Multicenter Selective Lymphadenectomy Trial Research Articles

Long-term outcomes of nodal surveillance practices in sentinel node positive melanoma: An early post MSLT-II cohort

BackgroundThe Second Multicenter Selective Lymphadenectomy Trial (MSLT-II), published in 2017, demonstrated equivalent melanoma-specific survival between nodal surveillance and completion lymph node dissection (CLND) for sentinel lymph node (SLN) positive melanoma. This study evaluated outcomes of nodal surveillance in an early post-MSLT-II institutional cohort. MethodsIncluded patients received nodal surveillance from 2017 to 2023. Primary outcomes were nodal basin and any site recurrence. Kaplan Meier curves and Cox proportional hazard models were used to evaluate recurrence-free survial and associated factors. ResultsThis 212 patient cohort (median age 61 years, 57.7 ​% male, 96.7 ​% white) had median primary tumor depth of 1.9 ​mm and one positive SLN. Sixty-three patients (29.7 ​%) recurred at 23 month median follow-up. Sixty percent received adjuvant therapy. Any site and nodal basin recurrence-free survival were 58.3 ​% and 80.9 ​% at 3 years. On adjusted analysis, older age and head/neck primary site were associated with worse recurrence-free survival. ConclusionLong-term outcomes at a single institution were comparable to clinical trial findings. Nodal surveillance remains a feasible management strategy for SLN ​+ ​melanoma.

Interdisciplinary Implementation of a Synoptic Reporting Template for Melanoma Nodal Surveillance Ultrasound

BackgroundWith nodal surveillance increasingly used for sentinel lymph node-positive (SLN+) melanoma following the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II), high-quality nodal ultrasonography (U/S) has become a critical need. Previous work has demonstrated low utilization of MSLT-II U/S criteria to define abnormal lymph nodes requiring intervention or biopsy. To address this gap, an evidence-based synoptic template was designed and implemented in this single-center study.MethodsSentinel lymph node-positive patients undergoing nodal surveillance at a tertiary cancer center from July 2017 to June 2023 were identified retrospectively. Ultrasound reporting language was analyzed for MSLT-II criteria reported and clinically actionable recommendations (e.g., normal, abnormal with recommendation for biopsy). Following a multidisciplinary design process, the synoptic template was implemented in January 2023. Postimplementation outcomes were evaluated by using U/S reports and provider surveys.ResultsA total of 337 U/S studies were performed on 94 SLN+ patients, with a median of 3 U/S per patient (range 1–12). Among 42 synoptic-eligible U/S performed postimplementation, 32 U/S (76.0%) were reported synoptically. Significant increases were seen in the number of MSLT-II criteria reported (Pre 0.5 ± 0.8 vs. Post 2.5 ± 1.0, p < 0.001), and clinically actionable recommendations for abnormal findings (Pre 64.0% vs. Post 93.0%, p = 0.04). Nearly all surgeon and radiologist survey respondents were “very” or “completely” satisfied with the clinical utility of the synoptic template (90.0%).ConclusionsFollowing implementation of a synoptic template, U/S reports were significantly more likely to document MSLT-II criteria and provide an actionable recommendation, increasing usefulness to providers. Efforts to disseminate this synoptic template to other centers are ongoing.

Interdisciplinary implementation of a synoptic reporting template for melanoma nodal surveillance ultrasound.

