Annals of Surgical Oncology 10:408-415 (2003)
© 2003 Society of Surgical Oncology
Sentinel Lymph Node Mapping for Thick (
4-mm) Melanoma: Should We Be Doing It?
Grant W. Carlson, MD,
Douglas R. Murray, MD,
Andrea Hestley, BA,
Charles A. Staley, MD,
Robert H. Lyles, PhD and
Cynthia Cohen, MD
From the Winship Cancer Institute (GWC, DRM, AH, CAS, CC), Emory University School of Medicine; and Department of Biostatistics, Rollins School of Public Health (RHL), Emory University, Atlanta, Georgia.
Correspondence: Address correspondence and reprint requests to: Grant W. Carlson, MD, Winship Cancer Institute, 1365B Clifton Rd., Atlanta, GA 30322; Fax: 404-778-4255; E-mail: grant_carlson{at}emory.org
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ABSTRACT
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Background: Thick (
4-mm) primary melanomas are believed to be associated with a high incidence of occult distant metastases. The use of sentinel lymph node (SLN) mapping and biopsy in the treatment lesions has been questioned.
Methods: A retrospective review of a computerized database identified 114 patients who underwent successful SLN mapping and biopsy from January 1, 1994, to December 31, 1999. Records were reviewed for clinicopathologic features of the patients and their tumors. Survival curves were constructed from Kaplan-Meier estimates and analyzed with log-rank tests and Cox proportional hazards modeling.
Results: There were 75 men and 39 women with a mean age of 57 years (range, 24–85 years). The primary tumor sites were head and neck (n = 29; 25.4%), trunk (n = 44; 38.6%), and extremities (n = 41; 36%). Tumor thickness ranged from 4 to 17 mm (median, 5.2 mm; mean, 6.3 mm). Ulceration was present in 40 (35.1%) tumors. Thirty-seven patients (32.5%) had a positive SLN biopsy, and 18 of these patients (48.6%) had a single tumor-positive lymph node after dissection. The mean follow-up was 37.8 months. The overall 3-year survival for SLN-negative patients was 82%, versus 57% for SLN-positive patients (P = .006). Lymph node status and tumor ulceration were independent predictors of overall survival in multivariate Cox regression analysis.
Conclusions: The pathologic status of the SLN in patients with thick melanomas is a strong independent prognostic factor for survival, and SLN mapping should be routinely performed.
Key Words: Sentinel lymph node • Thick melanoma • Prognostic factors • Distant metastasis
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INTRODUCTION
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The presence or absence of lymph node metastases is the most significant prognostic factor for survival and recurrence in malignant melanoma. Lymph node disease decreases the 5-year survival by 40% to 50% compared with patients with no evidence of metastases. Balch et al.1 reported an analysis of 1150 patients with nodal metastases in the American Joint Committee on Cancer Melanoma Database. The number of metastatic nodes and whether nodal metastases were clinically occult or apparent were independent predictors of survival.
Thick (4-mm) primary melanomas are believed to be associated with a high incidence of occult regional and distant metastases.2 No prospective randomized trials have demonstrated a survival benefit for patients with thick melanomas undergoing routine elective lymph node dissection. A recent review of 120 patients with thick melanomas by Kim et al.3 found that nodal status was an independent predictor of survival. Nodal status was found to be the strongest predictor of survival in a recent review, by Gershenwald et al.,4 of 126 patients with melanomas 4 mm thick treated by sentinel lymph node (SLN) biopsy.
SLN mapping was developed in the early 1990s as a relatively noninvasive method to stage the draining lymph node basins from primary melanoma. It targets patients who may benefit from a lymph node dissection and systemic therapy. Most SLN mapping studies in melanoma have included few patients with thick lesions.5–7 The use of SLN mapping and biopsy in the treatment of thick melanomas has been questioned because of the perceived poor prognosis. This study attempts to delineate the utility of SLN mapping in this subset of melanoma patients.
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PATIENTS AND METHODS
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Patients
A retrospective review of a computerized database identified 114 patients with thick (4-mm) primary melanoma who underwent successful SLN mapping and biopsy from January 1, 1994, to December 31, 1999, at Emory University Hospital. Records were reviewed for clinicopathologic features of the patients and their tumors. The following histopathologic features were analyzed: Breslow tumor thickness, ulceration, regional lymph node status, and total number of lymph nodes involved after completion lymphadenectomy.
