Non-surgical therapies for localized non-melanoma skin cancer in older adults: A review.

Non-melanoma skin cancers (NMSCs) represent the most common malignancies in the United States, with a rapidly rising incidence that disproportionately affects older adults. While surgery remains the gold-standard treatment for NMSCs, an often-overlooked reality is that many affected older adults face a combination of comorbidities, cognitive impairment, functional limitations, and logistical barriers that make surgical treatment impractical or unrealistic. Accordingly, this review examines the role of non-surgical therapies (NSTs) as essential alternatives for older patients, highlighting their mechanisms, clinical utility, and older adult-specific considerations. Specifically, topical agents such as 5-fluorouracil, imiquimod, tirbanibulin, retinoids, and trichloroacetic acid offer effective, less-invasive options for superficial lesions but rely heavily on adherence, which may be compromised in cognitively impaired or functionally-limited individuals. Intralesional therapies (including 5-fluorouracil and methotrexate), on the other hand, provide high clearance rates with minimal systemic toxicity, while also reducing patient responsibility and daily application. Mechanical techniques like cryosurgery and electrodessication and curettage offer efficient, cost-effective treatments but require wound care that may be difficult for some older adults to manage. Photodynamic therapy and radiation modalities (SRT, IGSRT, brachytherapy, and EBRT) demonstrate strong short-term efficacy but may be limited by treatment-related discomfort of the need for multiple visits, posing challenges for those with transportation barriers. Importantly, systemic therapies such as hedgehog pathway inhibitors and PD-1 inhibitors are effective for advanced or inoperable disease, but carry significant toxicities and treatment burdens that limit their suitability for older patients, especially those with polypharmacy concerns. Furthermore, this review emphasizes that across all modalities, NST selection must prioritize geriatric principles, balancing efficacy with safety, comfort, functional status, cognitive capacity, support systems, and patient preferences. As the aging population grows and NMSC numbers expand in parallel, individualized, patient-centered care and expanded older adult-focused research are essential to optimizing treatment outcomes for older adults.