Meta-Analysis

. 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 Wallis¹, Alyson L Mahar², Richard Choo³, Sender Herschorn², Ronald T Kodama², Prakesh S Shah⁴, Cyril Danjoux⁵, Steven A Narod⁶, Robert K Nam⁷

Affiliations

¹ Division of Urology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Room MG-406, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada Institute of Health Policy, Management and Evaluation, University of Toronto, Suite 425, 155 College Street, Toronto, ON M5T 3M6, Canada.
² Division of Urology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Room MG-406, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.
³ Department of Radiation Oncology, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55902, USA.
⁴ Institute of Health Policy, Management and Evaluation, University of Toronto, Suite 425, 155 College Street, Toronto, ON M5T 3M6, Canada Department of Pediatrics, Mount Sinai Hospital, University of Toronto, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
⁵ Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Room MG-406, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.
⁶ Department of Public Health Sciences, University of Toronto, 7th floor, 790 Bay Street, Toronto, ON M5G 1N8, Canada.
⁷ Division of Urology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Room MG-406, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada Robert.nam@utoronto.ca.

PMID: 26936410
PMCID: PMC4775870
DOI: 10.1136/bmj.i851

Meta-Analysis

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

Christopher J D Wallis et al. BMJ. 2016.

. 2016 Mar 2:352:i851.

doi: 10.1136/bmj.i851.

Authors

Christopher J D Wallis¹, Alyson L Mahar², Richard Choo³, Sender Herschorn², Ronald T Kodama², Prakesh S Shah⁴, Cyril Danjoux⁵, Steven A Narod⁶, Robert K Nam⁷

Affiliations

¹ Division of Urology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Room MG-406, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada Institute of Health Policy, Management and Evaluation, University of Toronto, Suite 425, 155 College Street, Toronto, ON M5T 3M6, Canada.
² Division of Urology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Room MG-406, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.
³ Department of Radiation Oncology, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55902, USA.
⁴ Institute of Health Policy, Management and Evaluation, University of Toronto, Suite 425, 155 College Street, Toronto, ON M5T 3M6, Canada Department of Pediatrics, Mount Sinai Hospital, University of Toronto, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
⁵ Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Room MG-406, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.
⁶ Department of Public Health Sciences, University of Toronto, 7th floor, 790 Bay Street, Toronto, ON M5G 1N8, Canada.
⁷ Division of Urology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Room MG-406, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada Robert.nam@utoronto.ca.

PMID: 26936410
PMCID: PMC4775870
DOI: 10.1136/bmj.i851

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.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PubMed Disclaimer

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

None — **Fig 1** Search strategy and final included and excluded studies of secondary malignancies after radiotherapy for prostate cancer

See this image and copyright information in PMC

Comment in

A (relatively) risky business: the link between prostatic radiotherapy and second malignancies.
Eyler CE, Zietman AL. Eyler CE, et al. BMJ. 2016 Mar 2;352:i1073. doi: 10.1136/bmj.i1073. BMJ. 2016. PMID: 26935234 Free PMC article.

Cited by

Endoplasmic Reticulum Stress and Tumor Microenvironment in Bladder Cancer: The Missing Link.
Nie Z, Chen M, Wen X, Gao Y, Huang D, Cao H, Peng Y, Guo N, Ni J, Zhang S. Nie Z, et al. Front Cell Dev Biol. 2021 May 31;9:683940. doi: 10.3389/fcell.2021.683940. eCollection 2021. Front Cell Dev Biol. 2021. PMID: 34136492 Free PMC article. Review.
High prevalence of secondary bladder cancer in men on radiotherapy for prostate cancer: evidence from a meta-analysis.
Zhao S, Xie Q, Yang R, Wang J, Zhang C, Luo L, Zhu Z, Liu Y, Li E, Zhao Z. Zhao S, et al. Cancer Manag Res. 2019 Jan 10;11:587-598. doi: 10.2147/CMAR.S185867. eCollection 2019. Cancer Manag Res. 2019. PMID: 30666156 Free PMC article. Review.
Androgen deprivation therapy for prostate cancer and the risk of hematologic disorders.
Liu JM, Liu YP, Chuang HC, Wu CT, Su YL, Hsu RJ. Liu JM, et al. PLoS One. 2020 Feb 19;15(2):e0229263. doi: 10.1371/journal.pone.0229263. eCollection 2020. PLoS One. 2020. PMID: 32074125 Free PMC article.
Second primary cancers among males with a first primary prostate cancer: a population-based study in Northern Portugal.
Taveira-Barbosa J, Morais S, Garcia T, Bento MJ, Lunet N. Taveira-Barbosa J, et al. Clin Exp Med. 2025 Apr 21;25(1):122. doi: 10.1007/s10238-025-01654-7. Clin Exp Med. 2025. PMID: 40257697 Free PMC article.
Radiation-induced sarcoma after radiation therapy for prostate adenocarcinoma.
Wakabayashi K, Konishi K, Komatsu T, Ishiba R, Ota N, Ito T, Aki R, Tsuchida T, Miyake H, Nakamura K. Wakabayashi K, et al. IJU Case Rep. 2019 Feb 24;2(2):98-101. doi: 10.1002/iju5.12052. eCollection 2019 Mar. IJU Case Rep. 2019. PMID: 32743384 Free PMC article.

See all "Cited by" articles

References

1. Heidenreich A, Bastian PJ, Bellmunt J, et al. European Association of Urology. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol 2014;65:124-37. 10.1016/j.eururo.2013.09.046. 24207135. - DOI - PubMed
1. Potosky AL, Davis WW, Hoffman RM, et al. Five-year outcomes after prostatectomy or radiotherapy for prostate cancer: the prostate cancer outcomes study. J Natl Cancer Inst 2004;96:1358-67. 10.1093/jnci/djh259. 15367568. - DOI - PubMed
1. Resnick MJ, Koyama T, Fan KH, et al. Long-term functional outcomes after treatment for localized prostate cancer. N Engl J Med 2013;368:436-45. 10.1056/NEJMoa1209978. 23363497. - DOI - PMC - PubMed
1. Wallis CJ, Cheung P, Herschorn S, et al. Complications following surgery with or without radiotherapy or radiotherapy alone for prostate cancer. Br J Cancer 2015;112:977-82. 10.1038/bjc.2015.54. 25688739. - DOI - PMC - PubMed
1. Wallis CJ, Herschorn S, Saskin R, et al. Complications after radical prostatectomy or radiotherapy for prostate cancer: results of a population-based, propensity score-matched analysis. Urology 2015;85:621-7. 10.1016/j.urology.2014.11.037. 25733275. - DOI - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

Canadian Institutes of Health Research/Canada

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

Similar articles

Cited by

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Miscellaneous