Skin biopsy rates have increased substantially in each of the nine geographical areas participating in the US National Cancer Institute's Surveillance Epidemiology and End Results programme. This growth is associated with an increased rate of melanoma detection—a finding that persisted even after assuming an increase in the true occurrence of disease. From stage specific analyses we found that this relation was confined to local and in situ melanoma and was not evident in advanced disease. This finding supports the idea that the increased incidence of melanoma is largely the result of increased diagnostic scrutiny—that is, skin lesions are being biopsied that would not have been in the past.
Our data for trend also suggest that the true occurrence of melanoma has not changed. outlines the expected change in stage specific incidence and mortality given different explanations for an apparent rise in incidence. The incidence of early stage disease has risen rapidly whereas the incidence for late stage disease and mortality have been relatively stable (), findings arguing against a dramatic increase in the true occurrence of disease. The predominant explanation for the apparent rise in melanoma incidence is instead overdiagnosis, the result of increased diagnostic scrutiny.
Expected change in disease stage incidence and mortality given competing explanations for apparent rise in cancer incidence
Some might posit an alternative explanation, arguing that stable mortality in the face of rising incidence reflects improved melanoma therapy. These improvements might be the net effect of two factors: starting treatment at earlier stages of disease, or better treatment for a given stage. But this seems implausible. For it to be true, the improvements afforded by early diagnosis and better treatment would need to exactly match the pace of the underlying increase in disease burden; they cannot be too slow or mortality would rise, nor can they be too fast or mortality would decrease.
The finding that the extent to which cancer is identified seems to be directly related to how closely it is looked for has been observed with several cancers, including lung cancer,12
renal cell carcinoma,14
Perhaps the most powerful example is prostate cancer, where the number of cancers detected is directly related to how aggressively urologists biopsy the prostate. Historically, six needle biopsies were done but now many advocate 12 or more, noting that the more biopsy samples that are taken, the more likely cancer is to be found.17–20
Some even advocate “saturation biopsy” (32-38 needle biopsies), as cancers can still be found microscopically in men who were cancer free on the basis of three or more prior biopsies.21
Our analysis has several limitations. Firstly, the data only represent people aged 65 and older. We do not know whether biopsy rates have changed in younger people or how any change might relate to the incidence of melanoma. Secondly, our biopsy rates include biopsies for lesions that were not considered to be related to melanoma before the biopsy, but rather basal or squamous cell carcinoma or a cutaneous manifestation of systemic disease. This concern is highlighted by biopsy rates that are nearly two orders of magnitude higher than melanoma incidence. Such imprecision in measuring exposure, however, only biases our results to the null.
Thirdly, some might question how we modelled an increase in the true occurrence of disease. Our analysis considers the independent effect of an area's biopsy rate on its melanoma rate if each area is allowed its own initial melanoma rate (an area specific y intercept) and its own melanoma growth rate (an area specific slope). By including a term for time to control for melanoma growth rate, we may have controlled for factors besides changes in true disease occurrence. Aspects of diagnostic scrutiny other than biopsy rate may also change over time, particularly the proportion of biopsies carried out for pigmented lesions. Although we are unable to estimate precisely the true effect of biopsy rate, we were able to bound the estimate by carrying out analyses after assuming both increasing and stable true occurrence of disease (with and without time). Thus the true effect of 1000 additional biopsies is likely to be between 6.9 and 12.6 extra cases of melanoma diagnosed.
What is already known on this topic
Some dermatologists suspect that the rise in incidence of melanoma may reflect more skin biopsies, not more disease
What this study adds
The increasing incidence of melanoma between 1986 and 2001 in the United States is closely associated with biopsy rates
The increased incidence was mostly in early stage disease; yet mortality from melanoma remained stable
This pattern suggests overdiagnosis, largely as a result of increased diagnostic scrutiny and not an increase in the true occurrence of disease
Finally, our investigation shares the limitation of all observational research in that although we show an association between biopsy rate and incidence, inferences about causation are more speculative. A causal relation is suggested, however, because the relation is confined to the category of disease (early stage melanoma) that would be expected to be related to diagnostic scrutiny. Furthermore, the finding of stable mortality in this population suggests that the bulk of these additional cases of melanoma may appear malignant on histology but are nonetheless biologically benign.