Rong Jiang

Surgery versus no surgery in platinum-sensitive relapsed ovarian cancer: final overall survival analysis of the SOC-1 randomized phase 3 trial

Surgery for platinum-sensitive, relapsed ovarian cancer (PSROC) is widely practiced but had contradictory survival outcomes in previous studies. In this multicenter, open-label, phase 3 trial, women with PSROC, and having had one previous therapy and no platinum-based chemotherapy (platinum-free interval) of 6 months or more, were randomly assigned to either the surgery group (182 patients) or the no-surgery group (control) (175 patients). Patients with resectable diseases were eligible according to the international model (iMODEL), combined with a positron emission tomography-computed tomography imaging. Overall survival (OS) and progression-free survival were coprimary endpoints in hierarchical testing, and a significantly longer progression-free survival with surgery was previously reported. Final analysis of OS was planned at data maturity of 59%. Between 19 July 2012 and 3 June 2019, 357 patients were enrolled. Median follow-up was 82.5 months. Median OS was 58.1 months with surgery and 52.1 months for control (hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.61-1.05, P = 0.11). The predefined threshold for statistical significance was not met, but prespecified sensitivity analysis was performed. Overall, 61 of 175 (35%) patients in control had crossed over to surgery following subsequent relapse, and adjusted HR for death in the surgery group compared with control was 0.76, 95% CI 0.58-0.99. In subgroup analysis of relapse sites by imaging, median survival was not estimable in the surgery group and was 69.5 months in control in patients with 60 months in the surgery group as compared with five of 175 (2.9%) patients in the control group. In patients with PSROC, surgery did not increase OS in the intention-to-treat population but resulted in a prolongation of survival following adjustment of crossover.ClinicalTrials.gov registration: NCT01611766 .

Supragastric lesser sac: an insidious site for surgical exploration during the debulking surgery in advanced ovarian cancer

Metastases in the supragastric lesser sac (SGLS) are not only occult but are also barriers to complete resection of ovarian cancer. We describe a cohort of patients with SGLS disease undergoing debulking surgery. We identified all patients who underwent evaluation and eventual resection of SGLS disease as part of cytoreductive surgery for stage IIIC-IVB high-grade epithelial ovarian cancer at our institution from January 2018 to August 2022. Thirty-three of 286 patients (11.5%) underwent resection of SGLS disease. Metastases in the SGLS were identified by preoperative imaging in 4 of 33 patients (12.1%). The median peritoneal cancer index score was 22 (range, 9-33). Through surgical exploration, metastases were frequently seen in the right diaphragm (100%), hepatorenal recess (97%), lesser omentum (81.8%), left diaphragm (78.8%), supracolic omentum (75.8%), anterior transverse mesocolon (72.7%), splenic hilum (63.6%), ligamentum teres hepatis (60.6%), and gallbladder fossa (51.5%). The lesser omentum was normal in 6 of 33 (18.2%) patients, despite metastases within the SGLS. A total of 54.5% of patients underwent complex surgery (surgical complexity scores; median, 8; range, 3-14). Complete resections were achieved in 19 (57.6%) patients. No complications were related to the resection of SGLS disease. The median length of progression-free survival was 24.8 months (95% confidence interval=16.6-32.9). Metastases to the SGLS are not uncommon in advanced ovarian cancer, particularly those with widely disseminated disease. Disease in this recess is rarely identified by preoperative imaging and deserves systematic surgical exploration to attain complete cytoreduction.

A phase II trial of cytoreductive surgery combined with niraparib maintenance in platinum-sensitive, secondary recurrent ovarian cancer: SGOG SOC-3 study

In China, secondary cytoreductive surgery (SCR) has been widely used in ovarian cancer (OC) over the past two decades. Although Gynecologic Oncology Group-0213 trial did not show its overall survival benefit in first relapsed patients, the questions on patient selection and effect of subsequent targeting therapy are still open. The preliminary data from our pre-SOC1 phase II study showed that selected patients with second relapse who never received SCR at recurrence may still benefit from surgery. Moreover, poly(ADP-ribose) polymerase inhibitors (PARPi) maintenance now has been a standard care for platinum sensitive relapsed OC. To our knowledge, no published or ongoing trial is trying to answer the question if patient can benefit from a potentially complete resection combined with PARPi maintenance in OC patients with secondary recurrence. SOC-3 is a multi-center, open, randomized, controlled, phase II trial of SCR followed by chemotherapy and niraparib maintenance vs chemotherapy and niraparib maintenance in patients with platinum-sensitive second relapsed OC who never received SCR at recurrence. To guarantee surgical quality, if the sites had no experience of participating in any OC-related surgical trials, the number of recurrent lesions evaluated by central-reviewed positron emission tomography-computed tomography image shouldn't be more than 3. Eligible patients are randomly assigned in a 1:1 ratio to receive either SCR followed by 6 cycles of platinum-based chemotherapy and niraparib maintenance or 6 cycles of platinum-based chemotherapy and niraparib maintenance alone. Patients who undergo at least 4 cycles of chemotherapy and must be, in the opinion of the investigator, without disease progression, will be assigned niraparib maintenance. Major inclusion criteria are secondary relapsed OC with a platinum-free interval of no less than 6 months and a possibly complete resection. Major exclusion criteria are borderline tumors and non-epithelial ovarian malignancies, received debulking surgery at recurrence and impossible to complete resection. The sample size is 96 patients. Primary endpoint is 12-month non-progression rate. ClinicalTrials.gov Identifier: NCT03983226.

Surgery and Niraparib in Secondary Recurrent Ovarian Cancer (SOC-3 Trial)

This is a Phase II, open-label, multicenter, randomized umbrella study to evaluate the efficacy of cytoreductive surgery and Niraparib maintenance in participants with platinum-sensitive secondary recurrent ovarian cancer. Cohort 1 will focus on participants without prior use of PARP inhibitor, and without prior secondary cytoreduction (SCR) when first recurrence. Cohort 2 will focus on participants with prior use of PARP inhibitor, but without prior SCR when first recurrence. Cohort 3 will focus on participants with SCR when first recurrence, but without prior use of PARP inhibitor.

Surgery or Chemotherapy in Recurrent Ovarian Cancer (SOC 1 Trial)?

The purpose of this study is to evaluate the role of secondary cytoreduction (SCR) and validate the risk model of patient selection criteria in platinum-sensitive recurrent ovarian cancer.