Clinical Practice Guidelines for the management of locally advanced ...

Recommendation
It is recommended that the prescriber take into account the following points when
commencing ADT:
The use of non-steroidal anti-androgens as monotherapy may have fewer and less severe
adverse events than medical or surgical castration but may still have a toxicity profile
that impairs quality of life, and there is little to no efficacy data to support their use as
monotherapy.
Extrapolating from evidence with metastatic disease (see chapter 5 Overt metastatic
disease and/or loco-regional progressive disease), Combined androgen blockade (CAB)
with an antiandrogen does increase the adverse event profile versus medical or surgical
castration monotherapy and this needs to be weighed up against its marginal additional
survival benefits seen in patients with metastatic disease.
When the unwanted effects of treatment are preferable to the unwanted effects of the
tumour (e.g. prevent recurrence with increased overall survival in adjuvant setting), the
side-effect profiles of the treatment options should be explained and strategies to
minimise these effects should be considered with the patient.
Grade B
Effects on bone health and the risk of fractures
There are numerous studies reporting the effects of medical or surgical castration on bone mineral
density (BMD) and fracture rates in men with prostate cancer. Most were observational with results
from both prospective and retrospective analyses of hospital and collated organisational data. There
were two randomised studies 24;25 comparing changes in BMD in patients randomised to bicalutamide
or LHRH agonists. Many studies had industry support, including the two randomised studies that
were supported by AstraZeneca.
Measurement methods: Two methods were used to measure BMD changes with Dual Energy X-ray
Absorptiometry (DEXA) was the more commonly employed method. However DEXA is not ideal for
measuring changes in lumbar spine BMD in older individuals as it does not distinguish aortic
calcification and sclerosis of spinal discs and joints known to increase with age. 35 There were fewer
manuscripts reporting use of the more sensitive barometer of quantitative computerised tomography
(QCT) which, however, exposes patients to more radiation and is subject to quality control issues.
This review focuses on changes in femoral BMD as measured by DEXA and lumbar BMD as
measured by QCT.
There were a number of other limitations arising out of study designs and the modes of reporting
outcomes. The criteria used for reporting changes in BMD varied, reflecting a lack of accepted and
standardised or validated yardsticks for men compared with those agreed and accepted for women.
Most studies reported the change in mean BMD rather than the incidence of clinically significant
decrease in bone mineral density or osteoporosis. Few studies attempted to distinguish osteoporotic
fractures from metastatic and traumatic fractures, and the definition of osteoporotic fractures varied.
Finally, in comparative studies there were usually baseline differences between the groups that have
the potential to confound the results. This was so even when comparing prostate cancer patients with
and without ADTs, as ADT may be associated with more aggressive disease or more advanced
disease stage. In many studies, disease stage was unclear.
Clinical practice guidelines for the management of locally advanced and metastatic prostate cancer
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