SLN Mapping Technique
Lymphatic mapping with dynamic lymphoscintigraphy and gamma probe–guided SLN biopsy were performed as previously described.8 All patients underwent cutaneous lymphoscintigraphy by using filtered technetium 99mTc-labeled sulfur colloid (100–450 µCi; CIS-US, Inc., Bedford, MA). The radioactive tracer was injected intradermally around the circumference of the primary melanoma or biopsy site. Dynamic lymphoscintigraphy was performed with a planar gamma camera imaging every 10 seconds for 10 minutes to identify focal areas of accumulation, followed by multiple 5-minute static images up to 60 minutes. In some patients, 2-hour postinjection delayed images were obtained.
Measurements of radioactivity in the radiolabeled lymph nodes were made during surgery with a handheld gamma probe, and SLNs demonstrated increased focal radiotracer uptake (hot spots). Counts were accumulated during a 10-second interval and recorded. Areas of increased activity, or hot spots, were removed and individual lymph nodes dissected out to find focal uptake of radioactivity. Ex vivo counts of the SLNs were obtained and compared with the nodal bed counts after removal. Vital blue dye injected at the time of surgery was used routinely only in the last 2 years of the study period. All harvested SLNs were carefully labeled, and, after serial sectioning, they were examined histopathologically by using routine hematoxylin and eosin and immunochemical staining for S-100 protein and the melanoma-associated antigen HMB-45.
Statistical Analysis
Associations among categorical risk factors were assessed via 
2 tests, and the log-rank test was used to compare Kaplan-Meier survival curves. Multivariate analysis was performed with the Cox proportional hazards regression model, with ulceration, SLN status, and tumor thickness as categorical predictors. All P values were two tailed, and P values <.05 were considered statistically significant.
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RESULTS
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The clinicopathologic characteristics of the study cohort are depicted in Table 1. There were 75 men and 39 women with a mean age of 57 years (range, 24–85 years). The primary tumor sites were head and neck (n = 29; 25.4%), trunk (n = 44; 38.6%), and extremities (n = 41; 36%). The mean follow-up was 37.8 months (median, 34.8 months). The 3-year disease-free and overall survival (OS) of the entire cohort was 58% and 74%, respectively (Figs. 1 and 2).
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FIG. 1. Kaplan-Meier survival for patients undergoing sentinel lymph node mapping and biopsy. The 3-year relapse-free survival was 60%.
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FIG. 2. Kaplan-Meier survival for patients undergoing sentinel lymph node mapping and biopsy. The 3-year overall survival was 74%.
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Tumor Thickness
Tumor thickness ranged from 4 to 17 mm (mean, 6.3 mm; median, 5.2 mm). Patients were stratified into two groups on the basis of tumor thickness: group 1 had a tumor thickness of 
6 mm (n = 72), and group 2 had a tumor thickness of >6 mm (n = 42). The 3-year relapse-free survival (RFS) for group 1 was 68%, versus 40% for group 2 (P = .015; Fig. 3). The 3-year OS rate for group 1 was 82%, versus 61% for group 2 (P = .085; Fig. 4).
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FIG. 3. Kaplan-Meier survival for patients stratified by tumor thickness. The 3-year relapse-free survival for tumor thickness 6 mm was 68%, versus 40% for tumor thickness >6 mm (P = .015).
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FIG. 4. Kaplan-Meier survival for patients stratified by tumor thickness. The 3-year overall survival for tumor thickness 6 mm was 82%, versus 61% for tumor thickness >6 mm (P = .085).
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Ulceration
Ulceration was documented in 40 (35.1%) of the 114 patients. The 3-year RFS rate in the nonulcerated group was 68%, versus 38% in the ulcerated group (P = .005;Fig. 5). The 3-year OS rate in the nonulcerated group was 82%, versus 57% in the ulcerated group (P = .013; Fig. 6).
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FIG. 5. Kaplan-Meier survival for patients stratified by the presence of ulceration. The 3-year relapse-free survival for patients without ulceration and with ulceration was 68% and 38%, respectively (P = .005).
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FIG. 6. Kaplan-Meier survival for patients stratified by the presence of ulceration. The 3-year overall survival for patients without ulceration and with ulceration was 82% and 57%, respectively (P = .013).
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SLN Status
Thirty-seven patients (32.5%) had a positive SLN biopsy. Patients without SLN metastases had a 3-year RFS rate of 71%, versus 31% for patients with SLN metastases (P < .001; Fig. 7). The 3-year OS rate for patients without SLN metastases was 82%, whereas patients with SLN metastases had a 3-year OS rate of 57% (P = .006; Fig. 8).
