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Original Investigation | Pacific Coast Surgical Association

Staging of Regional Lymph Nodes in Melanoma:  A Case for Including Nonsentinel Lymph Node Positivity in the American Joint Committee on Cancer Staging System

Anna M. Leung, MD1; Donald L. Morton, MD1; Junko Ozao-Choy, MD1; Danielle M. Hari, MD1; Myung Shin-Sim, PhD2; Andrew L. Difronzo, MD3; Mark B. Faries, MD1
[+] Author Affiliations
1Melanoma Research Program, John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, California
2Department of Biostatistics, John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, California
3Department of Surgery, Kaiser Sunset Medical Center, Los Angeles, California
JAMA Surg. 2013;148(9):879-884. doi:10.1001/jamasurg.2013.3044.
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Published online

Importance  Survival varies widely in patients with stage III melanoma. The existence of clinical significance for positive nonsentinel lymph node (NSLN) status would warrant consideration for incorporation into the American Joint Committee on Cancer staging system and better prediction of survival.

Objective  To evaluate whether disease limited to sentinel lymph nodes (SLNs) represents different clinical significance than disease spread into NSLNs.

Design, Setting, and Participants  The database of the John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, California, was queried for all patients with SLNs positive for cutaneous melanoma who subsequently underwent completion lymph node dissection.

Main Outcomes and Measures  Disease-free survival, melanoma-specific survival (MSS), and overall survival.

Results  A total of 4223 patients underwent SLN biopsy from 1986 to 2012. Of these patients, 329 had a tumor-positive SLN. Of the 329, 250 patients (76.0%) had no additional positive nodes and 79 (24.0%) had a tumor-positive NSLN. Factors predictive of NSLN positivity included older age (P = .04), greater Breslow thickness (P < .001), and ulceration (P < .02). Median overall survival was 178 months for the SLN-only positive group and 42.2 months for the NSLN positive group (5-year overall survival, 72.3% and 46.4%, respectively). Median MSS was not reached for the SLN-only positive group and was 60 months for the NSLN positive group (5-year MSS, 77.8% and 49.5%, respectively). On multivariate analysis, NSLN positivity had a strong association with recurrence (hazard ratio [HR], 1.75; 95% CI, 1.23-2.50; P = .002), shorter overall survival (HR, 2.24; 95% CI, 1.48-3.40; P < .001), and shorter MSS (HR, 2.23; 95% CI, 1.46-3.07; P < .001). To further control for the effects of total positive lymph nodes, comparison was done for patients with only N2 disease (2-3 total positive lymph nodes); the results of this comparison confirmed the independent effect of NSLN status (MSS; P = .04).

Conclusions and Relevance  Nonsentinel lymph node positivity is one of the most significant prognostic factors in patients with stage III melanoma. Subclassification of melanoma by NSLN tumor status should be considered for the American Joint Committee on Cancer staging system.

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Figure 1.
Disease-Free Survival, Overall Survival, and Melanoma-Specific Survival

A, Five-year disease-free survival for sentinel lymph node (SLN)–only positive patients was significantly shorter than that of the nonsentinel lymph node (NSLN) positive group (P < .001). B, Median overall survival was 178 months for SLN-only positive patients and 42.2 months for NSLN positive patients. Five-year overall survival was 72.3% for SLN-only positive patients vs 46.4% for NSLN positive patients (P < .001). C, Five-year disease-free survival (melanoma-specific survival) was 77.8% for the SLN-only positive group and 46.4% for the NSLN positive group (P < .001).

Graphic Jump Location
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Figure 2.
Comparison of Patients With Only 2 to 3 Total Positive Nodes

This confirms the independent effect of nonsentinel lymph node (NSLN) status on melanoma-specific survival (P = .04). SLN indicates sentinel lymph node.

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