Miodovnik Mor, Dolev Yardenna, Buchen Roni, Brezis Miriam Rivka, Nikolaevski-Berlin Alla, Finkel Inbar, Wolf Ido, Ospovat Inna, Gutfeld Orit, Leshem Yasmin
Oncology Division, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Oncologist. 2025 Aug 4;30(8). doi: 10.1093/oncolo/oyae326.
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.
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.
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).
This study suggests that immunotherapy is less beneficial in SCC-MU. More work is needed to verify our findings and explore other treatment options.
皮肤鳞状细胞癌（cSCC）因日光损伤而具有高肿瘤突变负荷，且对抗程序性死亡蛋白1（PD-1）免疫疗法反应良好。然而，我们遇到了一些在阳光暴露极少的部位发生的肿瘤，比如在慢性炎症皮肤中发生的cSCC，也称为马乔林溃疡（MU）。MU-SCC对免疫疗法的反应尚不清楚。
我们对在一家单一的三级医疗中心被诊断为cSCC并接受西米普利单抗或帕博利珠单抗治疗的患者进行了回顾性分析。失访患者被排除。
在84例符合条件的患者中，9例（11%）患有MU-SCC。其中，2例（22%）达到部分缓解（PR），无患者达到完全缓解（CR）。相比之下，在75例与日光损伤相关的cSCC患者中，40例有PR（53%），20例有CR（26%）。两种亚型之间的差异具有统计学意义（P <.001）。有趣的是，3例MU-SCC患者接受了二线化学免疫疗法并经历了持续5至21个月的部分缓解。MU-SCC患者的中位疾病进展时间（TTP）明显更短（1.6个月对51.6个月，P <.001），无进展生存期（PFS）也明显更短（1.6个月对15.4个月，P <.001）。总生存期（OS）没有明显更短（17.4个月对36.7个月，P =.096）。多因素分析证实，MU-SCC是TTP更短（风险比[HR] 5.5，95%置信区间[CI] 2.2 - 14.0，P <.001）和PFS更短（HR 3.5，95% CI 1.5 - 8.1，P =.003）的独立危险因素。
本研究表明免疫疗法对MU-SCC的益处较小。需要更多研究来验证我们的发现并探索其他治疗选择。
