We investigated the clinical course and causes of death in patients who underwent permanent iodine-125 seed brachytherapy (hereafter referred to as seed brachytherapy) for prostate cancer, with a particular focus on radiation-induced malignancies and adverse events associated with hormonal therapy.

A retrospective analysis was conducted on 1,516 patients who underwent seed brachytherapy at Showa Medical University Hospital and Showa Medical University Koto Toyosu Hospital between January 2005 and March 2021. Causes of death were analyzed, and the distribution of cancer-related and non-cancer-related deaths was compared with national data from the 2022 Vital Statistics by the Ministry of Health, Labour and Welfare and the Cancer Statistics from the National Cancer Center. At the time of treatment, the mean age of the patients was 70 years (range: 41–88). According to the NCCN classification, 446 (29%) were low-risk, 628 (41%) intermediate-risk, 392 (26%) high-risk, 28 (2%) very high-risk, and 18 (2%) were classified as other (e.g., N+ or M+).

During a median follow-up period of 84 months (range: 1–231), there were 23 deaths from prostate cancer (2%) and 198 deaths from other causes (13%). Among non-prostate cancer deaths, the leading causes were other malignancies in 73 cases (37%), cardiovascular disease in 34 cases (17%), pneumonia in 24 cases (12%), aspiration pneumonia in 13 cases (7%), senility in 11 cases (6%), and other causes in 43 cases (21%). Compared with national statistics, the proportion of malignancy-related deaths was higher (37% vs. 24.6%), while the proportion of cardiovascular deaths (17%) was similar to the national average (14.8%). There was no significant difference in cardiovascular mortality between patients who received hormonal therapy and those who did not. Among malignancies, lung cancer was most common (18 cases, 25%), followed by pancreatic cancer (9 cases, 12%), gastric cancer (8 cases, 11%), colorectal cancer (6 cases, 8%), and malignant lymphoma (5 cases, 7%). Bladder cancer was observed in 2 cases (3%), similar to general trends, but there were 2 rare cases of anal canal cancer (3%). Hematologic malignancies, including lymphoma, leukemia, and multiple myeloma, were observed in 10 cases (14%), indicating a higher tendency than in general population statistics.

Long-term follow-up after seed brachytherapy demonstrated excellent oncological outcomes, with a very low prostate cancer-specific mortality. However, a few cases raised suspicion of radiation-induced secondary malignancies, highlighting the need for further investigation to clarify the true incidence of such events.