Study Explores Gender Differences in Pediatric Melanoma

Doug Brunk

July 08, 2022

INDIANAPOLIS – Among children and adolescents diagnosed with melanoma, females had higher rates of superficial spreading disease, while males were more frequently affected by nodular melanoma.

In addition, male gender was independently associated with increased mortality, but age was not.

Those are key findings from a retrospective cohort analysis of nearly 5,000 records from the National Cancer Database.

Dr Rebecca Thiede

"There are multiple studies from primarily adult populations showing females with melanoma have a different presentation and better outcomes than males," co-first author Rebecca M. Thiede, MD, a dermatologist at the University of Arizona College of Medicne – Tucson, said in an interview with this news organization in advance of the annual meeting of the Society for Pediatric Dermatology, where the abstract was presented during a poster session.

"However, because melanoma is so rare in younger patients, little is known about gender differences in presentation and survival in pediatric and adolescent patients. To our knowledge, this is one of the largest studies to date in this population, and the first to explore gender differences in detail in pediatric and adolescent patients with melanoma."

Working with co-first author Sabrina Dahak, a fourth-year medical student at the University of Arizona College of Medicine – Phoenix, Thiede and colleagues retrospectively analyzed the National Cancer Database to identify biopsy-confirmed invasive primary cutaneous melanoma cases diagnosed in patients 0-21 years of age between 2004 and 2018.

The search yielded 4,645 cases, and the researchers used American Academy of Pediatrics definitions to categorize the patients by age, from infancy (birth to 2 years), to childhood (3-10 years), early adolescence (11-14 years), middle adolescence (15-17 years), and late adolescence (18-21 years). They used the Kaplan Meier analysis to determine overall survival and multivariate Cox regression to determine independent survival predictors.

Of the 4,645 pediatric melanoma cases, 63.4% were in females and 36.6% were in males, a difference that was significant (P < .001). Thiede and colleagues also observed a significant relationship between primary site and gender (P < .001). Primary sites included the trunk (34.3% of females vs. 32.9% of males, respectively), head and neck (16.4% vs. 30.9%), upper extremities (19.5% vs. 16%), lower extremities (27.9% vs. 16.5%), and "unspecified" (1.9% vs. 3.7%).

Females had higher rates of superficial spreading melanoma while males were affected by nodular melanoma more often. For example, the median Breslow depth was higher for males (1.05 mm; interquartile range [IQR] 0.50-2.31) than for females (0.80 mm; IQR, 0.40-1.67; P < .001).

Although females accounted for a higher percentage of cases than males overall, from birth to 17 years, a higher percentage of males than females were found to have later stage of melanoma at time of diagnosis: Females were more likely to be diagnosed with stage I disease (67.8%) than were males (53.6%), and males were more likely than were females to be diagnosed with stages II (15.9% vs. 12.3%), III (27.1% vs. 18.3%), and IV disease (3.3% vs. 1.6%; P < .001 for all).

In other findings, the 5- and 10-year overall survival rates were higher for females (95.9% and 93.9%, respectively) than for males (92.0% vs. 86.7%, respectively; P < .001). However, by age group, overall survival rates were similar between females and males among infants, children, and those in early adolescence – but not for those in middle adolescence (96.7% vs. 91.9%; P < .001) or late adolescence (95.7% vs. 90.4%; P < .001).

When the researchers adjusted for confounding variables, male gender was independently associated with an increased risk of death (adjusted hazard ratio 1.37; P < .001), but age was not.

"It was particularly surprising to see that even at such a young age, there is a significant difference in overall survival between males and females, where females have better outcomes than males," Thiede said. "When examining pediatric and adolescent patients, it is essential to maintain cutaneous melanoma on the differential," she advised. "It is important for clinicians to perform a thorough exam at annual visits particularly for those at high risk for melanoma to catch this rare but potentially devastating diagnosis."

She acknowledged certain limitations of the study, including its reliance on one database, "as comparing multiple databases would strengthen the conclusions," she said. "There was some missing data present in our dataset, and a large percentage of the histologic subtypes were unspecified, both of which are common issues with cancer registries. An additional limitation is related to the low death rates in adolescent and pediatric patients, which may impact the analysis related to survival and independent predictors of survival."

Dr Carrie Coughlin

Asked to comment on the study results, Carrie C. Coughlin, MD, who directs the section of pediatric dermatology Washington University/St. Louis Children's Hospital, said that the finding that males were more likely to present with stage II or higher disease compared with females "could be related to their finding that females had more superficial spreading melanomas, whereas males had more nodular melanoma." Those differences "could influence how providers evaluate melanocytic lesions in children," she added.

Coughlin, who directs the pediatric dermatology fellowship at Washington University/St. Louis Children's Hospital, said it was "interesting" that the authors found no association between older age and an increased risk of death. "It would be helpful to have more data about melanoma subtype, including information about Spitz or Spitzoid melanomas," she said. "Also, knowing the distribution of melanoma across the age categories could provide more insight into their data."

Dahak received an award from the National Cancer Institute to fund travel for presentation of this study at the SPD meeting. No other financial conflicts were reported by the researchers. Coughlin is on the board of the Pediatric Dermatology Research Alliance (PeDRA) and the International Immunosuppression and Transplant Skin Cancer Collaborative.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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