Cytoreductive surgery with multimodal therapies in advanced or metastatic ovarian, colorectal, and gastric cancers: a systematic review and meta-analysis of randomized trials.

Background: Emerging evidence supports cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced ovarian cancer, yet its efficacy in other malignancies, such as gastric and colorectal cancers, remains uncertain. This meta-analysis evaluates survival outcomes in patients with advanced or metastatic ovarian, colorectal, and gastric cancers treated with CRS and multimodal therapies (e.g., HIPEC, extensive intraoperative peritoneal lavage (EIPL), systemic chemotherapy, immunotherapy, targeted therapy) versus CRS alone or with control-based regimens, focusing on the applicability of these treatments to these specific cancers.

Methods: We systematically searched PubMed, EMBASE, Web of Science, the Cochrane Library, and the abstracts of the European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) congresses up to April 21, 2025, for randomized trials published in English. The primary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes included mortality, adverse events, and 3- and 5-year OS rates. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using fixed- or random-effects models, depending on heterogeneity (I²).

Findings: From 16,064 records, 13 studies (n = 3,925 patients, control group = 1,894, experimental group = 2,031) met inclusion criteria. The experimental group significantly improved OS (HR: 0.86, 95% CI: 0.77 - 0.95, P = 0.003, I² = 22%, P = 0.26) and PFS (HR: 0.67, 95% CI: 0.50 - 0.90, P = 0.009, I² = 83%, P < 0.001) compared to the control group. Subgroup analyses highlighted heterogeneity in PFS benefits, with recent trials (published in or after 2023) showing more potent effects (HR: 0.53, 95% CI: 0.44 - 0.64, P < 0.001). Mortality reduction favored the experimental group (risk ratio (RR): 0.86, 95% CI: 0.75 - 0.99, P = 0.03, I² = 26%, P = 0.24), though clinical relevance requires cautious interpretation. The experimental group significantly increased grade 3 or worse adverse events (RR: 1.31, 95% CI: 1.16 - 1.48, P < 0.001, I² = 31%, P = 0.04), with significant effects driven by digestive system (RR: 1.43, 95% CI: 1.06 - 1.93) and circulatory system (RR: 1.58, 95% CI: 1.07 - 2.32) events.

Interpretation: CRS combined with multimodal therapies, confers significant survival benefits in advanced ovarian, colorectal, and gastric cancers despite elevated complication risks. These findings support the tailored integration of multimodal strategies in selected patients, highlighting the need for robust randomized trials to validate long-term efficacy and safety.