Is SLNBx helpful? Study's claims debated

September 1, 2007

Sentinel lymph node biopsy (SLNBx) did not improve survival in the Melanoma Selective Lymphadenectomy Trial (MSLT-1). Authors of the published results concluded the procedure still had other benefits. Alternate interpretations of the data refute those conclusions and should be considered for patient counseling to provide true informed consent.

Pittsburgh - In its primary endpoint analysis of five-year survival, the Melanoma Selective Lymphadenectomy Trial (MSLT-1) showed no benefit of sentinel lymph node biopsy (SLNBx) compared with observation and complete lymph node dissection (CLND) for development of palpable nodes (N Engl J Med. 2006;355:1307-1317).

"The whole idea that SLNBx is beneficial was based on theory extending from an original theory that LND in melanoma patients with palpable nodes can prolong survival. The latter premise is unquestionably true, and while it seemed reasonable to extrapolate that removing nodes with detectable micrometastases would be even better, the hypothesis was not adequately tested until MSLT-1," Dr. Zitelli tells Dermatology Times.

"When the results of MSLT-1 turned out to be negative, the investigators tried to salvage the procedure by presenting other benefits.

"However, a careful look at the data suggests flaws in their analyses resulting in misleading conclusions. It is incumbent on clinicians treating patients with melanoma to understand the results of the MSLT-1 and the alternate views so that they can counsel their patients appropriately and offer true informed consent."

MSLT-1 enrolled 1,269 patients with melanomas 1.2 mm to 3.5 mm thick. All primary lesions were treated with wide excision and patients were randomized into two groups to 1) undergo SLNBx and immediate CLND if the SLN was positive, or 2) be followed with observation and undergo CLND for detected palpable nodes. The five-year survival rates for the SLNBx and observation groups were 87 percent and 86 percent, respectively.

Reviewing other data, the MSLT-1 authors determined SLNBx had value for staging and prognosis, as well as for prolonging overall and disease-free survival for patients found on SLNBx to have positive nodes.

Staging and prognosis

Dr. Zitelli says that data relating to the possible prognostic value of SLNBx in the MSLT-1 population of patients with intermediate thickness melanoma was available but not published.

The only other study that investigated this question showed the results of SLNBx were important only for patients with lesions 2 mm to 4 mm in thickness.

"For patients with a melanoma thinner than 2 mm or thicker than 4 mm, the prognosis was the same as that estimated from Breslow thickness alone, indicating that the results of SLNBx are not that helpful," Dr. Zitelli says.

"Furthermore, results of SLNBx are not useful for guiding therapeutic decisions because there is no treatment that provides a benefit to patients with microscopic nodal disease," he adds.

Prolongation of disease-free survival

In MSLT-1, the five-year disease-free survival rate for patients in the SLNBx group was 78.3 percent, which was significantly higher (p = 0.009) compared with the rate of 73.1 percent for the observation group.

However, the difference is an artifact of the method for calculating the disease-free interval in which the disease recurrence event differs between the two groups.

"The regional lymph node basin is the most common site of initial recurrence, but patients in the SLNBx group with positive nodes could be considered to have undergone treatment that reduced their risk for nodal recurrence. Their next recurrence would be distant metastasis, and it is not surprising that event occurred later than the first nodal metastasis in the observation group," Dr. Zitelli explains.

Survival benefit in patients with a positive SLNBx was also examined. Data from MSLT-1 were also analyzed to compare the five-year survival rate of patients in the SLNBx group with a positive SLN against those in the observation group who subsequently had CLND for palpable nodes.