Objective: To investigate the risk of radiation-induced secondary malignancy in patients with prostate cancer. Methods: We identified 690 references from PubMed, Embase and the Cochrane Library before August 1, 2012, that reported secondary malignancy in patients with prostate cancer after receiving radiation therapy (RT), and finally four studies were included. We calculated summary estimates using random-effects meta-analysis. Results: The overall standardized incidence ratio (SIR) of secondary malignancy in patients with prostate cancer receiving RT to the general population was 1.14 (95% CI 1.04-1.32). In the subgroup analysis, no increment in radiation-induced secondary malignancy risk was detected. In terms of SIR with different follow-up intervals, there was no difference in SIR (>6 months; <5 years) (SIR = 1.19, 95% CI 0.75-1.89) and SIR (>5 years; <10 years) (SIR = 1.39, 95% CI 0.87-2.23). When the follow-up extended to >10 years, a significantly increased secondary malignancy risk was observed (SIR = 1.45, 95% CI 1.23-1.72). There is no significantly increased secondary malignancy risk in patients receiving no RT. Conclusion: RT is associated with increased secondary malignancy in patients with prostate cancer; this effect only become conspicuous more than 10 years after treatment.

Keywords:
Radiation therapy, Prostate cancer, Secondary malignancy
1.
Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300.
2.
Mettlin CJ, Murphy GP, Rosenthal DS, Menck HR: The National Cancer Data Base report on prostate carcinoma after the peak in incidence rates in the U.S. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 1998;83:1679-1684.
3.
Cooperberg MR, Moul JW, Carroll PR: The changing face of prostate cancer. J Clin Oncol 2005;23:8146-8151.
4.
Speight JL, Roach M 3rd: Radiotherapy in the management of clinically localized prostate cancer: evolving standards, consensus, controversies and new directions. J Clin Oncol 2005;23:8176-8185.
5.
Brodak M, Kosina J, Holub L, Louda M, Odrazka K, Dolezel M, Sefrová J, Jansa J, Pacovsky J: Radical prostatectomy in high-grade prostate cancer, salvage and adjuvant radiotherapy. Urol Int 2011;86:146-151.
6.
Suzuki K, Nakano K, Morita T: Outcome of adjuvant radiotherapy after radical prostatectomy for prostate cancer patients. Urol Int 2010;84:382-387.
7.
Brenner H: Long-term survival rates of cancer patients achieved by the end of the 20th century: a period analysis. Lancet 2002;360:1131-1135.
8.
Thompson DE, Mabuchi K, Ron E, Soda M, Tokunaga M, Ochikubo S, Sugimoto S, Ikeda T, Terasaki M, Izumi S, et al: Cancer incidence in atomic bomb survivors. Part II: Solid tumors, 1958-1987. Radiat Res 1994;137(suppl 2):S17-S67.
9.
Neugut AI, Ahsan H, Robinson E, Ennis RD: Bladder carcinoma and other second malignancies after radiotherapy for prostate carcinoma. Cancer 1997;79:1600-1604.
10.
Heidenreich A, Aus G, Bolla M, Joniau S, Matveev VB, Schmid HP, Zattoni F: EAU guidelines on prostate cancer. Eur Urol 2008;53:68-80.
11.
Barre C: Open radical retropubic prostatectomy. Eur Urol 2007;52:71-80.
12.
Capitanio U, Scattoni V, Freschi M, Briganti A, Salonia A, Gallina A, Colombo R, Karakiewicz PI, Rigatti P, Montorsi F: Radical prostatectomy for incidental (stage T1a-T1b) prostate cancer: analysis of predictors for residual disease and biochemical recurrence. Eur Urol 2008;54:118-125.
13.
Moon K, Stukenborg GJ, Keim J, Theodorescu D: Cancer incidence after localized therapy for prostate cancer. Cancer 2006;107:991-998.
14.
Kendal W, Eapen L, Nicholas G: Second primary cancers after prostatic irradiation: ensuring an appropriate analysis. Cancer 2007;109:164; author reply 165.
15.
Huang J, Kestin LL, Ye H, Wallace M, Martinez AA, Vicini FA: Analysis of second malignancies after modern radiotherapy versus prostatectomy for localized prostate cancer. Radiother Oncol 2011;98:81-86.
16.
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: 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 2010;76:342-348.
17.
Hinnen KA, Schaapveld M, van Vulpen M, Battermann JJ, van der Poel H, van Oort IM, van Roermund JG, Monninkhof EM: Prostate brachytherapy and second primary cancer risk: a competitive risk analysis. J Clin Oncol 2011;29:4510-4515.
18.
