Men with a history of keratinocyte carcinoma are less likely to die of melanoma than those without this history, according to a study. The results highlight the importance of detecting skin cancer early to increase survival.


According to current data, melanoma is the most lethal of all common forms of skin cancer, and the disease ranks as the fifth most common cancer among men and sixth among women. While the incidence of melanoma has risen dramatically in recent years, the mortality rate associated with the disease has stabilized. Keratinocyte carcinoma (KC), which includes cutaneous basal cell carcinoma and squamous cell carcinoma, are the most commonly diagnosed non-melanoma skin cancers in the United States, representing about 3.5 million cases each year.

“People who get skin cancer tend to develop multiple forms of the disease during their lifetime,” explains Jiali Han, PhD, Professor and Chair of Epidemiology at the Richard M. Fairbanks School of Public Health of Indiana University and Professor of Cancer Research at the Melvin and Bren Simon Cancer Center. “Research has demonstrated an association between a personal history of KC with melanoma risk, but the association between KC and melanoma mortality has yet to be determined.” Studies are needed to establish if a history of KC increases risk for melanoma death and to find out if melanoma patients with a history of KC have poorer prognoses.


New Prospective Data

In a prospective analysis published in the Journal of the American Academy of Dermatology, Dr. Han and colleagues used data from the Health Professionals Follow-up Study to evaluate the risk of cutaneous melanoma (CM) death after KC in 908 subjects. “Our study found that individuals with invasive CM who had a personal history of KC had better survival than those without a history of KC,” says Dr. Han.

Among all participants, the risk for developing either lethal or nonlethal invasive CM was higher for those with a history of KC. The age-adjusted hazard ratio (HR) for developing a lethal melanoma among those with a history of KC was 1.63 when compared with those who had no such history, but the HR rose to 1.97 in a multivariate analysis. For the risk of nonlethal melanoma, the HRs for age-adjusted and multivariate-adjusted modeling were 1.70 and 1.61, respectively. In the melanoma case–only analysis, the study team found that a personal history of KC conferred an HR of 0.59 in the age-adjusted model. Multivariate modeling demonstrated an HR of 0.60 (Table).


Interpreting Data

The investigators noted that a history of KC may have a protective effect on melanoma death. They added that this may be explained by the fact that once patients have a KC, they are likely to see dermatologists more often and to undergo serial skin examinations more frequently. This means a diagnosis of CM is likely to be made earlier in the disease course, which in turn increases patients’ chances of having CMs that are diagnosed before tumors begin to metastasize. Findings from the study by Dr. Han and colleagues highlight the importance of early detection on skin cancer survival.

Additionally, melanomas that develop in patients with prior KC likely occur because they have similar pathways involving sun exposure. Some investigations have speculated that the inverse relationship between sun exposure and melanoma survival could be mediated by vitamin D status. “Studies are warranted to replicate our findings and investigate the mechanism underlying our observed inverse association,” Dr. Han says. “This includes gaining a better understanding of potential detection bias and how sun exposure relates to vitamin D status among KC patients. In the meantime, clinicians can use our study data to encourage and support greater vigilance for skin cancer screening. Information regarding a patient’s personal history of KC is relevant to making a prognosis for melanoma patients.”


Song F, Chen ST, Li X, Han J. Personal history of keratinocyte carcinoma is associated with reduced risk of death from invasive melanoma in men. J Am Acad Dermatol. 2018;78:957-963. Available at:

Song F, Qureshi AA, Giovannucci EL, et al. Risk of a second primary cancer after non-melanoma skin cancer in white men and women: a prospective cohort study. PLoS Med. 2013;10: e1001433.

Fang S, Sui D, Wang Y, et al. Association of vitamin D levels with outcome in patients with melanoma after adjustment for C-reactive protein. J Clin Oncol. 2016;34:1741-1747. Available at:

Wu S, Cho E, Li WQ, Qureshi AA. History of keratinocyte carcinoma and risk of melanoma: a prospective cohort study. J Natl Cancer Inst. 2017;109.