Malignancy after lung transplantation: Understanding risk and navigating treatment

Malignancy has become a major limitation to long-term survival after lung transplantation. Its risk is shaped by recipient susceptibility, transplant anatomy, oncogenic viruses, long-term immunosuppression, and drug exposure. This narrative review integrates epidemiological, mechanistic, and clinical evidence and proposes a management framework spanning pre-transplant assessment, post-transplant surveillance, and treatment after cancer diagnosis. Lung cancer arises predominantly in the retained native lung after single-lung transplantation; early detection and curative treatment are central to improving outcomes. Keratinocyte carcinoma is common and recurrent, requiring coordinated dermatological surveillance, preventive treatment, and review of relevant drug exposures. Post-transplant lymphoproliferative disorder (PTLD) is closely linked to impaired Epstein-Barr virus (EBV) immune control. High-risk recipients warrant longitudinal viral monitoring, but diagnosis still requires histopathology, and treatment is based on reduced immunosuppression and response-adapted rituximab-based strategies. After cancer diagnosis, immunosuppression should be reconfigured according to tumour lethality, allograft reserve, and rejection risk, while coordinating anticancer therapy with allograft protection. Biomarkers may support monitoring, antibody-drug conjugates may expand treatment options, and immune checkpoint inhibitors may cause fatal allograft injury. Future work should use prospective registries and auditable pathways to evaluate cancer control and allograft outcomes together.