By: Dan Sperling, MD

Radiation therapy (beam or seeds) as a treatment for prostate cancer (PCa) is often recommended for two categories of patients:

• Elderly men who are not surgical candidates but have at least 10 years of life expectancy
• Younger men who don’t want surgery because they want to preserve potency.

The majority of clinical evidence suggests a cause-effect relationship between radiation treatment for prostate cancer and the development of secondary bladder cancer. Harvard Medical School’s bulletin Harvard Men’s Health Watch states, “Radiation therapy for prostate cancer appears to increase risk for bladder cancer years later.”[i] This is especially bad news for men, who are 3 times more likely than women to develop bladder cancer (also called urothelial bladder cancer or UBC). While many factors such as genetics and environmental toxins can cause UBC, it is thought that male hormones (androgens) also play a role in the onset of bladder tumors which may account for greater male vulnerability to the disease.

The period between delivery of therapeutic radiation and the onset of a radiation-induced cancer is called the latency period. The greater the dosage, the shorter the latency period. For low-dose radiation, it can take up to 30 years for a secondary cancer to develop, but for the high-dose radiation typically used to treat prostate cancer, it can range from 5-15 years.

Because radiation has a scatter effect, it is not possible to have precise control over it. When radiation is targeted to the prostate gland, nearby healthy tissues in the bladder and rectum are also exposed to a certain amount. Efforts to contain the toxic side effects of radiation have led to the development of different delivery systems with theoretically less scatter, such as Intensity Modulated Radiation Therapy (IMRT) and Three Dimensional Conformal Radiation Therapy (3D-CRT). However, even these more targeted forms of beam radiation increase the risk of developing bladder cancer. This is true for brachytherapy (seed implants) as well.

Bladder cancer that is secondary to prostate cancer radiation is different from bladder cancer that occurs due to other causes such as smoking or exposure to industrial toxins.[ii] It is also different from prostate cancer that spreads to the bladder (metastatic prostate cancer of the bladder). Radiation-induced UBC is more aggressive and more likely to be muscle-invasive. UBC occurs more frequently among radiation patients than patients who undergo prostatectomy (5-6% incidence for radiation vs. 3.7% for RP).[iii]

Although this seems to be a gloomy scenario, a new population-based study surprisingly found that PCa patients who received radiation had a reduced risk of developing UBC. The study by Hafez et al. (Yale University) was presented in a poster session at the 2016 Genitourinary Cancers Symposium (San Francisco, Jan. 7-9).[iv] The research team noted that in animal studies and research with PCa patients who had been on androgen deprivation therapy (ADT or hormone therapy) had a reduced incidence of UBC. Therefore, they analyzed over 100,000 records of prostate cancer patients in the national SEER-Medicare database. As hypothesized, men who were on ADT, or who received a combination of radiation therapy and ADT, had a reduced risk of developing UBC within 5 years of treatment. However, their analysis produced an unexpected finding of reduced risk for patients receiving radiation therapy alone. “The finding of decreased UBC incidence in patients receiving RT [radiation therapy] was surprising, and in direct contradiction to previous studies of similar patient populations,” according to Daniel P. Petrylak, MD, professor at Yale School of Medicine, and colleagues. “Possible explanations include differences in cohort selection, changes in RT delivery, and differences in control group.”[v]

In noting the “direct contradiction to previous studies,” the team urged that more research is needed. When the vast preponderance of scientific evidence points in one direction, it is impossible to explain how a single analysis reaches the opposite conclusion, but the quality of analysis in the poster presentation suggests the findings are more than a fluke. While this study may be a source of hope for PCa patients who have radiation therapy, it is wise to keep in mind that the majority of research on secondary UBC still suggests increased risk.

[i] http://www.health.harvard.edu/mens-health/bladder-cancer-men-at-risk

[ii] Sountoulides, P. Secondary malignancies following radiation for prostate cancer. Ther Adv Urol. 2010 Jun; 2(3): 119–125.

[iii] Moon K., Stukenborg G., Keim J., Theodorescu D. (2006) Cancer incidence after localized therapy for prostate cancer. Cancer 107: 991–998

[iv] Hafez N, Wang R, Hurwitz ME, Ma X, and Petrylak DP. The impact of androgen deprivation and pelvic radiation on development of bladder cancer. J Clin Oncol [suppl 2S; abstr 439].

[v] http://www.renalandurologynews.com/genitourinary-cancers-symposium/study-adt-radiotherapy-possibly-reduce-bladder-cancer-risk/article/463909/