Long-Term Outcomes Support Sentinel-Node Biopsy for Staging Melanoma

Vernon K. Sondak, MD

Chair, Department of Cutaneous Oncology

Director, Surgical Education

Moffitt Cancer Center

Tampa, FL

Christopher Puleo, PA-C

Certified Physician Assistant

Moffitt Cancer Center

Tampa, FL

A 10-year follow-up study of regional melanoma staging strategies found that patients who underwent sentinel-node biopsies had significantly greater disease-free survival rates (DFSRs) compared with patients monitored through nodal observation.

The final results of the Multicenter Selective Lymphadenectomy Trial (MSLT-1), which began in 1994 and enrolled patients through 2002, also showed that biopsy-based staging provides important prognostic information, according to updated findings published in The New England Journal of Medicine.¹ During the phase III trial, 2001 patients with primary cutaneous melanomas were randomly assigned to undergo wide excision and nodal observation, with lymphadenectomy for nodal relapse (40%) or wide excision and sentinel-node biopsy with intermediate lymphadenectomy for nodal metastases detected on biopsy (60%).

In the MSLT-1 trial, researchers sought to determine whether the minimally invasive sentinel-node biopsy could be used after primary surgery to identify patients with clinically occult nodal metastases, instead of waiting for nodal recurrence. In the past, elective complete lymphadenectomy was recommended, despite its potential complications.

The study results support the benefits of sentinel- node biopsies, a procedure that was introduced in 1992, noted Vernon K. Sondak, MD, chair of the Department of Cutaneous Oncology at Moffitt Cancer Center in Tampa, Florida, in a press release announcing the findings. Sondak said Moffitt played a pioneering role in helping to develop the biopsy procedure, which he said has now become a “worldwide standard.”

Moffitt was among more than a dozen cancer centers and research institutions that participated in the multinational MSLT-1 study, which was initiated at the John Wayne Cancer Institute at Saint John’s Health Center in Santa Monica, California.

DFSR Outcomes Superior

Of the 2001 patients initially involved in the study, 1661 underwent randomization and 1638 were included in the 10-year follow-up. Of the initial patient population, 1347 had intermediate-thickness primary melanomas and 314 had thick primary melanomas.

Mean (± standard error [SE]) 10-year DFSRs, the primary endpoint of the study, were significantly improved in the biopsy group, as compared with the observation group, among patients with intermediate-thickness melanomas, defined as 1.20 to 3.50 mm (71.3±1.8% vs 64.7±2.3%) and among those with thick melanomas, defined as >3.50 mm (50.7±4.0% vs 40.5±4.7%). (Table).

Table. Key Outcomes at 10 Years in Melanoma Study¹

Tumor type/ Treatment

Patients (n)

Disease-free Survival (%)

Melanoma-Specific Survival (%)

Intermediate-thickness primary melanomas

OBS

500

64.7±2.3

78.3±2.0

SNB

770

71.3±1.8

(HR = 0.76; P = .01)

81.4±1.5

(HR = .84; P = .18)^a

Thick primary melanomas

OBS

117

40.5±4.7

64.4±4.6

SNB

173

50.7±4.0

(HR = 0.70; P = .03)

58.9±4.1

(HR= 1.12; P = .56)^a

^aNo survival advantage for SNB

HR indicates hazard ratio; OBS, observation; SNB, sentinel-node biopsy.

The study found that in the biopsy group, patients with sentinel-node metastases had poorer outcomes than patients with tumor-free sentinel nodes. Patients with intermediate-thickness melanomas who had sentinel-node metastases had a 10-year melanoma-specific survival rate of 62.1±4.8%, compared with 85.1±5% of patients with tumor-free sentinel, for a hazard ratio for death from melanoma of 3.09 (P = .001). For participants with thick melanomas, the survival rates were 48.0±7.0% without metastasis versus 64.6±2.9% with metastasis (HR = 1.75; P = .03). According to a multivariate analysis, sentinel-node status was the strongest predictor of disease recurrence or death from melanoma.Although sentinel-node biopsies resulted in better DFSRs, there was no significant treatment-related difference in the 10-year melanoma-specific survival rates among those in the biopsy group (81.4±1.5%) and those in the observation group (78.3±2.0%) among patients with intermediate-thickness melanomas. Similarly, there was no difference among patients with thick melanomas (Table).

Researchers said the lack of a survival advantage for patients with intermediate-thickness melanomas was not surprising because the overall event rates were lower than expected. In addition, they said the false-negative rates were higher in the earlier years of the study, possibly clouding therapeutic benefits, because staff members had not yet gained experience with the procedures.

Side Effects Avoided

Christopher Puleo, PA-C, a coauthor of the study from Moffitt Cancer Center who worked with the patients throughout the course of the trial, said there are long-term side effects associated with removing the lymph nodes prematurely.

“The one main long-term side effect associated with a node dissection is lymphedema,” Puleo said in an interview with OncologyLive. “This phenomenon occurs approximately as often as 5% of the time in the axilla and up to 15% to 20% of the time in the groin with rare effects in neck dissections. Depending upon whose statistics you review, the overall chances of patients developing spread of the melanoma to their lymph nodes was 16% to 25% on average. If you were to take 100% of your patients and electively remove their lymph nodes, only 16% to 25% of them would be getting a benefit from that procedure but 100% of your patients would have the potential for developing any and all of the side effects associated with the surgery.”

It was this concept that led researchers to wonder whether they could identify which patients would benefit from having their lymph nodes removed upfront, Puleo said.

In order to test sentinel melanoma lymph nodes, a radioactive tracer and a blue-colored dye are injected at or near the melanoma site on the skin and tracked to the sentinel nodes.

“It’s kind of revolutionized the way that we can stage these patients,” Puleo said. “It has made it much easier without doing surgeries that are potentially debilitating.”

Reference

1. Morton DL, Thompson JF, Cochran AJ, et al. Final report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370(7):599-609.