Is a History of Optimal Staging by Sentinel Lymph Node Biopsy in the Era Prior to Adjuvant Therapy Associated with Improved Outcome Once Melanoma Patients have Progressed to Advanced Disease?

Introduction: Sentinel lymph node biopsy (SLNB) is important for staging in patients with primary cutaneous melanoma. Did having previously undergone SLNB also affect outcomes in patients once they have progressed to metastatic melanoma in the era prior to adjuvant therapy?Methods: Data were retrieved from the Dutch Melanoma Treatment Registry, a prospectively collected, nationwide database of patients with unresectable stage IIIC or IV (advanced) melanoma between 2012 and 2018. Melanoma-specific survival (MSS) was compared between patients with advanced cutaneous melanoma, previously treated with a wide local excision (WLE) or WLE combined with SLNB as initial treatment of their primary tumor. Cox regression analyses were used to analyze the influence of different variables on MSS.Results: In total, 2581 patients were included, of whom 1412 were treated with a WLE of the primary tumor alone and 1169 in whom this was combined with SLNB. At a median follow-up of 44 months from diagnosis of advanced melanoma, MSS was significantly longer in patients who had previously undergone SLNB {median 23 months (95% confidence interval [CI] 19–29) vs. 18 months (95% CI 15–20) for patients treated with WLE alone; p = 0.002}. However, multivariate Cox regression did not identify SLNB as an independent favorable prognostic factor for MSS after diagnosis of advanced melanoma.Conclusion: Prior to the availability of adjuvant systemic therapy, once patients have unresectable stage IIIC or IV (advanced) melanoma, there was no difference in disease outcome for patients who were or were not previously staged with SLNB.</p

Adjuvant treatment for melanoma in clinical practice - Trial versus reality

Background: Little is known about outcomes of adjuvant-treated melanoma patients beyond the clinical trial setting. Since 2019, adjuvant-treated melanoma patients have been registered in the DMTR, a population-based registry to monitor the quality and safety of melanoma care in the Netherlands. This study aims to describe treatment patterns, relapse, and toxicity rates of adjuvant-treated melanoma patients beyond the clinical trial setting. Methods: Analyses were performed on adjuvant-treated melanoma patients included in the DMTR. Descriptive statistics were used to analyse patient-, and treatment characteristics. A baseline registration completeness analysis was performed, and an analysis on trial eligibility in clinical practice patients. Recurrence-free survival (RFS) at 12-months was estimated with the Kaplan-Meier method. Results: A total of 641 patients were treated with adjuvant anti-PD-1 therapy. RFS at 12-months was 70.6% (95% CI, 66.9-74.6) with a median follow-up of 12.8 months. Sex, stage of disease and Breslow thickness were associated with a higher hazard for RFS. Eighteen per cent of the anti-PD-1-treated patients developed grade >= 3 toxicity. Sixty-one per cent of patients prematurely discontinued anti-PD-1 therapy. Conclusion: Adjuvant anti-PD-1 treatment of resected stage III/IV melanoma in daily practice showed slightly higher toxicity rates and more frequent premature discontinuation but similar RFS rates compared to trials. (C) 2021 The Authors. Published by Elsevier Ltd

The end of wide local excision (WLE) margins for melanoma ?

Clinical question: Is there nowadays any benefit of continuing the practice of routine wide local excision (WLE) for primary stage I/II cutaneous melanoma? Background: WLE aims to eradicate potential microsatellites around melanomas and thereby reduce local recurrence rates and improve overall survival. Six large prospective randomised trials investigated WLE versus wider WLE, they all failed to show any effect on overall survival (OS). Methods: A literature search was performed to identify data on outcome after omitting WLE. Additionally circumstantial evidence was gathered from pathology studies and outcomes of modified surgical techniques, as well as publications on morbidity. Results: No prospective and one retrospective study was found. The retrospective study showed no difference in OS after correction for confounding factors. Pathology studies showed a low incidence of residual melanoma in WLE specimen (0–4.2%). Mohs surgery does not show a difference in recurrence rates or OS. WLE is associated with considerable postoperative morbidity, which increases with wider excision margins. Conclusion: There is no solid prospective evidence to support the classic dogma of a 2-step approach with the use of WLE for primary cutaneous melanoma that has been completely excised on diagnostic excision biopsy. We recommend to setup and conduct a prospective randomised trial to compare the classical 2-step approach with WLE to a complete diagnostic excision only to abolish the routine practice of WLE in the future

Adjuvant Therapy for Melanoma: Past, Current, and Future Developments

This review describes the progress that the concept of adjuvant therapies has undergone in the last 50 years and focuses on the most recent development where an adjuvant approach has been scientifically evaluated in melanoma clinical trials. Over the past decade the development of immunotherapies and targeted therapies has drastically changed the treatment of stage IV melanoma patients. These successes led to trials studying the same therapies in the adjuvant setting, in high risk resected stage III and IV melanoma patients. Adjuvant immune checkpoint blockade with anti-CTLA-4 antibody ipilimumab was the first drug to show an improvement in recurrence-free and overall survival but this was accompanied by high severe toxicity rates. Therefore, these results were bypassed by adjuvant treatment with anti-PD-1 agents nivolumab and pembrolizumab and BRAF-directed target therapy, which showed even better recurrence-free survival rates with more favorable toxicity rates. The whole concept of adjuvant therapy may be integrated with the new neoadjuvant approaches that are under investigation through several clinical trials. However, there is still no data available on whether the effective adjuvant therapy that patients finally have at their disposal could be offered to them while waiting for recurrence, sparing at least 50% of them a potentially long-term toxic side effect but with the same rate of overall survival (OS). Adjuvant therapy for melanoma has radically changed over the past few years&mdash;anti-PD-1 or BRAF-directed therapy is the new standard of care

Alternatives and reduced need for sentinel lymph node biopsy (SLNB) staging for melanoma

Sentinel lymph node biopsy (SLNB) has been introduced in the 1990s to identify patients who might benefit from completion lymph node dissection. Neither SLNB nor CLND improved survival, but SLNB staging did provide the best staging, above Breslow thickness and ulceration. The SLN status and SLN tumour burden were used in all trials until date looking at modern adjuvant systemic therapy with immune checkpoint inhibition (ICI) or targeted therapies (TT). Adjuvant ICI and TT are shifting towards stage II melanoma. The question is whether there is still role for SLNB in melanoma, in this day and age, and if so, how does the future look for SLNB staging? The SLN status and SLN tumour burden might be useful for a consultation to discuss the number needed to treat in a risk/benefit discussion. For stage IIB/C patients, it seems likely, however, that patients will forego a nuclear scan followed by the risk of surgical intervention and morbidity associated with SLNB if they opt to receive adjuvant therapy regardless of the SLNB result. For stage I/IIA, it is still required to detect high-risk patients who might benefit from adjuvant therapy. However, biomarkers are emerging, such as gene expression profilers (GEP), immunohistological signatures and liquid biopsies with ctDNA. There still is a role for SLNB staging in melanoma today, but we expect that the availability of therapeutic option independent of SLNB status as well as emergence of validated biomarkers to predict risk will reduce the need for SLNB staging in the upcoming decade to the point it will no longer be used