35 Background: As nodal surveillance is increasingly used for sentinel lymph node positive (SLN+) melanoma following the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II), availability of high-quality nodal surveillance ultrasonography (U/S) has become a critical need. Based on MSLT-II, U/S criteria concerning for nodal recurrence should be evaluated to determine indication for lymph node (LN) biopsy. We previously demonstrated low utilization of MSLT-II criteria for reporting nodal U/S at our tertiary cancer center, diminishing the clinical utility of these reports. Working in an interdisciplinary team of surgeons and radiologists, we aimed to implement and evaluate a synoptic reporting template for melanoma nodal ultrasound at our institution. Methods: Patients undergoing melanoma nodal surveillance at a tertiary cancer center from July 2017 to June 2023 who received at least one nodal U/S were identified retrospectively. Reporting language from each U/S was analyzed for number of MSLT-II criteria reported and presence of clinically actionable recommendations for the referring surgical team (e.g. normal LN appearance or abnormal LN with recommendation for biopsy or observation). The synoptic report was designed collaboratively by a group of radiologists and surgical oncologists to include MSLT-II U/S criteria and thresholds for biopsy versus continued surveillance, with the institutional U/S dictation template revised accordingly. Dissemination to clinical teams was conducted and utilization was monitored in the course of clinical care. Following implementation of the synoptic template in January 2023, post-implementation adherence and outcomes were reviewed. Descriptive statistics and bivariate analysis were performed. Results: 337 nodal U/S studies were performed on 94 SLN+ melanoma patients, with a median of 2.5 U/S per patient (range 1 to 12). Forty-two U/S (12.5%) were performed in the post-implementation period and eligible for synoptic reporting; of these, 32 (76.0%) were reported with the synoptic template. The mean number of MSLT-II criteria reported was greater post-implementation (Pre 0.5 ± 0.8 vs Post 2.5 ± 1.0, p&lt;0.001). Abnormal findings were reported in 73 U/S (21.7%), with a significant increase in the proportion of clinically actionable recommendations for abnormal findings reported in the Post versus Pre group (93.0% vs 64.0%, p=0.037). Conclusions: Following the implementation of a collaboratively designed synoptic reporting template for melanoma nodal U/S, reports were much more likely to have MSLT-II criteria reported in addition to an actionable recommendation. There was notable improvement when ultrasounds had abnormal findings, when the application of these reporting criteria is most crucial. Further iterative improvement to increase adherence to the synoptic report and dissemination to other cancer centers is ongoing.

Prognostic Significance of Sentinel Lymph Node Status in Thick Primary Melanomas (> 4 mm)

BackgroundThe key prognostic factors for staging patients with primary cutaneous melanoma are Breslow thickness, ulceration, and sentinel lymph node (SLN) status. The multicenter selective lymphadenectomy trial (MSLT-I) verified SLN status as the most important prognostic factor for patients with intermediate-thickness melanoma (Breslow thickness, 1–4 mm). Although most international guidelines recommend SLN biopsy (SLNB) also for patients with thick (> 4 mm, pT4) melanomas, its prognostic role has been questioned. The primary aim of this study was to establish whether SLN status is prognostic in T4 melanoma tumors.MethodsData for all patients with a diagnosis of primary invasive cutaneous melanoma of Breslow thickness greater than 1 mm in Sweden between 2007 and 2020 were retrieved from the Swedish Melanoma Registry, a large prospective population-based registry. A multivariable Cox proportional hazard model for melanoma-specific survival (MSS) was constructed based on Breslow thickness stratified for SLN status.ResultsThe study enrolled 10,491 patients, 1943 of whom had a Breslow thickness greater than 4 mm (pT4). A positive SLN was found for 34% of these pT4 patients. The 5-year MSS was 71%, and the 10-year MSS was 62%. There was a statistically significant difference in MSS between the patients with a positive SLN and those with a negative SLN (hazard ratio of 2.4 (95% confidence interval CI 1.6–3.5) for stage T4a and 2.0 (95% CI 1.6–2.5) for satage T4b.ConclusionSentinel lymph node status gives important prognostic information also for patients with thick (> 4 mm) melanomas, and the authors thus recommend that clinical guidelines be updated to reflect this.

Investigating the patterns of treatment failure in patients with advanced stage III and IV melanoma receiving adjuvant therapy.

