Clinical Context

Melanoma is the most prevalent potentially fatal skin cancer, but prognosis is very good for American Joint Committee on Cancer (AJCC) stage T1 disease. Prognostic modeling can predict survival in patients with melanoma and identify prognostic variables.

AJCC staging uses Breslow thickness and primary tumor ulceration. Mitotic rate, Clark levels of invasion III and greater, and tumorigenicity or vertical growth phase also strongly correlate with poorer outcomes.

Study Synopsis and Perspective

Although melanoma is the most serious skin cancer, most patients do have high chances of survival. New research has now identified a subset of patients with early disease who have a very low risk of dying from the disease.

In a cohort of almost 11,600 patients, the overall 7-year rate of death from melanoma was 2.5%, but the risk in a subset of 25% of patients was below 1%.

Conversely, the study authors were also able to identify a small subset of high‐risk patients with a greater than 20% risk for death.

Although more data are needed and the findings should be verified in other studies, the use of a different term such as “melanocytic neoplasms of low malignant potential,” rather than “melanoma,” may be more appropriate and may help to begin to address the problem of overdiagnosis, the authors note.

“While the topic of very low risk melanomas has been presented at national and international meetings, there have been no formal discussions to define the classification of ‘melanocytic neoplasms of low malignant potential’ at this time,” first author Megan M. Eguchi, MPH, from the Department of Medicine, University of California, Los Angeles, said in an interview. “Criteria would need to be established using study designs beyond those available using [Surveillance, Epidemiology, and End Results (SEER)] data.”

She emphasized that at this time, they do not propose any change to treatment of these lesions, just a change to the terminology.

The study was recently published online in Cancer.

Even though melanoma is considered to be the most common potentially lethal tumor of the skin, prognosis is often very good for those with T1 tumors--those in the lowest risk category. Prognostic modeling has been used to predict survival in patients with melanoma and to identify prognostic variables, the authors note, with the most prominent attributes being Breslow thickness and ulceration of the primary tumor, which form the basis of the current AJCC staging system.

There is evidence that the increasing incidence of melanoma is partly a result of overdiagnosis, meaning the diagnosis of lesions that will not lead to symptoms or death. The authors write that they were interested in identifying lesions that are currently diagnosed as melanoma but might lack the capacity for metastasis--cases that could potentially be part of the phenomenon of overdiagnosis.

In the study, Dr Eguchi and colleagues analyzed information from the SEER database and identified 11,594 patients who were diagnosed in 2010 and 2011 with stage 1 melanoma that was 1.0 mm in thickness or smaller and had not spread to the lymph nodes. Prognostic models for risk for death from melanoma in patients with low-risk melanomas were developed, and then the ability of the models to identify very low risk subsets of patients with melanoma‐specific survival surpassing that of T1 overall was evaluated.

The median age of the patients was 58 years, the median Breslow thickness was 0.45 mm (interquartile range [IQR], 0.30-0.65 mm), and 71% were assigned stage IA. Ulceration was present in 4% of cases, 27% were mitogenic, and 45% were Clark level II, and within this cohort, 292 (2.5%) patients died of melanoma within 7 years. In the training data set, 177 (2.3%) of 7652 patients died of melanoma within 7 years; numbers were similar in the testing set (115 of 3942; 2.9%).

Overall, the investigators identified 3 large subsets of patients who were in the AJCC 7th edition classification for stage I (“thin”) melanoma, who had a risk for death of approximately less than 1%. This was a marked improvement from the rate of the overall sample. In the simplest model (model 1A), patients who were younger than 70 years at diagnosis with Clark level II invasion were deemed at very low risk.

In model 1B the same initial classification was used, but it was further refined and limited to patients who were either aged 43 years or younger or aged 44 to 69 years with Breslow thickness less than 0.40 mm. At 10 years postdiagnosis this subset also showed a less than 1% risk for death from melanoma. The logistic regression model (model 2) was similar, as it identified about 25% of patients with a predicted risk for death of less than 0.5%, incorporating patient age, sex, mitogenicity, Clark level, and ulceration. Model 2 was also able to further identify a small subset of patients with no deaths.

The logistic regression model was also able to identify a very small subset (0.7% and 0.8%) of patients who had a risk for death that exceeded 20%, which was markedly higher compared with that of most patients with T1b tumors.

Commenting on the study, Beth Goldstein MD, a dermatologist and cofounder of Modern Ritual Health, Chapel Hill, North Carolina, noted that in the future, when there is the ability to determine which lesions have an aggressive biologic potential, “then ideally, we can avoid unnecessary removals.”

Dr Goldstein acknowledged that there are unnecessary procedures performed perhaps for lesions that would never become life threatening, but at the same time, it is known that there are certain early lesions that are more likely to metastasize and are only known after a complete removal and pathologic assessment. 

In addition, besides concerns with removing a suspicious lesion, such as scarring, “there is very limited morbidity associated with this procedure,” she said. “Most patients with early melanomas do not require more than an outpatient procedure under local anesthetic and are already reassured of the low-risk nature of their early melanoma.”

At this time, “we do not have the ability to differentiate these tumors further from the initial assessment,” Dr Goldstein continued. “While there is an ability to screen melanomas for higher likelihood for metastasis with the 31 genetic expression profile test, there is still much work to be done to refine these resources.”

This study was supported by National Cancer Institute. Dr Eguchi and Dr Goldstein have disclosed no relevant financial relationships.

Cancer. November 7, 2022.^[1]

Clinical Implications

• Prognostic models identified patients with very low risk for melanoma death within 7 years of diagnosis. A small number of patients classified as stage I may be at sufficiently high risk to potentially consider more aggressive treatment.
• This warrants further study and consensus discussion to develop classification criteria, as well as potential use of an alternative term (melanocytic neoplasms of low malignant potential).
• Implications for the Health Care Team: As new data emerges about very low-risk melanomas, members of the healthcare team should advise patients that removal remains recommended and that there is very limited morbidity associated with the procedure as it is done in an outpatient setting under local anesthetic.

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