Study: Older Patients With Actinic Keratoses at Increased Risk of Skin Cancer

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Patients enrolled in the study had substantial absolute risks and elevated relative risks, suggesting that AKs may be a clinical marker of UV exposure and increased skin cancer risk.

Key Takeaways:

  1. High Skin Cancer Risk in Patients with Actinic Keratoses (AKs): The study, which is based on a large Medicare claims dataset, finds that patients with AKs have an increased risk of developing various skin cancers, including keratinocyte carcinoma (KC), squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma.
  2. Dose-Response Relationship and Burden of AKs: The analysis indicates a dose-response relationship, with a higher burden of AKs associated with a statistically significant increased risk of any skin cancer, KC, and melanoma compared to those with a lower burden of AKs, emphasizing the importance of considering the severity of AKs when assessing skin cancer risk.
  3. AKs as Potential Markers of UV Exposure: The study authors suggest that AKs may serve as potential markers of cumulative UV exposure, leading to an increased risk of skin cancer. Despite AKs not being direct precursors to these cancers, the elevated risks of SCC, BCC, and melanoma in patients with AKs highlight the significance of AKs and indicating heightened skin cancer risks.

Actinic keratoses (AKs) are common pre-malignant skin lesions that occur in older individuals with considerable UV exposure and have a small risk of progressing to cutaneous squamous cell carcinoma (SCC). Although there is prior evidence suggesting that patients with AKs have an increased risk of skin cancers other than SCC, the absolute risks of skin cancer in patients with AKs are not known. Using a large Medicare claims data set, a study published in JAMA Dermatology investigated the absolute and relative risks of future skin cancer in Medicare beneficiaries with AKs.

The retrospective cohort study used a de-identified, random sample of nearly 5 million fee-for-service Medicare beneficiaries from 2009 to 2018. The investigators calculated the absolute risks of skin cancer overall, keratinocyte carcinoma (KC), and melanoma in beneficiaries with AKs. In addition, the risks of basal cell carcinoma (BCC) and SCC compared with beneficiaries with SKs were calculated.

Outcomes included first surgically treated skin cancer including KC, SCC, BCC, and melanoma. In a dose-response analysis with adjustments made for competing risk regression of skin cancer overall, KC, and melanoma, investigators compared dose-response from beneficiaries with a higher burden of AKs compared to those with a lower burden of AKs.

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Burden category was determined based on the year following AK diagnosis. Beneficiaries were considered to have a higher burden if they had at least 1 encounter with an AK destruction code for more than 15 lesions or at least 2 encounters with potential field treatment topical medication or photodynamic therapy, or at least 3 encounters with AK destruction codes for 12 to 14 lesions. Further, all other beneficiaries with AK were considered to have a lower burden. Follow-up occurred 1 year following the first AK diagnosis.

A total of 555,945 patients with AKs were enrolled in the study, including patients with seborrheic keratoses (SKs) as a comparative group. Patients were required to have at least 1 year between data set entry and their first AK or SK, and patients who had a previous history of skin cancer, HIV, or solid organ transplant were excluded from the study.

The absolute risk of any skin cancer among beneficiaries after a first AK was approximately 6.3% (95% CI, 6.3%-6.4%) at 1 year, 18.4% (95% CI, 18.3%-18.5%) at 3 years, and 28.5% (95% CI, 28.4%-28.7%) at 5 years. In addition, beneficiaries with AKs had an increased risk of any skin cancer (aHR, 2.17; 95% CI, 2.15-2.19), KC (aHR, 2.20; 95% CI, 2.18-2.22), SCC (aHR, 2.63; 95% CI, 2.59-2.66), BCC (aHR, 1.85; 95% CI, 1.82-1.87), and melanoma (aHR, 1.67; 95% CI, 1.60-1.73). The propensity score-weighted analysis presented similar results among skin cancers; however, the time-varying AK status analysis had found higher risks (any skin cancer: aHR, 3.09; 95% CI, 3.05-3.13), and the adjusted dermatology encounters analysis found similar results (any skin cancer: aHR, 2.12; 95% CI, 2.10-2.14).

A total of 77,453 beneficiaries with AKs were considered higher burden and 478,592 were lower burden. In a dose-response analysis, a higher burden of AKs were associated with a statistically significant increased risk of any skin cancer (aHR, 1.74; 95% CI, 1.71-1.76), KC (aHR, 1.63; 95% CI, 1.63-1.64) and melanoma (aHR, 1.48; 95% CI, 1.41-1.54) compared to those with a lower burden of AKs.

Approximately 1 in 4 patients included in the study had a skin cancer diagnosis within a 5-year follow-up period. In addition, higher risks of SCC, BCC, and melanoma were present, despite AKs not being biologic precursors to melanoma or BCC. According to the investigators, this could be an indication that AKs may be a marker of UV exposures that result in increased risks of skin cancer.

The investigators note that a study limitation is the limited population for the analyses, and that further research is needed in younger patients with AKs. In addition, they acknowledge that surveillance bias through increased screening is a potential explanation for the increased skin cancer risk in patients with AKs; however, the researchers made attempts to minimize this by placing patients with SKs as the comparator group and making adjustments for dermatology encounters in the sensitivity analysis. Further, the AK and SK beneficiary groups had demographic differences; however, similar results in a propensity score-weighted analysis were found.

Although AKs can be valuable in indicating skin cancer risk, such as SCC, BCC, and melanoma, further efforts to develop evidence-based recommendations for skin cancer surveillance in patients with AKs are necessary, according to the study authors. Further, future research can evaluate younger patients with AKs and their risk for skin cancer.

Reference

Mohr C, Li Y, Navsaria LJ, et al. Skin Cancers in Medicare Beneficiaries With Actinic Keratoses. JAMA Dermatol. Published online November 08, 2023. doi:10.1001/jamadermatol.2023.4266

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