e21532 Background: The landscape of treatment of patients with resectable stage III melanoma has evolved considerably given studies demonstrating survival benefit of anti-PD-1 immunotherapy and BRAF/MEK-inhibitor (BRAF/MEKi) therapy in the adjuvant setting, as well as surgical changes relating to the Multicenter Selective Lymphadenectomy Trial (MSLT)-II trial. Currently, the decision to treat with anti-PD-1 or BRAF/MEKi therapy in the adjuvant setting is dependent upon patient, provider, and institutional preferences, but no comparative analysis has been done between adjuvant therapy options. Methods: Clinical data from 141 surgically-resected staged III and oligometastatic stage IV patients receiving adjuvant anti-PD-1 (n = 66), BRAF/MEKi (n = 36), or surgery only (n = 39) between 2017 and 2021 was analyzed retrospectively. Primary endpoints were overall survival (OS) and progression free survival (PFS) between the three treatment groups. Secondary endpoints include the duration of adjuvant treatment and reasons for termination of therapy. Results: During a mean follow-up period of 17 months, 33.3% of anti-PD-1 patients and 16.7% of BRAF/MEKi patients experienced recurrence, while 41.0% of the surgery only patients experienced recurrence. In univariate Cox regression analyses of the survival data, patients who received anti-PD-1 (HR = 0.46, 95% CI: 0.25-0.87, p = 0.016) or BRAF/MEKi (HR = 0.44, 95% CI:0.21-0.90, p = 0.024) had significantly improved PFS compared to patients treated with surgery only, but the OS was not significantly different with treatment. A multivariate Cox regression model was performed, adjusting for age, sex, and melanoma disease stage. In this model, anti-PD-1 was still associated with improved PFS (HR = 0.33, p &lt; 0.001), while BRAF/MEKi also trended towards improved PFS, but was not statistically significant (HR = 0.54, p = 0.13). Other associations include males having a significantly worse PFS (HR = 2.32, p = 0.009) and OS (HR = 5.86, p = 0.02), and patients with stage IIIC or worse disease having worse PFS (HR = 4.56, p &lt; 0.001), but not significantly worse OS (HR = 4.84, p = 0.05). The average duration of adjuvant therapy was similar between both groups (250-260 days) with approximately half of the patients completing the treatment course. A larger proportion of BRAF/MEKi patients stopped treatment due to intolerable side effects compared to anti-PD-1 patients (83.3% vs. 64.0%). Conclusions: Adjuvant treatment decreases the chance of recurrence compared to surgery alone, but the benefit on overall survival is still inconclusive. Male and more advanced stage III melanoma prior to initiating adjuvant therapy are factors associated with an increased likelihood of recurrence. Although it appears that more patients terminated BRAF/MEKi therapy early due to side effects compared to anti-PD-1, additional follow-up will be needed to confirm this finding.

Intermediate-thickness melanoma: A population-based study of surgical quality metrics

BackgroundVariability in guideline compliance for melanoma lymph node surgery is partially attributable to controversy about patient selection. Prior data has indicated suboptimal practice of sentinel lymph node biopsy and undertreatment of clinically node-positive disease, predating Multicenter Selective Lymphadenectomy Trial II publication. To minimize bias, we studied compliance with lymph node surgery guidelines in T2/T3 (intermediate-thickness) melanoma patients, where the greatest agreement exists. MethodsT2/T3 and metastasis 0 melanoma cases were identified from 2004 to 2018 Surveillance, Epidemiology, and End Results data. Analysis used Cochran-Armitage test for trends, multivariable logistic regression, and Kaplan-Meier survival estimates. ResultsOf 66,319 eligible T2/T3 patients, 57,211 were clinically node negative; 2,191 were clinically node positive; 6,197 were clinical node unreported; and 19,044/66,319 (28.8%) had no lymph node surgery. Among clinically node-negative patients, 36,433 (63.7%) underwent sentinel lymph node biopsy and 31,026 (85.2%) were pathologically node negative; 1,499 clinically node-positive patients (68.4%) had a lymph node dissection. Lymph node dissection rates declined from 2004 to 2018, 79.8% to 32.0% for clinically node-negative/pathologically node-positive patients and 80.4% to 61.2% for clinically node-positive/pathologically node-positive patients (both P < .0001). For clinically node-negative patients, lymph node surgery compliance improved from 63.7% (2004) to 70.4% (2018) (P < .0001). Compliance correlated with younger age, male sex, tumor mitotic rate, and site (extremity > trunk/head/neck) in multivariable analysis and improved 5-year cancer-specific survival (90.0% vs 83.4%) (all P < .0001). ConclusionsDespite clear guidelines, one-third of intermediate-thickness melanoma patients in a recent cohort did not have recommended lymph node surgery. Lymph node status is a key determinant of the relative benefit of adjuvant systemic therapy and the need for active surveillance of pathologically node-positive/clinically node-negative patients. These data highlighted a clinical care gap. Efforts to improve guideline compliance are a logical strategy to improve cancer outcomes for intermediate-thickness melanoma patients.

Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma

Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery. To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases. The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022. Nodal observation with ultrasonography rather than CLND. In-basin nodal recurrence. Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P < .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P < .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P < .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors. This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients. ClinicalTrials.gov Identifier: NCT00297895.

Real-World Adherence to Nodal Surveillance for Sentinel Lymph Node-Positive Melanoma.

