Excess mortality in radiotherapy-treated pituitary adenoma patients: 50-year follow-up

CONTEXT: We report the long-term survival and the causes of excess mortality in a cohort of pituitary adenoma (PA) patients treated with radiotherapy, with or without prior surgery at up to 50 years of follow-up. OBJECTIVE: To evaluate long-term survival and causes of excess mortality in patients with PAs treated with radiotherapy, with or without prior surgery, and to examine the relationship between treatment factors, particularly radiotherapy dose and mortality outcomes over extended follow-up. METHODS: 426 patients treated with radiotherapy at the Royal Marsden Hospital during 1962 and 1994 with or without prior surgery were followed up via the NHS Central Register to identify deaths and emigrations. Standardized mortality ratios (SMRs) and absolute excess risks (AERs) were calculated by comparing observed deaths with expected rates based on national age, sex, year, and period-specific mortality rates for England and Wales. RESULTS: 260 deaths were recorded compared to 144 expected (SMR 1.8; AER 140.7). The main contributors to excess mortality were cerebrovascular disease (SMR 4.9; AER 61.4), endocrine/metabolic disease (SMR 5.6), and mental and behavioral disorders (SMR 5.0). Both all-cause and cerebrovascular-specific mortality were associated with increasing radiotherapy dose and with the use of surgery. CONCLUSION: Patients with PAs treated with surgery and radiotherapy have an increased mortality compared to the general population, with the principal contributor cerebrovascular accident mortality. The observed dose-response suggests a potential relationship between radiotherapy and vascular morbidity. The findings highlight the need for long-term surveillance and proactive management of vascular risk factors and in patients requiring radiotherapy and avoiding excessive radiotherapy doses. Whether modern high-precision fractionated radiotherapy techniques reduce the risk of cerebrovascular morbidity and mortality requires long-term studies.