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FIG. 7. Kaplan-Meier survival for patients stratified by sentinel lymph node (SLN) status. The 3-year relapse-free survival for SLN-negative patients and SLN-positive patients was 71% and 31%, respectively (P < .001).
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FIG. 8. Kaplan-Meier survival for patients stratified by sentinel lymph node (SLN) status. The 3-year overall survival for SLN-negative patients and SLN-positive patients was 82% and 57%, respectively (P = .006).
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Number of Positive Lymph Nodes
All patients underwent a completion lymph node dissection after a positive SLN biopsy. Eighteen (48.6%) of the 37 SLN-positive patients had nodal metastases isolated to a single SLN. Eleven patients (29.7%) had two positive lymph nodes after completion lymph node dissection, and eight patients had three or more metastatic lymph nodes. Patients were stratified into three groups on the basis of the number of metastatic lymph nodes involved: group 1, n = 0; group 2, n = 1; and group 3, n > 1. There was not a statistically significant difference between groups 2 and 3 in OS (P = .08; data not shown).
SLN Status and Ulceration
Patients were stratified into three groups on the basis of SLN status and the presence of ulceration. Group 1 was SLN negative and nonulcerated (n = 56), group 2 was either SLN positive and nonulcerated or SLN negative and ulcerated (n = 39), and group 3 was SLN positive and ulcerated (n = 19). The 3-year OS rate was 88% for group 1, 61% for group 2, and 53% for group 3 (P = .002; Fig. 9).
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FIG. 9. Kaplan-Meier survival for patients stratified by both sentinel lymph node (SLN) status and the presence or absence of ulceration. The 3-year overall survival for patients with a negative SLN and without ulceration was 88%, versus 61% for patients with a positive SLN or ulceration, versus 53% for patients with a positive SLN and ulceration (P = .002).
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Cox Regression Analysis
By univariate analysis, SLN status (relative hazard, 2.50; P = .008) and ulceration (relative hazard, 2.32; P = .016) were found to have significant prognostic value in predicting the OS in patients with thick melanomas. Age >60 years, sex, and tumor thickness >6 mm were included as prognostic factors assessed by multivariate Cox regression analysis (Table 2). SLN status was a strong independent risk factor for both RFS and OS relative to the other variables.
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DISCUSSION
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The long-term survival for patients with thick melanomas is not universally poor. Several authors have reported 5-year survival rates of 47% to 62%.3,9–11 Previous studies before the development of SLN mapping have shown that lymph node involvement and ulceration are independent predictors of OS in this group.3,4,11–13
This is the third study that has examined SLN mapping in thick melanomas. The results of this study are strikingly similar to those previously reported4,14 (Table 3). Ferrone et al.,14 in their review of 126 patients, found that age 60 years, tumor depth >5.5 mm, ulceration, and SLN status were independent predictors of survival. They developed a prognostic model based on these predictors. They found that the relative risk of recurrence ranged from 1 in patients with no adverse factors present to 29.4 when all four factors were present. Gershenwald et al.4 also found that ulceration and SLN status were independent predictors of survival. In their study, age and increasing tumor thickness were not significant predictors of recurrence. They found that patients with a negative SLN biopsy and absent ulceration had a 3-year OS rate of 86%, whereas T4 patients with a positive SLN biopsy and ulceration present had a 3-year OS rate of 57% (P < .003). This study of 114 patients with T4 melanoma confirms the interaction between positive lymph node status and ulceration in predicting OS. Figure 9 demonstrates a 3-year OS rate of 89% for patients with a negative SLN biopsy and absent ulceration, whereas for patients with a positive SLN biopsy and ulceration, it was 51% (P = .002). In this study and the two previously reported, SLN status was the strongest independent risk factor for survival in patients with thick melanoma.
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CONCLUSIONS
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The pathologic status of the SLN in thick melanomas is the strongest independent predictor of survival, and SLN mapping should be routinely performed.
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Footnotes
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The utility of sentinel lymph node mapping in thick melanomas has been questioned. The pathologic status of the sentinel lymph node in these patients was found to be a strong, independent prognostic factor for survival, and sentinel lymph node mapping should be routinely performed.
Received for publication March 19, 2002.
Accepted for publication December 23, 2002.
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TOP
ABSTRACT
INTRODUCTION
