BACKGROUND: Residual disease following cytoreductive surgery in patients with ovarian cancer has been associated with poorer survival outcomes compared with no residual disease. We performed a meta-analysis to assess the impact of varying levels of residual disease status on survival outcomes in patients with ovarian cancer who have undergone primary cytoreductive surgery or interval cytoreductive surgery in the setting of new therapies for this disease. METHODS: Medline, Embase, and Cochrane databases (January 2011 - July 2020) and grey literature, bibliographic and key conference proceedings, were searched for eligible studies. Fixed and random-effects meta-analyses compared progression and survival by residual disease level across studies. Heterogeneity between comparisons was explored via type of surgery, disease stage, and type of adjuvant chemotherapy. RESULTS: Of 2832 database and 16 supplementary search articles screened, 50 studies were selected; most were observational studies. The meta-analysis showed that median progression-free survival and overall survival decreased progressively with increasing residual disease (residual disease categories of 0 cm, > 0-1 cm and > 1 cm). Compared with no residual disease, hazard ratios (HR) for disease progression increased with increasing residual disease category (1.75 [95% confidence interval: 1.42, 2.16] for residual disease > 0-1 cm and 2.14 [1.34, 3.39] for residual disease > 1 cm), and also for reduced survival (HR versus no residual disease, 1.75 [ 1.62, 1.90] for residual disease > 0-1 cm and 2.32 [1.97, 2.72] for residual disease > 1 cm). All comparisons were significant (p < 0.05). Subgroup analyses showed an association between residual disease and disease progression/reduced survival irrespective of type of surgery, disease stage, or type of adjuvant chemotherapy. CONCLUSIONS: This meta-analysis provided an update on the impact of residual disease following primary or interval cytoreductive surgery, and demonstrated that residual disease was still highly predictive of progression-free survival and overall survival in adults with ovarian cancer despite changes in ovarian cancer therapy over the last decade. Higher numerical categories of residual disease were associated with reduced survival than lower categories.

OBJECTIVES: This analysis aimed to better define the relationship between progression-free survival and overall survival in adult patients with ovarian cancer (including fallopian tube or primary peritoneal cancer) following primary cytoreductive surgery or interval cytoreductive surgery. METHODS: A systematic literature review was carried out across the Medline, Embase, and Cochrane Central databases on 7 July 2020 (date limits 1 January 2011 to 7 July 2020) to identify studies with the following eligibility criteria: clinical trials/observational studies including >200 patients with ovarian cancer aged ≥18 years, evaluating overall survival/progression-free survival following cytoreductive surgery by residual disease status in the United States, Europe, Japan, or China. Weighted linear regression models were used to assess any correlation between median progression-free survival and overall survival, and between logHR for progression-free survival and logHR for overall survival. Risk of bias was assessed for all included studies. RESULTS: Of the 50 studies reported, 43 were observational studies (41 retrospective and two prospective cohort studies), and seven were reporting for randomized clinical trials-of which four were retrospective data analyses. For analyses of the relationship between overall survival and progression-free survival, 21 studies were eligible. The weighted linear regression model showed a strong positive association between the two survival endpoints. Goodness-of-fit analysis measured the adjusted R2 as 0.84 (p<0.001); a positive association was also observed between logHRs for overall survival and progression-free survival in the included studies. CONCLUSIONS: Median progression-free survival was predictive of median overall survival. This correlation between progression-free survival and overall survival after primary treatment for ovarian cancer highlights the validity of progression-free survival as a primary endpoint. Observational studies contributed most data, with limited information on disease stage and histology.