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. 2025 Aug 4;30(8):oyae326.
doi: 10.1093/oncolo/oyae326.

Squamous cell carcinoma arising in chronically damaged skin (Marjolin's Ulcer): still an unmet need in the era of immunotherapy

Mor Miodovnik  1 , Yardenna Dolev  1 , Roni Buchen  2 , Miriam Rivka Brezis  1 , Alla Nikolaevski-Berlin  1 , Inbar Finkel  1 , Ido Wolf  1   2 , Inna Ospovat  1 , Orit Gutfeld  1 , Yasmin Leshem  1   3
Affiliations

Squamous cell carcinoma arising in chronically damaged skin (Marjolin's Ulcer): still an unmet need in the era of immunotherapy

Mor Miodovnik et al. Oncologist. .

Abstract

Background: Cutaneous squamous cell carcinoma (cSCC) is characterized by a high tumor mutational burden due to solar damage and a favorable response to anti-PD-1 immunotherapy. Yet, we encounter tumors arising in areas with minimal sun exposure, such as cSCC that develops in chronically inflamed skin, also known as Marjolin's Ulcer (MU). The response of MU-SCC to immunotherapy remains unknown.

Methods: We performed a retrospective analysis of patients diagnosed with cSCC and treated with cemiplimab or pembrolizumab in a single tertiary medical center. Patients lost to follow up were excluded.

Results: Of the 84 eligible patients, 9 (11%) had MU-SCC. Of these, 2 (22%) reached partial response (PR), and none reached complete response (CR). In contrast, of the 75 patients with solar damage-related cSCC, 40 had PR (53%), and 20 had CR (26%). The difference between the two subtypes was significant (P < .001). Interestingly, 3 patients with MU-SCC received a second-line chemo-immunotherapy and experienced a partial response that continued for 5 to 21 months. Patients with MU-SCC had a significantly shorter median time to progression (TTP) (1.6 vs 51.6 months, P < .001) and progression-free survival (PFS) (1.6 vs 15.4 months, P < .001). Overall survival (OS) was not significantly shorter (17.4 vs 36.7 months, P = .096). Multivariate analysis confirmed that MU-SCC is an independent risk factor for shorter TTP (HR 5.5, 95% CI 2.2-14.0, P < .001) and PFS (HR 3.5, 95% CI 1.5-8.1, P = .003).

Conclusions: This study suggests that immunotherapy is less beneficial in SCC-MU. More work is needed to verify our findings and explore other treatment options.

Keywords: PD-1; cutaneous squamous cell carcinoma; immunotherapy; marjolin’s ulcer.

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Conflict of interest statement

All authors have no conflict of interest.

Figures

Figure 1.
Figure 1.
Kaplan-Meier curves for (A) time to progression (TTP), (B) progression-free survival (PFS), and (C) overall survival (OS) of patients with MU-SCC and non-MU cSCC receiving pembrolizumab or cemiplimab.
See this image and copyright information in PMC

Comment in

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