The Journal of Urology
Volume 179, Issue 5, Supplement , Pages S12-S13, May 2008

Commentary on the Etiologic Relationship Between Prostate Radiation and Bladder Cancer: The Scourge for One is Poison for the Other

Department of Urology, Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California

Article Outline

 

The associations between malignancy and radiation exposure have been well documented since World War II and more recently through other nuclear disasters such as Chernobyl.1 Based on observations in patients treated for cervical cancer, radiation is a well recognized risk factor for the development of bladder cancer.2 There have been several population based studies documenting the increased risk of bladder cancer in patients receiving radiation therapy for prostate cancer,3, 4, 5 and more recent studies have further substantiated these earlier findings.6, 7, 8, 9, 10

Several observations have emerged from the aforementioned studies. 1) Patients receiving radiation therapy for prostate cancer appear to have a 2 to 4-fold higher risk of subsequently being diagnosed with bladder cancer, and this risk of developing bladder cancer appears to be further enhanced in smokers.7 2) The latency period for the diagnosis of bladder cancer is 4 to 5 years after prostate radiation. 3) The propensity for bladder cancer is more consistently observed in patients receiving external beam radiation than in those undergoing brachytherapy. 4) Patients with bladder cancer after prostate radiation tend to have higher grade tumors although not necessarily at higher stage. 5) Tumors with atypical histology and prostate invasion may also be noted with greater frequency in post radiation patients undergoing cystectomy after radiation.9 6) Lymphadenectomy appears to be limited by prior prostate radiation.6 7) Survival from bladder cancer appears to be worse in patients undergoing cystectomy following radiation for prostate cancer compared to those undergoing cystectomy without history of prostate radiation.6

The often cited preceding article by Chrouser et al describes results and conclusions that are in stark contrast with most other recently published studies on the same topic. As indicated in their discussion, the results are in concordance with those of 2 prior tumor registry based studies.11, 12 Both studies were published in 1985, and one included patients from 1932 to 1982 and the other included patients from 1943 to 1980. Given the huge variations in time horizons, changes in treatment patterns and case ascertainment among other factors, it is not clear that one can freely apply these findings from the 20th to the 21st century. Furthermore, at least 3 other registry based studies using more contemporary data directly contradict these findings.6, 7, 8, 9

Based on the overwhelming epidemiologic and biological evidence in the literature, it appears likely that radiation for prostate cancer is related to the subsequent development of bladder cancer.13 What may be in question is the magnitude of this risk and the absolute risk of bladder cancer in men receiving prostate radiation. The largely contrary findings of the study by Chrouser et al could perhaps be explained by 1) short median followup of 7.1 years given that median time to bladder cancer occurrence is 5 years after prostate radiation, 2) limited followup due to older patient age at the time of radiation therapy, 3) lack of a true comparison cohort to establish risk relative to therapy (eg radiation vs surgery) and 4) reporting errors. This last factor is suggested by the fact that limiting the analysis of adjuvant radiation to patients in the local geographic area (presumably with better followup) converted an insignificant association between prostate radiation and risk of bladder cancer to a statistically significant association. Although the study by Chrouser et al did not demonstrate an association between prostate radiation and bladder cancer overall, it did confirm that in the subset of patients receiving adjuvant radiation postoperatively there was a 5-fold higher risk of subsequent bladder cancer.

Based on a broad overview of the literature, one must conclude that there is an association between prostate radiation and bladder cancer, and it behooves us to keep this in mind when counseling patients regarding prostate cancer therapy as well evaluating them after radiation therapy. The problem may manifest itself to a greater degree in the future with a larger number of younger men now receiving brachytherapy. It also serves as a cautionary note to temper the rush towards more lucrative, radiation based approaches to prostate cancer treatment such as intensity modulated radiation therapy rather than surgery or active surveillance. The scourge of one is poison for the other.

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References 

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  2. Boice JD, Day NE, Andersen A, Brinton LA, Brown R, Choi NW, et al. Second cancers following radiation treatment for cervical cancer (An international collaboration among cancer registries). J Natl Cancer Inst. 1985;74:955
  3. Neugut AI, Ahsan H, Robinson E, Ennis RD. Bladder carcinoma and other second malignancies after radiotherapy for prostate carcinoma. Cancer. 1997;79:1600
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  8. Liauw SL, Sylvester JE, Morris CG, Blasko JC, Grimm PD. Second malignancies after prostate brachytherapy: incidence of bladder and colorectal cancers in patients with 15 years of potential follow-up. Int J Radiat Oncol Biol Phys. 2006;66:669
  9. Shah SK, Lui PD, Baldwin DD, Ruckle HC. Urothelial carcinoma after external beam radiation therapy for prostate cancer. J Urol. 2006;175:2063
  10. Sandhu JS, Vickers AJ, Bochner B, Donat SM, Herr HW, Dalbagni G. Clinical characteristics of bladder cancer in patients previously treated with radiation for prostate cancer. BJU Int. 2006;98:59
  11. Kleinerman RA, Liebermann JV, Li FP. Second cancer following cancer of the male genital system in Connecticut, 1935-1982. Natl Cancer Inst Monogr. 1985;68:139
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PII: S0022-5347(08)00549-1

doi:10.1016/j.juro.2008.03.007

The Journal of Urology
Volume 179, Issue 5, Supplement , Pages S12-S13, May 2008

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