Huo D, Hetzel JT, Roy H, Rubin DT: Association of colorectal cancer and prostate cancer and impact of radiation therapy. Cancer Epidemiol Biomarkers Prev 2009;18:1979-1985.
19.
Margel D, Baniel J, Wasserberg N, Bar-Chana M, Yossepowitch O: Radiation therapy for prostate cancer increases the risk of subsequent rectal cancer. Ann Surg 2011;254:947-950.
20.
Rapiti E, Fioretta G, Verkooijen HM, Zanetti R, Schmidlin F, Shubert H, Merglen A, Miralbell R, Bouchardy C: Increased risk of colon cancer after external radiation therapy for prostate cancer. Int J Cancer 2008;123:1141-1145.
21.
Nieder AM, Porter MP, Soloway MS: Radiation therapy for prostate cancer increases subsequent risk of bladder and rectal cancer: a population based cohort study. J Urol 2008;180:2005-2009; discussion 2009-2010.
22.
Greenberg RS, Rustin ED, Clark WS: Risk of genitourinary malignancies after cancer of the prostate. Cancer 1988;61:396-401.
23.
Liskow AS, Neugut AI, Benson M, Olsson CA, Birkhoff J, Chang CH: Multiple primary neoplasms in association with prostate cancer in black and white patients. Cancer 1987;59:380-384.
24.
Pandha HS, Waxman J: Multiple primary cancers in association with prostate cancer. Cancer Surv 1995;23:235-246.
25.
Kleinerman RA, Liebermann JV, Li FP: Second cancer following cancer of the male genital system in Connecticut, 1935-82. Natl Cancer Inst Monogr 1985;68:139-147.
26.
Osterlind A, Rorth M, Prener A: Second cancer following cancer of the male genital system in Denmark, 1943-80. Natl Cancer Inst Monogr 1985;68:341-347.
27.
Baxter NN, Tepper JE, Durham SB, Rothenberger DA, Virnig BA: Increased risk of rectal cancer after prostate radiation: a population-based study. Gastroenterology 2005;128:819-824.
28.
Brenner DJ, Curtis RE, Hall EJ, Ron E: Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery. Cancer 2000;88:398-406.
29.
Kendal WS, Eapen L, Macrae R, Malone S, Nicholas G: Prostatic irradiation is not associated with any measurable increase in the risk of subsequent rectal cancer. Int J Radiat Oncol Biol Phys 2006;65:661-668.
30.
Bhatia S, Sklar C: Second cancers in survivors of childhood cancer. Nat Rev Cancer 2002;2:124-132.
31.
Sountoulides P, Koletsas N, Kikidakis D, Paschalidis K, Sofikitis N: Secondary malignancies following radiotherapy for prostate cancer. Ther Adv Urol 2010;2:119-125.
32.
Chrouser K, Leibovich B, Bergstralh E, Zincke H, Blute M: Bladder cancer risk following primary and adjuvant external beam radiation for prostate cancer. J Urol 2005;174:107-110; discussion 110-111.
33.
Johnstone PA, Powell CR, Riffenburgh R, Rohde DC, Kane CJ: Second primary malignancies in T1-3N0 prostate cancer patients treated with radiation therapy with 10-year followup. J Urol 1998;159:946-949.
34.
Movsas B, Hanlon AL, Pinover W, Hanks GE: Is there an increased risk of second primaries following prostate irradiation? Int J Radiat Oncol Biol Phys 1998;41:251-255.
35.
Pickles T, Phillips N: The risk of second malignancy in men with prostate cancer treated with or without radiation in British Columbia, 1984-2000. Radiother Oncol 2002;65:145-151.
36.
Chen Z, Mostafavi HS, Shevrin DH, Morgan R, Vye MV, Stone JF, Sandberg AA: A case of therapy-related extramedullary acute promyelocytic leukemia. Cancer Genet Cytogenet 1996;86:29-30.
37.
Audet JF, Ruiz L, Sèbe P, Totobenazsara JL, Paule B, Lagrange JL, Abbou CC, de la Taille A: Neoplasms induced by radiotherapy for prostate cancer: report of a case of pelvic sarcoma and review of the literature (in French). Prog Urol 2004;14:420-422.
38.
Miro AG, De Seta L, Lizza N, Kartheuser A, Detry R: Malignant fibrous histiocytoma after radiation therapy for prostate cancer: case report. J Chemother 1997;9:162.
39.
Jao SW, Beart RW Jr, Reiman HM, Gunderson LL, Ilstrup DM: Colon and anorectal cancer after pelvic irradiation. Dis Colon Rectum 1987;30:953-958.
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2014
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