EUROPEAN UROLOGY 72 (2017) 521–531

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Platinum Priority – Review – Prostate Cancer

Editorial by Jeremy P. Grummet, Karin Plass and James N’Dow on pp. 532–533 of this issue

Management of Prostate Cancer in Elderly Patients:

Recommendations of a Task Force of the International
Society of Geriatric Oncology

Jean-Pierre Droz a,*, Gilles Albrand b, Silke Gillessen c, Simon Hughes d, Nicolas Mottet e,
Stéphane Oudard f, Heather Payne g, Martine Puts h, Gilbert Zulian i, Lodovico Balducci j,
Matti Aapro k
a
Cancer–Environment Research Unit, Centre Léon-Bérard and Claude-Bernard Lyon 1 University, Lyon, France; b Groupement Hospitalier Sud des Hospices
Civils de Lyon, Hôpital Antoine Charial, Francheville, France; c Department of Oncology/Hematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland;
d e
Oncology Management Offices, Guy’s Hospital, London, UK; Department of Urology, Saint-Etienne University Hospital, Saint-Priest en Jarez, France;
f
Oncology Department, Georges Pompidou Hospital, René-Descartes Faculty, Paris 5 University, Paris, France; g Department of Oncology, University College
London Hospitals, London, UK; h Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, Canada; i Hôpital de Bellerive, Geneva University
Hospitals, Geneva, Switzerland; j H. Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa, FL, USA;
k
Clinique de Genolier, Genolier, Switzerland

Article info Abstract

Article history: Context: Prostate cancer is the most frequent male cancer. Since the median age of
Accepted December 29, 2016 diagnosis is 66 yr, many patients require both geriatric and urologic evaluation if
treatment is to be tailored to individual circumstances including comorbidities and
Associate Editor: frailty.
James Catto Objective: To update the 2014 International Society of Geriatric Oncology (SIOG) guide-
lines on prostate cancer in men aged >70 yr. The update includes new material on health
status evaluation and the treatment of localised, advanced, and castrate-resistant
Keywords: disease.
Prostate cancer Data acquisition: A multidisciplinary SIOG task force reviewed pertinent articles pub-
lished during 2013–2016 using search terms relevant to prostate cancer, the elderly,
Geriatric assessment
geriatric evaluation, local treatments, and castration-refractory/resistant disease. Each
Health evaluation member of the group proposed modifications to the previous guidelines. These were
Comorbidities collated and circulated. The final manuscript reflects the expert consensus.
Elderly Data synthesis: Elderly patients should be managed according to their individual health
Guidelines status and not according to age. Fit elderly patients should receive the same treatment as
younger patients on the basis of international recommendations. At the initial evalua-
tion, screening for cognitive impairment is mandatory to establish patient competence
in making decisions. Initial evaluation of health status should use the validated G8
screening tool. Abnormal scores on the G8 should lead to a simplified geriatric assess-
ment that evaluates comorbid conditions (using the Cumulative Illness Score Rating-
Geriatrics scale), dependence (Activities of Daily Living) and nutritional status (via
estimation of weight loss). When patients are frail or disabled or have severe comorbid-
ities, a comprehensive geriatric assessment is needed. This may suggest additional
geriatric interventions.

* Corresponding author. Cancer–Environment Research Unit, Centre Léon-Bérard and Claude-Bernard

Lyon 1 University, 24 Allée de Verdun, 69500 Bron, France. Tel. +33 643 178411.
E-mail address: jpdroz@orange.fr (J.-P. Droz).
http://dx.doi.org/10.1016/j.eururo.2016.12.025
0302-2838/# 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.
522 EUROPEAN UROLOGY 72 (2017) 521–531

