Active surveillance of patients who have sentinel node positive melanoma: An international, multi‐institution evaluation of adoption and early outcomes after the Multicenter Selective Lymphadenectomy Trial II (MSLT‐2)

Abstract

Background For patients with sentinel lymph node (SLN)‐positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease‐specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown. Methods In a retrospective cohort of SLN‐positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all‐site recurrence‐free survival (RFS), isolated nodal RFS, distant metastasis‐free survival (DMFS), and DSS using Kaplan‐Meier curves and Cox proportional hazard models. Results Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty‐nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti–PD‐1 immunotherapy. After a median follow‐up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty‐eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk‐adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15‐0.88), but not all‐site RFS (HR, 0.68; 95% CI, 0.45‐1.02). Adjuvant therapy improved all‐site RFS (HR, 0.52; 95% CI, 0.47‐0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment. Conclusions Active surveillance has been adopted for most SLN‐positive patients. At initial assessment, real‐world outcomes align with randomized trial findings, including in adjuvant therapy recipients. Lay Summary For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real‐world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up‐front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma.

A survey of surgical management of the sentinel node positive melanoma patient in the post‐MSLT2 era

“…Over half of the respondents still selectively use immediate CLND, despite the lack of high‐level evidence to support this practice 2 . A recent retrospective study confirmed this change in practice with 86% of patients in their post‐publication of MSLT2 cohort of 965 positive SLNBs receiving active surveillance 7 …”

Active surveillance of patients who have melanoma with a positive sentinel node in an era of effective adjuvant therapy: Early lessons learned … and still learning

“…As reported in this issue of C ancer , Broman and colleagues 14 recently examined the adoption and early outcomes of active surveillance for patients who had primary cutaneous melanoma and a positive SLN between mid‐2017 and late 2019 and whose management was likely informed by the recently published MSLT‐II and DeCOG‐SLT randomized clinical trials. Remarkably, this analysis includes clinicopathologic, treatment, follow‐up, and recurrence data comprised of 1154 SLN‐positive patients from 21 institutions from the United States, Australia, and Europe that, together, contributed to a robust data set to perform these exploratory studies.…”

“…Among the patients who underwent CLND, Broman and colleagues noted that they were more likely to be younger, have a head and neck primary, or have high‐risk primary and/or regional factors (including increased tumor thickness, more positive SLNs, extranodal extension, increased SLN tumor burden, or microsatellite disease). On multivariable analysis, patients who had clinicopathologic features often considered under‐represented in the MSLT‐II study cohort, including a head and neck primary (13.7% of patients in MSLT‐II), high SLN tumor burden (33.9% of patients had >1.0 mm maximum SLN tumor dimension in MSLT‐II), or a high number of SLNs (<3% of patients had ≥3 positive SLNs in MSLT‐II), were more likely to undergo CLND 11,14 . It is notable that several clinicopathologic factors that portend an increased risk of tumor‐involved non‐SLNs at CLND—eg, thicker primary tumors, higher SLN tumor burden—have also been associated with decreased MSS 15 .…”

Health-related quality of life using the FACT-M questionnaire in patients with malignant melanoma: A systematic review

“…Again, this is consistent with clinical observation and practice, where advanced surgery is routinely utilized to manage lymph node disease which can create long-term irreversible morbidity for the patient, most notably, lymphoedema. However, based on evidence from trials such as MSLT-2 and DeCOG-SLT, clinical practice has begun to shift away from immediate surgery of confirmed nodal disease and towards observation [51,52]. As such, a corresponding future increase in MSS score is expected.…”