Natural history of high-risk cutaneous primary melanoma and risk factors for disease progression

Background:\ua0Melanoma is a potentially fatal cancer of the skin that is associated with high disease burden in Australia. Exposure to ultraviolet radiation is the most important environmental risk factor.\ua0When diagnosed early, primary melanoma is curable, however melanomas greater than 1mm in thickness and those with ulceration have a high risk of recurrence and metastases, and little is known about factors influencing their progression.\ua0Aims:\ua0The primary aim was to describe the natural history of localised high-risk primary melanomas after treatment, for up to 2 years post-diagnosis and to identify risk factors for disease progression. My two secondary aims were to investigate patients’ use of health services, and explore sun protection behaviours and risk of subsequent primary melanoma.Methods:\ua0This project was conducted among a cohort of patients who had newly-diagnosed primary melanoma (tumour stage T1b-T4b) treated in Queensland, 2010 to 2014. Melanomas were histologically confirmed, and patients completed questionnaires at baseline and at regular intervals thereafter. Statistical techniques, including survival analyses, regression models and latent class analyses were used to answer the research questions.\ua0Results:\ua0Amongst 700 patients with high-risk primary melanoma, 94 (13%) developed a recurrence within 2 years. Most first recurrences occurred at local or regional sites, whereas subsequent recurrences were more common at distant sites. Higher risk of melanoma recurrence was observed with increasing tumour thickness, tumour ulceration, mitotic rate >3/mm2\ua0and head or neck location of primary. Ulcerated tumours occurred more commonly in patients with diabetes, whereas patients regularly taking statins had a lower likelihood of an ulcerated tumour. Long-term statin users, especially male users, also had a lower risk of melanoma recurrence. Secondary outcomes demonstrated that patients with inadequate sun protection behaviour after melanoma diagnosis were at higher risk of developing a subsequent primary; and that the use of support services after melanoma diagnosis was lower in patients above the age of 65, males, those with lower education and patients residing in rural Queensland.Conclusions:\ua0Whilst there was a strong association between tumour factors and recurrence, our findings suggest that patient factors also affect melanoma recurrence, particularly those associated with systemic inflammation. It is possible that anti-inflammatory medications such as statins render the tumour micro-environment less inflamed, thereby decreasing metastatic potential. Further investigation is now required to investigate the significance and applicability of our findings in a clinical setting.\ua0Dissemination of findings:\ua0These findings have been published as five original articles and two research letters, all in the highest-ranked dermatology journals (JAMA Dermatology, Journal of American Academy of Dermatology, British Journal of Dermatology, Journal of Investigative Dermatology) except one published in an Australian public health journal. Results have been presented at ten local and international conferences and seminars, and there was media coverage of two publications reaching a national audience of over 3 million Australians