DT: I’m John Jesitus, personal correspondent for Dermatology time. With me today is Professor David Whiteman. Could you please introduce yourself with your name and title and where you work?
Dr. Whiteman: Of course. Hello. My name is David Whiteman. I am the head of the cancer control group at the QIMR Berghofer Medical Research Institute in Brisbane, Australia.
DT: What are the main conclusions of your study?
Dr. Whiteman: We looked at this issue of oversensing or overdiagnosis in cutaneous melanoma. We have long known that melanoma rates are rising rapidly in Queensland and other parts of the world, including the United States. And much of the increase in incidence is due to the detection of on the spot melanomas, preinvasive melanomas.
We therefore followed a large cohort of over 43,000 Queensland residents who had completed a baseline questionnaire with a detailed survey of risk factors. And the key question, or series of questions that we asked them, was to have their skin examined by a doctor for the purpose of screening for skin cancers in the 3 years preceding recruitment. Then we followed these people for 7 years and linked their records to the cancer registry. We found that there was a 29% excess of melanomas detected in the screened arm compared to the unscreened arm over this 7-year period. And that was after adjusting for all known melanoma risk factors. This suggests that there is this inherent detection rate that is higher in screened people than in unscreened people. And that’s a sign that there’s oversensing of indolent lesions.
DT: And what do these results mean for dermatologists in clinical practice? Should they do less screening, and why or why not?
Dr. Whiteman: This is not a randomized trial, and we are very quick to point out that these come from observational data. We have no definitive evidence that this screening causes harm. There is also a very strong clinical opinion that early detection does indeed save lives. We are not at all advocating a change in practice at this stage. But what we’re doing is assessing the scale, quantifying the magnitude of this potential problem of overdiagnosis. This is a flag for future research. What we really need to do now is be able to identify melanocytic neoplasms that are harmful, and ensure that they are excised and treated correctly, but also have the ability to diagnose melanomas or melanoma-like lesions that are not not harmful and may be associated with a very good prognosis. It is really a signal for researchers to work on this problem of detecting harmful melanomas and distinguishing them from non-harmful melanomas.
DT: And in your number one outcome measure on the screening side, what does it mean that in a separate analysis of on the spot melanoma, the higher risk (of being diagnosed with melanoma) associated with skin examination was only evident for on the spot and not for invasive?
Dr. Whiteman: This discovery was not unexpected. There has been a big campaign in Australia, particularly for people to come forward for medical attention if they notice a pigmented lesion on their skin. This leads to increased rates of biopsies in the population. And this leads to an increase in the diagnosis rates of both on the spot melanomas and very thin invasive melanomas.
What we saw in our study was that among people who had a skin exam, who had their skin examined by a doctor, the excess newly detected melanoma was for on the spot melanomas; i.e. pre-invasive melanoma. This suggests that in the population we are now harvesting a pool of lesions that are not yet fully invasive cancers and may in fact never become fully invasive cancers. They may never be destined to break through the basement membrane and become truly invasive melanomas. And so, the assumption is that we find lesions that would cause no long-term harm to the patient. But they need to be removed because at this point we cannot predict what their future behavior will be.
DT: And what are the main weaknesses or limitations of the study design?
Dr. Whiteman: As I said, this study is an observational study. The best way to test and look for overdiagnosis in screening is to run a randomized controlled trial, where people are randomized to receive a skin exam or usual care, and then follow those people for a long time. We haven’t done that study, and frankly, it’s unlikely that any group in the world will ever have the resources or the budgets to be able to conduct a melanoma screening trial. So that’s a weakness. We don’t have random data.
The other weakness is that the main exposure measure was based on self-reporting. That is, people at baseline completed a risk factor questionnaire and self-reported their history of skin examinations. I have to say that our secondary measure of exposure was having a skin biopsy in the first year of follow-up. It was an objective measure taken from medical administration databases. It is therefore unlikely that there is measurement error in a systematic sense for this item. And we found that the same thing happened no matter what exposure meter we used. It is therefore unlikely to be a critical weakness of the study.
DT: And what were the main strengths of the study design?
Dr. Whiteman: The main strengths of the study design are the large sample size — we recruited over 40,000 people. We had full risk factor information captured at baseline and we had full follow-up of study participants through record linkage with cancer registries in Australia, which have mandatory reporting for cancer and melanoma. Thus, a large sample size long-term follow-up and high-quality outcome information were the main strengths. Also, the analysis we performed was a propensity-weighted analysis, which emulates a clinical trial but is not a clinical trial.
Whiteman reports no relevant financial interests.
Whiteman DC, Olsen CM, MacGregor S, et al. The effect of screening on melanoma incidence and biopsy rates [published online ahead of print, 2022 May 9]. Br J Dermatol. 2022;10.1111/bjd.21649. doi:10.1111/bjd.21649
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