Patients with sentinel lymph node-positive (SLN+) melanoma are increasingly undergoing active nodal surveillance over completion lymph node dissection (CLND) since the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II). Adherence to nodal surveillance in real-world practice remains unknown. In a retrospective cohort of SLN+ melanoma patients who underwent nodal surveillance at a single institution from July 2017 through April 2021, this study evaluated adherence to nodal surveillance ultrasound (US). Adherence to nodal US was compared with adherence to other surveillance methods based on receipt of adjuvant therapy. Early recurrence data were reported using descriptive statistics. Among 109 SLN+ patients, 37 (34%) received US surveillance at recommended intervals. Of the 72 (66%) non-adherent patients, 16 were lost to follow-up, and 33 had planned follow-up at an outside institution without available records. More patients had a minimum of bi-annual clinic visits (83%) and cross-sectional imaging (53%) compared to those who were adherent with nodal US. The patients who received adjuvant therapy (60%) had fewer ultrasounds (p < 0.01) but more exams (p < 0.01) and a trend toward more cross-sectional imaging (p = 0.06). Of the overall cohort, 26 patients (24%) experienced recurrence at a median follow-up period of 15 months. Of these recurrences, 10 were limited to the SLN basin, and all of these isolated nodal recurrences were resectable. Pragmatic challenges to real-world delivery of nodal surveillance remain after MSLT-II, and adjuvant therapy appears to be associated with a decreased likelihood of US adherence. Understanding US utility alongside cross-sectional imaging will be critical as increasingly more patients undergo nodal surveillance and adjuvant therapy.

Does Residual Invasive Disease in Wide Local Excision after Diagnosis with Partial Biopsy Technique Influence Survival in Melanoma? Matched-Pair Analysis of Multicenter Selective Lymphadenectomy Trial I and II.

Current guidelines recommend excisional/complete biopsy for melanoma diagnosis, owing to high rates of residual disease found at wide local excision (WLE) after partial biopsy techniques. We sought to determine any survival disadvantage associated with the presence of residual invasive melanoma in the WLE after diagnosis with a partial biopsy technique. Data were examined from Multicenter Selective Lymphadenectomy Trials I and II (MSLT-I and -II), 2 large melanoma trials. Patients diagnosed with excisional/complete biopsy were excluded. Clinicopathologic characteristics, melanoma-specific survival (MSS), distant disease-free survival (DDFS), and disease-free survival (DFS) of those with residual invasive melanoma in the definitive WLE and those with no residual melanoma were compared. Matched pairing was used to reduce variability between groups. From 1994 through 2014, 3,939 patients were enrolled in these trials and 874 (22%) were diagnosed using partial biopsy techniques. Of these, 399 (46%) had residual tumor in the WLE. Only 6 patients had residual tumor in their WLE resulting in T-upstaging of their tumor. Match-pairing formed two cohorts (1:1) of patients with and without residual invasive tumor after WLE. A total of 514 patients were paired; 288 (56%) males, 148 (28.8%) aged 60 or older, 192 (37.4%) with truncal melanomas, 214 (41.6%) had Breslow thickness 2 mm or greater, and 376 (73.2%) had positive sentinel nodes. Kaplan-Meier analysis showed no statistical difference in 10-year MSS (73.6% ± 3.3% vs 73.9% ± 3.7%, p = 0.891), DDFS (68.7% ± 3.4% vs 65.3% ± 4.0%, p = 0.548), or DFS (59.6% ± 3.7% vs 59.4% ± 3.9%, p = 0.783). Survival in patients with primary melanoma does not appear to be worse in patients who undergo a partial biopsy technique and are later found to have residual invasive tumor in the WLE specimen.

Oncologic Outcomes of Multi-Institutional Minimally Invasive Inguinal Lymph Node Dissection for Melanoma Compared with Open Inguinal Dissection in the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II).

