Recurrence of Melanoma After a Negative Sentinel Node Biopsy: Predictors and Impact of Recurrence Site on Survival.

BACKGROUND: Factors that predict melanoma recurrence after a negative sentinel lymph node biopsy (SLNB) are not well-defined. We evaluated melanoma recurrence patterns, factors prognostic for recurrence, and the impact of recurrence on outcomes after a negative SLNB. METHODS: The Sentinel Lymph Node Working Group database was evaluated from 1996 to 2016 for negative SLNB melanoma patients. Clinicopathologic characteristics were correlated with recurrence, overall survival (OS), and melanoma-specific survival (MSS). RESULTS: Median follow-up was 32.1 months. Recurrences developed in 558 of 5351 negative SLN patients (10.4%). First-site of recurrence included a local or in-transit recurrence (LITR) in 221 cases (4.1%), nodal recurrence (NR) in 109 cases (2%), and distant recurrence (DR) in 220 cases (4.1%). On multivariable analysis, age, thickness, head/neck or lower extremity primary, and microsatellitosis significantly predicted for an LITR as first-site. Having an LITR as first-site significantly predicted for a subsequent NR and DR, and significantly predicted for worse OS and MSS. Furthermore, thickness and head/neck or lower extremity primary significantly predicted for an NR as first-site, while a prior LITR significantly predicted for a subsequent NR. Factors significantly predictive for a DR included thickness, head/neck or trunk primary, ulceration, and lymphovascular invasion. Patients with any type of locoregional recurrence were at higher risk for a DR. CONCLUSIONS: Recurrences occur in 10.4% of negative SLN patients, with LITR and DR being the most common types. Importantly, having an LITR significantly predicts for a subsequent NR and DR, and is prognostic for worse survival after a negative SLNB.

Completion lymphadenectomy for a positive sentinel node biopsy in melanoma patients is not associated with a survival benefit.

BACKGROUND: 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). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Factors predictive of the status of sentinel lymph nodes in melanoma patients from a large multicenter database.

BACKGROUND: Numerous predictive factors for cutaneous melanoma metastases to sentinel lymph nodes have been identified; however, few have been found to be reproducibly significant. This study investigated the significance of factors for predicting regional nodal disease in cutaneous melanoma using a large multicenter database. METHODS: Seventeen institutions submitted retrospective and prospective data on 3463 patients undergoing sentinel lymph node (SLN) biopsy for primary melanoma. Multiple demographic and tumor factors were analyzed for correlation with a positive SLN. Univariate and multivariate statistical analyses were performed. RESULTS: Of 3445 analyzable patients, 561 (16.3%) had a positive SLN biopsy. In multivariate analysis of 1526 patients with complete records for 10 variables, increasing Breslow thickness, lymphovascular invasion, ulceration, younger age, the absence of regression, and tumor location on the trunk were statistically significant predictors of a positive SLN. CONCLUSIONS: These results confirm the predictive significance of the well-established variables of Breslow thickness, ulceration, age, and location, as well as consistently reported but less well-established variables such as lymphovascular invasion. In addition, the presence of regression was associated with a lower likelihood of a positive SLN. Consideration of multiple tumor parameters should influence the decision for SLN biopsy and the estimation of nodal metastatic disease risk.

Impact of sentinel node status and other risk factors on the clinical outcome of head and neck melanoma patients.

OBJECTIVE: To determine the impact of sentinel lymph node (SLN) status and other risk factors on recurrence and overall survival in head and neck melanoma patients. DESIGN: The SLN Working Group, based in San Francisco, Calif, with its 11 member centers, the John Wayne Cancer Institute, and The University of Texas M. D. Anderson Cancer Center pooled data on 629 primary head and neck melanoma patients who had selective sentinel lymphadenectomy. A total of 614 subjects were analyzable. All centers obtained internal review board approval and adhered to the Health Insurance Portability and Accountability Act of 1996 regulations. A Cox proportional hazards model was used to identify factors associated with overall and disease-free survival. SETTING: Tertiary care medical centers. MAIN OUTCOME MEASURE: Clinical outcome of head and neck melanoma patients undergoing selective sentinel lymphadenectomy. RESULTS: Overall, 10.1% (n = 62) of the subjects had at least 1 positive node. Subjects with positive SLN status had significantly thicker tumors (mean thickness, 2.8 vs 2.1 mm; P < .001), and were more likely to have ulcerated tumors (P = .004). During the median follow-up of 3.3 years, the overall mortality from head and neck melanoma was 10%, with more than 20% experiencing at least 1 recurrence. Multivariate analysis showed that tumor site was an independent predictor of mortality; location on the scalp had a more than 3-fold (P < .001) greater mortality than tumors on the face. Tumor thickness was also an independent predictor of overall survival, and SLN status was the most important predictor of disease-free survival in the multivariate model (P < .001). Tumors on the scalp had the highest rate of recurrence, while those on the neck had the lowest. Tumor ulceration was the significant predictor of time to recurrence or disease-free survival (P < .001). CONCLUSION: In this multicenter study, SLN status and other risk factors have an effect on recurrence and/or overall survival.

Clinicopathologic predictors of sentinel lymph node metastasis in thin melanoma.

PURPOSE: Indications for sentinel lymph node biopsy (SLNB) for thin melanoma are continually evolving. We present a large multi-institutional study to determine factors predictive of sentinel lymph node (SLN) metastasis in thin melanoma. PATIENTS AND METHODS: Retrospective review of the Sentinel Lymph Node Working Group database from 1994 to 2012 identified 1,250 patients who had an SLNB and thin melanomas (≤ 1 mm). Clinicopathologic characteristics were correlated with SLN status and outcome. RESULTS: SLN metastases were detected in 65 (5.2%) of 1,250 patients. On univariable analysis, rates of Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, ulceration, and absence of regression differed significantly between positive and negative SLN groups (all P < .05). These four variables and mitotic rate were used in multivariable analysis, which demonstrated that Breslow thickness ≥ 0.75 mm (P = .03), Clark level ≥ IV (P = .05), and ulceration (P = .01) significantly predicted SLN metastasis with 6.3%, 7.0%, and 11.6% of the patients with these respective characteristics having SLN disease. Melanomas < 0.75 mm had positive SLN rates of < 5% regardless of Clark level and ulceration status. Median follow-up was 2.6 years. Melanoma-specific survival was significantly worse for patients with positive versus negative SLNs (P = .001). CONCLUSION: Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, and ulceration significantly predict SLN disease in thin melanoma. Most SLN metastases (86.2%) occur in melanomas ≥ 0.75 mm, with 6.3% of these patients having SLN disease, whereas in melanomas < 0.75 mm, SLN metastasis rates are < 5%. By using a 5% metastasis risk threshold, SLNB is indicated for melanomas ≥ 0.75 mm, but further study is needed to define indications for SLNB in melanomas < 0.75 mm.