麻豆传媒

In the last 4 decades, the of cutaneous melanoma has increased 6-fold in the United States, making it the third most commonly diagnosed cancer, after breast and lung cancer. Whether this sharp rise represents a true epidemic of disease or an "epidemic of diagnosis" remains controversial.

In a report in the , Adewole S. Adamson, MD, from the division of dermatology at Dell Medical School at the University of Texas, Austin, and colleagues, make a case for overdiagnosis. The incidence of melanoma has skyrocketed but melanoma mortality has remained stable, the authors noted. This pattern "should be viewed as pathognomonic for overdiagnosis," they said.

Increased diagnostic scrutiny has contributed to this upward trend with widespread skin cancer screening acting as the primary driver, the authors explained: "[A]lthough the conventional response has been to recommend regular skin checks, it is far more likely that more skin checks are the cause of the epidemic -- not its solution."

Now that the global coronavirus pandemic has put a temporary halt to much skin cancer screening, "what is important is not to restart it," they emphasized.

Falling for biopsy have also played a role, the authors said, noting that nearly 90% of melanomas sent for evaluation are less than 1.0 mm in thickness. The authors recommend dermatologists and primary care physicians use previous threshold to avoid sending pigmented lesions smaller than 6 mm (roughly the size of a pencil eraser) for biopsy.

Currently, however, no definitive diagnostic criteria for the pathological diagnosis of melanoma exist. "A combination of subjective criteria, increased frequency of ambiguous lesions, and asymmetric incentives (penalties for underdiagnosing but not for overdiagnosing) may explain the lower pathological threshold to diagnose melanoma," the authors wrote.

In the following interview, Adamson discussed the issues in greater detail.

You describe the role of upstaging in the increased incidence of metastatic cutaneous melanoma diagnoses. Since mortality rates have not increased, what is the clinical significance of these tiny metastases?

Adamson: The incidence of cutaneous melanoma that is metastatic at first detection has been rising in recent years. Some may believe that this could be consistent with an increase in true cancer occurrence. However, there is a similar rise seen for metastatic non-cutaneous melanoma, also with flat mortality. This suggests that upstaging may be the reason for the rise of cutaneous metastatic melanoma.

The growing use and sensitivity of imaging technology such as positron-emission tomography combined with computed tomography has increased our ability to see tiny metastases. Given flat overall melanoma mortality over time, the clinical significance of these tiny metastases is uncertain. However, in the recent era of effective therapy, perhaps some of these patients would now benefit from treatment.

Do the factors driving this "epidemic of inspection, surveillance, and biopsy of pigmented skin lesions" parallel those leading to overdiagnosis of thyroid cancer? If so, might common lessons be applied to other cancers in which there is a risk of overdiagnosis?

Adamson: Yes, in some ways, they do parallel those related to overdiagnosis in thyroid cancer. The incidence of thyroid cancer has increased 3-fold over the past 40 years in the United States, yet mortality has remained flat, as with melanoma. The reasons are in large part explained by increased intensity of inspection with more powerful imaging modalities, and biopsies of many small lesions with abnormalities that likely represent indolent neoplasms.

However, in thyroid cancer, pathologists have pursued linguistic de-escalation, and some papillary thyroid carcinomas are now labeled as "thyroid neoplasms." This linguistic de-escalation could be considered for melanoma in situ. A diagnosis of "melanocytic neoplasm" would be less distressing for patients, and a recent indicated that renaming low-risk cancers can effectively reduce continued surveillance and overtreatment.

Why is it difficult to balance the need for early diagnosis of melanoma with the risk of overdiagnosis?

Adamson: Randomized controlled trials of screening for melanoma do not exist. In fact, the U.S. Preventive Services Task Force concluded that there was insufficient evidence to recommend for or against screening for melanoma, due in large part to the lack of high-quality data. In the absence of widely accepted or formalized screening recommendations, clinicians are left to decide what is best for their patients. They often err on the side of more surveillance rather than less, which increases the likelihood of overdiagnosis.

The so-called baby boomers are part of a pre-sunscreen, "Coppertone Tan" generation. Given the size of this demographic and the number of severe sunburns likely sustained at an early age, would a significant proportion be considered at "substantially high risk"?

Adamson: The strongest risk fact for the development of melanoma -- and cancer, in general -- is age. By that metric alone, baby boomers, most of whom are older than the median age for a diagnosis of melanoma, are at higher risk. UV exposure, particularly early in life, is the most consistent, modifiable risk for the development of melanoma. A history of severe sunburns doubles the risk of melanoma. Therefore, UV protection is a reasonable public health recommendation.

However, UV exposure cannot explain the 6-fold rise in melanoma over the past 40 years. I hesitate to use the word "substantial" to describe risk here because the threshold for this distinction may be different depending upon who you ask. However, I do not believe sunburn history alone should determine whether we should screen all baby boomers for melanoma. This a separate and still open question that should be addressed within a clinical trial.

You say that when melanoma is overdiagnosed, the morbidity associated with unnecessary treatment is only part of the harm experienced by patients. Can you elaborate?

Adamson: The downside of melanoma overdiagnosis extends well beyond the immediate physical harms associated with treatment. Overdiagnosis results in increased out-of-pocket costs and the prospect of frequent surveillance in the future. Receiving an unnecessary diagnosis of cancer can also threaten patient resilience. Some may limit healthy outdoor activities for fear of melanoma recurrence, for instance. In addition, patients with a diagnosis of melanoma may find it difficult to qualify for certain health insurance plans or life insurance.

Any other comments?

Adamson: The epidemiologic data clearly point to overdiagnosis as a rapidly growing phenomenon in melanoma. The question now is not whether or not melanoma overdiagnosis exists, but what, if anything, clinicians should do about it.