Lymphadenectomy and Postoperative Complications in Stage III Melanoma: A Single-Center Analysis

BackgroundLimited studies have exclusively investigated the role of completion lymph node dissection (CLND) in acral melanoma (AM) with lymph node macrometastasis (macroLNM). This multicenter study aimed to evaluate the impact of CLND and its performance timing on AM patients with macroLNM.Patients and methodsThe study enrolled 384 non-metastatic AM patients with initial or recurrent macroLNM from 4 tertiary hospitals. These patients were categorized into 3 groups based on the type of CLND: No CLND, CLND, or therapeutic lymph node dissection (TLND). The CLND group was further divided into early and late groups according to the timing of CLND. Kaplan-Meier and Cox multivariable analyses were performed to assess survival differences.ResultsOf the total cohort, both the 5-year overall survival (OS) and recurrence-free survival (RFS) in the No CLND group were significantly worse than those in the CLND and TLND groups (P = .009 and P = .021, respectively). Multivariate analysis demonstrated that CLND performance remained to be significantly associated with both OS and RFS (all P < .05). Among the CLND group, CLND timing independently predicted worse RFS (P = .049) but not OS at multivariate analysis. Notably, the late CLND group tended to significantly have more large-size metastatic nodes. Pearson correlation analysis revealed a significant correlation between preoperative time interval and the enlargement in size of lymph node metastasis (r = 0.356, P = .002).ConclusionsCLND remains crucial for improving prognosis for AM with macroLNM. Furthermore, delayed CLND might lead to larger metastatic lymph nodes and decreased RFS. Thus, performing CLND earlier may be beneficial for this patient population.

Nodal staging with sentinel node biopsy (SNB) and completion lymph node dissection (CLND) provides prognostic information to patients with melanoma and their physicians. It is not known whether the timing of CLND is associated with survival outcome and/or CLND tumour load. This study investigated whether CLND timing is associated with CLND tumour load, disease-free survival (DFS) and/or melanoma-specific survival (MSS). A retrospective cohort of patients with SNB-positive melanoma from nine European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group centres undergoing surgery between 1993 and 2009 were examined. Patients were selected based on availability of CLND and follow-up data. The CLND interval was defined as the number of days between diagnosis and CLND. Patient and tumour characteristics were collected. Five-year DFS and MSS rates were calculated. Cox and logistic regression analysis were performed, adjusting for known prognostic/predictive indicators. A total of 784 patients were included in the study. Their median age was 51 (i.q.r. 40-62) years, and 418 patients (53·3 per cent) were men. Median Breslow thickness was 3·0 (i.q.r. 2·0-5·0) mm, and 148 patients (18·9 per cent) had a residual tumour load. Median CLND interval was 84 (i.q.r. 65-105) days. Five-year DFS and MSS rates were not significantly different for patients operated on with a median CLND interval of less than 84 days and those with an interval of at least 84 days (DFS: 54·2 versus 53·3 per cent respectively; MSS: 66·9 versus 65·1 per cent). In a multivariable Cox model, CLND interval was not a significant prognostic indicator. CLND interval was negatively correlated with identification of positive non-sentinel nodes, but following adjustment for known risk factors this effect was no longer found. The time interval between diagnosis of melanoma and CLND did not influence CLND tumour load, DFS or MSS.

Sentinel lymph node biopsy (SLNB) is useful for staging of patients with melanoma. Although SLNB is mostly performed under general anesthesia (GA), tumescence local anesthesia (TLA) can also be used. However, less data are available regarding feasibility of SLNB under TLA. Here we present a post-operative follow-up of 150 patients. We prospectively analyzed data from 150 patients with primary cutaneous malignant melanoma. We assessed pain, post-operative complications and patients' satisfaction after SLNB under TLA. 32% of the patients reported post-operative pain within the first 48h after SLNB. Seroma was the most frequent complication, as 29 seromas after SLNB were observed. Wound infection was observed in 3.3% of the patients. 98.7% of the patients were satisfied with SLNB under TLA. SLNB under TLA is a safe and feasible option and should be considered for patients with melanoma. Especially with multimorbid or elderly patients, the risks of GA can be avoided.

