarian cancer has the highest mortality rate among gynecologic malignant tumors. Data are lacking on the survival benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in women with ovarian cancer who underwent primary or interval cytoreductive surgery. <h3>Objective</h3> To assess the clinical benefit of HIPEC after primary or interval maximal cytoreductive surgery in women with stage III or IV primary advanced ovarian cancer. <h3>Design, Setting, and Participants</h3> In this single-blind randomized clinical trial performed at 2 institutions in South Korea from March 2, 2010, to January 22, 2016, a total of 184 patients with stage III or IV ovarian cancer with residual tumor size less than 1 cm were randomized (1:1) to a HIPEC (41.5 °C, 75 mg/m<sup>2</sup>of cisplatin, 90 minutes) or control group. The primary end point was progression-free survival. Overall survival and adverse events were key secondary end points. The date of the last follow-up was January 10, 2020, and the data were locked on February 17, 2020. <h3>Exposures</h3> Hyperthermic intraperitoneal chemotherapy after cytoreductive surgery. <h3>Main Outcomes and Measures</h3> Progression-free and overall survival. <h3>Results</h3> Of the 184 Korean women who underwent randomization, 92 were randomized to the HIPEC group (median age, 52.0 years; IQR, 46.0-59.5 years) and 92 to the control group (median age, 53.5 years; IQR, 47.5-61.0 years). After a median follow-up of 69.4 months (IQR, 54.4-86.3 months), median progression-free survival was 18.8 months (IQR, 13.0-43.2 months) in the control group and 19.8 months (IQR, 13.7-55.4 months) in the HIPEC group (<i>P</i> = .43), and median overall survival was 61.3 months (IQR, 34.3 months to not reported) in the control group and 69.5 months (IQR, 45.6 months to not reported) in the HIPEC group (<i>P</i> = .52). In the subgroup of interval cytoreductive surgery after neoadjuvant chemotherapy, the median progression-free survival was 15.4 months (IQR, 10.6-21.1 months) in the control group and 17.4 months (IQR, 13.8-31.5 months) in the HIPEC group (hazard ratio for disease progression or death, 0.60; 95% CI, 0.37-0.99;<i>P</i> = .04), and the median overall survival was 48.2 months (IQR, 33.8-61.3 months) in the control group and 61.8 months (IQR, 46.7 months to not reported) in the HIPEC group (hazard ratio, 0.53; 95% CI, 0.29-0.96;<i>P</i> = .04). In the subgroup of primary cytoreductive surgery, median progression-free survival was 29.7 (IQR, 17.2-90.1 months) in the control group and 23.9 months (IQR, 12.3-71.5 months) in the HIPEC group, and the median overall survival was not reached in the control group and 71.3 months (IQR, 45.6 months to not reported) in the HIPEC group. <h3>Conclusions and Relevance</h3> The addition of HIPEC to cytoreductive surgery did not improve progression-free and overall survival in patients with advanced epithelial ovarian cancer. Although the results are from a subgroup analysis, the addition of HIPEC to interval cytoreductive surgery provided an improvement of progression-free and overall survival. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT01091636