Is there an increased risk of second primaries following prostate irradiation?

Purpose/Objective: As radiotherapy is a standard therapeutic option for patients with prostate cancer, its possible role in the development of secondary cancers must be evaluated. Some urologists have raised this issue as a potential advantage of surgery over irradiation; this question is thus of particular relevance to patients faced with the choice of prostatectomy versus radiation. The purpose of this study is to assess the risk of developing a second primary cancer following prostate irradiation compared to the underlying risk in patients with prostate cancer. Materials and Methods: The baseline rate of secondary cancers following prostate cancer was obtained from a study of 18,135 patients from the Connecticut Tumor Registry (NCI Monograph 68: 139-147, 1985), of whom only 12.5% received radiotherapy as treatment of their prostate cancer. As these patients, with a mean age of 72, had been followed for a mean of 3.9 years, they were compared to a cohort of 543 patients (median age 70) with similar follow-up (median 3.8 years), all of whom were treated with definitive radiotherapy at a single institution. In order to determine if the risk of developing a second primary increased over time, the ratios of number of secondary cancers over the number of patients at risk were tabulated for the following time periods (<1 year, 1-4.9, 5-9.9, ≥10). The possible association between various co-variates (age, dose, palpation stage, field size, Gleason score, pretreatment PSA) and the development of a secondary cancer was assessed. Results: 1,053/18,135 patients (5.8%) in the Connecticut Tumor Registry developed a second primary cancer compared with 31/543 (5.7%) patients treated with prostate radiation (p=0.99). As shown in the Table below, the risk increases gradually over time, but is not significantly different, at any time period, between the two groups of patients. Of 75 irradiated patients who also received adjuvant hormonal therapy, 4% developed secondary cancers (p=.74). The distribution of the 31 secondary primaries in the irradiated group was as follows: 11 lung, 5 gastrointestinal, 4 bladder, 4 head and neck, 4 melanoma, 1 lymphoma, 1 AML, and 1 mesothelioma. Of these, 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<.001). Five of the 31 secondary cancers occurred within the radiation field (4 bladder, 1 colon), 4 within 3 yrs (3 within 1.3 yrs) and only 1 occurred 9 years after radiotherapy. No association was found between age (<60 vs. ≥60), dose (<7400 vs. ≥7400), palpation stage (<T2C vs. ≥T2C), field size (prostate vs. pelvic), Gleason score (2-6 vs. 7-10) or pretreatment PSA (<15 vs. ≥15) and the risk of developing a second primary. Of the 543 irradiated patients, there were 2.8% deaths due to a second primary, 10% from prostate cancer and 12% from intercurrent illness. 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 (<60) with localized disease (<T2C), who often must choose between surgery and radiation. The secondary cancers were not associated with radiation dose or field size; the vast majority occurred outside of the radiation field (84%) and/or within 3 years of radiotherapy (97%). Most of these patients had lifestyles with predisposing risk factors. As noted in other studies, patients with prostate cancer manifested a significantly increased risk of developing melanomas, suggesting that they may benefit from patient education and skin screening examinations