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Review
. 2016 Mar 2:352:i851.
doi: 10.1136/bmj.i851.

Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis

Christopher J D Wallis  1 , Alyson L Mahar  2 , Richard Choo  3 , Sender Herschorn  2 , Ronald T Kodama  2 , Prakesh S Shah  4 , Cyril Danjoux  5 , Steven A Narod  6 , Robert K Nam  7
Affiliations
Review

Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis

Christopher J D Wallis et al. BMJ. .

Abstract

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.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; no financial relationships with organizations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work. SH, RTK, SAN, and RKN were authors of one of the included studies.

Figures

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Fig 1 Search strategy and final included and excluded studies of secondary malignancies after radiotherapy for prostate cancer
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Fig 2 Risk of bladder cancer after any radiotherapy compared with no radiation in studies with no restriction to lag period, studies with five year lag period, and studies with 10 year lag period
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Fig 3 Risk of cancer after any radiotherapy compared with no radiation in studies reporting adjusted hazard ratios
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Fig 4 Risk of colorectal cancer after any radiotherapy compared with no radiation in studies with no restriction to lag period, studies with five year lag period, and studies with 10 year lag period
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Fig 5 Risk of rectal cancer after any radiotherapy compared with no radiation in studies with no restriction to lag period, studies with five year lag period, and studies with 10 year lag period
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