Background: Standard treatment for stage III melanoma with lymph node metastases involves complete lymph node dissection, which is a radical surgical procedure aimed at the removal of the entire regional lymph node basin. Conservative surgery for low-burden nodal metastasis involves removal of the metastatic lymph node or nodes ("node-picking"), leaving uninvolved nodes within the regional basin. This is expected to provide adequate regional control of the disease with no negative impact on patient survival and a lower rate of surgical complications.

Aims: The MelConSurg Cohort will provide the first data on conservative surgery for patients with stage III melanoma with nodal metastases detected clinically or by imaging.

Methods: A multicentre, single-arm prospective cohort study. Inclusion criteria: Patients with melanoma aged between 18 and 90 years, Eastern Cooperative Oncology Group performance status 0-1, non-matted regional lymph node metastasis (N1b or N2b) in a single regional basin detected clinically or by imaging (ultrasound, CT scan, PET scan). Study period: A 3-year recruitment period and a 3-year follow-up phase.

Intervention: Patients will undergo conservative nodal surgery using conventional surgery, radio-guided surgery, or imaging guided surgery.

Outcome measures: 3-year nodal relapse-free survival, 3-year disease-free survival, 3-year melanoma-specific survival, rate of surgical complications, and quality of life (SF-36 questionnaire).

Sample size & Statistics: the estimated sample size to be recruited is 68 patients. Survival outcomes will be analysed through the Kaplan-Meier method, with the log-rank test. Conclusions: This Project is expected to provide unique evidence regarding a less radical nodal surgery for patients with melanoma. If favourable results are obtained, controlled studies could be conducted and changes in current clinical practice could be considered.

Inclusion Criteria:

• Patients with melanoma aged between 18 and 90 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Nodal stage N1b or N2b (American Joint Committee on Cancer 8th edition) in a single regional basin detected clinically or by imaging (ultrasound, CT scan, PET scan).

Exclusion Criteria:

• Single lymph node metastasis in more than one regional basin.
• Multiple primary melanoma (except for limb melanoma).
• Primary occult melanoma.
• Previous nodal, locoregional, or distant metastasis.
• Previous lymph node surgery, except for SLNB.
• Distant metastases detected at the screening evaluations or first postoperative PET-CT scan.

Melanoma patients (stage III N1b or N2b) fulfilling inclusion criteria and with no exclusion criteria managed at any of the participant centers.