Conclusions: Advances in geriatric evaluation and treatments for localised and advanced
disease are contributing to more appropriate management of elderly patients with prostate
cancer. A better understanding of the role of active surveillance for less aggressive disease is
also contributing to the individualisation of care.
Patient summary: Many men with prostate cancer are elderly. In the physically fit,
treatment should be the same as in younger patients. However, some elderly prostate
cancer patients are frail and have other medical problems. Treatment in the individual
patient should be based on health status and patient preference.
# 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

1. Introduction their values and treatment goals [9]. Although relatively

Prostate cancer is the most frequent male cancer in
developed countries [1] and is also common in less
developed countries. The median age at diagnosis is
66 yr, and 69% of deaths occur in men aged 75 yr. Since
incidence and mortality rise steeply with age, the prostate
cancer burden will increase with exponential ageing of the
population.
The current paper, which focuses on men aged >70 yr,
updates existing International Society of Geriatric Oncology
(SIOG) guidelines for the management of elderly prostate
cancer patients [2–4]. Issues considered include the risks of
both overtreatment and undertreatment and the impor-
tance of assessing overall health status, comorbidities, and
cognitive function in personalising management. Previous-
ly published SIOG guidelines on prostate cancer [3,4] argued
that age alone should not preclude effective treatment.
Since 2014, the SIOG recommendations have been fully
endorsed by the European Association of Urology (EAU) and
are now referred to as the EAU/ESTRO/SIOG guidelines [5,6].
The most important new features of these updated
guidelines are: (1) the introduction of initial screening for
cognitive function; (2) the rewording of health status
classification to align with terms currently used in the
geriatric literature; (3) consideration of the most important
advances in the treatment of advanced prostate cancer and
their implications for elderly patients; and (4) a recommen-
dation for the early introduction of palliative management.
Choice of therapy should not be based on chronological
aging, which proceeds at the same pace for all, but on
biological aging and health status, which differ greatly from
one person to another. In the USA, a 70-yr-old man in the
healthiest 25% of his peers can expect to live 18 yr, while for
the frailest 25% life expectancy is only 7 yr [7]. Evaluation of
health status is therefore vital to appropriate management.
Assessment of social situation is also important and can
usefully include whether or not a family care-giver is
present, financial resources, and access to services. A further
factor, of course, is patient preference, both in relation to the
goals of therapy and the means of attaining them.
The gold standard for evaluating health status is the
Comprehensive Geriatric Assessment (CGA) [8]. This
includes data on demographic, social, functional, nutrition-
al, cognitive, and mental health status; and the presence of
comorbidities and geriatric syndromes. It predicts survival
and chemotherapy toxicity, identifies reversible conditions,
and reflects patients’ capacity to make decisions as well as
simple, the Activities of Daily Living (ADL) measure of
dependency has been used to determine the need for social
and healthcare interventions and has prognostic value.
Aside from prostate cancer itself, comorbidity is the
strongest predictor of death among men with localised
disease [10]. The Cumulative Illness Score Rating-Geriatrics
(CISR-G) [11] is used to assess comorbidity. In this context,
it is helpful to ascertain the stage and potential reversibility
of the condition, its history, and the risk of acute organ
failure.
However, a CGA is time-consuming and requires
specialist staff. Moreover, it is probably needed in only a
minority of patients. A rational approach is to screen all
patients to identify those who need further assessment. This
further assessment can take the form of a simplified
geriatric evaluation or a full CGA.
2. Evaluation of health status
Evaluation of health status involves a stepwise process
starting with screening using the G8 and mini-COG[TM 4_TD$IF]
[12]. This is followed, where indicated, by a simplified
geriatric assessment and then, again when indicated, by full
geriatric assessment, particularly when complex geriatric
interventions are needed.
2.1. G8 screening
In a comprehensive review of tools to establish the need for
CGA, the G8 (Table 1) was the most robust [8,13]. Thus, a
rational approach is to screen with the G8 scale, which was
developed specifically for older cancer patients and can be
completed in less than 5 min [13]. Its eight components
cover food intake, weight loss, body mass index, mobility,
neuropsychological problems, polypharmacy, self-per-
ceived health status and age.
In a prospective noninterventional study of almost a
thousand men aged 70 yr, an abnormal score on the G8
(14 on a scale from 0 to 17) strongly predicted mortality
over 3 yr and hence a need for full assessment [13]. Follow-
ing studies showing that the G8 is a good way of identifying
patients requiring a CGA, the European Organisation for
Research and Treatment of Cancer (EORTC) made G8
screening compulsory for all patients aged 70 yr included
in the organisation’s trials. It is also recommended in EAU
guidelines.
 EUROPEAN UROLOGY 72 (2017) 521–531 523