Completion lymph node dissection (CLND) for sentinel lymph node (SLN) disease in melanoma patients is debated. We evaluated the impact of CLND on survival and assessed for predictors of nonsentinel node metastasis (positive CLND). Positive SLN melanoma patients were retrospectively identified in the Sentinel Lymph Node Working Group database. Clinicopathological factors were correlated with CLND status, overall survival (OS), and melanoma-specific survival (MSS). There were 953 positive SLN patients of whom 831 (87%) had CLND. Positive CLND was seen in 141 (17%) cases and was associated with worse OS and MSS (both P < 0.001). CLND was not performed (No-CLND) in 122 of 953 positive SLN cases (13%), of whom 100 had follow-up and 18 (18%) developed a nodal recurrence (NR). No significant differences in OS and MSS were seen comparing CLND with No-CLND (P = 0.084, P = 0.161, respectively) and comparing positive CLND with No-CLND NR patients (P = 0.565, P = 0.998, respectively). Gender, primary site, ulceration, and number of positive SLNs were correlated with nonsentinel node metastasis. Performance of CLND provides prognostic information but is not associated with a survival benefit. Clinical variables can predict a positive CLND in patients who may be at high risk of recurrence.

Nodal basin recurrence following lymph node dissection for melanoma: implications for adjuvant radiotherapy

The diagnosis of subungual melanoma (SUM) can be challenging and SUMs generally have a worse prognosis than melanomas arising elsewhere. Due to their rarity, the evidence to guide management is limited. This study sought to identify clinicopathological features predictive of outcome and to provide guidelines for management. From a large, single-institution database, 103 patients with in situ (n = 9) or invasive (n = 94) SUMs of the hand treated between 1953 and 2014 were identified and their features analyzed. The most common site of handSUMs was the thumb (53%). Median tumor thickness was 3.1mm, and SUMs were commonly of the acral subtype (57%), ulcerated (58%), amelanotic (32%), and had mitoses (73%). Twenty-one patients reported prior trauma to the tumor site. Twenty-two patients were stage III at diagnosis; 7 underwent therapeutic lymph node dissection and 22 underwent elective lymph node dissection (5 positive), while 36 had sentinel node biopsy (SNB), 28% of which were positive. Forty percent of SNB-positive patients had involved non-sentinel nodes (SNs) in their completion lymph node dissection. Five-year melanoma-specific survival (MSS) and disease-free survival (DFS) rates were 70% and 52%, respectively. On multivariate analysis, regional node metastasis and right-hand tumor location were significant predictors of shorter DFS and MSS, whereas mitoses negatively impacted DFS only and increasing Breslow thickness impacted MSS only. This study confirms that SUMs on the hand usually present at an advanced stage. Distal amputation appearssafe for invasive SUMs, and SNB should be considered as these patients have a high risk of both SN and non-SN metastasis.

The Role of Completion Lymphadenectomy in Positive Regional Lymph Nodes in Melanoma: A Meta-analysis

