EURURO Vol. 72 No. 4

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arm never received ADT. It was suggested that only those
with initial PSA >50 ng/ml or a PSA doubling time <12 mo
with PSA of 8–50 ng/ml were at higher risk of death. Three
major randomised trials have clearly demonstrated that
ADT alone is inferior to ADT plus RT in terms of prostate
cancer-specific survival . ADT may be palliative in
patients too sick or frail for a local treatment combined with
ADT. However, ADT alone must be considered under-
treatment since the survival benefit of combination with RT
is evident even after 6–7 yr . The combination also
reduces local progression and associated side effects.
However, ADT increases the risk of fractures, cognitive
impairment, diabetes, thromboembolic events, and all-
cause mortality in patients with a history of cardiovascular
disease
4.1.6. Watchful waiting and active surveillance
Patients with low-risk disease are likely to benefit from
watchful waiting (ie, expectant management) or active
surveillance with curative intervention delayed until
progression.
SIOG recommendations for the management of localised
prostate cancer in elderly patients are summarised in
.
4.2. Advanced prostate cancer
4.2.1. Metastatic hormone-naive prostate cancer
Until 2014, ADT was the mainstay of treatment. Recently,
three studies (GETUG-AFU-15 , CHAARTED , and
STAMPEDE ) assessed the efficacy and tolerability of
ADT with or without docetaxel in metastatic hormone-
naive prostate cancer. All included some patients who
developed metastases following local treatment, but the
majority had de novo metastatic disease. A meta-analysis
revealed that addition of docetaxel to the standard of
care improved survival. The HR of 0.77 (95% CI 0.68–0.87;
p < 0.0001) translates into a 9% absolute improvement in 4-
yr survival. Adding docetaxel to ADT also improved failure-
free survival (HR 0.64; p < 0.0001), translating into a
reduction in absolute 4-yr failure rates of 16% (95% CI
12–19%). The addition of docetaxel to ADT should be
considered the new standard of care for men suitable for
chemotherapy with M1 hormone-sensitive prostate cancer
starting treatment for the first time. Zoledronic acid does
not significantly improve survival or decrease the incidence
of skeletal-related events in this setting
The median age in all three trials was <67 yr. We
therefore need more information on whether the results of
chemohormonal therapy can be extrapolated to elderly
patients. It is likely that patients with metastatic prostate
cancer, especially those with high-volume disease, who are
fit to receive docetaxel in addition to ADT may benefit from
such a regimen. However the risk/benefit balance should be
discussed carefully with each patient.
4.2.2. Metastatic castration-resistant prostate cancer
When prostate cancer becomes resistant to castration, ADT
should be continued, but no available data support this
approach in elderly patients specifically. Care should be
taken to prevent an increase in the risk of osteoporosis and
fracture .
Table 4 – International Society of Geriatric Oncology recommendations for the management of prostate cancer in elderly patients
Treatment should be based on health status (mainly severity of associated comorbidities) rather than age, and on patient preference
Localised disease
Fit and frail patients in the D’Amico high-risk group with a chance of surviving >10 yr are likely to benefit from treatment with curative intent
Patients at low- to intermediate-risk are likely to benefit from active surveillance or watchful waiting, based on their individual expected survival.
A curative approach must be discussed with intermediate risk patients who have the longest expected survival
The balance of benefits and harms of ADT for localised prostate cancer should be carefully assessed. Note the higher risk of diabetes, cardiovascular
complications, osteoporosis, bone fractures, and cognitive dysfunction
Advanced disease
ADT plus six cycles of docetaxel is the recommended first-line treatment in fit men with newly diagnosed hormone-sensitive metastatic prostate cancer.
It is also appropriate (especially in the setting of high-volume disease) in some frail patients, but detailed information should have been collected in a CGA
and comorbidities treated. In all other cases ADT alone remains the standard
Patients treated with ADT should have their bone mineral status evaluated and should receive calcium supplementation (if dietary intake is insufficient)
and vitamin D. In those at high risk of osteoporosis, use of bisphosphonates/denosumab is recommended
In mCRPC, docetaxel 75 mg/m2
[1_TD$DIFF] every 3 wk is suitable for both fit and ‘‘frail’’ senior adults, while the biweekly regimen should be considered in those who
are disabled or have severe comorbidities
In mCRPC, abiraterone and enzalutamide are suitable first-line options
In patients who have received docetaxel, options include cabazitaxel, abiraterone, and enzalutamide
The optimum sequencing of therapies is subject to research. After failure of a novel endocrine agent, agents with another mechanism of action including
taxanes or radium-223 should be the preferred option because of cross-resistance between androgen receptor–targeted agents
Careful evaluation of drug-drug interactions and proactive management of adverse events is needed in senior adults
Patients (with no visceral or bulky lymph node metastases) receiving first-line treatment for mCRPC, and after failure to docetaxel, are eligible for
radium-223
Palliative treatments include radiotherapy, radiopharmaceuticals, bone-targeted therapies, palliative surgery, and medical treatments for pain and
symptoms
Early palliation should be implemented
Management of the patient and family should include a multidisciplinary approach ([8_TD$DIFF]Urologist, medical oncologist, radiation oncologist, geriatrician, nurse and
palliative medicine specialist)
ADT = androgen deprivation therapy; mCRPC = metastatic castration-resistant prostate cancer; CGA = Comprehensive Geriatric Assessment.
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