Long-term outcomes following melanoma metastasectomy categorized by response to immune checkpoint inhibitor (ICI) therapy.

9563 Background: Patients undergoing surgical resection of Stage III/IV melanoma after response to ICIs show favorable survival, particularly with pathologic complete response (pCR). However, long-term outcomes of such patients stratified by ICI response remain undescribed. As surgery is increasingly employed in both PD-1 sensitive and refractory settings (e.g. tumor-infiltrating lymphocytes (TIL) therapy), better-defined outcomes and a clearer understanding of surgery's role are much needed. Methods: Patients treated with ICI (2003-2023) followed by metastasectomy were identified from a prospectively maintained database. Pre-surgery ICI response was assessed radiographically, and patients were categorized as having either stable/responding disease (R), an isolated site of disease progression (IP), or multiple progressing sites of disease (MP) for which surgery was pursued due to acute symptoms or palliative intent. Clinicopathologic factors examined included response to ICI, resection to no evidence of disease (NED), and pCR. Kaplan-Meier analyses with log-rank tests were used to compare disease-specific survival (DSS) from surgery date. Cox proportional hazards models identified independent predictors of DSS. Results: Among 513 patients, 426 (83%) had stage IV and 87 (17%) had stage III disease at ICI initiation. Patients were categorized as either R (n=76), IP (n=227), or MP (n=210). Fifty-three percent of patients received subsequent systemic therapy including 20 TIL patients, 12 of whom were in the MP group. Median follow-up after surgery among survivors was 2.51 years (IQR 0.93, 6.72). Median DSS following surgery was 4.1 years (95% CI: 2.5, NR). Resection to NED at the first operation post-ICI (n = 202, 39%) was associated with improved 5-year DSS [81% (75%, 88%) vs. 26% (20%, 33%); p < 0.001], with similar findings in only Stage IV patients (n = 426) [75% (67%, 84%) vs. 24% (19%, 32%); p<0.001]. Patients who underwent resection for an R or IP tumor had a 5-yr DSS of 89% (80%, 98%) or 62% (55%, 70%), respectively, compared to 20% (14%, 28%) for MP lesions (p < 0.001). Independent predictors of DSS also included NED resection and pCR (Table 1). Conclusions: Disease control after metastasectomy following ICI is durable, especially in patients with responding, stable, or isolated progressing disease, in addition to those achieving resection to NED or pCR. Alternative therapeutic strategies should be considered for patients with MP tumors as DSS remains poor after surgery alone. Multivariate model of DSS. p-value HR [95% CI] NED Status <0.001 0.31 [0.20, 0.49] Pre-operative Neutrophil-Lymphocyte Ratio 0.014 1.02 [1.01, 1.04] Response to ICI (R, IP, MP) <0.001 1.31 [0.65, 2.65] (R v. IP) 2.75 [1.35, 5.63] (R v. MP) pCR Status <0.001 0.22 [0.08, 0.65] Surgery Site 0.074 1.33 [0.97,1.83] Time from ICI Initiation to Surgery 0.006 0.85 [0.76, 0.97] M Stage 0.003 2.01 [1.21, 3.34]