Table 1 – G8 screening tool[5_TD$IF]. According to 2014 Soubeyran et al. [13]

A. Has food intake declined over the past 3 mo due to loss of appetite, Severe decrease in food intake 0
digestive problems, chewing, or swallowing difficulties? Moderate decrease in food intake 1
No decrease in food intake 2
B. Weight loss during the last 3 mo? Weight loss >3 kg 0
Does not know 1
Weight loss 1–3 kg 2
No weight loss 3
C. Mobility Bed- or chair-bound 0
Able to get out of bed/chair but does not go out 1
Goes out 2
D. Neuropsychological problems? Severe depression or dementia 0
Mild dementia 1
No psychological problems 2
E. Body mass index (BMI)? BMI <19 kg/m2 0
BMI 19 to <21 kg/m2 1
BMI 21 to <23 kg/m2 2
BMI 23 kg/m2 3
F. Takes more than 3 prescription drugs per day? Yes 0
No 1
G. In comparison to other people of the same age, how does the Not as good 0
patient consider his health status? Does not know 0.5
As good 1
Better 2
H. Age 86 yr 0
80–85 yr 1
<80 yr 2

Screening with G8 has two principal aims: to decide if a
CGA is needed to identify reversible conditions that can be
addressed by geriatric interventions integrated into the
cancer treatment plan [14,15]; and to aid in choosing
appropriate prostate cancer treatment (see below).
2.2. Cognitive screening
The task force considered that cognitive evaluation was
mandatory to assess the patient’s capacity to evaluate
information and make informed decisions. This represents
an addition to previous guidelines, and one that is likely to
assume increasing importance. A recent meta-analysis
compared the validity of cognitive screening tools
[16]. The authors identified 102 studies that used the
Mini Mental State Examination (MMSE). However, this is
time-consuming to complete. Of ten alternative tests, the
mini-COG[4_TD$IF]TM [12] had a diagnostic performance that most
closely matched that of the MMSE, and was chosen. A cutoff
point of 3/5 indicates a need to refer the patient for full
evaluation of potential dementia (Table 2).
2.3. Simplified geriatric evaluation
exception of incontinence—is considered abnormal [2]. The
presence of more than two ADL impairments is unlikely to
be reversible.
2.3.2. Comorbidities
The CISR-G [11] is a good tool for assessing the risk of non–
prostate cancer death [2,11]. The CIRS-G, which rates
nonfatal conditions according to their severity and degree of
control by treatment, is subjective but practical [19]. The
task force judged that geriatric interventions following a
CGA are likely to reverse grade 2 comorbidities. Single grade
3 comorbidities are generally irreversible, but need to be
individually evaluated. Grade 4 comorbidities are, by
definition, irreversible.
2.3.3. Nutritional status
Malnutrition increases mortality in elderly patients [20]
but, unless severe, may be reversible via geriatric interven-
tion. The task force decided to screen for malnutrition using
weight loss during the last three months. Good nutritional
status is defined as <5% loss; risk of malnutrition as loss
between 5% and 10%; and severe malnutrition as weight
loss >10%.

