Qualified treatment for melanoma patients

A better prediction for sentinel node positivity

James Fleck, MD, PhD: Anticancerweb 06 (10), 2021

Melanoma ranks fifth in cancer incidence in USA. In 2021, Cancer Facts & Figures of the American Cancer Society estimated 106,110 new cases and 7,180 melanoma-related deaths. Data from the International Agency for Research on Cancer show Australia and New Zealand with the highest incidence (ASR = 36.6) and mortality rate (ASR = 4.7), respectively. In fact, melanoma ranks fourth in incidence in Australia and sixth in mortality in New Zealand. The incidence of melanoma is increasing worldwide, and the 324,635 new cases diagnosed in 2020 appear to be underestimated. Although the incidence tends to increase, the mortality from melanoma has been decreasing. The downward trend in the mortality rate has been attributed to education in sun protection, screening for early diagnosis and new and efficient therapeutic approaches. The physician should be encouraged to perform a full-body skin examination. Global training in dermoscopy would increase diagnostic sensitivity and specificity. Controversy persists over the effectiveness of systematic screening for melanoma. Although not based on a randomized trial, a national statutory program for the early detection of skin cancer has been implemented in Germany since 2008. It was supported by the results of the SCREEN project, which brought together 360,288 participants from a total of 1.8 million eligible citizens. Five years after SCREEN, a substantial decrease in melanoma mortality was observed in both men and women. Nevertheless, disease progression leads to sequential molecular changes that make melanoma more refractory to therapeutic interventions, worsening prognosis. Tumor progression is characterized by aberrant proliferation, loss of apoptosis, metastatic spread and induction of angiogenesis, which is mediated by a signal transduction pathway called MAPK (Mitogen-Activated Protein Kinase). Some molecular abnormalities, such as the BRAF V600E mutation, have been used for specific therapeutic interventions in more advanced melanoma and, together with early diagnosis, have recently reduced its mortality rate. However, much remains to be done and qualified treatment for melanoma should include better outcomes as well as careful selection against unnecessary iatrogenic interventions.

In June 2020, the Journal of Clinical Oncology published the Melanoma Institute Australia (MIA) nomogram, better predicting sentinel node positivity. The model is available on line (www.melanomarisk.org.au). As shown in the figure below, the calculated risk is based on six parameters: age, tumor thickness, melanoma subtype, number of mitoses/mm2, ulceration and lymphovascular invasion. Postoperative complications related to sentinel biopsy include infection, lymphedema and neuropathic pain, which could be avoided using MIA calculated risk threshold in the range of 5% to 10%. Sentinel node positivity is an important prognostic factor, also contributing in the adjuvant treatment decision-making. Based on the area under the curve (AUC) of receiver operating characteristic (ROC), using both sensitivity (true positives) and specificity (true negatives) MIA nomogram was validated. MIA nomogram showed an AUC = 73.9%, which compared favorable with previously used MSKCC nomogram (AUC = 67.7 %), providing an absolute gain of 6.2%. Consequently, the number of patients undergoing unnecessary sentinel lymph node biopsy was significantly reduced, contributing to a more qualified care for melanoma.



Breitbart EW, Waldmann A, Nolte S, et al: Systematic skin cancer screening in Northern Germany, J Am Acad Dermatol, Feb 66(2): 201-11, 2012

Serigne N. Lo, Jiawen Ma, Richard A. Scolyer, et al: Improved Risk Prediction Calculator for Sentinel Node Positivity in Patients with Melanoma: The Melanoma Institute Australia Nomogram, J Clin Oncol 38:2719-2727, 2020