O’Donoghue, Cristina

9568 Background: Stage IIB/C cutaneous melanoma is associated with high recurrence risk, however stratification of risk in relation to time after surgery has not been comprehensively evaluated. We evaluated recurrence-free survival (RFS) at key time points, stratified by clinicopathologic factors, to identify patients (pts) at higher recurrence risk and personalize postoperative surveillance strategies. Methods: In this multi-institutional, international retrospective cohort study from the Sentinel Lymph Node Working Group database, we included pts with pathologic T3b/T4a/T4b and N0 disease who underwent surgical resection and sentinel node biopsy from 1994-2025. The type of first recurrence (local, regional, distant) was characterized based on time category (0-12, 12-24, 24-60, and 60+ months after surgery). Restricted mean survival time (RMST) analysis was used to measure the average survival time up to a specified time point (6-, 12-, 24-, and 60-months after surgery), and associations of clinicopathologic variables (age, sex, Breslow thickness, ulceration and lymphovascular invasion [LVI]) with RFS. Results: We included 2514 stage IIB/C pts from 19 sites in 4 countries, with a median follow-up of 53 (stage IIB) and 49 (stage IIC) months. 675 (27%) pts experienced a recurrence (92 [14%] local, 238 [35%] regional and 345 [51%] distant), and 400 (59%) recurrences occurred within 24 months. The proportion of distant recurrences as the first recurrence increased significantly with time, comprising 39%, 50%, 62%, and 59% of recurrences in the 0-12, 12-24, 24-60, and 60+ month time categories respectively (χ 2 p<0.001). No significant differences were observed for the included clinicopathologic variables for 6-month RMST estimates. At 12 months, RMST estimates for thickness ≥4 mm (11.2 vs 11.6 months for thickness 2-3.99 mm, p<0.001) and presence of LVI (10.7 vs 11.4 months, p=0.009) were significantly different. 24-month RMST estimates differed for male sex (20.7 vs 21.5 months vs females, p=0.002), thickness ≥4 mm (20.5 vs 21.9 months, p<0.001), and presence of LVI (19.0 vs 21.1 months, p<0.001). Lastly, 60-month RMST estimates differed for male sex (42.0 vs 45.2 months, p=0.001), thickness ≥4 mm (41.5 vs 46.2 months, p<0.001), LVI (36.0 vs 43.7 months, p<0.001), and age >65 years (41.5 vs 46.4 for age <42, p=0.022). Conclusions: In this real-world, multi-center analysis of pathologic stage IIB/C melanoma pts, recurrence patterns varied based on time after surgery. Breslow thickness, LVI, male sex, and age were significantly associated with earlier recurrence at different time intervals on RMST analysis. Additionally, given that >50% of first recurrences 12+ months after surgery were distant, active surveillance for distant relapses may be warranted.

Abstract Background Recently, a model to predict 5-year recurrence-free survival (RFS) and melanoma-specific survival (MSS) after sentinel lymph node biopsy (SLNB) was published. The aim of this study was to validate that model in a large independent international cohort. Methods The database of the Sentinel Lymph Node Working Group (SLNWG) was analysed for patients with malignant melanoma who underwent SLNB. Patients with clinical stage III melanoma, a history of other malignancies, or receiving concomitant systemic therapies during follow-up were excluded. The model’s predictive performance was evaluated using discrimination and calibration metrics in the eligible cohort. Decision curve analysis was performed to assess the clinical value of the model. Results The external validation cohort consisted of 6174 patients of the SLNWG from the USA, Europe, and Israel. A positive sentinel node was found in 788 patients (12.8%). The area under the time-dependent receiver operating characteristic (ROC) curve of the external validation was 0.76 (95% c.i. 0.74 to 0.77) for RFS and 0.79 (95% c.i. 0.76 to 0.81) for MSS. The model was well calibrated, as the observed 5-year survival rates aligned closely with the predicted survival rates (calibration slope of 0.98 for RFS and calibration slope of 0.99 for MSS). The model provided a net benefit versus the ‘treat all’ and ‘treat none’ strategies at the predetermined probability threshold for recurrence of 45%. Conclusion The model demonstrated good performance in a large heterogeneous independent cohort, emphasizing its robustness. Decision curve analysis revealed a clear net benefit of the model over a treat all strategy, highlighting its potential for clinical use.