International Journal of Colorectal Disease

, Volume 33, Issue 9, pp 1149–1158 | Cite as

Risk of secondary rectal cancer and colon cancer after radiotherapy for prostate cancer: a meta-analysis

  • Zhiguo Zhu
  • Shankun Zhao
  • Yangzhou Liu
  • Jiamin Wang
  • Lianmin Luo
  • Ermao Li
  • Chaofeng Zhang
  • Jintai Luo
  • Zhigang ZhaoEmail author



To investigate whether radiotherapy for prostate cancer increases the risk of therapy-related rectal cancer and colon cancer.


A systematic literature search was carried out using the Medline (PubMed), EMBASE, and the Cochrane Library to identify studies examining the association between radiotherapy for prostate cancer and secondary colorectal cancer (rectal cancer and colon cancer) published before March 19, 2018. The risk of second colorectal cancer after radiotherapy was summarized using unadjusted odds ratio (OR) and adjusted hazard ratio (HR) with their 95% confidence interval (CI). Subgroup and sensitivity analyses were conducted to detect potential bias and heterogeneity.


After study selection, 16 reports were retrieved for analysis. When patients received radiotherapy compared with those unexposed to radiation, there was an increased risk of the rectal cancer (OR 1.37, 95%CI 1.01 to 1.85), but not colon cancer. According to adjusted HR, there was an increased risk of the rectal cancer (HR 1.64, 95%CI 1.39 to 1.94), and colon cancer (HR 1.33, 95%CI 1.02 to 1.76). The OR for rectal cancer showed an increased risk with longer latent period (5 years lag time versus 10 years lag time, OR: 1.56 versus 2.22). Brachytherapy had no association with second cancer across all analyses.


Radiotherapy was associated with an increased risk of subsequent rectal cancer compared with patients unexposed to radiation. Colon may be free from the damage of radiation. Brachytherapy had no association with second rectal cancer or colon cancer.


Prostatic neoplasms Radiotherapy Rectal neoplasms Colonic neoplasms Neoplasms Second primary 



This work was supported by the grants from National Natural Science Foundation of China (No. 81372774, No. 81572537 for Zhigang Zhao), The Key Program of Natural Science Foundation of Guangdong Province (No. 2015A030311007 for Zhigang Zhao), Yangcheng Scholar Project of Guangzhou Education Bureau (No. 12A014G for Zhigang Zhao), Science and Technology Program of Guangzhou (No. 201607010376 for Zhigang Zhao), and Science and Technology Planning Project of Guangdong Province (No.2017B030314108).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

For this type of study informed consent is not required.

Supplementary material

384_2018_3114_Fig7_ESM.png (84 kb)
Supplementary fig. 1

Begg’s and Egger’s tests to detect publication bias Footnotes: Rectal cancer: RT versus no-RT, 10 studies, Begg’s P > |z| = 0.152, Egger’s P > |t| = 0.634, 95%CI -3.34-2.16; RT: radiotherapy (PNG 84 kb)

384_2018_3114_MOESM3_ESM.tif (3.8 mb)
High resolution image (TIF 3938 kb)
384_2018_3114_MOESM1_ESM.doc (46 kb)
Supplementary table 1 Newcastle-Ottawa Scale assessment of the quality of the cohort studies (DOC 45 kb)
384_2018_3114_MOESM2_ESM.doc (36 kb)
Supplementary table 2 Search strategy (DOC 36 kb)


