The effect of smoking in melanoma outcome still remains an enigma

Abstract

Sentinel lymph node biopsy is an established standard procedure in the care of carefully selected patients with melanoma. Back to the eighties up to our decade, the question was raised regarding the relationship between socioeconomic status (SES) and melanoma. It is well established that those with higher income and higher education are at an increased risk of developing melanoma, attributed to greater exposure to lifestyle factors such as sun holidays and use of sunbeds. However, once diagnosed those with a lower socioeconomic status have a worse prognosis, a finding scene across multiple jurisdictions with different health care systems. Understanding and addressing this worsened prognosis is therefore a clear public health priority. Hardie et al. recently published their data on 2183 patients, recruited in the Leeds Melanoma cohort between 2000 and 2012. They approved the documented risk factors for melanoma-specific survival as increased thickness of primary tumours, dependently associated with increased age, male sex, tumour in sunprotected sites and low Vitamin D. Interesting findings were that smoking and increased BMI were also independently associated with increased Breslow thickness, and conversely, higher alcohol consumption was protective. Nevertheless, they did not evaluate the sentinel status. They documented that smoking may be regarded as a strong independent risk factor for melanoma deaths in high immune response groups. Pozniak et al. observed a positive correlation between smoking and the expression of the GPR15 gene, which codes for a chemoattractant receptor that is regarded as a biomarker smoking known to be hypo-methylated and hence overexpressed in the circulating immune cells in smokers. On the other hand, in the case-controlled study performed, Sondermeijer et al. showed a strong inversed association between cigarette smoking and melanoma risk in men without any focus on the sentinel status. Other risk factors are long-term occupational exposure to ionising radiation at low dose rates on malignant skin neoplasms. However, in the study performed by Azizova et al., this correlation could not be observed for increasing rates of melanoma in a population of more than 20 000 individuals. In the current issue of the Journal of the European Academy of Dermatology, A. Tejera-Vaquerizo et al. addressed the question regarding an association between smoking and sentinel lymph node metastasis and survival in cutaneous melanoma. They used as a reliable statistical method the comprehensive examination with the propensity score matching to determine whether smoking is associated with a higher risk of SLN metastasis or worse prognosis in patients with cutaneous melanoma. This statistical method is highly approved and used in several other clinical relevant studies. In the study by Tejera-Vaquerizo, 762 patients were analysed and matched in three groups as pairs of smokers versus never smokers, pairs of smokers versus former smokers and pairs of former smokers versus current smokers. With this matching procedure, they could convincingly show in this cohort study that smoking is not associated with a higher rate of SLN metastasis or with worse survival in patients with cutaneous melanoma. However, as the authors stated, there are limitations regarding this study based on the observational study with a limited number that the smoking status was based on patients’ accounts. Nevertheless, these data are supported in a population-based, case-control study in which no association of smoking with melanoma-specific mortality was observed. In a large study performed by Jones et al. on the impact on sentinel node metastasis of primary cutaneous melanoma, current smoking was strongly associated with SLN metastases. Data for this analysis derived from MSLT-I trial and the screening phase of MSLT-II. They used as statistical method an univariable and multivariable analysis with current smoking and never smoking. Besides smoking other factors as age, Breslow thickness and ulceration were also associated with increased SLN positivity. However, they could not account alternative aetiologies of increased tumour thickness, ulceration and nodal metastasis. In future studies, clinical data basis should include more detailed quantitative smoking assessment, number of smoking years and time interval since quitting. As the general role of smoking regarding melanoma prognosis is unclear, smoking is associated in general with many types of postoperative complications in various types of surgery. In a recently published paper by Ona-Diana Persa et al. in a cohort of 615 patients, they identified smoking as an independent risk factor for seroma formation following sentinel node biopsy for the first time. In general, it is accepted by profound studies that the risk of developing melanoma is positively associated with socioeconomic status, supporting the notion that this group has greater exposure to lifestyle factors that increase melanoma incidence and are less likely to smoke. However, lower socioeconomic status is related to poor survival once melanoma is diagnosed. The