Malignancy risk and mortality after lung transplantation: a single institution experience over 31 years

Background Malignancy is a long-term complication of lung transplantation (LTx); however, contemporary Australian data and detailed evaluation of non-reportable cancers are lacking. Methods Retrospective review of LTx recipients’ medical records and registry data linkage were performed to identify histologically proven malignancies. Baseline clinico-demographic variables were collected, and cancer incidence was compared with reported data for the general Australian population. Results There were 1,715 LTx in 1,631 patients between 1989-2021, with a follow-up of 9,696 person-years. 893 (54.8%) patients were male, and the median age at first LTx was 54.7 years. There were 886 deaths with a median overall survival of 7.5 years (95% CI 6.8-8.3 years). 1,774 separate invasive cancer events occurred across 407 patients, of which, 1,588 (89.5%) were non-melanoma skin cancers (NMSCs). This translated to a 9-fold increased incidence of NMSCs, and a 4-fold increased incidence of other cancers compared with the general population. Cancer mortality reached parity with chronic lung allograft dysfunction ten years post-first transplant, and was independently associated with age (HR per year increase in age 1.02 [95% CI 1.01-1.03], p=0.001), EBV primary mismatch (HR 3.24 [95% CI 1.68-6.25], versus non-mismatch, p=0.002) and cancer count (HR per cancer event 1.19 [95% CI 1.13-1.24], p<0.0001), but was not associated with a pre-transplant malignancy history. Conclusions Our 31-year single-center experience demonstrates that malignancies are a significant mortality burden to long-term LTx survivors, dominated by NMSCs that are poorly reported in cancer datasets. A history of pre-transplant malignancy was associated with shorter time to post-transplant malignancy, but was not associated with cancer death.