Minimally invasive inguinal lymphadenectomy (MILND) is safe and feasible, but limited data exist regarding oncologic outcomes. This study performed a multi-institutional retrospective cohort analysis of consecutive MILND performed for melanoma between January 2009 and June 2016. The open ILND (OILND) comparative cohort comprised patients enrolled in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II) between December 2004 and March 2014.The pre-defined primary end point was the same-basin regional nodal recurrence, calculated using properties of binomial distribution. Time to events was calculated using the Kaplan-Meier method. The secondary end points were overall survival, progression-free survival, melanoma-specific survival (MSS), and distant metastasis-free survival (DMFS). For all the patients undergoing MILND, the same-basin regional recurrence rate was 4.4 % (10/228; 95 % confidence interval [CI], 2.1-7.9 %): 8.2 % (4/49) for clinical nodal disease and 3.4 % (6/179) for patients with a positive sentinel lymph node (SLN) as the indication. For the 288 patients enrolled in MSLT-II who underwent OILND for a positive SLN, 17 (5.9 %) had regional node recurrence as their first event. After controlling for ulceration, positive LN count and positive non-SLNs at the time of lymphadenectomy, no difference in OS, PFS, MSS or DMFS was observed for patients with a positive SLN who underwent MILND versus OILND. This large multi-institutional experience supports the oncologic safety of MILND for melanoma. The outcomes in this large multi-institutional experience of MILND compared favorably with those for an OILND population during similar periods, supporting the oncologic safety of MILND for melanoma.

Sentinel lymph node melanoma metastases: Assessment of tumor burden for clinical prediction of outcome in the first Multicenter Selective Lymphadenectomy Trial (MSLT-I)

PurposeAs clinical management decisions in patients with Stage III melanoma have become more complex, precise pathologic characterization of sentinel lymph node (SLN) metastases has become critical to guide management. The extent of SLN involvement correlates with risk of adverse outcomes, but reported methods of disease quantification vary. We examined SLN metastases from patients participating in an international clinical trial and compared several methods of tumor burden quantification. MethodsSLNs from 146 node-positive patients in the first Multicenter Selective Lymphadenectomy Trial (MSLT-I) were centrally-reviewed and characterized by number of tumor-positive nodes, percent nodal area tumor replacement, maximum dimension of largest metastasis, tumor penetrative depth, number of tumor foci, metastasis microanatomic location, and extracapsular extension. These data were analyzed for correlation with non-SLN metastasis and melanoma-specific survival (MSS). ResultsThe median number of tumor-involved SLNs was 1. The median maximum metastasis dimension was 1.11 mm. Median SLN area involvement was 1.5%. Tumor burden measures were highly correlated with each other. Factors associated with non-SLN metastasis by univariable analysis were primary tumor ulceration and extent of metastases. Tumor thickness, ulceration, non-SLN metastasis and multiple measures of SLN tumor burden were significantly related to MSS on univariable analysis. After multivariable adjustment, number of involved SLNs (p = 0.05) and percent nodal area tumor replacement (p = 0.02) were independent predictors of MSS. ConclusionCentral review of MSLT-I pathology indicates that primary tumor and SLN tumor characteristics predict non-SLN metastasis and MSS. Percent nodal involvement was more powerfully prognostic than the more commonly used maximum dimension of largest metastasis.

Melanoma sentinel lymph node biopsy and completion lymph node dissection: A regional hospital experience

Completion lymph node dissection (CLND) following positive sentinel lymph node biopsy (SLNB) for cutaneous melanoma is a topic of controversy. The second Multicenter Selective Lymphadenectomy Trial (MSLT-II) suggested no survival benefit with CLND over observation amongst patients with a positive SLNB. The findings of the MSLT-II may have limited applicability to our high-risk population where nodal ultrasound and non-surgical melanoma treatment is rationed. In this regional, retrospective study, we reviewed primary melanoma, SLNB and CLND histopathological reports in the Bay of Plenty District Health Board (BOPDHB) across a 10-year period. The primary outcomes measured were size of sentinel lymph node metastases and non-sentinel node (NSN) positivity on CLND for patients with a positive SLNB. In the 157 SLNB identified, the mean sentinel lymph node metastatic deposit size was larger in BOPDHB compared with MSLT-II (3.53 vs 1.07/1.11mm). A greater proportion of BOPDHB patients (54.8%) had metastatic deposits larger than 1mm compared with MSLT-II (33.2/34.5%) and the rate of NSN involvement on CLND was also higher (23.8% vs 11.5%). These findings indicate that the BOPDHB is a high-risk population for nodal melanoma metastases. Forgoing CLND in the context of a positive SLNB may place these patients at risk.

