In a skin cancer epidemic, primary prevention is more important than ever.
Early data suggest just 15 minutes in moderate Australian sun causes DNA damage after a few days’ exposure, delegates at the Australasian College of Dermatologists scientific meeting in Brisbane heard last month.
The unpublished research, presented by Brisbane medical epidemiologist Professor David Whiteman, underscored how important primary prevention was in combatting sun damage.
His team exposed patients to a specified dose of UV on small areas of previously unexposed skin for 15 minutes each day for several days, then took biopsies to assess photolesions with immunohistochemistry.
They found patients exposed to 1.6 Standard Erythemal Dose (SEDs), equivalent to a UV index of 6, had unrepaired DNA damage after just four days. Professor Whiteman pointed out this was the equivalent of “grabbing a quick cup of coffee and coming back inside”.
“Why that’s important is that in places like Australia, with a fair skin type population, this is happening all the time,” said Professor Whiteman, a leading skin cancer expert and fellow of the Australian Academy of Health and Medical Sciences.
DNA damage and mutations don’t necessarily lead to cancer.
“We have evolved so many mammalian processes to keep rogue cells in check or to eliminate them,” Professor Whiteman said.
“We just, I guess, hope that they get repaired quite quickly.”
The issue is when those rogue cells aren’t kept in check.
“As you get repeated exposures – you go through life and you age – your DNA polymerases are less effective [and] you’re going to acquire more and more mutations,” he said.
“That, almost inevitably in Australia, leads to either keratinocyte cancers or, in unlucky people, to melanomas through different pathways.”
The state of the nation
While new treatments have had impressive effects on melanoma mortality rates, the epidemiological data painted a mixed picture of skin cancer success.
“I want to convince you that we have an epidemic of skin cancer in this country,” Professor Whiteman said.
In Queensland, age-standardised rates of melanomas have grown 1-2% annually, with a fourfold increase of cases overall due to population growth and ageing.
“We’re seeing a lot more invasive melanomas in our state. But of course, this has been overtaken by the rates of increase in the in-situ melanomas, which are now occurring at a rate of 2:1 in Queensland, and in a similar ratio in other states,” Professor Whiteman said.
“We’re also seeing incredible, steady rises in the number of people being treated for BCCs and SCCs,” he said, pointing to Medicare data for excisions of histologically confirmed keratinocyte cancers.
“These rates that we see are an order of magnitude higher than other populations in the world, with more than 1 million services for skin cancer treatments in Australia, and 120,000 hospital admissions, mostly day cases, but still contributing 760 deaths per year in Australia.”
Professor Whiteman said there was a slight downturn in 2020 due to covid, but rates were “very likely” to bounce back.
The costs of treating these preventable cancers were enormous, he added.
AIHW data showed the cost of treating skin cancer was $1.9 billion in 2020-21, making it the most expensive cancer in the health budget, he said.
Prevention
While there had been a drop in melanoma mortality rates since 2010 thanks to new therapies, there was a continued need for ongoing primary prevention efforts, Professor Whiteman said.
He praised Australia’s work so far, from banning solariums to the Slip, Slop, Slap campaign. The good news was that rates of melanoma in younger Australians were “steeply” falling, despite rates rising in older people over the last two decades.
This was supported by Medicare data on excisions for basal and squamous cell carcinomas which showed similarly falling rates in younger people and rising rates in older people – despite more biopsies in all age groups.
“It indicates to us that people are still presenting to their GPs, healthcare providers and dermatologists,” Professor Whiteman said.
“They’re still being assessed, and lesions are still being biopsied. But we’re actually looking more and finding less so we are seeing less skin cancer in the community.”
Professor Whiteman said primary prevention wasn’t the sole driver of that improvement though.
Findings from his 2024 MJA paper show that Australia’s changing ethnic makeup had a noticeable effect of melanoma rates, while incidence was still declining in young, high-risk, fair-skinned Australians.
Some of this was probably attributable to primary prevention, but some was likely due to patterns of behaviour such as more screen time and less outdoor play, he said.
The overdiagnosis problem
Early detection was vital to fighting melanomas and other skin cancers before they invaded deeper into the dermis, Professor Whiteman said.
“We have very sound, rational reasons for doing this,” he said.
“We know that melanoma survival is correlated inversely with the thickness of the lesion.”
Queensland data from 2021 shows the thickness at first diagnosis has dropped over time.
“We’re seeing the majority of invasive melanomas are less than one millimetre,” Professor Whiteman said.
“They’re very thin. And even within the one-millimetre category, the majority of melanomas are thin.”
This meant Australian clinicians were “doing really well at finding thin melanomas”, he said.
However, this raised questions about overdiagnosis.
Professor Whiteman pointed to a “sobering” 2021 editorial in JAMA Dermatology that said the “ultimate goal of early detection is not to find thinner melanomas but to reduce melanoma-associated morbidity and mortality”.
While this could sound like “heresy”, he said it was important to recognise the diversity and heterogeneity of the biology of cancer.
This meant that there was a class of cancers that had all the hallmarks of cancer, but were very slow, non-progressive cancers, including some that would even regress.
Professor Whiteman said the challenge with screening was that fast-moving cancers would grow quickly between screens, but these slow-moving ones would be picked up by screening.
Despite being captured more by screening, their discovery may not shift the morbidity and mortality rates.
Professor Whiteman pointed to Queensland data showing rates of very thin melanomas, of less than one millimetre, were rising around 1-2% every year, but rates of two-millimetre melanomas were dropping “probably because we’re harvesting early”.
Meanwhile, rates of thick melanomas, of more than four millimetres, had been rising at a rate of 1.4% per year for 20 years.
Professor Whiteman wondered how these thick melanomas were being missed, given the reasonably high levels of awareness patients had and contact with their doctors.
“Are they the fast-growing melanomas that we just can’t pick up in between screens?” he said.
“We don’t have an answer to this problem yet. Early diagnosis is clearly better than late diagnosis. Everyone would prefer their melanomas diagnosed early, and so we want people to be looking for melanomas, but we do have this unsolved problem about overdiagnosis.”
Early this year, the federal government announced funding for the development of a roadmap for a targeted skin cancer screening program. The teams will be developing a blueprint to present to the government in around three years.
New therapies
Australia has experienced a significant decline in melanoma deaths since 2010, driven by the introduction of new targeted therapies and immune checkpoint inhibitors
“The last 15 or so years has seen an extraordinary explosion in knowledge about the ways of treating cancer with combination therapies and neoadjuvant therapy, such that we’re looking into a future where maybe the primary form of treatment might involve some form of immunotherapy,” Professor Whiteman said.
Australian melanoma mortality rates were rising from around 2011 and dropped distinctly after that.
But Professor Whiteman cautioned these interventions were “not magic cures”.
“Survival rates in people treated with these new therapies and new combinations are, at best, about 60%,” he said, adding that these figures come from selected populations in clinical trials.
He noted that while survival rates were hugely improved, survivors could suffer from quality-of-life issues and side effects from treatment.
The costs could not be ignored either.
Professor Whiteman pointed to PBS data showing the various classes of immune checkpoint inhibitors and targeted therapies for melanoma were costing about $120 million per quarter, or around half a billion dollars per year.
“Even if we have 1% of that budget put into primary prevention, we’d be in a much stronger place,” he said.
“We can’t treat our way out of the skin cancer epidemic,” Professor Whiteman said, adding that skin cancer control required primary, secondary and tertiary strategies working together.
“Primary prevention is the only strategy that we have for turning off the tap.”
