Is There an Increased Risk of Second Primaries Following Prostate Irradiation?

Abstract

Purpose: To assess the risk of developing a second primary cancer following prostate irradiation compared to the underlying risk in patients with prostate cancer. Methods and Materials: The baseline rate of secondary cancers following prostate cancer was obtained from a study of 18,135 patients from the Connecticut Tumor Registry, of whom only 12.5% received radiotherapy. These patients, with a mean age of 72 and a mean follow-up of 3.9 years, were compared to a cohort of 543 patients (median age 70) with similar follow-up (median 3.9 years), all of whom were treated with definitive radiotherapy at Fox Chase Cancer Center. The possible association between various covariates (age, dose, palpation stage, field size, Gleason score, pretreatment PSA) and the development of a secondary cancer was assessed. Results: 1,053 of 18,135 patients (5.8%) in the Connecticut Tumor Registry developed a second primary cancer compared with 31 of 543 (5.7%) patients treated with prostate radiation ( p = 0.99). Although this risk increases gradually over time, it is not significantly different, at any time period, between the two groups of patients. Of the 31 secondary primaries in the irradiated group, 82% had a history of tobacco and/or alcohol use. Only melanomas were significantly increased compared to the expected rate in an age-matched population ( p <0.001). Five of the 31 secondary cancers occurred within the radiation field (four bladder, one colon), four within 3 years and only one occurred 9 years after radiotherapy. No association was found between age (<70 vs. ≥70 and as a continuous variable), dose (<74 vs. ≥74 Gy), palpation stage (<T2C vs. ≥T2C), field size (prostate vs. pelvic), radiation technique (conventional vs. conformal), Gleason score (2–6 vs. 7–10), or pretreatment PSA (<15 vs. ≥15 and as a continuous variable) and the risk of developing a second primary. Although a lower radiation dose (as a continuous variable) correlated with an increased risk of developing a secondary cancer ( p = 0.04), this phenomenon is likely due to differences in follow-up time. Conclusion: Up to at least 10 years, there is no increased risk of developing a second primary cancer following prostate irradiation compared to the baseline rate from prostate cancer itself. This risk is not higher in younger patients with localized disease (<T2C), who often must choose between surgery and radiation. The vast majority of secondary cancers occurred outside of the radiation field (84%) and/or within 3 years of radiotherapy (97%), suggesting they were not caused by radiation. Most of these patients had lifestyles with predisposing risk factors. Patients with prostate cancer manifested a significantly increased risk of developing melanomas, suggesting that they may benefit from patient education and skin screening examinations.