Upfront HIPEC May Improve Advanced Ovarian Cancer Outcomes

Author: By Shreeya Nanda, Senior medwireNews Reporter 

medwireNews: Supplementing primary cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) leads to better survival outcomes in patients with stage III epithelial ovarian cancer, suggests a retrospective cohort study published in JAMA Network Open. 

Noting that earlier studies of HIPEC have generally been conducted in the interval or recurrent setting, the authors of a linked commentary say that the current analysis, which comprises “the largest cohort of patients treated with HIPEC in the upfront setting, supports its use in the primary cytoreductive setting.” 

The study included 584 women aged an average of 55 years who underwent primary cytoreductive surgery with (72.8%) or without (27.2%) HIPEC at one of five Chinese institutions between January 2010 and May 2017. The HIPEC procedure involved the administration over 60 minutes of cisplatin 50 mg/m2 in heated saline (temperature within 0.1°C of 43°C) on days 1, 3 and 5. 

Using the inverse probability of treatment weighting model to adjust for confounders, the researchers found that the median overall survival (OS) duration was 49.8 months for the HIPEC group and 34.0 months for the surgery alone group, a significant difference equating to a hazard ratio (HR) for death of 0.64. 

The OS rates at 3 years were similarly significantly improved among patients who did versus did not receive HIPEC, at 60.3% and 49.5%, respectively. 

Of note, the addition of HIPEC appeared to be beneficial regardless of whether the cytoreductive surgery was complete (residual lesions ≤1 cm in diameter) or not, but the investigators highlight that survival outcomes were best with the combinatorial approach “when complete surgery was possible”. 

Among patients who had complete cytoreduction, the median OS times were 53.9 months with HIPEC plus surgery and 42.3 months with surgery alone (HR=0.67), while in the incomplete cytoreduction subgroup, the corresponding durations were 29.2 and 19.9 months (HR=0.65). 

Commentator Ernst Lengyel and co-authors from the University of Chicago in Illinois, USA, say: “Because HIPEC only superficially penetrates tumors, patients with large residual tumors are not thought to be ideal candidates for the procedure; however, the findings of [this study] suggest that there might be an oncological effect even in this cohort.” 

Reporting on safety, the study authors say that “[t]he addition of HIPEC had little association with postoperative toxic events or on grade 3 and 4 adverse events, except electrolyte disturbance”, the incidence of which was significantly higher in the HIPEC than surgery alone group (28.1 vs 11.5%). 

Furthermore, “HIPEC did not result in higher morbidity and mortality”, say Shuzhong Cui, from the Affiliated Cancer Hospital and Institute of Guangzhou Medical University in China, and co-researchers, but add that the mean hospital stay (13.8 vs 10.0 days) and time to first flatus (4.3 vs 4.0 days) were significantly longer with versus without HIPEC. 

Ernst Lengyel and colleagues note several limitations, such as the selection bias inherent to retrospective studies and the difficulty in generalizing the findings to other institutions due to the “unusual method of multiday HIPEC with lower-dose cisplatin”. 

But in light of “the available published evidence supporting the use of HIPEC”, they believe that clinicians “should discuss the use of HIPEC preoperatively with patients with stage III, low-volume disease who are thought to likely experience optimal (R0) cytoreduction.” 

The commentators “expect that remaining questions will be conclusively answered by a phase 3 randomized trial [OVHIPEC-2] that just opened this year”, which is anticipated to report initial results in 2026. 

References  

Lei Z, Wang Y, Wang J, et al. Evaluation of cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for stage III epithelial ovarian cancer. JAMA Netw Open; 3: e2013940. Published online 25 August 2020. doi: 10.1001/jamanetworkopen.2020.13940

Alter R, Turaga K, Lengyel E. Are we ready for hyperthermic intraperitoneal chemotherapy in the upfront treatment of ovarian cancer? JAMA Netw Open; 3: e2014184. Published online 25 August 2020. doi: 10.1001/jamanetworkopen.2020.14184