Simple SummaryThe aim of the present study was to investigate long-term outcomes of melanoma patients who had micrometastasis on sentinel lymph node (SLN) biopsy. We focused on the comparison between melanoma patients with and without complete lymph node dissection (CLND) following a positive SLN biopsy result. Patients without CLND did not significantly differ from patients with CLND in regard to age, gender, tumor thickness, tumor ulceration, capsule infiltration of SLN, and invasion level of SLN. On 10-year analysis, we did not observe a significantly increased risk for melanoma relapse or melanoma-specific death in patients who did not undergo CLND after the detection of micrometastases on SLN biopsy. On 20-year analysis, again, the patients without CLND had no significantly increased risk of melanoma relapse and worse melanoma-specific survival. Hence, our 10-year survival data confirm the current notion that waiving CLND in SLN-positive patients does not result in clinical disadvantages with respect to melanoma-specific survival. For the first time, we demonstrate on 20-year survival analysis that relapse rates and melanoma-specific survival does not significantly differ between patients with or without CLND on long-term follow-up.Complete lymph node dissection (CLND) following positive sentinel lymph node (SLN) biopsy has been the standard of care for decades. We aimed to study melanoma patients with an emphasis on the outcome of patients with versus without CLND following positive SLN biopsy. SLN-positive patients with or without CLND were compared regarding important prognostic clinical and histological characteristics. Ten-year and 20-year survival curves for melanoma relapse and melanoma-specific survival (MSS) were determined by the Kaplan-Meier method and Cox proportional-hazards regression. We studied 258 patients who had micrometastases in their SLN biopsy. CLND was performed in 209 of 258 patients (81%). Hence, in 49 of 258 patients (19%) with SLN micrometastases, CLND was not performed. These patients did not significantly (p > 0.05) differ from patients with CLND in regard to age, gender, tumor thickness, tumor ulceration, capsule infiltration of SLN, or invasion level of SLN. On 10-year analysis, we did not observe a significantly increased risk for melanoma relapse and worse in MSS in patients who did not undergo CLND (hazard ratio: 1.1 (95% CI 0.67 to 1.7) and 1.1 (95% CI 0.67 to 1.9), respectively). On 20-year survival analysis, we confirmed that the risk of melanoma relapse and impaired MSS does not significantly increase in patients without CLND (hazard ratio: 1.2 (95% CI 0.8 to 1.9) and 1.3 (95% CI 0.8 to 2.3), respectively). On 10-year as well as 20-year multivariable follow-up analysis (including several important prognostic factors), Cox proportional-hazards regression showed that the status of CLND did not remain in the regression model (p > 0.1). Our 10-year data give conclusive support to previous investigations indicating that waiving CLND in patients with SLN micrometastases does not affect MSS. More importantly, our long-term follow-up data confirm for the first time the 10-year survival data of previous investigations.

Complete lymph node dissection (CLND) following a positive sentinel lymph node biopsy (SLNB) has been the standard treatment for years. However, there is increasing evidence that CLND could be omitted. Approximately 80% of patients with a positive sentinel node biopsy do not have additional nodal involvement; in these contexts, the SLNB could be diagnostic and therapeutic. However, in this group of patients, the therapeutic effect of CLND is unclear.A systematic search was performed in EMBASE and MEDLINE (PubMed), for studies published between January 1, 2014 and December 31, 2019. Studies were included when they compared immediate CLND and observation after a positive sentinel node. The outcomes of interest were: Overall Survival (OS), melanoma-specific survival (MSS), and disease-free survival (DFS).Eleven studies met the inclusion criteria. Two randomized clinical trials reported no differences in OS or MSS when complete lymph dissection was compared with observation alone. An increase in regional relapse was observed in the CLND group, and in one randomized controlled trial (RCT) the rate of disease-free survival was superior in those patients.Most populations in both RCTs had low sentinel lymph node biopsy (SLNB) metastatic deposits, and head and neck melanomas were not included or underrepresented. When CNLD was omitted, an active surveillance protocol was carried out.The evidence supports that CLND in SLNB positive patients does not confer a survival benefit. Sentinel tumor burden, localization of primary tumor, and feasibility of active surveillance should be taken into account in treatment decisions.