1092 Impact Of MSLT-II on Lymph Node Clearance Surgery in A Tertiary Plastic Surgery Centre

Abstract Aim Cutaneous malignant melanoma is a significant public health challenge in the United Kingdom. Wide local excision with Sentinel Lymph Node Biopsy (SLNB) is the current standard of treatment for most lesions. Some patients with positive SLNB would routinely undergo locoregional Lymph Node Clearance (LNC). Results of the Multicenter Selective Lymphadenectomy Trial II (MSLT-II) published in August 2017 challenged this approach, showing no melanoma specific survival benefit, but significant morbidity associated with routine LNC. Our study aims to show a change in practice at a tertiary plastic surgical referral centre in response to these results. Method We retrospectively reviewed our prospectively maintained database for all LNCs performed for cutaneous, non-head and neck malignant melanoma using the search terms ‘clearance’ and ‘dissection’ between 2015 and 2019. Results We performed 128 axillary and groin LNCs for cutaneous malignant melanoma 2015-2019. The range of LNCs per year varied from 38 in 2015 to 10 in 2019 (mean 25.6, median 28). The total number of LNCs, as well as LNCs performed following positive SLNB decreased after August 2017. Conclusions The data shows that our centre acknowledged evidence and reduced the number of LNCs performed after publication of MSLT-II. We expect that the number of avoided LNCs has saved significant resources due to reduced length of stay, and avoided our patient’s significant morbidity, including seromas, infections and lymphoedema. We recommend all skin cancer treatment centres to follow the evidence in order to provide excellent care and save resources.

Survival of sentinel node biopsy versus observation in intermediate-thickness melanoma: A Dutch population-based study.

The Multicenter Selective Lymphadenectomy Trial (MSLT-1) comparing survival after a sentinel lymph node biopsy (SLNB) versus nodal observation in melanoma patients did not show a significant benefit favoring SLNB. However, in subgroup analyses melanoma-specific survival among patients with nodal metastases seemed better. To evaluate the association of performing a SLNB with overall survival in intermediate thickness melanoma patients in a Dutch population-based daily clinical setting. Survival, excess mortality adjusted for age, gender, Breslow-thickness, ulceration, histological subtype, location, co-morbidity and socioeconomic status were calculated in a population of 1,989 patients diagnosed with malignant cutaneous melanoma (1.2-3.5 mm) on the trunk or limb between 2000-2016 in ten hospitals in the South East area, The Netherlands. A SLNB was performed in 51% of the patients (n = 1008). Ten-year overall survival after SLNB was 75% (95%CI, 71%-78%) compared to 61% (95%CI 57%-64%) following observation. After adjustment for risk factors, a lower risk on death (HR = 0.80, 95%CI 0.66-0.96) was found after SLNB compared to observation only. SLNB in patients with intermediate-thickness melanoma on trunk or limb resulted in a 14% absolute and significant 10-year survival difference compared to those without SLNB.

Fallen dogmas – recent advances in locoregionally advanced melanoma

Last decade brought new achievements in the melanoma research, which resulted in an important changes in the clinical management of stage III melanoma. The article summarizes recent updates with particular focus on practical aspects. Results from surgical studies, Multicenter Selective Lymphadenectomy Trial II (MSLT-II) and German Dermatologic Cooperative Oncology Group (DeCOG-SLT) proved that surgical dogmatic approach that all sentinel node melanoma metastasis warrants completion lymphadenectomy is no longer valid; omission of completion lymphadenectomy in large proportion of sentinel node positive melanoma patients has no negative impact on survival rates. Moreover oncological trials (COMBI-AD, EORTC 1325/KEYNOTE-054 and CheckMate 238) showed that in stage III melanoma patients' chances of recurrence-free survival can be improved by 10-20% by modern immunotherapy and/or molecular targeted therapy. These findings led to fall of another dogma in oncology: lack of effective adjuvant therapy for stage III melanoma at acceptable toxicity. At the end of the day in 2021 modern multidisciplinary approach incorporating newest findings offer stage III melanoma patients less surgical complications of better tailored surgery and longer survival in result of efficient adjuvant therapy.

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)

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. 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. 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. 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. 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.

Recent Evolution in the Management of Lymph Node Metastases in Melanoma.