  1. 1.
    Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68(1):7–30.
  2. 2.
    Liu S, Yang L, Yuan Y, Li H, Tian J, Lu S, Wang N, Ji J (2018) Cancer incidence in Beijing, 2014. Chin J Cancer Res 30(1):13–20. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Shuryak I, Sachs RK, Brenner DJ (2010) Cancer risks after radiation exposure in middle age. J Natl Cancer Inst 102(21):1628–1636. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Fried DV, Das SK, Marks LB (2017) Imaging radiation-induced normal tissue injury to quantify regional dose response. Semin Radiat Oncol 27(4):325–331. %/ Copyright (c) 2017 Elsevier Inc. All rights reservedCrossRefPubMedGoogle Scholar
  5. 5.
    Robbins ME, Brunso-Bechtold JK, Peiffer AM, Tsien CI, Bailey JE, Marks LB (2012) Imaging radiation-induced normal tissue injury. Radiat Res 177(4):449–466CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Warkentin M, Hopkins JB, Badeau R, Mulichak AM, Keefe LJ, Thorne RE (2013) Global radiation damage: temperature dependence, time dependence and how to outrun it. J Synchrotron Radiat 20(Pt 1):7–13. CrossRefPubMedGoogle Scholar
  7. 7.
    Hegemann NS, Schlesinger-Raab A, Ganswindt U, Horl C, Combs SE, Holzel D, Gschwend JE, Stief C, Belka C, Engel J (2017) Risk of second cancer following radiotherapy for prostate cancer: a population-based analysis. Radiat Oncol 12(1):2. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Joung JY, Lim J, Oh CM, Jung KW, Cho H, Kim SH, Seo HK, Park WS, Chung J, Lee KH, Won YJ (2015) Risk of second primary cancer among prostate cancer patients in Korea: a population-based cohort study. PLoS One 10(10):e0140693. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Margel D, Baniel J, Wasserberg N, Bar-Chana M, Yossepowitch O (2011) Radiation therapy for prostate cancer increases the risk of subsequent rectal cancer. Ann Surg 254(6):947–950. CrossRefPubMedGoogle Scholar
  10. 10.
    Moon K, Stukenborg GJ, Keim J, Theodorescu D (2006) Cancer incidence after localized therapy for prostate cancer. Cancer 107(5):991–998. CrossRefPubMedGoogle Scholar
  11. 11.
    Hinnen KA, Schaapveld M, van Vulpen M, Battermann JJ, van der Poel H, van Oort IM, van Roermund JG, Monninkhof EM (2011) Prostate brachytherapy and second primary cancer risk: a competitive risk analysis. J Clin Oncol 29(34):4510–4515. CrossRefPubMedGoogle Scholar
  12. 12.
    Rapiti E, Fioretta G, Verkooijen HM, Zanetti R, Schmidlin F, Shubert H, Merglen A, Miralbell R, Bouchardy C (2008) Increased risk of colon cancer after external radiation therapy for prostate cancer. Int J Cancer 123(5):1141–1145. CrossRefPubMedGoogle Scholar
  13. 13.
    Lehnert BE, Goodwin EH, Deshpande A (1997) Extracellular factor(s) following exposure to alpha particles can cause sister chromatid exchanges in normal human cells. Cancer Res 57(11):2164–2171PubMedGoogle Scholar
  14. 14.
    Azzam EI, de Toledo SM, Gooding T, Little JB (1998) Intercellular communication is involved in the bystander regulation of gene expression in human cells exposed to very low fluences of alpha particles. Radiat Res 150(5):497–504CrossRefPubMedGoogle Scholar
  15. 15.
    Murray L, Henry A, Hoskin P, Siebert FA, Venselaar J (2014) Second primary cancers after radiation for prostate cancer: a systematic review of the clinical data and impact of treatment technique. Radiother Oncol 110(2):213–228. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Murray EM, Werner D, Greeff EA, Taylor DA (1999) Postradiation sarcomas: 20 cases and a literature review. Int J Radiat Oncol Biol Phys 45(4):951–961CrossRefPubMedGoogle Scholar
  17. 17.
    Wallis CJ, Mahar AL, Choo R, Herschorn S, Kodama RT, Shah PS, Danjoux C, Narod SA, Nam RK (2016) Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis. BMJ (Clin Res Ed) 352:i851Google Scholar
  18. 18.
    Fan CY, Huang WY, Lin CS, Su YF, Lo CH, Tsao CC, Liu MY, Lin CL, Kao CH (2017) Risk of second primary malignancies among patients with prostate cancer: a population-based cohort study. PLoS One 12(4):e0175217. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Bhojani N, Capitanio U, Suardi N, Jeldres C, Isbarn H, Shariat SF, Graefen M, Arjane P, Duclos A, Lattouf JB, Saad F, Valiquette L, Montorsi F, Perrotte P, Karakiewicz PI (2010) The rate of secondary malignancies after radical prostatectomy versus external beam radiation therapy for localized prostate cancer: a population-based study on 17,845 patients. Int J Radiat Oncol Biol Phys 76(2):342–348. CrossRefPubMedGoogle Scholar
  20. 20.