In his companion editorial, Dr. Coit lauds the final analysis of the first Multicenter Selective Lymphadenectomy Trial (MSLT-I), reported recently in the New England Journal of Medicine, saying that it ‘‘has provided clinicians with invaluable very high quality information to interpret and use in the management of their melanoma patients’’. However, he expresses concern about ‘‘how the authors have presented this information to the readers’’. The planning and conduct of MSLT-1 was a mammoth project, and the fact that the final report was not publishable until 20 years after the first of the 2001 trial patients was randomized highlights not only the scale of the undertaking but also the dedication and commitment of clinicians, trial personnel, and patients around the world to its successful completion, when 10 years of follow-up had been achieved for all trial participants. The mass of data collected in MSLT-I over the 20-year period was large, making it impossible to report and discuss all the results in a single journal publication. However, we can reassure Dr. Coit and others that hitherto unreported trial data will be presented in subsequent publications. The broad statement by Dr. Coit that ‘‘this is a negative trial’’ refers only to the primary endpoint—improvement in melanoma-specific survival. This sweeping claim ignores the multiple statistically significant benefits that were demonstrated for critically important, predetermined secondary endpoints, notably a significant improvement in disease-free survival in the sentinel lymph node biopsy (SLNB) group and significantly improved melanoma-specific survival in sentinel lymph node (SLN)-positive patients treated by immediate completion lymph node dissection (CLND). In relation to melanoma-specific survival, the results of MSLT-I are consistent with those of previous randomized trials of elective lymph node dissection (ELND), and Dr. Coit concedes this. Although these previous trials were insufficiently powered (as was MSLT-1) to demonstrate an overall survival benefit for patients undergoing ELND (or SLNB/CLND), they consistently demonstrated a likely survival benefit for the cohort of patients with intermediate-thickness melanomas. In addition, although neither MSLT-I nor the earlier ELND trials showed a statistically significant improvement in overall melanoma-specific survival following early nodal surgery, they demonstrated a consistent advantage that falls short of statistical significance. Lack of statistical significance in an underpowered trial should not be interpreted as a demonstration of equality. For patients with thick melanomas, Dr. Coit accepts that MSLT-I data (Fig. 3b) support the concept that finding melanoma cells in an SLN predicts the eventual development of clinically detectable nodal disease (if the SLN is not removed). However, he is unwilling to accept that the same is true for patients with intermediate thickness melanomas because the incidence of ‘positive’ nodes after 10 years is 2.4 % higher after SLN biopsy and follow-up than after observation alone. He suggests that the curves in Fig. 3a are ‘‘remarkably parallel’’ beyond 5–6 years follow-up. This is not true. As we have previously indicated, over 25 % of the numerical difference between the curves reporting cumulative incidence of nodal metastasis vanishes between 8 and 10 years of follow-up. Formal followup of MSLT-1 patients did not extend beyond 10 years, but Society of Surgical Oncology 2014

To assess the nature and rates of complications and recurrences after completion lymph node dissection (CLND) following positive sentinel lymph node biopsy (SLNB) in melanoma patients. In contrast to SLNB, CLND is associated with considerable morbidity. CLND delays nodal recurrence, thereby prolonging disease-free survival (DFS), but not overall melanoma-specific survival. Elaborate studies on morbidity and recurrence rates after CLND are scarce. Therefore, many controversies concerning extent and nature of CLND exist. We conducted a retrospective study on 100 melanoma patients, on whom we performed CLND between October 1999 and December 2005. The median observation period was 38.8 months. We performed a total of 102 CLNDs, [46.1% axillary (47/102), 42.2% groin (43/102), 11.8% neck (12/102)]. Groin dissection (GD) and axillary dissection (AD) led to comparable morbidity (47.6% and 46.8%), but complications were more severe in GD, mandating additional surgery in 25.6% (11/43), versus 8.5% (4/47) in AD. Of the GD patients, 18.5% (8/43) were readmitted for complications compared with 10.4% (5/47) of AD patients. Only 8.3% (1/12) of ND patients suffered complications, mandating neither readmittance nor further surgery. During the median observation period, 65 (65%) of these patients showed DFS, and 35 (35%) exhibited recurrences after a median DFS of 12.5 months. Of the recurrences, 31.4% were nodal, 42.9% distant, and 25.7% local/in-transit. Of our AD patients, 28.3% suffered recurrences (13/46), as did 33.3% of the GD (14/42) and 66.7% of the ND patients (8/12). CLND is fraught with considerable morbidity. Local control of the dissected nodal basins was achieved with a modified radical approach in ADs (levels I + II only) and, to a lesser extent, GDs, but not in NDs. Clinical trials are necessary to establish guidelines on the extent of lymphatic dissection.

