Associations between pretreatment systemic immune-inflammation index and tumor-specific prognosis in breast and gynecological cancers: an updated systematic review, meta-analysis, and certainty-of-evidence assessment

Introduction Recent meta-analyses have assessed the prognostic value of the systemic immune-inflammation index (SII) in individual breast or gynecological cancers, but pooling these biologically distinct malignancies into one analysis has limited validity. Substantial differences in disease stage, treatment, SII thresholds, covariate adjustment, and outcome definitions add further uncertainty. This revised study therefore used a tumor-specific framework without assuming a common effect across female malignancies. Methods Four databases were searched through July 22, 2023, with structured top-up search and citation tracking through August 5, 2026. Current disease-specific meta-analyses served as quantitative sources when more robust than the original evidence; post-review primary studies were synthesized narratively to avoid double counting. Breast, cervical, ovarian, endometrial, and vulvar cancers were evaluated separately, with assessment of cohort overlap, residual confounding, sparse endpoints, threshold validity, heterogeneity, and certainty of evidence. No overall pooled estimate was calculated. Results The updated evidence map used current quantitative sources comprising 28 breast cancer studies (17,291 participants), 16 cervical cancer studies(2,840 participants), 10 ovarian cancer studies representing 11 cohorts (2,852 participants), and 8 endometrial cancer studies(2,315 participants). Targeted post-review updates included one additional cervical cancer cohort (470 participants), three later endometrial cancer reports, and three vulvar cancer reports(295 participants); these narrative updates were not added to the source-review denominators. Elevated SII was associated with poorer overall survival(OS), disease-free survival(DFS), and distant metastasis-free survival (DMFS) in breast cancer; poorer OS and progression-free survival (PFS) in cervical cancer; poorer OS and DFS in ovarian cancer; and poorer OS and PFS in endometrial cancer. The pathologic complete response (pCR) in breast cancer was not significantly associated with SII. The findings related to DMFS and vulvar cancer were statistically sparse. Substantial or very high heterogeneity persisted in several analyses, and all principal outcomes were rated as very-low-certainty evidence. Conclusions Elevated pretreatment SII was associated with adverse outcomes in several tumor-specific settings, but the magnitude and transportability of associations remain uncertain. Evidence cannot establish a universal threshold, confirm incremental prognostic value beyond established clinical factors, or support sufficient net benefit for treatment decisions. SII should therefore serve as an adjunct rather than a stand-alone clinical tool. Systematic review registration: https://www.crd.york.ac.uk/prospero/ , identifier CRD 42023444334.