    Zelefsky MJ, Pei X, Teslova T, Kuk D, Magsanoc JM, Kollmeier M, Cox B, Zhang Z (2012) Secondary cancers after intensity-modulated radiotherapy, brachytherapy and radical prostatectomy for the treatment of prostate cancer: incidence and cause-specific survival outcomes according to the initial treatment intervention. BJU Int 110(11):1696–1701. CrossRefPubMedGoogle Scholar
  21. 21.
    Boorjian S, Cowan JE, Konety BR, DuChane J, Tewari A, Carroll PR, Kane CJ (2007) Bladder cancer incidence and risk factors in men with prostate cancer: results from Cancer of the Prostate Strategic Urologic Research Endeavor. J Urol 177(3):883–887; discussion 887-888. CrossRefPubMedGoogle Scholar
  22. 22.
    Baxter NN, Tepper JE, Durham SB, Rothenberger DA, Virnig BA (2005) Increased risk of rectal cancer after prostate radiation: a population-based study. Gastroenterology 128(4):819–824CrossRefPubMedGoogle Scholar
  23. 23.
    Berrington DGA, Curtis RE, Kry SF, Gilbert E, Lamart S, Berg CD, Stovall M, Ron E (2011) Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries. Lancet Oncol 12(4):353–360.
  24. 24.
    Nieder AM, Porter MP, Soloway MS (2008) Radiation therapy for prostate cancer increases subsequent risk of bladder and rectal cancer: a population based cohort study. J Urol 180(5):2005–2009; discussion 2009-2010. CrossRefPubMedGoogle Scholar
  25. 25.
    Davis EJ, Beebe-Dimmer JL, Yee CL, Cooney KA (2014) Risk of second primary tumors in men diagnosed with prostate cancer: a population-based cohort study. Cancer 120(17):2735–2741. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Neugut AI, Ahsan H, Robinson E, Ennis RD (1997) Bladder carcinoma and other second malignancies after radiotherapy for prostate carcinoma. Cancer 79(8):1600–1604CrossRefPubMedGoogle Scholar
  27. 27.
    Van Hemelrijck M, Feller A, Garmo H, Valeri F, Korol D, Dehler S, Rohrmann S (2014) Incidence of second malignancies for prostate cancer. PLoS One 9(7):e102596. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Jin T, Song T, Deng S, Wang K (2014) Radiation-induced secondary malignancy in prostate cancer: a systematic review and meta-analysis. Urol Int 93(3):279–288. %/ 2014 S. Karger AG, BaselCrossRefPubMedGoogle Scholar
  29. 29.
    Muller AC, Ganswindt U, Bamberg M, Belka C (2007) Risk of second malignancies after prostate irradiation? Strahlenther Onkol 183(11):605–609. CrossRefPubMedGoogle Scholar
  30. 30.
    Hall EJ, Wuu CS (2003) Radiation-induced second cancers: the impact of 3D-CRT and IMRT. Int J Radiat Oncol Biol Phys 56(1):83–88CrossRefPubMedGoogle Scholar
  31. 31.
    Bezak E, Takam R, Yeoh E, Marcu LG (2017) The risk of second primary cancers due to peripheral photon and neutron doses received during prostate cancer external beam radiation therapy. Phys Med 42:253–258. CrossRefPubMedGoogle Scholar
  32. 32.
    Murray LJ, Thompson CM, Lilley J, Cosgrove V, Franks K, Sebag-Montefiore D, Henry AM (2015) Radiation-induced second primary cancer risks from modern external beam radiotherapy for early prostate cancer: impact of stereotactic ablative radiotherapy (SABR), volumetric modulated arc therapy (VMAT) and flattening filter free (FFF) radiotherapy. Phys Med Biol 60(3):1237–1257. CrossRefPubMedGoogle Scholar
  33. 33.
    Murray L, Henry A, Hoskin P, Siebert FA, Venselaar J (2013) Second primary cancers after radiation for prostate cancer: a review of data from planning studies. Radiat Oncol 8:172. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Berrington de Gonzalez A, Wong J, Kleinerman R, Kim C, Morton L, Bekelman JE (2015) Risk of second cancers according to radiation therapy technique and modality in prostate cancer survivors. Int J Radiat Oncol Biol Phys 91(2):295–302. CrossRefPubMedGoogle Scholar
  35. 35.
    Travis LB, Demark WW, Allan JM, Wood ME, Ng AK (2013) Aetiology, genetics and prevention of secondary neoplasms in adult cancer survivors. Nat Rev Clin Oncol 10(5):289–301. CrossRefPubMedGoogle Scholar
  36. 36.
    Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, Henry AM, Joniau S, Lam TB, Mason MD, van der Poel HG, van der Kwast TH, Rouviere O, Wiegel T, Mottet N (2017) EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur Urol 71(4):630–642. CrossRefPubMedGoogle Scholar
  37. 37.
    Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, Fossati N, Gross T, Henry AM, Joniau S, Lam TB, Mason MD, Matveev VB, Moldovan PC, van den Bergh RCN, Van den Broeck T, van der Poel HG, van der Kwast TH, Rouviere O, Schoots IG, Wiegel T, Cornford P (2017) EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol 71(4):618–629. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Urology & Andrology, Minimally Invasive Surgery Center, Guangdong Provincial Key Laboratory of UrologyThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina

Personalised recommendations