Factors associated with sentinel lymph node status and prognostic role of completion lymph node dissection for thick melanoma

9033 Background: The therapeutic benefit of completion lymph node dissection (CLND) in melanoma patients with a positive sentinel lymph node (SLN) remains unknown. This study describes the natural history of selected patients undergoing nodal observation (no-CLND) after a positive SLN biopsy and compares outcomes with those undergoing immediate CLND. Methods: A prospective database was used to identify melanoma patients with a positive SLN biopsy from 1994 to 2012. Patient and tumor characteristics, reasons for not undergoing CLND, patterns of initial recurrence, and melanoma-specific survival data were analyzed. Results: Of 4319 patients undergoing SLN biopsy, 505 (12%) had a positive SLN. 170 (34%) patients underwent nodal observation and 335 (66%) had an immediate CLND. Patients in the no-CLND group were older (65 vs. 56 years, p&lt;0.001) and more likely to have lower extremity lesions (43% vs. 30%, p=0.004). There were no differences in tumor thickness, Clark level of invasion, presence of ulceration, or degree of SLN tumor between groups. In 89% of cases, the reason to forgo CLND was due to doctor and/or patient decision. Median follow up was 23.5 and 78.5 months for no-CLND and CLND groups and median time to first recurrence was similar at 9 and 12 months (p=NS) respectively. There was no difference in regional recurrence rates between groups (20%). Nodal disease as a site of first recurrence occurred in 16% of patients in the no-CLND group compared with 7% of CLND patients (p&lt;0.001). In contrast, systemic disease as first site of recurrence occurred in 8% of no-CLND patients compared with 27% of CLND patients (p&lt;0.001). While median relapse-free survival was better after CLND (34.5 vs. 20.9 months, p=0.02), melanoma-specific survival was similar (not reached, no-CLND vs. 110 months, CLND, p=0.14). Conclusions: Immediate CLND after a positive SLN biopsy is associated with fewer initial nodal basin recurrences but similar melanoma-specific survival. These results support ongoing equipoise in the two arms of MSLT-II.

Adjuvant Regional Nodal Radiation in Sentinel Lymph Node Positive Merkel Cell Carcinoma without Completion Lymph Node Dissection

The benefit of completion lymph node dissection (CLND) in melanoma patients with a positive sentinel lymph node (SLN) remains unknown. We identified patients with a positive SLN from 1994 to 2012. Patient and tumor characteristics, reasons for not undergoing CLND, patterns of recurrence, and melanoma-specific survival data were analyzed. Of 4,310 patients undergoing SLN biopsy (SLNB), 495 (11 %) had a positive SLN-167 (34 %) patients underwent nodal observation and 328 (66 %) had immediate CLND. Patients in the no-CLND group were older (66 vs. 56 years; p < 0.001) and more likely to have lower extremity lesions (57 vs. 42 %; p = 0.006). There were no differences in tumor thickness, Clark level of invasion, ulceration, or SLN tumor burden. Median follow-up was 23 and 80 months for the no-CLND and CLND groups, respectively, and median time to recurrence was similar at 9 and 12 months, respectively (p = 0.48). There was no difference in local and in transit recurrence rates between groups (16 %, no CLND, and 18 %, CLND; p = 0.48). Nodal disease as a site of first recurrence occurred in 15 % of patients in the no-CLND group and 6 % of CLND patients (p = 0.002). In contrast, systemic recurrences occurred in 8 % of no-CLND patients compared with 27 % of CLND patients (p < 0.001). While median recurrence-free survival was higher after CLND (34.5 vs. 20.9 months; p = 0.02), melanoma-specific survival was similar (not reached, no CLND vs. 110 months, CLND; p = 0.09). Immediate CLND after a positive SLNB is associated with fewer initial nodal basin recurrences but similar melanoma-specific survival. These results support ongoing equipoise in the Multicenter Selective Lymphadenectomy Trial II (MSLT-II).