A Systematic Review and Meta-Analysis of Surgical Feasibility and Outcomes Following Neoadjuvant Immune Checkpoint Inhibition in Resectable Stage III and IV Melanoma.

Abstract

Background: Neoadjuvant immune checkpoint inhibition (ICI) has demonstrated high pathological response rates in resectable stage III melanoma and is increasingly used for selected patients with low-volume stage IV disease. However, the surgical and perioperative implications remain incompletely defined. A systematic review and meta-analysis were performed to evaluate oncologic, surgical, and immune-related outcomes following neoadjuvant ICI and curative-intent surgery.

Materials and methods: MEDLINE, EMBASE, and the Cochrane Library, were systemically searched for both prospective and retrospective studies including adults with resectable stage III or oligometastatic stage IV melanoma treated with neoadjuvant ICI followed by planned surgery. Outcomes included pathological response, recurrence, failure or delay to surgery, perioperative complications, and treatment-related adverse events. Pooled estimates were calculated using random-effects meta-analyses.

Results: A total of 20 studies comprising 1384 patients were included. The pooled proportions of pathological complete response were 0.33 (CI 0.26-0.40), major pathological response 0.46 (CI 0.38-0.54), and overall pathological response 0.59 (CI 0.51-0.67). Pathological nonresponse occurred in 0.30 (CI 0.25-0.36). Failure or delay to surgery occurred in 0.09 (CI 0.07-0.12), with disease progression during neoadjuvant therapy reported in 0.06 (CI 0.04-0.10). Major perioperative complications (Clavien-Dindo ≥ III) occurred in 0.08 (CI 0.05-0.13), while major treatment-related toxicities (CTCAE grade ≥ III) occurred in 0.25 (CI 0.18-0.34). Comparative analyses demonstrated similar perioperative complication rates between neoadjuvant and adjuvant approaches, with lower recurrence risk favoring neoadjuvant therapy (p < 0.01).

Conclusions: Neoadjuvant ICI produces substantial pathological responses while preserving surgical feasibility in resectable stage III and selected stage IV melanoma. Operative morbidity appears acceptable; however, systemic toxicity is common, and perioperative reporting remains heterogeneous.