SUMMARY: It is estimated that in the United States, approximately 19,880 women will be diagnosed with ovarian cancer in 2022 and 12,810 women will die of the disease. Ovarian cancer ranks fifth in cancer deaths among women, and accounts for more deaths than any other cancer of the female reproductive system. Approximately 75% of the ovarian cancer patients are diagnosed with advanced disease. Approximately 85% of all ovarian cancers are epithelial in origin, and approximately 70% of all epithelial ovarian cancers are High-Grade Serous adenocarcinomas. Patients with advanced ovarian cancer often receive primary cytoreductive surgery with the goal of resecting all macroscopic tumor, followed by chemotherapy with carboplatin and paclitaxel combination chemotherapy with or without Bevacizumab or a PARP inhibitor. This intervention has been associated with superior Progression Free Survival. However, approximately 70% of these patients will relapse within the subsequent 3 years and are incurable. Following a relapse, patients are treated with systemic therapy, and very few trials have shown evidence of a significant Overall Survival benefit in this setting. The role of a second cytoreductive surgery in relapsed ovarian cancer has not been well defined.
The researchers therefore conducted a prospectively randomized Phase III trial (DESKTOP III), that evaluated secondary cytoreductive surgery in platinum-sensitive, recurrent ovarian cancer. This study was designed based on previously published studies, showing the beneficial role of complete resection at first relapse, which superseded the effect of cytoreduction in upfront surgery, as well as the confirmed value of the AGO (ArbeitsgemeinschaftGynäkologischeOnkologie) score in predicting complete resectability of a tumor. A total of 407 patients with recurrent ovarian cancer, who had a first relapse after a platinum-free interval of 6 months or more, were randomly assigned 1:1 to secondary cytoreductive surgery and chemotherapy with a platinum-based regimen (N=206) or platinum-based chemotherapy alone (N=201). Eligible patients had relapsed histologically confirmed epithelial ovarian cancer (clinically defined as a lesion that is palpable or visible or that is visible on ultrasonographic imaging) or relapsed disease radiologically diagnosed at least 6 months after the last course of initial platinum-based chemotherapy (platinum-sensitive disease) and had a positive AGO score. A positive AGO score was defined as an ECOG Performance Status of 0, ascites of less than 500 ml, and complete resection at initial surgery, and this score was used to identify patients in whom a complete resection might be achieved. An elevated Cancer Antigen 125 level alone was not deemed to be an acceptable entry criterion. A complete macroscopic resection was achieved in 75.5% of the patients in the surgery group who underwent the procedure. The median duration of surgery was 3.7 hours, the median estimated blood loss was 250 ml, and was associated with low incidence of adverse events related to surgery. The Primary end point was Overall Survival (OS) and additionally Quality of Life and prognostic factors for survival were also assessed.
With a median follow up of 70 months, the median Overall Survival was significantly longer at 53.7 months in the surgery group and 46.0 months in the no-surgery group (HR for death= 0.75; P=0.02). Patients with a complete resection had the most favorable outcome, with a median Overall Survival of 61.9 months among patients in the surgery group who had complete resection, as compared with 27.7 months among patients who did not have complete resection. The median Progression Free Survival was also longer at 18.4 months in the surgery group and 14.0 months in the no-surgery group (HR for progression or death=0.66). A benefit from surgery was seen in all prognostic subgroups analyzed including age, Stage at initial diagnosis, histologic subtype, treatment history that included previous maintenance therapy, and platinum-free interval (6-12 months or more than 12 months). Quality of life measures were similar between the treatment groups at 6 months and 12 months and there was no perioperative mortality within 30 days after surgery. These findings underscore the importance of surgical skill needed to successfully perform secondary cytoreductive surgery, with resulting complete macroscopic resection.
It was concluded that in women with platinum-sensitive recurrent ovarian cancer, cytoreductive surgery performed before second line chemotherapy resulted in longer Overall Survival and Progression Free Survival, as compared to chemotherapy alone, without negatively impacting Quality of Life.
Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer. Harter P, Sehouli J, Vergote I, et al., for the DESKTOP III Investigators. N Engl J Med 2021;385:2123-2131.
