Subsequent Anal Malignancies In Patients With Prostate Adenocarcinoma Treated With Brachytherapy Or External Beam Radiotherapy Compared With Surgery

Abstract

It is important to understand the potential long-term sequelae of treatment of prostate adenocarcinoma, as patients are being diagnosed at a younger age and surviving longer. The risk of subsequent malignancies after brachytherapy (BT) has been reported to be low due to the limited exposure of normal tissue to radiation given the rapid dose fall off. However, our clinical experience suggested an increased risk of subsequent anal malignancy in patients receiving prostate BT. This risk may have implications for post-treatment surveillance. Therefore, we sought to compare the risk of subsequent anal malignancy after BT or external beam radiotherapy (EBRT) compared to surgery for prostate adenocarcinoma. Data regarding the rate of incidence from the Surveillance, Epidemiology, and End Results Program cancer registry (1988–2016) were used to directly compare subsequent anal malignancy risk in men with prostate adenocarcinoma treated with BT or EBRT versus surgery alone using two-sided Poisson exact rate ratio tests. We also compared risks in patients whose follow up time since prostate cancer diagnosis was ≥ 5 years. The year 1988 represents the first year in which radiotherapy modality (EBRT versus BT) was reported. Directly comparing the risks in each radiotherapy group with the surgery group helps to avoid problems associated with underreporting subsequent malignancies. Subsequent anal malignancies developed in 12 of 25,011 men with prostate adenocarcinoma who received BT, 28 of 65,353 who underwent EBRT, and 10 of 85,868 men who underwent surgery. BT was associated with a statistically significant increase in the risk of subsequent anal cancer (rate ratio (RR) 3.83 [95% confidence interval (CI): 1.52, 9.90] relative to surgery; P = 0.004). EBRT for prostate adenocarcinoma was also associated with a statistically significant increase in the risk of subsequent anal cancer (RR 3.39 [95 % CI: 1.60, 7.81] relative to surgery; P < 0.001). Among patients whose follow up time since prostate cancer diagnosis was ≥ 5 years, EBRT was not associated with an increased risk of subsequent anal cancer (RR 2.66 [95% CI: 0.87, 9.64] relative to surgery; P = 0.09); however, BT was associated with a statistically significant increase in the risk of subsequent anal cancer (RR 5.03 (95% CI: 1.45 – 19.53) relative to surgery; P = 0.009). Both BT and EBRT for prostate adenocarcinoma were associated with a statistically significant enhancement in the risk of subsequent anal cancers. While subsequent anal cancers occurred rarely, the increased risk of subsequent anal cancers after prostate BT, especially in those with follow up ≥ 5 years after prostate cancer diagnosis, may have implications for surveillance after treatment.