IntroductionBased upon two large randomized international clinical trials (German Dermatologic Cooperative Oncology Group (DeCOG-SLT) and Multicenter Selective Lymphadenectomy Trial II (MSLT-II)) published in 2016 and 2017, respectively, active surveillance has been demonstrated to have equivalent survival outcomes to completion lymphadenectomy (CLND) for a subset of patients who have microscopic lymph node disease. In this study, the changes in national practice patterns were examined regarding the utilization of CLND after positive sentinel lymph node biopsy (SLNB).MethodsUsing the National Cancer Database, CLND utilization was examined in SLN-positive patients diagnosed with melanoma between 2012 and 2016. A hierarchal logistical regression model with hospital-level random intercepts was constructed to examine the factors associated with SLNB followed by observation vs. SLNB with CLND.ResultsOf the 148,982 patients identified, 43% (n = 63,358) underwent SLNB and 10.3% (n = 6,551) had a SLNB with microscopic disease. CLND was performed for 57% (n = 2,817) of these patients. Patients were more likely to undergo CLND if they were ≤ 55 years of age (OR, 1.454; p ≤ 0.0001), ages 56 – 65 (OR, 1.127; p = 0.026), Charlson Deyo Score = 0 (OR, 2.088; p = 0.043), or were diagnosed with melanoma in 2012 (OR, 2.259, p ≤ 0.0001).ConclusionsThe utilization of CLND among patients with microscopic nodal melanoma was significantly lower in 2016 compared to 2012. Younger age, lack of comorbidities, and primary tumor location on the trunk or head/neck were associated with higher utilization of CLND.

Surgeon decision-making for management of positive sentinel lymph nodes in the post-Multicenter Selective Lymphadenectomy Trial II era: A survey study.

Completion lymph node dissection (CLND) did not improve melanoma-specific survival for patients with sentinel lymph node (SLN)-positive melanoma in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II). We assessed surgeons' awareness of MSLT-II and its impact on CLND recommendations. An anonymous online cross-sectional survey of the Society of Surgical Oncology membership evaluated surgeon thresholds in offering CLND using patient scenarios and clinicopathologic characteristics ranking. Of the 2881 e-mails delivered, 146 surgeons (5.1%) completed all seven scenarios. Most (129 of 131, 98%) were aware of MSLT-II and 125 (95%) found it practice-changing. Specifically, 52% (65 of 125) always, 40% usually, 6% rarely, and 3% never offered CLND before MSLT-II. Meanwhile, 4% always, 9% usually, 78% rarely, and 8% never offer CLND now, after MSLT-II (p < .0001). The most important clinicopathologic factors in determining CLND recommendations were extracapsular extension, number of positive SLN, and SLN tumor deposit size, while primary tumor mitotic index and nodal basin location were the least important. Surgical oncology fellowship training, melanoma patient volume, and academic center practice also influenced CLND recommendations. Most surgeon respondents are aware of MSLT-II, but its application in practice varies according to several clinicopathologic and surgeon factors.

18620 Ultrasound follow-up rates in patients undergoing surveillance after positive sentinel lymph node biopsy

Background: The Multicenter Selective Lymphadenectomy Trial II (MSLT-II) demonstrated that complete lymph node dissection (CLND) following positive SLNB is not associated with improved melanoma-specific survival when compared with close clinical follow-up and ultrasound of the affected nodal basin.

Completion lymph node dissection in patients with sentinel lymph node positive cutaneous head and neck melanoma.

Relatively few cutaneous head and neck melanoma (CHNM) patients with were included in the multicenter selective lymphadenectomy trial II (MSLT-II). Our objective was to investigate whether immediate completion lymph node dissection completion of lymph node dissection (CLND) was associated with survival benefit for sentinel lymph node (SLN) positive CHNM using the National Cancer Database. SLN positive patients with CHNM from 2012 to 2014 were retrospectively analyzed. Patients were divided into two groups: those who underwent SLN biopsy (SLNB) only versus those who underwent SLNB followed by CLND (SLNB + CLND). The primary outcome was 5-year overall survival (OS). Among 530 SLNB + patients, 342 patients underwent SLNB followed by CLND (SLNB + CLND). The SLNB only group had fewer positive SLN, less advanced pathologic stage, and a lower rate of adjuvant immunotherapy. There was no significant difference in 5-year OS between the two groups (51.0% vs 67%; P = .56). After adjusting for pathologic stage, there remained no difference in 5-year OS among patients with stage IIIA (63.0% vs. 73.6%, P = 0.22) or IIIB/IIIC disease (39.1% vs 57.8%; P = .52). Conclusions Using a large nationwide database, CLND was not shown to be associated with improved OS for patients with SLNB positive CHNM, validating the results of MSLT-II.