While response rates are impressive, several practical considerations apply:

*New lesion risk during treatment: xeroderma pigmentosum patients on anti-PD-1 therapy may develop new keratoacanthomas or squamous cell carcinoma in already photodamaged skin, thought to arise from immune activation combined with the underlying DNA repair defect. This is manageable but requires close dermatologic follow-up during treatment.
*No substitute for photoprotection: Immunotherapy treats existing malignancy as it does not reduce ongoing UV-driven mutation accumulation. Strict sun avoidance must continue throughout and after treatment.
*Small evidence base: Total published/reported xeroderma pigmentosum patients treated with immune checkpoint inhibitors remain in the dozens, not hundreds, so while trends are consistently positive, guidelines are based on case-level and cohort-level evidence rather than large trials.
*Multidisciplinary care is essential: Oncology, dermatology, ophthalmology, and (where relevant) neurology should coordinate, since xeroderma pigmentosum is a multisystem condition and cancer treatment decisions affect overall disease management.

ICI therapy should be considered specifically for XP patients with metastatic, unresectable, or recurrent skin cancers where surgery and radiation are no longer viable options.