Role of regression: Single criterion doesn't warrant sentinel lymph node biopsy in thin melanomas

September 1, 2008

In a recent study, investigators found that regression alone is an insufficient criterion to validate the use of sentinel lymph node biopsy (SLNB) in patients with thin melanomas.

Key Points

Montreal - According to a recent study, using solely regression as a criterion for performing a sentinel lymph node biopsy (SLNB) in thin melanomas is not sufficient.

"Several factors affect the prognosis of melanoma," says Pierre-Luc Dion, M.D., dermatology resident at the Centre Hospitalier Universitaire de Quebec, Quebec City, Canada. "There are factors such as nodal status, Clark's level, vascular invasion, ulceration and regression."

Factors such as Breslow thickness and ulceration are recognized as predictors of nodal metastasis and survival.

Dr. Dion says, however, that there has been some debate about the significance of regression and the interpretation of what regression means in terms of disease status.

One argument has been that regression signifies an adverse prognostic factor, because it leads to underestimating what would have been "real" Breslow thickness in the absence of regression.

Another argument, however, is that regression may represent a host immune response against the tumor cells, which could mean that regression has a protective effect.

A study published in the Archives of Dermatology in 2002 that looked at 43 cases of metastasizing thin melanomas and compared those cases to controls found the only different characteristic between the two groups was the presence of regression of the primary tumor in the metastasizing group.

Those study results prompted Dr. Dion and co-investigators to further analyze the significance of histological evidence of regression in thin melanomas, defined as having a thickness of less than 1 mm.

"Thin melanomas usually have a good prognosis, and there is usually not a reason to perform a sentinel lymph node biopsy in these patients," Dr. Dion says.

"The five-year survival is about 95 percent, but still, some of these melanomas do recur," he says.

In Dr. Dion's study, he and co-investigators looked at 40 thin melanoma cases in which there was significant regression. In those cases, the lesions did not meet the usual criteria for SLNB.

They were compared to 653 historic control cases that met the criteria for conducting a SLNB. Those criteria include a Breslow thickness of 1 mm or more, a Clark level of IV/V or the presence of ulceration. SLNB was performed in all cases.

Study details

The melanoma cases that were categorized as having significant regression had to demonstrate pathological regression of at least 15 percent of the tumor to be included in the study, Dr. Dion tells Dermatology Times.

The mean age of the 653 patients who all met the criteria for SLNB was 54.7. The patients had been treated at the melanoma clinic between August 1996 and November 2007. The median Breslow thickness was 2.28 mm, and 22.4 percent had one or more positive sentinel lymph nodes.

The mean age of the 40 patients who did not meet all the criteria for SLNB but demonstrated significant regression was 55.

Six patients had an in situ melanoma, one patient had a completely regressed lesion, and the median Breslow thickness in the remaining 33 patients was 0.60 mm.

Investigators found that none of the 40 patients who experienced regression had a positive sentinel lymph node.

The patients have been followed for a mean of nearly four years. There have been two recurrences in the 40 patients; one, local, and the other, in-transit metastases.

Dr. Dion and researchers conclude that regression alone should not be used as a single criterion to justify SLNB in thin melanoma in the absence of other recognized, high-risk predictive factors of sentinel lymph node involvement, indicated by measurements such as a Breslow thickness of 1 mm or more and a Clark level of IV/V or ulceration.

Dr. Dion says the study results are consistent with data from similar research efforts.

In one study of 65 patients who had thin melanomas and regression, investigators found positive sentinel lymph nodes in two cases. The Breslow thickness of the primary tumor was more than 0.75 mm in both cases.

In another study, there was only one case of a positive sentinel lymph node in 68 thin melanomas. The Clark level was IV in that case, providing sufficient basis for a SLNB.