Development and validation of a novel model to predict recurrence-free survival and melanoma-specific survival after sentinel lymph node biopsy in patients with melanoma: an international, retrospective, multicentre analysis.

Background: The introduction of adjuvant systemic treatment for patients with high-risk melanomas necessitates accurate staging of disease. However, inconsistencies in outcomes exist between disease stages as defined by the American Joint Committee on Cancer (8th edition). We aimed to develop a tool to predict patient-specific outcomes in people with melanoma rather than grouping patients according to disease stage.
Methods: Patients older than 13 years with confirmed primary melanoma who underwent sentinel lymph node biopsy (SLNB) between Oct 29, 1997, and Nov 11, 2013, at four European melanoma centres (based in Berlin, Germany; Amsterdam and Rotterdam, the Netherlands; and Warsaw, Poland) were included in the development cohort. Potential predictors of recurrence-free and melanoma-specific survival assessed were sex, age, presence of ulceration, primary tumour location, histological subtype, Breslow thickness, sentinel node status, number of sentinel nodes removed, maximum diameter of the largest sentinel node metastasis, and Dewar classification. A prognostic model and nomogram were developed to predict 5-year recurrence-free survival on a continuous scale in patients with stage pT1b or higher melanomas. This model was also calibrated to predict melanoma-specific survival. Model performance was assessed by discrimination (area under the time-dependent receiver operating characteristics curve [AUC]) and calibration. External validation was done in a cohort of patients with primary melanomas who underwent SLNB between Jan 30, 1997, and Dec 12, 2013, at the Melanoma Institute Australia (Sydney, NSW, Australia).
Findings: The development cohort consisted of 4071 patients, of whom 2075 (51%) were female and 1996 (49%) were male. 889 (22%) had sentinel node-positive disease and 3182 (78%) had sentinel node-negative disease. The validation cohort comprised 4822 patients, of whom 1965 (41%) were female and 2857 (59%) were male. 891 (18%) had sentinel node-positive disease and 3931 (82%) had sentinel node-negative disease. Median follow-up was 4·8 years (IQR 2·3-7·8) in the development cohort and 5·0 years (2·2-8·9) in the validation cohort. In the development cohort, 5-year recurrence-free survival was 73·5% (95% CI 72·0-75·1) and 5-year melanoma-specific survival was 86·5% (85·3-87·8). In the validation cohort, the corresponding estimates were 66·1% (64·6-67·7) and 83·3% (82·0-84·6), respectively. The final model contained six prognostic factors: sentinel node status, Breslow thickness, presence of ulceration, age at SLNB, primary tumour location, and maximum diameter of the largest sentinel node metastasis. In the development cohort, for the model's prediction of recurrence-free survival, the AUC was 0·80 (95% CI 0·78-0·81); for prediction of melanoma-specific survival, the AUC was 0·81 (0·79-0·84). External validation showed good calibration for both outcomes, with AUCs of 0·73 (0·71-0·75) and 0·76 (0·74-0·78), respectively.
Interpretation: Our prediction model and nomogram accurately predicted patient-specific risk probabilities for 5-year recurrence-free and melanoma-specific survival. These tools could have important implications for clinical decision making when considering adjuvant treatments in patients with high-risk melanomas.
Funding: Erasmus Medical Centre Cancer Institute.
Competing Interests: Declaration of interests RCS reports honoraria (paid to their institution) from Amgen. AAMvdV reports consultancy fees (paid to their institution) from Bristol Myers Squibb, Merck Sharp & Dohme, Sanofi, Pierre Fabre, Ipsen, Eisai, Merck, Pfizer, Novartis, and Roche. RPMS has received honoraria for advisory board participation from Merck Sharp & Dohme, Novartis, and Qbiotics, and speaker fees from Bristol Myers Squibb and Novartis. AHRV has received honoraria from Novartis. RAS has received fees for professional services from MetaOptima Technology, F Hoffmann-La Roche, Evaxion, Provectus, Qbiotics, Novartis, Merck Sharp & Dohme, NeraCare, Amgen, Bristol Myers Squibb, Myriad Genetics, and GlaxoSmithKline. GVL reports consultancy or advisory fees from Agenus, Amgen, Array Biopharma, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Evaxion, Hexal, Highlight Therapeutics, Innovent Biologics, Novartis, OncoSec, PHMR, Pierre Fabre, Provectus, Qbiotics, and Regeneron. JFT has received honoraria for advisory board participation from Bristol Myers Squibb, Merck Sharp & Dohme, GlaxoSmithKline, and Provectus, and travel and conference support from GlaxoSmithKline, Provectus, and Novartis. PR reports research funding (paid to their institution) from Merck Sharp & Dohme and Pfizer, and has received honoraria for lectures and advisory board participation from Merck Sharp & Dohme, Bristol Myers Squibb, Novartis, Pierre Fabre, Sanofi, Merck, Philogen, and Blueprint Medicines. UK has received consulting fees from Merck Sharp & Dohme, travel support from Merck Serono and Pfizer, and grants for educational activities from Merck Serono, Bristol Myers Squibb, and Pierre-Fabre. ACJvA reports honoraria for consultancy and serving on advisory boards (all paid to their institution) from Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Merck, Pfizer, Neracare, Novartis, Pierre Fabre, Provectus, Sanofi, Sirius Medical, and 4SC, and research grants (paid to their institution) from Amgen, Merck, and Pfizer. DvK has participated on the data and safety monitoring boards of the FAST CABG and Multivessel Talent trials. DJG has served on data and safety monitoring boards for Amgen and Novartis (funds paid to their institution). All other authors declare no competing interests.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)