Optimizing Nonsurgical Management of Skin Tumors at Maui Derm 2026

During Maui Derm Hawaii 2026, a session on nonsurgical management of skin tumors and field cancerization delivered practical, experience-driven guidance on topical and intralesional chemotherapies, niacinamide safety, and real-world dosing strategies for 5-fluorouracil (5-FU) and methotrexate. Speakers emphasized tailoring treatment to patient risk, tolerability, and long-term disease burden, particularly in those with extensive actinic keratosis (AK) damage or recurrent keratinocyte cancers.¹

“If you follow an AK patient long enough—10 years—6% to 20% [of patients] will develop a squamous cell carcinoma,” Ted Rosen, MD, said in his presentation. “And that's why we treat AKs.”

Opening the discussion, Rosen, professor of dermatology at Baylor College of Medicine and chief of dermatology service at Michael E. DeBakey Veterans Affairs Medical Center, reviewed the expanding toolbox of topical and intralesional chemotherapies for skin tumors. While agents such as bleomycin and methotrexate remain viable intralesional options, Rosen made clear that 5-FU is his preferred choice. He described it as affordable, widely available, and typically used undiluted straight from the vial. Importantly, he noted that intralesional dosing for skin tumors is comparable to the doses used intravenously for gastrointestinal cancers, underscoring its potency despite its routine dermatologic use.

Chemoprevention and Niacinamide Safety

The conversation then turned to chemoprevention, particularly niacinamide, which has gained traction for reducing the risk of squamous cell carcinoma and managing field cancerization, citing a study that demonstrated that a brief course of calcipotriol combined with 5-FU on the face and scalp stimulates durable T-cell immunity against actinic keratoses and significantly reduces squamous cell carcinoma risk for up to 3 years.² George Martin, MD, of Dr. George Martin and Associates, brought up the commonly used dose of 300 mg twice daily and its appropriateness for patients with extensive actinic damage. Rosen clarified that niacinamide and nicotinamide are the same compound, but he cautioned that their safety profile is not uniform across all patients.¹

Rosen warned that niacinamide can impair uric acid excretion, creating problems for individuals prone to gout or uric acid kidney stones. Given this risk, he advised against niacinamide in patients with gout and recommended avoiding it in those with pseudo-gout, emphasizing that although pseudo-gout is mechanistically distinct, niacinamide is still not safe in this population. Patients with a history of uric acid kidney stones should similarly avoid the supplement, he said. Rosen noted that calcium oxalate stones are far more common overall, but gout and uric acid stones remain important contraindications that clinicians should actively screen for before prescribing niacinamide.

Dosing Strategies for Topical Chemotherapy

Dosing strategy and sequencing of topical chemotherapies was another focal point of the session. Martin asked about the optimal schedule for combining 5-FU and methotrexate, referencing a prior study in which patients applied 5-FU in the morning and methotrexate at night for 1 week, repeated 4 times. He also described his own chronic “immune surveillance” approach using methotrexate 5% applied for 1 week, then pausing to allow crusts to resolve. After that initial cycle, patients often continue treatment once weekly indefinitely, with escalation to 2 consecutive days per week if lesions persist.

Martin emphasized that responses to methotrexate are not uniform. Some patients respond briskly, while others show minimal improvement, a variability he suggested may be related to receptor expression or individual immunologic differences. This unpredictability, he noted, reinforces the need for close follow-up and willingness to adjust regimens over time.

Identifying Patients at Highest Risk for Squamous Cell Carcinoma

Chrysalyne D. Schmults, MD, MScE, FAAD, Howard and Wendy Cox Distinguished Chair in Dermatology and professor of dermatology at Harvard Medical School, emphasized that the patients most likely to develop dangerous cutaneous squamous cell carcinomas are those with a heavy lifetime burden of invasive disease. “People who’ve had 10 or more dermally invasive squamous cell cancers in their lifetime have almost a 40% risk of local recurrence…and a 26% risk of metastasis,” she said in the session.

Drawing on cohort study data, these “super–high-risk” patients are most often solid-organ transplant recipients or people with chronic lymphocytic leukemia, underscoring the role of chronic immunosuppression. In this population, Schmults stressed, each new squamous cell carcinoma must be treated as a high-risk lesion, warranting aggressive management and close surveillance rather than routine care.

Transforming Outcomes in Merkel Cell Carcinoma

Paul Nghiem, MD, PhD, board-certified physician at the Fred Hutchinson Cancer Center and founding chair of the University of Washington Department of Dermatology, underscored that outcomes in Merkel cell carcinoma have been fundamentally transformed by coordinated, modern care, particularly the use of immune checkpoint inhibitors. He contrasted historical approaches of surgery plus chemotherapy, which were associated with rapid relapse and a median progression of roughly 90 days after chemotherapy, with current strategies that incorporate baseline PET/CT staging, timely adjuvant radiation ideally within 8 weeks of surgery, and PD-1–based immunotherapy.

“For Merkel, it’s really different,” he explained. “One in 6 patients will have a radical upstage of their disease based on [baseline imaging]. That keeps you—if you know what’s going on—from overly aggressively treating the local disease or delaying systemic therapy.”

In the presented data, patients who received immunotherapy after progressing on chemotherapy achieved substantially better long-term outcomes, including meaningful 6-year survival, compared with almost no durable survival on additional chemotherapy.³ Nghiem emphasized that dermatologists play a central role in coordinating multidisciplinary care, thus ensuring imaging, surgery, radiation, and immunotherapy are thoughtfully integrated to maximize both survival and quality of life.¹

The Evolving Role of Dermatologists in Cutaneous Oncology

Taken together, these presentations underscore how quickly the management of cutaneous oncology is evolving and how central dermatologists are to that progress. From optimizing field therapies for actinic damage and leveraging combination topicals or PDT to rigorously staging and surgically managing high-risk squamous cell carcinoma to coordinating imaging, radiation, and immunotherapy for Merkel cell and other rare tumors, the speakers emphasized that nuanced, evidence-based decisions can substantially alter patients’ trajectories.

By embracing risk stratification tools, margin-controlled surgery, smarter use of systemic agents, and thoughtful long-term surveillance, dermatologists can not only reduce morbidity from recurrent procedures and toxic treatments, but also meaningfully improve survival for patients with the most aggressive forms of skin cancer.

References

1. Rosen T, Martin G, Ngheim P, Schmults C. Cutaneous oncology update 2026. Presented at: Maui Derm 2026; January 25-29, 2026; Maui, HI.
2. Rosenberg AR, Tabacchi M, Ngo KH, et al. Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. JCI Insight. 2019;4(6):e125476. doi:10.1172/jci.insight.125476
3. Alexander NA, Schaub SK, Goff PH, et al. Increased risk of recurrence and disease-specific death following delayed postoperative radiation for Merkel cell carcinoma. J Am Acad Dermatol. 2024;90(2):261-268. doi:10.1016/j.jaad.2023.07.1047