In a meta-analysis of some 10,000 melanoma patients, the risk for sentinel lymph node (SLN) positivity was significantly lower in those with histologic progression than in those without.
The result suggests that regression may be used to select those patients who would be the most appropriate for SLN biopsy (SLNB), the researchers state.
The study was published online September 2 in JAMA Dermatology.
This finding is "practice changing," comments Claus Garbe, MD, from the Department of Dermatology, University Hospital Tubingen, Germany, in an accompanying editorial.
The lead author of the study, Simone Ribero, MD, PhD, from the University of Turin, Italy, and King's College London, in the United Kingdom, agrees that the finding is practice changing.
"Yes, we believe that considering histological regression differently could change some clinical approaches to melanoma patients," Dr Ribero told Medscape Medical News.
The prognostic significance of regression has been a matter of discussion in the literature for many years, he said.
"Its association with sentinel lymph node biopsy was not confirmed up to now. We previously reported a prognostic protective role on survival in a large cohort of melanoma patients in Turin, and wanted to explore further whether regression may affect SLN status," Dr Ribero said.
His team carried out a systematic review of the literature by searching in MEDLINE, Scopus, and the Cochrane Library for articles published from January 1, 1990, through June, 2014.
Ultimately, they selected 14 studies, comprising 10,098 patients, in which odds ratios (ORs) for tumor regression with respect to lymph node micrometastasis were analyzed.
Their analysis revealed that patients with histologic regression had a lower likelihood of having micrometastasis in SLNB (OR, 0.56; 95% confidence interval [CI], 0.41-0.77) in comparison with patients without regression.
In studies that Dr Ribero and his team classified as "high quality," as per the Strengthening of Reporting of Observational studies in Epidemiology (STROBE) checklist, the OR was even lower, at 0.48 (95% CI, 0.32 - 0.72).
One limitation of the meta-analysis is that it included studies that may have used different definitions of histologic regression, Dr Ribero said.
"Sometimes, the definition of histological regression is discussed from a pathological point of view. The subjectivity of pathology could influence the final report of each melanoma," he said.
However, "the strength of evidence of a meta-analysis including more than 10,000 patients gives us confidence in what we are reporting. Of course, other prospective studies are needed to confirm our results," Dr Ribero said.
Asked how clinicians might use regression to select a patient who should undergo SLNB, he replied: "Regression is still considered, in some centers, as a factor that increases the risk of SLN metastases. This is why some clinicians still perform SLN biopsy on the basis of this prognostic factor. This is an old concept that should be avoided."
In the editorial, Dr Garbe writes that the "unexpected finding" that the risk for micrometastases in SLNB in patients with histologic regression is only half that of patients without regression gives a clear answer to the question of whether patients with thin melanoma and regression should undergo SLNB.
"The answer is 'No,' " he writes.
"Sentinel lymph node biopsy has been established as a standard in melanoma care and is performed in patients with tumors more than 1 mm thick," Dr Garbe writes.
"Detection of micrometastases by SLNB is the most powerful prognostic factor in primary melanomas, followed by the tumor thickness. There is an ongoing debate as to whether SLNB should also be applied in thinner tumors -- for example, in melanomas more than 0.75 mm thick and additional unfavourable prognostic factors like ulceration or detection of mitosis," he writes.
"Histological regression in primary melanoma has also been considered to be an unfavourable factor, and in France and sometimes in the United States, SLNB has been recommended for patients with this constellation. The large meta-analysis by Ribero and colleagues demonstrates that regression is not a criterion for recommendation of SLNB in thin melanomas. This will change the treatment of patients with melanoma in a considerable number of skin cancer centers," Dr Garbe concludes.
Dr Ribero and Dr Garbe report no relevant financial relationships.
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