OBJECTIVE: To determine the association between exposure to radiotherapy for the 
treatment of prostate cancer and subsequent second malignancies (second primary 
cancers).
DESIGN: Systematic review and meta-analysis of observational studies.
DATA SOURCES: Medline and Embase up to 6 April 2015 with no restrictions on year 
or language.
STUDY SELECTION: Comparative studies assessing the risk of second malignancies 
in patients exposed or unexposed to radiotherapy in the course of treatment for 
prostate cancer were selected by two reviewers independently with any 
disagreement resolved by consensus.
DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted study 
characteristics and outcomes. Risk of bias was assessed with the 
Newcastle-Ottawa scale. Outcomes were synthesized with random effects models and 
Mantel-Haenszel weighting. Unadjusted odds ratios and multivariable adjusted 
hazard ratios, when available, were pooled.
MAIN OUTCOME MEASURES: Second cancers of the bladder, colorectal tract, rectum, 
lung, and hematologic system.
RESULTS: Of 3056 references retrieved, 21 studies were selected for analysis. 
Most included studies were large multi-institutional reports but had moderate 
risk of bias. The most common type of radiotherapy was external beam; 13 studies 
used patients treated with surgery as controls and eight used patients who did 
not undergo radiotherapy as controls. The length of follow-up among studies 
varied. There was increased risk of cancers of the bladder (four studies; 
adjusted hazard ratio 1.67, 95% confidence interval 1.55 to 1.80), colorectum 
(three studies; 1.79, 1.34 to 2.38), and rectum (three studies; 1.79, 1.34 to 
2.38), but not cancers of the hematologic system (one study; 1.64, 0.90 to 2.99) 
or lung (two studies; 1.45, 0.70 to 3.01), after radiotherapy compared with the 
risk in those unexposed to radiotherapy. The odds of a second cancer varied 
depending on type of radiotherapy: treatment with external beam radiotherapy was 
consistently associated with increased odds while brachytherapy was not. Among 
the patients who underwent radiotherapy, from individual studies, the highest 
absolute rates reported for bladder, colorectal, and rectal cancers were 3.8%, 
4.2%, and 1.2%, respectively, while the lowest reported rates were 0.1%, 0.3%, 
and 0.3%.
CONCLUSION: Radiotherapy for prostate cancer was associated with higher risks of 
developing second malignancies of the bladder, colon, and rectum compared with 
patients unexposed to radiotherapy, but the reported absolute rates were low. 
Further studies with longer follow-up are required to confirm these findings.