Association between endometriosis and prognosis of ovarian cancer: an updated meta-analysis

Review question / Objective: Increased risk o f o v a r i a n c a n c e r ( O C ) a m o n g endometriosis patients has been proposed. However, the association between endometriosis and prognosis of OC remains controversial. This study evaluated whether endometriosis had influence on the survival outcomes of OC through a meta-analysis. Condition being studied: Relevant studies were retrieved from PubMed, Embase, and Web of Science databases and were evaluated using the Newcastle-Ottawa Quality Assessment Scale. Effect size was presented as hazard ratio (HR) and 95% INPLASY 1 International Platform of Registered Systematic Review and Meta-analysis Protocols INPLASY PROTOCOL Association between endometriosis and prognosis of ovarian cancer: an updated meta-analysis Chen, P1; Zhang, CY2. To cite: Chen et al. Association between endometriosis and prognosis of ovarian cancer: an updated meta-analysis. Inplasy protocol 202230109. doi: 10.37766/inplasy2022.3.0109 Received: 21 March 2022 Published: 21 March 2022 Review question / Objective: Increased risk of ovarian cancer (OC) among endometriosis patients has been proposed. However, the association between endometriosis and prognosis of OC remains controversial. This study evaluated whether endometriosis had in fluence on the survival outcomes of OC through a meta-analysis. Eligibility criteria: (1) non-original articles, such as reviews, conference abstracts and comments; (2) the studies that provide only a figure but not a detailed HR (95% CI) to show the results of survival analysis; (3) duplicate studies or multiple studies involving the same data, with only the one with the most complete information included. INPLASY registration number: This protocol was registered with the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) on 21 March 2022 and was last updated on 21 March 2022 (registration number INPLASY202230109). Corresponding author: Chi-Yuan Zhang [email protected] Author Affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University. Support: The Natural Science Foundation. Review Stage at time of this submission: Completed and published. Conflicts of interest: None declared. Chen et al. Inplasy protocol 202230109. doi:10.37766/inplasy2022.3.0109 Chen et al. Inplasy protocol 202230109. doi:10.37766/inplasy2022.3.0109 Downloaded from https://inplasy.com/inplasy-2022-3-0109/ confidence interval (CI). Heterogeneity test evaluation was performed using Cochran’s Q test and I2 statistics. Publication bias was determined using Egger’s test. Statistical analysis was performed using Stata 12.0 software.

Search strategy: According to a pre- established retrieval strategy, the relevant studies were systematically retrieved from PubMed, Embase, Web of Science databases with the retrieval time up to May 11, 2021 and without language restrictions. The search terms contained three categories: research object ("ovarian neoplasm", "ovarian cancer", "ovary neoplasm", "ovary cancer", "ovarian carcinoma", "ovary carcinoma"), exposure factors (“endometriosis”, “endometrioses”) and outcomes ("mortality", "survival", "prognosis"). Two search terms in the same category are combined with "OR", while "AND" was used between two search terms of different categories. The detailed retrieval strategies for different databases are listed in Table S1. Additionally, manual retrieval was carried out for the paper version of the relevant studies, and the

of the relevant reviews and included studies were also retrieved. Participant or population: Patients who were pathologically and histologically diagnosed as epithelial ovarian cancer were included. I n t e r v e n t i o n : P a t i e n t s w h o w e r e pathologically and histologically diagnosed as epithelial ovarian cancer were included. Comparator: Patients with or without endometriosis. S t u d y d e s i g n s t o b e i n c l u d e d : Retrospective or prospective cohort studies or nested case-control studies. Eligibility criteria: (1) non-original articles, such as reviews, conference abstracts and comments; (2) the studies that provide only a figure but not a detailed HR (95% CI) to show the results of survival analysis; (3) duplicate studies or multiple studies involving the same data, with only the one with the most complete information included. Information sources: The relevant studies were systematically retrieved from PubMed, Embase, Web of Science databases. Main outcome(s): EAOC patients tended to have better OS and PFS than non-EAOC patients. Conducting higher quality prospective cohort studies with large sample sizes is recommended to confirm the authenticity of the current study’s results. Quality assessment / Risk of bias analysis: On the basis of the above selection criteria, study retrieval was carried out by two independent investigators. Strategy of data synthesis: All statistical analyses were completed using Stata 12.0 software. HR and 95% CI were utilized as effect size indicators to evaluate the differences on PFS and OS of EAOC vs. non-EAOC. Cochran’s Q test and I2 test were used to assess the heterogeneity among studies. Significant heterogeneity was determined with P50%, and a random- effects model was utilized. A fixed-effects model was utilized when no signi ficant heterogeneity was observed (P≥0.05 and I2≤50%). The effect of region, confounding factors adjusted or not for heterogeneity, and the pooled results were evaluated with a subgroup analysis. Publication bias evaluation was conducted using Egger’s test. If there was significant publication bias, the stability of the results of the meta- analysis was evaluated using the trim-and- fill method. The stability of the results was also evaluated using the method of elimination one by one. Subgroup analysis: All statistical analyses were completed using Stata 12.0 software. HR and 95% CI were utilized as effect size indicators to evaluate the differences on PFS and OS of EAOC vs. non-EAOC. Cochran’s Q test and I2 test were used to assess the heterogeneity among studies. INPLASY 2Chen et al. Inplasy protocol 202230109. doi:10.37766/inplasy2022.3.0109 Chen et al. Inplasy protocol 202230109. doi:10.37766/inplasy2022.3.0109 Downloaded from https://inplasy.com/inplasy-2022-3-0109/ Significant heterogeneity was determined with P50%, and a random-effects model was utilized. A fixed-effects model was utilized when no significant heterogeneity was observed (P≥0.05 and I2≤50%). The effect of region, confounding factors adjusted or not for heterogeneity, and the pooled results were evaluated with a subgroup analysis. Publication bias evaluation was conducted using Egger’s test. If there was significant publication bias, the stability of the results of the meta- analysis was evaluated using the trim-and- fill method. The stability of the results was also evaluated using the method of elimination one by one. Sensitivity analysis: All statistical analyses were completed using Stata 12.0 software. HR and 95% CI were utilized as effect size indicators to evaluate the differences on PFS and OS of EAOC vs. non-EAOC. Cochran’s Q test and I2 test were used to assess the heterogeneity among studies. Significant heterogeneity was determined with P50%, and a random-effects model was utilized. A fixed-effects model was utilized when no significant heterogeneity was observed (P≥0.05 and I2≤50%). The effect of region, confounding factors adjusted or not for heterogeneity, and the pooled results were evaluated with a subgroup analysis. Publication bias evaluation was conducted using Egger’s test. If there was significant publication bias, the stability of the results of the meta- analysis was evaluated using the trim-and- fill method. The stability of the results was also evaluated using the method of elimination one by one. Country(ies) involved: China.

endometriosis, ovarian cancer, prognosis, meta-analysis. Contributions of each author: Author 1 - Peng Chen. Author 2 - Chi-Yuan Zhang. INPLASY 3Chen et al. Inplasy protocol 202230109. doi:10.37766/inplasy2022.3.0109 Chen et al. Inplasy protocol 202230109. doi:10.37766/inplasy2022.3.0109 Downloaded from https://inplasy.com/inplasy-2022-3-0109/