Efficacy of immune checkpoint inhibitors in patients with xeroderma pigmentosum and advanced cutaneous squamous-cell carcinoma and literature review.

AIMS: Xeroderma pigmentosum (XP) is a disorder characterized by defective DNA repair, leading to the early development of cutaneous malignancies, including cutaneous squamous cell carcinomas (cSCC). The management of locally advanced and metastatic cSCC in XP patients is particularly challenging, primarily due to the risk of major surgical sequelae and the hazardous use of radiotherapy. This study aims to evaluate the efficacy and safety of anti-PD1 immunotherapy in XP patients with unresectable cSCC in Mayotte and Réunion Island and to conduct a literature review.

METHODS

This retrospective multicenter study included XP patients treated with anti-PD1 for advanced or metastatic inoperable cSCC between June 2023 and February 2025. The efficacy and safety of the treatment were assessed based on clinical, biological, and radiological data from patient records. A literature review of similar cases was also conducted.

RESULTS

Four XP patients, with a median age of 16 years, were treated with immunotherapy for cSCC or sarcomatoid carcinoma, achieving rapid and complete tumour regression in all cases. No major adverse effects were reported. The literature review identified 14 additional cases, including 7 complete responses and 6 partial responses.

CONCLUSION

Anti-PD1 therapy is effective in XP patients with advanced cSCC, offering a therapeutic alternative to surgery. These findings raise the question of earlier neoadjuvant initiation to reduce the risk of major surgical sequelae or prevent metastatic progression.