Subjects
We reviewed the clinical characteristics and outcomes of patients diagnosed with advanced-stage HGSOC who were treated in West China Second Hospital, Sichuan University, People's Republic of China, from January 2013 to December 2017. Signed informed consent forms were obtained from all patients whose clinical data were collected.
Inclusion And Exclusion Criteria
Our study included OC patients who met all of the following criteria: (1) whose histologic subtype was high-grade (grade 2 or 3) serous ovarian cancer; (2) who was staged at an advanced disease (FIGO stage IIB to IVA); (3) who received a debulking surgery (through an open laparotomy) performed by experienced gynecologic oncologists with qualification for OC surgery; (4) who achieved optimal cytoreduction after debulking surgery; (5) who received postoperative chemotherapy with recommended regimens, such as paclitaxel (135–175 mg/m2, intravenously) followed by carboplatin (300–400 mg/m2, intravenously) or paclitaxel (135–175 mg/m2, intravenously) followed by cisplatin (75–100 mg/m2, intraperitoneally) for 6–8 cycles; (6) who achieved CR after primary treatment (optimal cytoreduction with fist-line postoperative chemotherapy); and (7) who had complete clinical data during follow-up after the primary treatment. CR, partial response (PR), stable disease (SD), and progressive disease (PD) were defined using Response Evaluation Criteria in Solid Tumor (RECIST 1.1) and evaluated by chest/abdominal/pelvic computed tomography (CT) scans and serum cancer antigen 125 (CA-125) level.
We excluded patients: (1) who was diagnosed with other histologic subtype or at an early stage; (2) who underwent debulking surgery with minimally invasive techniques; (3) who had residual disease ≥ 1cm after debulking surgery;(4) who did not complete the postoperative chemotherapy or was resistant to platinum-based chemotherapy; (6) who had a PR, SD, or even PD at the end of primary treatment; (7) who had missing information during follow-up; or (8) who had comorbidities (e.g., severe cardiac, hepatic, renal, or blood system diseases) or was not a good candidate for systematic treatment of OC.
Study Design
This was a retrospective study, designed as a nested case-control study to evaluate the prognostic factors in the risk of OC relapse. The preexisting cohort included advanced-stage epithelial OC patients who had achieved CR after successful primary treatment in our hospital during the study period. Medical records of each participant were carefully reviewed. The information of eligible patients who met the inclusion criteria was collected from the hospital electronic medical database. The primary outcome in our study was clinical recurrence of disease within 3 years after CR. Recurrent disease was identified by symptoms, signs, imaging (chest/abdominal/pelvic CT, magnetic resonance imaging or fluorodeoxyglucose-positron emission/CT scans) and elevated serum CA-125 levels during follow-up. The recurrent group included cases who had a progression of disease within 3 years after primary treatment. Progression of disease was defined using RECIST 1.1. The control group included patients in the same cohort who had a disease-free survival more than 3 years.
The following patient characteristics were evaluated as variables in the analyses: age, body mass index (BMI), family history of cancer, serum CA-125 level, serum Human Epididymis Protein 4 (HE-4) level, FIGO stage, sign of pleural/ascitic fluid, diagnostic approach, the application of neoadjuvant chemotherapy (NACT) or primary debulking surgery (PDS), the outcome of primary surgery treatment, the amount and area of residual disease after primary surgery, the identification of lymph node metastasis, the regimen and number of cycles of chemotherapy, and the application of postremission therapy.
Other clinical outcomes, including duration of overall response (DOR), progression-free survival (PFS), and adverse events (e.g., myelosuppression, postoperative lymphocyst, deep venous thrombosis, or ileus), were further evaluated in the subgroup analysis.
Statistical analysis
The statistical analyses were performed using the software of IBM SPSS Statistics 23.0. Data were appropriately analyzed by parametric tests or non-parametric tests. Continuous variables were reported as mean ± standard deviation (SD) and compared by independent-sample t tests between two groups. Categorical variables were reported as number (n, %) and compared by chi-square (x2) tests between two groups. A P value < 0.05 (two-sided) was considered statistically significant. Confounding factors were adjusted by subgroup analysis. Cox regression was used to calculate the time to event (PFS or DOR) analysis. Odds radio (OR) and 95% confidence interval (CI) of each variable were calculated to evaluate the potential prognostic factors of OC relapse. Survival curve in each subgroup was analyzed using the software of GraphPad Prism 8.3.0 and compared by Log-rank test.