Like melanoma, CSCC is a cancer of the skin (that’s what cutaneous means). It affects keratinocytes, the cell that makes up 80 per cent of our skin; the keratin they produce gives our hair, nails and skin their strength.
Keratinocytes, like all healthy cells, carefully follow the instructions coded into your DNA. But when DNA is damaged – most often through the photons in sunlight smashing into it – the instructions can be garbled. These new instructions can cause the cell to start dividing uncontrollably, eventually forming a cancerous tumour.
CSCCs typically appear on the most sun-exposed parts of our skin – the hands, the neck, the scalp or ears – as a firm bump or scaly sore. Bailey recalls “a scabby sort of thing on my head”.
As soon as his doctor saw it, he cut it out. Surgical excision, and sometimes additional radiation therapy, is the typical treatment for CSCC. In more than 90 per cent of cases, simple treatment is entirely curative. “You cut them out, you send it off, you stitch it up, and they are cured,” says McCormack.
But occasionally, the cancer has spread before it is spotted. Of every 100 cases, one to three people will die, as the cancer grows back in their lungs or livers or bones.
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Deaths from non-melanoma skin cancers have almost doubled in Australia in the past 20 years; globally, CSCC causes more deaths than melanoma does, despite its lack of name recognition. About 70 per cent of us will get a non-melanoma skin cancer in our lives – hence the high number of deaths, even though the disease itself has a relatively low mortality rate.
“It’s so common, people tend to trivialise it a bit,” says the University of the Sunshine Coast’s Associate Professor Andrew Dettrick, who has published papers on CSCC. “Five per cent does not sound like a lot, but it is when you times it by 200,000 people.”
A new standard of treatment for an invisible disease
If a doctor cuts out the tumour, and then uses beams of radiation to kill any cells they cannot reach, why does cancer sometimes come back?
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“They have got microscopic disease left, either in the area that’s been treated, or it has already spread. And we don’t have any way of knowing that,” says Professor Danny Rischin, head of research for head and neck cancer at the Peter MacCallum Cancer Centre.
The focus of Rischin’s career has been on stopping that cancer from coming back. In 2018, he co-authored a study testing whether Carboplatin, a chemotherapy drug, could prevent relapse.
Like many experiments, it did not work. The drug did not improve survival.
But scientists often learn more from failure than success. Rischin’s team was able to isolate a subgroup of CSCC patients within the trial who had certain features that put them at a dramatically higher rate of cancer recurrence. “They were in need of better treatment,” he says.
For this group, Rischin’s team turned to one of the medicines that has revolutionised cancer treatment in the past decade: checkpoint inhibitors.
Stephen Bailey is a cancer patient participating in an immunotherapy trial.Credit: Luis Enrique Ascui
Our immune system needs to run certain checks to ensure it is attacking an enemy, not one of our own cells. Cancer often takes advantage of this, generating its own codes to pass the checks.
Using genetically modified antibodies, scientists in the past two decades have learned to block our own immune system’s checkpoints. “It unmasks the cancer cell, so your immune system can see it again,” says Dettrick.
Perhaps a souped-up immune system could ferret out the microscopic cancers the surgeons could not?
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In a study sponsored by the therapy’s manufacturer, published in the New England Journal of Medicine, Rischin’s team randomised 415 patients, who had been treated for CSCC but had a risk of recurrence, between immunotherapy and a placebo: 87 per cent of patients on the therapy were still disease-free after 24 months, compared to 64 per cent on the placebo.
About 10 per cent of patients getting the therapy had severe side effects, and one died – consistent with the normal side effects from immunotherapy.
Rischin expects the trial will lead to a change in practice. A request for approval for the new therapy is before drug regulators in Europe and Australia.
“It’s incredibly rewarding,” says Rischin. “This is what we all aspire to: have ideas and develop treatments that make a difference to patients.”
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