Multicenter observational study on recurrence patterns and health care resource utilization in stage II cutaneous melanoma in Spain: real-world evidence from the METHEOR study

• Adjuvant therapies for stage IIB/IIC melanoma are now being developed. • Recurrence rates were higher in stage IIB/IIC than in stage IIA disease; most were distant recurrences. • Recurrence led to increased healthcare use and higher associated costs. • Stage IIB/IIC melanoma requires improved follow-up and treatment strategies to reduce recurrence. Introduction: More than 7,000 cases of cutaneous melanoma (CM) were diagnosed in Spain in 2023, and approximately 15% were stage II. Patients with stage IIB-C CM typically have lower survival rates than those with stage IIIB disease. Objective: To describe recurrence patterns and variations in healthcare resource utilization (HCRU) at disease progression in Spanish patients with stage II primary CM. Methods: This retrospective study included patients diagnosed with stage II CM (AJCC, 8 th edition) between January 2013 and December 2017 at 11 Spanish hospitals. Disease characteristics, recurrence patterns, treatment after recurrence, survival outcomes, and HCRU were examined. Stages at diagnosis and time-to-event endpoints were also compared. Results: A total of 324 patients were included (52.2% male; median age, 64 years): 44.4% had stage IIA, 35.5% stage IIB, and 20.1% stage IIC disease. Ninety patients (27.8%) had at least 1 recurrence of CM; recurrence was lymphatic in 41.1%, hematogenous in 34.4%, and both in 20.0%. Most recurrent patients (54.4%) progressed to stage IV disease, mainly with lung metastases (70.1%). Eighty-one patients (90.0%) received treatment after recurrence: 58 (71.6%) received systemic treatment, 45 (55.6%) underwent surgery, and 25 (30.9%) received radiotherapy. Five-year recurrence-free survival was 74.5% for stage IIA, 62.6% for stage IIB, and 65.7% for stage IIC disease, with a significantly higher risk of recurrence in stages IIB/C vs IIA (HR, 1.52; 95%CI, 1.02-2.25; P = .039). After first recurrence, annual HCRU rates increased by 251%, with annual cost increases of euro3,018.68 for visits and euro9,428.73 for tests. Conclusions: A substantial proportion of patients with stage II melanoma experience recurrence, often with distant metastases and a marked impact on healthcare resource utilization. These findings reinforce the need to optimize follow-up and advance adjuvant strategies.