The interval between primary melanoma excision and sentinel node biopsy is not associated with survival in sentinel node positive patients - An EORTC Melanoma Group study.

BACKGROUND: Worldwide, sentinel node biopsy (SNB) is the recommended staging procedure for stage I/II melanoma. Most melanoma guidelines recommend re-excision plus SNB as soon as possible after primary excision. To date, there is no evidence to support this timeframe. AIM: To determine melanoma specific survival (MSS) for time intervals between excisional biopsy and SNB in SNB positive patients. METHODS: Between 1993 and 2008, 1080 patients were diagnosed with a positive SNB in nine Melanoma Group centers. We selected 1015 patients (94%) with known excisional biopsy date. Time interval was calculated from primary excision until SNB. Kaplan-Meier estimated MSS was calculated for different cutoff values. Multivariable analysis was performed to correct for known prognostic factors. RESULTS: Median age was 51 years (Inter Quartile Range (IQR) 40-62 years), 535 (53%) were men, 603 (59%) primary tumors were located on extremities. Median Breslow thickness was 3.00 mm (IQR 1.90-4.80 mm), 442 (44%) were ulcerated. Median follow-up was 36 months (IQR 20-62 months). Median time interval was 47 days (IQR 32-63 days). Median Breslow thickness was equal for both <47 days and ≥47 days interval: 3.00 mm (1.90-5.00 mm) vs 3.00 mm (1.90-4.43 mm) (p = 0.402). Sentinel node tumor burden was significantly higher in patients operated ≥47 days (p = 0.005). Univariate survival was not significantly different for median time interval. Multivariable analysis confirmed that time interval was no independent prognostic factor for MSS. CONCLUSIONS: Time interval from primary melanoma excision until SNB was no prognostic factor for MSS in this SNB positive cohort. This information can be used to counsel patients

Practice-Changing Developments in Stage III Melanoma: Surgery, Adjuvant Targeted Therapy, and Immunotherapy.

In this article, we will focus on the practice-changing developments for stage III melanoma, from the use of the sentinel node (SN) biopsy to complete lymph node dissection (CLND) and upcoming adjuvant therapies. MSLT-1 (Multicenter Selective Lymphadenectomy Trial-1) was the first and only prospective randomized controlled trial to examine whether the SN biopsy has any notable melanoma-specific survival benefit (primary endpoint). MSLT-1 randomly assigned 2,001 patients to undergo either wide local excision (WLE) and an SN biopsy or WLE and nodal observation. Two prospective randomized controlled trials have examined the potential benefit for immediate CLND versus delayed CLND after sequential observation. Both the DECOG-SLT and MSLT-2 trials failed to demonstrate a notable benefit for immediate CLND; therefore, sequential follow-up with ultrasonography and a delayed CLND in the case of relapse should be considered the new standard of care. The CheckMate 238 study demonstrated a notable benefit for adjuvant nivolumab in terms of 18-month relapse-free survival (RFS) rates compared with high-dose adjuvant ipilimumab. Single-agent adjuvant BRAF inhibition has been examined and failed to improve RFS. However, the COMBI-AD study did demonstrate a substantial benefit for combination BRAF and MEK inhibition for patients with BRAF-mutated resected stage IIIA to IIIC melanoma