Melanoma Increasing, but Is This Overdiagnosis?

Roxanne Nelson, RN, BSN

March 29, 2022

Melanoma has been increasing in incidence in the United States over the last few decades, but is this a true increase? Or is this a case of overdiagnosis, fueled by screening?

A new study argues the case for overdiagnosis.

"The incidence of melanoma has risen sixfold in the past 40 years in the US, while mortality has remained largely flat, an epidemiological signature consistent with overdiagnosis," commented lead author lead author Adewole Adamson, MD, an assistant professor of Internal Medicine (Division of Dermatology) at Dell Medical School at the University of Texas at Austin.

He posted this conclusion on Twitter after the study was published this month in JAMA Dermatology.

"The discrepancies in incidence and mortality trends found in this cohort study suggest considerable overdiagnosis of melanoma occurring among White patients in the US," the authors conclude.

They estimate that an estimated 59% of White women and 60% of White men with melanoma were overdiagnosed in 2014.

These results are similar to those from a recent study from Australia, which  used a different method of assessing overdiagnosis. Those findings estimated that 54%-58% of melanoma cases represented overdiagnosis in Australia, Adamson noted

"Our estimates shed light on the HUGE scope of this problem in the United States that we need to address," Adamson commented on Twitter. "Calls for screening for melanoma in the general public will only push these numbers higher, and make patients out of healthy people."

"Screening the general population for melanoma has never been shown to save lives and likely is responsible for the increase in melanoma overdiagnosis," Adamson told Medscape Medical News. "Screening average- and/or low-risk patients is of low value and the harms may outweigh the theoretical benefits."

Screening programs should be directed to those who may derive the most benefit, he asserts. "Screening should be limited to high-risk patients such as older white men, patients with a lot of atypical nevi, heavy sun exposure, fair skin, and red hair," he said. "Just like for other cancers, such as breast, prostate, and colorectal, there should be clear guidelines as to which populations to screen, as well as when to start and when to stop screening."

Overdiagnosis is defined as the diagnosis of cancer that would never have caused any symptoms or problems in a patient's lifetime. But therein lies the problem, explained Adamson. "Because we do not know which early, screen-detected skin cancers would be destined to progress, we are obligated to treat all of them," he said. There is evidence to suggest that melanoma in situ is not an obligate precursor lesion to invasive melanoma, similar to the situation in which not all ductal carcinoma in situ leads to invasive breast cancer, he explained. "It is possible that less aggressive management strategies could be the subject of future studies."

Patients Out of Healthy People

For their study, Adamson and colleagues compared rates of melanoma among White and Black patients. Melanoma is much less common among Black individuals, and they are also less likely to be screened. Additionally, screening rates among Black patients have remained more or less the same over the last decades, whereas screening has increased in White patients. 

The team used trends in mortality as a result of melanoma in Black patients as a marker for improvements in medical care. From this, they estimated the expected mortality trends in White patients if medical care had not improved. This served as a marker for the change in true cancer occurrence. Overdiagnosis was calculated as the difference between observed incidence and estimated true cancer occurrence.

The incidence of melanoma rose dramatically among White patients from 1975 to 2014, increasing about fourfold in White women (IRR, 4.01) and sixfold in White men (incidence rate ratio, 5.97).

At the same time, there was much smaller increase (of less than 25%) in the incidence of melanoma in both Black women and Black men.

In that time period, melanoma-related mortality decreased approximately 25% in Black women and men; it remained stable in White women, but increased almost 50% in White men.

Had medical care not improved, estimated mortality would have increased 60% in White women and more than doubled in White men, the authors assert.

Guidelines Needed

"Recognizing and addressing overdiagnosis is important," said Anthony J. Olszanski, MD, RPh, associate professor, Department of Hematology/Oncology at Fox Chase Cancer Center, Philadelphia, who was approached for comment on the paper.

That said, Olszanski noted that this particular study has important limitations. "It is, by nature, a retrospective study using data from the SEER database registry, limited to patients only in the US, and uses a control group of Black patients to estimate overdiagnosis in White patients," he said. "These important factors can certainly influence their findings. However, the paper also notes that White men have realized a true increase in diagnosis, backed by a notable increase in mortality."

The findings should and do raise a number of provocative questions, Olszanski emphasized. "Should we curtail public screening? Should we mandate revised guidelines for biopsies or pathologic diagnosis?"

"As a medical oncologist," he continued, "I treat patients who clearly do not have benign disease and so it is easy for me to be biased toward aggressive screening. However, it is my opinion that we should develop guidelines aimed at lessening this apparent overdiagnosis."

These guidelines should be based on prospective studies and would better define which lesions are most suspect and should be biopsied, which are rational for ongoing surveillance, and what pathologic features are most consistent with melanoma, he noted. "We also need to continue to educate the public, as all too often I see the patient who ignored a lesion that was changing over time," he added. "A changing lesion requires medical attention. Importantly, we likewise need to improve our commitment in educating the public about the risks of excessive ultraviolet radiation exposure and how to avoid it, as prevention continues to be a most prudent course."

Screening Catches Disease Early

Another expert approached for comment emphasized that identifying melanomas early on may prevent the need for aggressive therapy. "Many primary melanomas in the US are diagnosed now at an early stage and are cured with surgery, and that hardly constitutes overdiagnosis," said Jeffrey S. Weber, MD, PhD, deputy director of the Perlmutter Cancer Center and co-director of the Melanoma Research Program, NYU Langone Health, New York City.

"In addition, the death rate from melanoma is likely decreased due to the advent of more effective therapies for metastatic disease, and the increasing use of adjuvant immune and targeted therapies that are highly effective at preventing relapse and undoubtedly at prolonging survival, but they have been approved only since 2017-2018," he added.

This study was supported in part by the Robert Wood Johnson Foundation (Dr Adamson). Adamson and Olszanski have disclosed no relevant financial relationships. Weber has disclosed relationships with Merck, Genentech, AstraZeneca, Pfizer, Regeneron, GSK, Alkermes, Novartis, Celldex, Incyte, EMD Serono, BMS, and holds equity in CytoMx, Biond, Neximmune and Immunimax.

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