Among patients who had primary treatment for EOC in Samsung Medical Center, 99 EOC patients were identified for having SCS after recurrence. Patients who had undergone SCS were included according to the following inclusion criteria: (1) optimal debulking after primary treatment, (2) platinum-free interval (PFI) ≥6 months, (3) good performance status before surgery as defined by Eastern Cooperative Oncology Group (performance status 0 to 2), (4) single or multiple recurrence sites without extensive intraperitoneal dissemination or ascites on imaging. These inclusion criteria were based on those used in other major retrospective studies [161819]. None of the candidates had received chemotherapy prior to SCS. Flowchart of included patients is shown in Fig. 1.

Patients who underwent SCS were divided into two groups according to the initial diagnostic methods: CA-125 elevation or positive imaging findings. None of the patients showed the symptoms as initial sign of recurrence. The diagnostic criteria for recurrence or metastasis during the follow-up period included rising CA-125 levels or clinical signs of recurrence, which include positive conventional imaging findings.

The standard primary surgical treatment consisted of hysterectomy, bilateral salpingo-oophorectomy, omentectomy, retroperitoneal (pelvic and paraaortic) lymphadenectomy, and tumorectomy of any metastatic lesions. Peritoneal washing was routinely performed. Peritoneal biopsies were performed if any abnormalities were identified. After primary debulking surgery (PDS), either abdominopelvic computed tomography (CT) or pelvic magnetic resonance imaging (MRI) was performed to confirm the disease status.

Within two weeks of surgery, patients started their first cycle of platinum based combination chemotherapy. Cycles were repeated every 3 weeks until 4 to 6 cycles were completed. The CA-125 level was routinely checked to determine whether CA-125 was in the normal range. After primary treatment, patients were assessed by physical examination, complete blood count and chemistries, including CA-125 levels, every 3 months for the first 3 years, and every 6 months thereafter. Chest radiography and abdominopelvic CT scan (or alternatively abdominopelvic MRI) were performed every 6 months for the first 3 years, and every 12 months thereafter (although this may not be standard follow-up schedule, it had been proceeding in our institution as routine protocol). Additional diagnostic procedures were performed according to specific clinical suspicions. If recurrence was suspected with symptoms or CA-125 elevation, additional imaging studies were performed. Recurrence could have been detected by imaging studies with or without CA-125 elevation. After detection of recurrence in EOC patients, time and method of secondary treatment were decided by physicians, usually SCS or chemotherapy. After secondary treatment was performed, the same follow up schedules and treatment were conducted as were those after PDS.

For each patient, the method of recurrence detection was determined from a review of the electric medical record. Detection was attributed to an office visit if the patient presented with symptoms of recurrence or clinical signs on exam. In contrast, detection was attributed to imaging if this was the first or only evidence of disease recurrence. Lastly, detection was attributed to CA-125 level if elevations in this marker were the initial abnormal finding leading to the diagnosis. Elevated CA-125 levels were defined as >35.0 U/mL by the laboratory at our institution. Forty-one of the 99 patients who underwent SCS were initially diagnosed with recurrence based on a CA-125 elevation. In contrast, 58 patients were diagnosed by imaging findings, and did not have elevated CA-125 levels. Patients with both CA-125 elevation and imaging findings were categorized as CA-125 elevation group, and no patients were diagnosed by symptoms alone.

Summary statistics were used to describe the data. Continuous variables are presented as medians (range). Categorical variables are presented as frequencies (percentages). The baseline clinical characteristics and study outcomes were compared between the two groups using the Mann-Whitney test for continuous variables, and the chi-square test or Fisher exact test for categorical variables, as appropriate. In order to define the recurrence pattern, the location of the recurrence site was divided into two categories. Recurrences in the pelvis occurring below the pelvic brim were considered pelvic recurrences. Extra-pelvic recurrences were those outside of this defined area. The spread patterns were classified as peritoneal, lymphatic, or hematogenous metastases. Peritoneal recurrences were defined as cases with a recurrence of metastatic lesions in the peritoneum of the pelvis and abdominal area. Hematogenous recurrences were defined as visceral metastases, such as in the liver and lung parenchyma. Lymphatic metastases were defined as metastases to lymph nodes, mostly pelvic and paraaortic, as well as distant lymph nodes. The Kaplan-Meier method was used for survival analysis. Multivariate analyses were performed with the Cox proportional hazards model to evaluate the importance of the recurrence type and other clinicopathological features as prognostic factors. Multivariate p-values were used to characterize the independence of these factors. A 95% CI was used to quantify the relationship between survival time and each independent factor. Statistical analyses were performed using SPSS ver. 21.0 (IBM Co., Armonk, NY, USA). A two-sided p≤0.05 was considered statistically significant. The PFI was defined as the time from the completion of primary treatment to recurrence, death or loss to follow-up. The overall survival from initial diagnosis (OS1) was described as the time between diagnosis and the patient's death or loss to follow-up. The overall survival after SCS (OS2) was described as the time from SCS to the date of the patient's death or loss to follow-up. We defined the progression-free survival from the initial treatment (PFS1) as the time between the diagnosis and first relapse, or the final follow-up visit. We defined progression-free survival from SCS (PFS2) as the period between the time of SCS to relapse, or the final follow-up visit.