Researchers identify risk factors for recurrence in early-stage melanoma

Even when melanoma is caught early, many patients still worry about whether the cancer might return. New research suggests clinicians may need to look beyond standard staging factors to better estimate that risk.

A study published in JAMA Dermatology this month found that several clinical and tumor characteristics may help predict recurrence in people with stage 1 or stage 2 melanoma. In a cohort of more than 1,000 patients with localized melanoma, investigators identified several factors associated with a higher likelihood of recurrence.

The investigation was conducted by a team of researchers including senior author Maria L. Wei, M.D., Ph.D., professor of dermatology at the University of California, San Francisco, and director of the Melanoma Surveillance Clinic and the Dermatology Familial Cancers Clinic.

Melanoma is the deadliest form of skin cancer, and its incidence has been rising in the United States in recent decades. While early-stage disease is often highly treatable, recurrence remains a major concern. Although staging systems traditionally rely on tumor thickness and ulceration to predict prognosis, researchers say those measures may not fully capture which patients face the greatest risk of melanoma returning.

To better understand recurrence risk in localized disease, investigators evaluated medical records for 1,092 patients treated at a tertiary medical center, examining a range of clinical and pathological characteristics and tracking whether and when melanoma recurrence occurred.

Participants had a median age of 60 years, and most were men (57%). Overall, 16.3% of patients experienced a recurrence during follow-up, with a median time to recurrence of approximately two years.

In a multivariable analysis, six clinicopathologic variables were significantly associated with time to recurrence: ulceration, tumor thickness, tumor location, neurotropism (tumor growth along nerves), lymphovascular invasion (cancer cells present in lymphatic or blood vessels) and the presence of mitoses.

Ulceration was among the strongest predictors of recurrence. Patients whose tumors were ulcerated had more than three times the risk of recurrence compared with those without ulceration. Tumor thickness was also associated with recurrence risk, with thicker tumors linked to shorter time to recurrence.

Tumor location also appeared to influence recurrence risk. Compared with melanomas on the arms, tumors on the scalp or neck were associated with more than a threefold higher risk of recurrence, whereas melanomas on the face were linked to more than double the risk.

Mitotic rate, which is an indicator of how quickly cancer cells are dividing, was particularly notable. Tumors with higher mitotic activity were associated with nearly four times the risk of recurrence compared with those with lower rates. Although mitotic rate was included in earlier melanoma staging systems, it is not currently emphasized in the same way for recurrence prediction.

The authors discussed how their findings compare with emerging predictive models. Prior studies have developed risk models for melanoma recurrence using clinicopathologic variables such as tumor thickness, ulceration and mitotic rate, and some have used machine learning approaches to improve prediction. Although several of the most important predictors identified in those models — including thickness, stage and mitotic rate — were consistent with the current findings, other variables such as age, insurance type and median income have shown mixed results across studies.

The study authors noted that incorporating a broader set of clinical and pathological features into risk models could help clinicians better tailor follow-up care and counseling for melanoma survivors. “Consideration of these factors could help guide surveillance for recurrences,” Wei and her colleagues wrote, while noting that larger multi-institutional studies will be needed to validate the findings.