Side Effects

Risk of Fracture after Androgen Deprivation for Prostate Cancer

New England Journal of Medicine 352(2):154-164, January 13 2005
Vahakn B Shahinian, Yong-Fang Kuo, Jean L Freeman and James S Goodwin

Study purpose: In order to sustain itself and grow, prostate cancer needs testosterone, a male sex hormone or androgen secreted by a man’s testicles and adrenal gland. Androgen-deprivation therapy uses testosterone-blocking medications to stop the growth of cancer cells, easing symptoms and delaying the disease’s development. For this reason, it is used to treat many patients with a diagnosis of advanced prostate cancer. However, the therapy is also linked to a loss of bone-mineral density and the risk of breaking a bone after treatment. This American meta-analysis looks at fracture rates and hospital stays for broken bones among prostate cancer patients treated with androgen-deprivation therapy.

Study description: A meta-analysis is a statistical method that combines different study results in order to re-examine all the data together. The medical records of 50,613 men who received a prostate cancer diagnosis between 1992 and 1997 were retrieved for study from Medicare and the linked database of the U.S. Surveillance, Epidemiology, and End Results program. The analyses were adjusted for the characteristics of the prostate cancer and the patient, other treatment for cancer, and whether patients had broken a bone or had a diagnosis of osteoporosis in the year before they found out they had cancer.

Findings: In men alive five years after a prostate cancer diagnosis, 19.4% who had received androgen-deprivation therapy had fractures as compared with 12.6% who had suffered fractures without having therapy. Crucially, there was a link between the number of doses of a specific testosterone-blocking medication (gonadotropin-releasing hormone) given during the year after cancer diagnosis and the later risk of fracture.

Conclusions: The meta-analysis concludes that androgen-deprivation therapy for prostate cancer increases the risk of fracturing a bone.

Meta-analysis of rates of erectile function after treatment of localized prostate carcinoma

International Journal of Radiation Oncology, Biology, Physics 54(4):1063-1068, November 15 2002
J W Robinson, S Moritz and T Fung

Study purpose: Prostate cancer and its treatment often impair a man’s ability to have an erection. This meta-analysis updates the results of a 1997 meta-analysis of erectile function rates in men with prostate cancer after treatment with ERBT or external beam radiotherapy (radiation directed throughout the body by machine) and radical prostatectomy (surgery to remove a cancerous prostate). A meta-analysis is a statistical method that combines study results in order to re-examine overall evidence.

Study description: Using studies published in the interim, the 2002 meta-analysis takes the original 1997 overview a step further. It evaluates erectile function rates after standard and nerve-sparing radical prostatectomy, external beam radiotherapy, and brachytherapy (radiation-emitting pellets implanted in the prostate) with or without external beam therapy. It also looks at erectile function after cryotherapy, the use of liquid nitrogen probes guided by ultrasound to freeze the prostate to extremely low temperatures that kill all tissue, including cancerous portions. Patients studied all had “localized” prostate cancer contained within the prostate gland.

Findings: Overall pooled results from the meta-analysis showed that the predicted probability of maintaining erectile function after brachytherapy was 0.76, after brachytherapy and EBRT 0.60, after EBRT alone 0.55, after nerve-sparing radical prostatectomy 0.34, after standard radical prostatectomy 0.25, and after cryotherapy 0.13. When studies that followed patients for more than two years were considered, the only change was a decline in erectile function for men who had undergone nerve-sparing radical prostatectomy. However, no brachytherapy studies had a follow-up period of more than two years. When overall odds were adjusted for the age of patients, the differences between the radiotherapy methods and surgical approaches was greater, with surgery showing a greater benefit.

Conclusions: Differences in the chances of maintaining erectile function after different treatments for localized prostate cancer are statistically important.

Note: In real terms, all of these treatments have a negative impact on a man’s ability to have an erection.

Variations in Morbidity after Radical Prostatectomy

New England Journal of Medicine 346(15):1138-1144, April 11 2002
Colin B Begg, Elyn R Riedel, Peter B Bach, Michael W Kattan, Deborah Schrag, Joan L Warren and Peter T Scardino

Study purpose: Recent studies of cancer surgery have shown that patients have varying experiences afterwards because of differences between hospitals as well as surgeons. This meta-analysis looks at surgery-related health issues experienced by men who underwent radical prostatectomy, an operation to remove a cancerous prostate gland. A meta-analysis is a statistical method that combines the results of a number of studies.

Study description: The authors used the U.S. Surveillance, Epidemiology, and End Results-Medicare database to look at patients’ surgery-related health issues after radical prostatectomy. The analysis examines various negative effects from radical prostatectomy, such as complications after surgery, serious difficulties urinating experienced a month to a year afterwards, and long-term incontinence continuing more than one year after the operation. The rate of these negative effects was inferred from the Medicare claims records of 11,522 patients who had undergone prostatectomies between 1992 and 1996. The rates were analyzed in relation to the number of radical prostatectomies performed at individual hospitals (“hospital volume”), and by individual surgeons (“surgeon volume”).

Findings: Neither hospital volume nor surgeon volume was linked to surgery-related death. However, important trends in the link between numbers of operations performed and patients’ surgery-related health issues were seen in complications after surgery and long-term urinary complications. Problems after surgery were lower in “high volume” hospitals with many surgeries than in “low-volume” hospitals with fewer surgeries (27% vs. 32%). There were also fewer problems when a “very high volume” surgeon performed the prostatectomy: 32% of the patients of “low volume” surgeons had complications after their surgeries, versus 26% of patients operated on by the very-high-volume surgeons. The rates of late urinary complications followed a similar pattern. Results for preserving continence over the long term were less clear-cut.

Conclusions: In men undergoing prostatectomy, the rates of urinary complications and other complications after surgery are lessened if the operation is performed in a “high volume” hospital by a surgeon who does many of these procedures.