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Comparative Study
. 2025 Jul;93(1):73-81.
doi: 10.1016/j.jaad.2025.02.076. Epub 2025 Feb 28.

riSCC: A personalized risk model for the development of poor outcomes in cutaneous squamous cell carcinoma

Anokhi Jambusaria-Pahlajani  1 , Vincent Jeanselme  2 , David M Wang  3 , Nina A Ran  3 , Emily E Granger  4 , Javier Cañueto  5 , David G Brodland  6 , David R Carr  7 , Joi B Carter  8 , John A Carucci  9 , Kelsey E Hirotsu  10 , Emily E Karn  3 , Shlomo A Koyfman  11 , Aaron R Mangold  12 , Fabio Muradás Girardi  13 , Kathryn T Shahwan  7 , Divya Srivastava  14 , Allison T Vidimos  15 , Tyler J Willenbrink  6 , Ashley Wysong  16 , William Lotter  17 , Emily S Ruiz  18
Affiliations
Comparative Study

riSCC: A personalized risk model for the development of poor outcomes in cutaneous squamous cell carcinoma

Anokhi Jambusaria-Pahlajani et al. J Am Acad Dermatol. 2025 Jul.

Abstract

Background: Cutaneous squamous cell carcinoma (CSCC) is a prevalent disease for which improved risk stratification strategies are needed.

Objective: To develop a novel prognostic model (herein "riSCC") for CSCC and compare riSCC performance to Brigham and Women's Hospital and American Joint Committee on Cancer Staging eighth edition T staging systems.

Methods: Retrospective 12-center, multinational cohort study of CSCCs from 1991 to 2023. Clinical and pathologic risk factors, treatments, and outcomes were collected. Fine-Gray model was employed for each outcome with inverse probability of treatment weighting. A final model was trained for prospective use and estimation of hazard ratios.

Results: Twenty-three thousand one hundred sixty-six localized CSCC tumors were included. riSCC prognostic model performed superiorly to American Joint Committee on Cancer eighth edition and Brigham and Women's Hospital T staging for all outcomes. At 5 years, the C-index for riSCC ranged from 0.74 for local recurrence to 0.87 for disease specific death.

Limitations: Retrospective study design.

Conclusion: riSCC prognostic model offers fine-grained risk estimates and improved stratification for important CSCC outcomes compared to T staging systems.

Keywords: American Joint Committee on Cancer eighth edition; Brigham and Women's Hospital T Staging; Mohs micrographic surgery; cutaneous oncology; cutaneous squamous cell carcinoma; metastasis; nonmelanoma skin cancer; oncology; outcomes; recurrence.

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Conflict of interest statement

Conflicts of interest Dr Ruiz serves as a consultant for Regeneron Inc, Checkpoint Therapeutic, Feldan Pharmaceuticals, and Merck Pharmaceuticals. She serves as a Principal Investigator/Co-Investigator for the following companies: Regeneron (PI/Co-I), Merck (Co-I), and Castle Biosciences (PI/Co-I). She is on the Board of Directors of Skin Cancer Outcomes Consortium (SCOUT). Dr Carr is an Investigator for Regeneron, no direct funds. Dr Carucci reports Grants to institution: Sanofi/Regeneron, Castle-Biosciences; Lectures honoraria: Sanofi, Almirall, Abbvie, Regeneron, Sun Pharma; Payment for expert testimony: Sanofi, Regeneron, Almirall; Support for attending meetings: Pfizer, Almirall, Lilly, Castle-Biosciences; Advisory board: Almirall, Sanofi, Regeneron, Kyowa, Roche, InflaRx; Funding: support by the Gerencia Regional de Salud de Castilla y León (GRS2549/A/22) and by the Instituto de Salud Carlos III (PI21/01207), co-financed by European Union. Dr Mangold reports relevant disclosures and patent Methods and Materials for assessing and treating cutaneous squamous cell carcinoma (provisional PCT/US2023/078902) and Regeneron Consulting with payments to the institution. He has consulted for Phelecs BV, Kyowa, Eli Lilly, Momenta, UCB, and Regeneron in the past, more than 24 months ago. He has consulted for Incyte, Soligenix, Clarivate, Argenyx, and Bristol Myers Squibb in the past, less than 12 months ago. He currently consults for Nuvig, Tourmaline Bio, Janssen, and Boehringer Ingelheim. He currently consults for Pfizer with payments to the institution. He has grant support from Kyowa, Miragen, Regeneron, Corbus, Pfizer, Incyte, Eli Lilly, Argenx, Palvella, Abbvie, Priovant, and Merck in the last 24 months. Beyond 24 months, grant support has come from Sun Pharma, Elorac, Novartis, and Janssen. His current patents include Use of Oral Jaki in Lichen Planus- PCT/US2024/020149; and Topical Ruxolitinib in Lichen Planus- PCT/US2021/053149, 2023-520085, & 21805700.8, respectively. Dr Carucci receives funding for investigator-initiated basic science research from Regeneron and is a PI for a clinical trial sponsored by Regeneron. Dr Koyfman is on the Advisory board (paid): Merck, BMS, Regeneron, Galera therapeutics; Advisory board (unpaid): Castle Biosciences; Research support: Castle biosciences, Merck, BMS, Regeneron; Honoraria: UpToDate. Dr Vidimos receives Research Support – Castle; Advisory Board - Inhibitor Therapeutics; Honoraria - Up to Date. Dr Wysong receives institutional research grant from Castle Biosciences. Drs Granger, Ran, Girardi, Srivastava, Carter, Shahwan, Hirotsu, Brodland, Jeanselme, Lotter, Willenbrink, and Author Karn have no conflicts of interest to declare.