Prostate Cancer Treatments – Increased Risk of Hip Fracture

AUA: Pelvic Radiation Boosts Hip Fracture Risk in Men

By Charles Bankhead, Staff Writer, MedPage Today

May 30, 2010


SAN FRANCISCO — External beam radiation therapy (EBRT) for prostate cancer increased the risk of hip fracture by almost 70% compared with radical prostatectomy, according to a study reported here.

The hip fracture risk doubled in men treated with EBRT plus androgen suppression therapy, but remained below the risk associated with hormonal therapy alone.

The risk of fragility fractures outside the radiation field did not increase with EBRT, supporting an association between pelvic radiation and hip fracture, according to Sean Elliott, MD, of the University of Minnesota in Minneapolis.

“The cumulative incidence of hip fracture in elderly prostate cancer patients was 10% at 10 years,” Elliott said at the American Urological Association meeting.

“External beam radiation therapy increases the risk of hip but not wrist fracture versus radical prostatectomy. EBRT plus androgen suppression therapy appears to be protective versus androgen suppression alone,” he continued.

More than half of prostate cancer patients receive radiation therapy, according to data from Medicare and the Surveillance, Epidemiology and End Results program. In about a third of cases, conventional EBRT is employed, and another 20% or so receive intensity-modulated radiation therapy, said Elliott. Additionally, EBRT plus androgen suppression therapy improves survival in prostate cancer (N Engl J Med 2009; 360: 2516-2527).

But late complications of radiation therapy have been poorly characterized, Elliott said. Radiation therapy is associated with vascular thrombosis and osteonecrosis within the radiation field. Pelvic EBRT in women has been shown to increase the risk of hip fracture by as much as threefold, but does not affect a woman’s risk of arm or spinal fractures.

Given that background, Elliott and colleagues hypothesized that pelvic EBRT for prostate cancer would increase the risk of hip fractures without changing the fracture risk at skeletal sites outside the radiation field, specifically wrist fracture.

They also hypothesized that EBRT plus androgen suppression therapy would increase the risk of hip fracture compared with EBRT alone.

So they analyzed SEER and Medicare data related to prostate cancer therapy for 1992 to 2005. They limited the study to men who were at least 66 at diagnosis. Using radical prostatectomy as the reference, they examined fracture risk in men who had EBRT alone, EBRT plus androgen suppression (six to 36 months), or androgen suppression alone (no duration limit).

The databases yielded 55,448 patients for the analysis. The population comprised 9,463 men who had radical prostatectomy, 13,701 who had EBRT, 7,239 who had EBRT plus androgen suppression, and 19,455 who had androgen suppression alone.

Elliott and colleagues determined the incidence of osteoporosis and related comorbidities in the year before diagnosis of prostate cancer and one year after diagnosis. The outcomes of interest were hip and wrist fractures. The investigators used multivariate Cox modeling to compare the hazard for hip and wrist fracture in each treatment group relative to that of the prostatectomy group.

As expected, treatment varied by age group — 55% of men 60 to 69 had surgery compared with about 1% of men 80 and older. Conversely, older patients were more likely to have androgen suppression as sole therapy.

Compared with radical prostatectomy, EBRT alone was associated with an adjusted hazard for hip fracture of 1.665.

EBRT combined with androgen suppression doubled the hip fracture hazard (HR 2.007), and androgen suppression alone further increased the risk (HR 2.518).

EBRT alone was associated with a reduced risk of wrist fracture compared with prostatectomy (HR 0.857).

The addition of androgen suppression to EBRT increased the wrist fracture risk by almost 30% (HR 1.287) versus surgery, and the risk jumped to almost 70% higher than that of prostatectomy in patients treated solely with androgen suppression (HR 1.694).

Elliott acknowledged potential limitations of the study but maintained that the results warrant consideration in clinical decision making.

“The possibility of residual confounding or selection bias exists, but it was minimized by the comparison to wrist fracture,” he said. “These findings suggest a need to consider osteoprotective interventions in men receiving pelvic EBRT.”

Elliott reported no disclosures.

Primary source: American Urological Association

Source reference:

Elliott S et al. “EBRT for prostate cancer increases the risk of hip fracture” AUA 2010; Abstract 48.


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