Final results validate sentinel-node biopsy for melanoma

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‘Landmark’ trial results

The final data from this landmark trial "corroborate the profound prognostic significance of micrometastasis identified by sentinel-node biopsy," said Dr. Charles M. Balch and Dr. Jeffrey E. Gershenwald.

The finding that early lymphadenectomy improved melanoma-specific survival by 44% implies that delaying lymphadenectomy until there was clinical evidence of metastasis allowed an opportunity for further dissemination of regional disease. And the fact that the primary end point (improved melanoma-specific survival across the entire cohort of patients with intermediate thickness melanomas) of MSLT-I was not achieved "doesn’t detract from the clinical importance of regional lymph-node staging," they said.

Dr. Balch is at the University of Texas Southwestern Medical Center, Dallas; he reported ties to Merck and Amgen. Dr. Gershenwald is in the department of surgical oncology at the melanoma and skin center at the University of Texas M.D. Anderson Cancer Center, Houston.; he reported ties to Navidea, GlaxoSmithKline, UpToDate, and Mercator Therapeutics. These remarks were taken from their editorial accompanying Dr. Morton’s report (N. Engl. J. Med. 2014 Feb. 12 [doi:10.1056e1313690]).



Sentinel-node biopsy clearly benefits patients with intermediate-thickness or thick primary melanomas who are found to have nodal involvement and undergo immediate lymphadenectomy, tripling their disease-free survival and doubling their melanoma-specific survival and distant disease-free survival, according to a report published online Feb. 12 in the New England Journal of Medicine.

These long-term findings, the final results of 20 years of investigation in MSLT-I (Multicenter Selective Lymphadenectomy Trial), "clearly validate the use of sentinel-node biopsy" in this patient population. Among patients found to have no nodal involvement, "the procedure provides accurate and important staging information," while among those found to have nodal involvement, it enhances regional disease control and substantially improves survival, said Dr. Donald L. Morton of the John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, Calif., and his associates.

Courtesy Wikimedia Commons/Dr. Ed Uthman

Metastatic melanoma in a lymph node.

Dr. Morton passed away shortly before publication of this final MSLT-I report.

The MSLT-I, which began in 1994, was intended to determine whether sentinel-node biopsy – a new procedure at the time that was developed by Dr. Morton – could accurately identify clinically occult metastases. More important, since only about 20% of such patients are found to have metastases, the MSLT-I was to determine whether it was worthwhile to subject all patients to the procedure. In other words, did sentinel-node biopsy with immediate lymphadenectomy of involved nodes yield better outcomes than did watchful waiting with delayed lymphadenectomy, performed only when nodal recurrence became evident during observation?

This final report involved 1,560 patients with localized cutaneous primary melanomas: 1,270 with intermediate-thickness (1.20-3.50 mm) lesions and 290 with thick (greater than 3.50 mm) lesions. A total of 943 patients were randomly assigned to undergo sentinel-node biopsy plus immediate lymphadenectomy if metastases were detected in sentinel nodes, and 617 were randomly assigned to close observation with delayed lymphadenectomy if nodal metastases developed during observation.

All the study participants were monitored periodically throughout follow-up using clinical examination, blood testing for biomarkers of melanoma, chest radiography, PET scanning, CT scanning, and/or nodal ultrasonography.

The primary end point, melanoma-specific survival across the entire study cohort, was not significantly different between patients who underwent sentinel-node biopsy (81.4%) and those who had observation only (78.3%). This is not surprising as only the 20% of patients who actually had nodal metastases could potentially derive a survival benefit from the procedure.

Latent-subgroup statistical methods were used to assess only this 20% of patients with nodal metastases. In this, the most relevant, data analysis, disease-free survival was increased by a factor of 3.2, distant disease-free survival was increased by a factor of 2.1, and melanoma-specific survival was increased by a factor of 2.0 for patients who underwent sentinel-node biopsy compared with those who had observation only, Dr. Morton and his associates wrote (N. Engl. J. Med. 2014 Feb 12 [doi:10.1056/NEJMoa1310460]).

Among patients with intermediate-thickness melanomas, the estimated treatment effect on disease-free survival was 1.17 (P less than .001), and the estimated effect on distant disease-free survival was 0.73 (P = .04). For melanoma-specific survival, the estimated treatment effect was 0.68 (P = .05).

"Our long-term results confirm that sentinel-node biopsy correctly determines the pathologic status of the nodal basin in 96% of cases and is the most powerful prognostic indicator," they noted.

The data also indicate that "essentially all metastases detected by sentinel-node biopsy eventually would have become clinically evident if [they had] not [been] removed," the investigators added.

The MSLT-I was supported by the National Cancer Institute and the Australian and New Zealand Melanoma Trials Group. Dr. Morton reported no financial conflicts of interest; his associates reported ties to GlaxoSmithKline, Roche, Provectus, Merck, Myriad Genetics, and Melanoma Diagnostics.

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