Dr. Darrell Rigel Highlights Advances in Skin Cancer Care
Darrell S. Rigel, MD, MS, provided a comprehensive update on the rapidly evolving landscape of skin cancer diagnosis, treatment, and prognostication at the 2025 Fall Clinical Dermatology Conference. From novel genetic assays to refinements in field therapy and systemic strategies, Dr. Rigel’s talk covered exponential growth in research and innovation across basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma.
“Over 5 million cases of skin cancer are expected in the US this year,” Dr. Rigel said, citing a growing literature base with more than 2,700 new publications in the past year alone. “The sheer volume of data reflects the urgency and scale of this public health challenge.”
Historically, topical treatments for actinic keratoses (AKs) were evaluated over 25-cm² areas. However, Dr. Rigel discussed a recent pivotal study validating the use of tirbanibulin over a 107-cm² field, demonstrating comparable efficacy and adverse event profiles.
“This aligns with real-world usage and provides a more practical field therapy option,” he said.
He also addressed advancements in photodynamic therapy (PDT), highlighting newer protocols that allow simultaneous application and activation of the photosensitizer, significantly reducing patient pain without compromising efficacy.
Moving on to SCC, Dr. Rigel examined the limitations of traditional staging systems, including AJCC-8 and the Brigham and Women's Hospital (BWH) system. Both demonstrated low sensitivity in identifying high-risk lesions and showed subpar concordance, he said.
Newer tools such as the 40-gene expression profile (40-GEP) test offer significantly improved risk stratification. Unlike morphology-based staging, the 40-GEP test provides molecular-level insight, identifying Class 2B tumors with a 45.9% risk of metastasis, compared to just 14% using standard staging. Dr. Rigel noted that one in 18 SCC patients may harbor high-risk tumors that traditional systems fail to detect, and Class 2B patients also appear more likely to benefit from adjuvant radiation therapy (ART), supported by emerging data. This molecular approach enhances prognostic precision even in low-stage tumors, enabling earlier and more appropriate escalation of care.
Dr. Rigel cautioned that pathology reports indicating "SCC in situ with concern for invasion" should not be passively accepted. In one study, 1 in 12 cases labeled as in situ were later found to harbor invasive disease. He urged dermatologists to re-biopsy or re-review suspicious cases, particularly in high-risk locations or persistent lesions.
Mohs micrographic surgery continues to show superior outcomes over wide local excision for high-stage SCC, Dr. Rigel noted, and adjuvant therapy improves outcomes in advanced cutaneous SCC, based on recent trial data. Hedgehog inhibitors (HHIs) such as sonidegib and vismodegib remain central to managing advanced BCC. Among these, Dr. Rigel said, sonidegib appears to offer a more favorable adverse effect profile, including lower rates and delayed onset of muscle spasms and alopecia. HHIs are increasingly used in neoadjuvant settings, with evidence suggesting that early cessation following tumor clearance may be appropriate and effective.
Although incidence rates may appear flat due to earlier detection, Merkel cell carcinoma (MCC) remains aggressive. Key updates included pembrolizumab, a PD-1 inhibitor, emerging as a first-line therapy in advanced MCC; a novel serologic test measuring Merkel polyomavirus T-antigen antibodies correlating with prognosis and treatment response; and the increased risk of MCC patients for secondary malignancies warranting close surveillance.
Dr. Rigel noted that melanoma rates continue to climb, particularly among US women, where it is now the most common cancer. Though mortality declined briefly following the introduction of effective immunotherapies around 2010, incidence and deaths are again rising.
Dr. Rigel presented data from a recent study that correlated recurrence risk with patient-reported symptoms, such as appetite loss, lymphadenopathy, and shortness of breath. These insights may help identify patients who warrant earlier imaging or referral. He also revisited a landmark study from his early career showing that melanomas associated with nevi have worse prognoses—a finding still echoed in contemporary literature.
Melanoma in situ is not always benign, Dr. Rigel said. A 2024 review of 101 such cases revealed that 12% were later reclassified as invasive melanomas. Dr. Rigel emphasized the need for careful correlation of clinical and histologic findings, especially in ambiguous lesions.
He also addressed a long-standing debate: Is incisional biopsy acceptable in melanoma? Based on recent evidence, the answer is yes, he said. Wide excision does not compromise diagnostic accuracy or patient outcomes, making incisional biopsy a valid and often necessary tool for challenging or large lesions.
Skin cancer care is entering a precision era in which molecular diagnostics, field-wide therapies, and predictive modeling are augmenting clinical acumen. Dr. Rigel concluded that dermatologists are uniquely positioned to integrate these tools and improve early detection, risk assessment, and therapeutic outcomes.