Abstract
BackgroundAndrogen deprivation therapy (ADT) administered as a prostate cancer treatment is known to exert multiple side effects including bone deterioration leading to bone fracture. The current analysis is to evaluate the burden of fracture risk in the New Zealand prostate cancer (PCa) population treated with ADT, and to understand the subsequent risk of mortality after a fracture.MethodsUsing datasets created through linking records from the New Zealand Cancer Registry, National Minimal Dataset, Pharmaceutical Collection and Mortality Collection, we studied 25,544 men (aged ≥40 years) diagnosed with PCa between 2004 and 2012. ADT was categorised into the following groups: gonadotropin-releasing hormone (GnRH) agonists, anti-androgens, combined androgen blockade (GnRH agonists plus anti-androgens), bilateral orchiectomy, and bilateral orchiectomy plus pharmacologic ADT (anti-androgens and/or GnRH agonists).ResultsAmong patients receiving ADT, 10.8 % had a fracture compared to 3.2 % of those not receiving ADT (p < 0.0001). After controlling for age and ethnicity, the use of ADT was associated with a significantly increased risk of any fracture (OR = 2.83; 95 % CI 2.52–3.17) and of hip fracture requiring hospitalisation (OR = 1.82; 95 % CI 1.44–2.30). Those who received combined androgen blockade (OR = 3.48; 95 % CI 3.07–3.96) and bilateral orchiectomy with pharmacologic ADT (OR = 4.32; 95 % CI 3.34–5.58) had the greatest risk of fracture. The fracture risk following different types of ADT was confounded by pathologic fractures and spinal cord compression (SCC). ADT recipients with fractures had a 1.83-fold (95 % CI 1.68–1.99) higher mortality risk than those without a fracture. However, after the exclusion of pathologic fractures and SCC, there was no increased risk of mortality.ConclusionsADT was significantly associated with an increased risk of any fracture and hip fracture requiring hospitalisation. The excess risk was partly driven by pathologic fractures and SCC which are associated with decreased survival in ADT users. Identification of those at higher risk of fracture and close monitoring of bone health while on ADT is an important factor to consider. This may require monitoring of bone density and bone marker profiles.
Highlights
Androgen deprivation therapy (ADT) administered as a prostate cancer treatment is known to exert multiple side effects including bone deterioration leading to bone fracture
Among patients who received ADT, 2398 (25.6 %) received gonadotropin-releasing hormone (GnRH) agonists, 1445 (15.4 %) received anti-androgens, 4784 (51 %) received combined androgen blockade (CAB) consisting of GnRH agonists and anti-androgens, 268 (2.9 %) underwent orchiectomy alone, and 482 (5.1 %) underwent orchiectomy plus pharmacologic ADT
The rate of use of anti-androgen monotherapy, CAB consisting of GnRH agonists and anti-androgens, orchiectomy and orchiectomy plus pharmacologic ADT increased with increasing age
Summary
Androgen deprivation therapy (ADT) administered as a prostate cancer treatment is known to exert multiple side effects including bone deterioration leading to bone fracture. Prostate cancer (PCa) is the most commonly registered male cancer and the third leading cause of cancer deaths for New Zealand men, making up 27.3 % of all male cancer registrations and 12.6 % of male cancer deaths in 2011 [1]. Studies indicate that ADT together with radiation therapy have a better survival advantage compared to ADT alone especially in patients with locally advanced disease [4]. ADT is used for the treatment of biochemical relapse (rise in prostatespecific antigen level) after the failure of primary treatment, and as primary therapy for men with localized disease who are unable or unwilling to undergo radical prostatectomy or radiation therapy [2, 5]
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