Second cancers following radiotherapy in prostate cancer patients in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial

INTRODUCTION AND OBJECTIVES:

An increased risk of second cancers has been observed after radiotherapy (RT) for the treatment of prostate cancer. The increase in bladder and rectal cancers is likely due to the direct effect of radiation. However, the explanation for an increase in cancers at sites far outside the radiation therapy field, particularly lung cancer, is less clear but may be due to confounding. We examined the association between RT and second cancers in PLCO and assessed the impact of adjusting for potential confounders such as smoking.

METHODS:

During 1993-2001, 76,685 men aged 55-74 years were randomized into the PLCO trial. For this study, men diagnosed with first primary prostate cancer and who had a baseline questionnaire, known treatment data and at least 30 days of follow-up post initial treatment were followed for a second cancer diagnosis (other than prostate cancer). Poisson regression models were used to estimate the risk of any second cancer diagnosis and site-specific cancers following initial prostate cancer treatment. The mean (SD) age at prostate cancer diagnosis was 68.7 (5.8) years; mean follow-up time was 6.0 (range 0.1-12.9) years.

RESULTS:

Of the 7479 men with prostate cancer, 43% were treated with RT, 37% underwent radical prostatectomy, 8% received primary hormone therapy and 12% received no definitive or other treatment. Men who received RT were slightly older than those who did not, but there were no differences in smoking history, co-morbidities, BMI or education. In total, 570 second cancers were diagnosed. The rate of second cancers was 15.5/1000 person-years in those treated with RT versus 11.4 in men not treated with RT [relative risk (RR =1.25, 95% CI 1.1-1.5). Men treated with RT had significantly increased risk of lung cancer (RR=1.6; 95% CI 1.1-2.4) compared to men not treated with RT, after adjusting for age, race, education, family history of cancer, COPD and smoking. The RRs for any second cancer and for lung cancer were greater 5+ years post-treatment (RR=1.6, 95%CI: 1.2-2.1 and RR=3.1, 95%CI: 1.7-5.7 respectively). The RRs for bladder cancer (RR=1.6, 95% CI.: 0.9-2.8) and colorectal cancer (RR=1.5, 95% CI.: 0.9-2.4) were non-significantly elevated.

CONCLUSIONS:

In PLCO, men treated with RT for prostate cancer had an increased risk of developing any second cancer compared to men who did not receive RT. This is the first study to examine these risks and control for potential confounding factors. The increased risk of lung cancer is intriguing and warrants further investigation given the frequency and fatality of this disease.