Patients with an abnormal G8 score (14/17) should have a
simplified geriatric evaluation (Table 3). This consists of the
ADL measure of dependence, the CIRS-G to assess comor-
bidities, and weight loss as an indication of malnutrition.
This may determine firstly whether specific geriatric
interventions are needed, and secondly whether a full
CGA is required.
2.3.1. Dependence
Dependence is typically evaluated using the ADL scale
[17,18]. The presence of one ADL impairment—with the
3. Categorisation of patients and implications for
treatment
It is generally argued that candidates for definitive therapy
for localised prostate cancer should have a life expectancy of
10 yr. In metastatic castration-resistant prostate cancer
(mCRPC) it is important to assess 2-yr and 5-yr survival.
Available tools can predict 1-yr or 5-yr survival for patients
living at home or in hospital or nursing home settings [21],
but no classification or prognostic model based on health
status has been validated in urologic oncology. Recent
524 EUROPEAN UROLOGY 72 (2017) 521–531

Table 2 – The Mini-COG[4_TD$IF]TM screening tool[6_TD$IF]. Copyright S. Borson, reprinted with permission of the author (soob@uw.edu). [12]

Step 1: Three words registration

Look directly at person and say, ‘‘Please listen carefully. I am going to say three words that I want you to repeat back to me now and try to remember. The words
are [select a list of words from the versions below]. Please say them for me now.’’ If the person is unable to repeat the words after three attempts, move on to
Step 2 (clock drawing).
The following and other word lists have been used in one or more clinical studies. For repeated administrations, use of an alternative word list is recommended.

Version 1 Version 2 Version 3 Version 4 Version 5 Version 6

Banana Leader Village River Captain Daughter

Sunrise Season Kitchen Nation Garden Heaven
Chair Table Baby Finger Picture Mountain

Step 2: Clock drawing

Say: ‘‘Next, I want you to draw a clock for me. First, put in all of the numbers where they go.’’ When that is completed, say: ‘‘Now, set the hands to 10 past 11.’’
Use a preprinted circle for this exercise. Repeat the instructions as needed, as this is not a memory test. Move to Step 3 if the clock is not complete within 3 min.

Step 3: Three words recall

Ask the person to recall the three words you stated in Step 1. Say: ‘‘What were the three words I asked you to remember?’’ Record the word list version
number and the person’s answers.

Scoring
Word recall: ______ (0–3 points)
=1 point for each word spontaneously recalled without cueing.
Clock draw: ______ (0 or 2 points)
=Normal clock: 2 points. A normal clock has all numbers placed in the correct sequence and approximately correct position (eg, 12, 3, 6, and 9 are in anchor
positions) with no missing or duplicate numbers. Hands are pointing to the 11 and 2 (11:10). Hand length is not scored.
Inability or refusal to draw a clock (abnormal) = 0 points.
Total score: ______ (0–5 points)
=Total score: word recall score + clock draw score.
A cut point of <3 on the Mini-COG[4_TD$IF]TM has been validated for dementia screening, but many individuals with clinically meaningful cognitive impairment will
score higher. When greater sensitivity is desired, a cut point of <4 is recommended as it may indicate a need for further evaluation of cognitive status.

Table 3 – Summary of the different steps in health status evaluation and estimated time required

Step Tools Time Who can do it?

Mandatory initial step G8 5 min Trained nurse

Mini-COG[7_TD$IF]TM 5 min Trained nurse
Simplified geriatric evaluation if G8 score is 14 ADL 1 min Trained nurse
CIRS-G 15 min Trained nurse and/or doctor
Weight loss 1 min Trained nurse
Comprehensive geriatric assessment if geriatric Screening tools and complete 2 h to 1 d in hospital Geriatrician + other health professionals
intervention needed clinical examination

recommendations are to estimate life expectancy based on
the combination of age and comorbidity [22,23]. Therefore,
the choice remains pragmatic and open to debate. However
for future research better tools are desirable. It is vital that
decision-making is shared with patients and that they
receive detailed information, including assessment of
potential risks and benefits [24].
Health status in SIOG guidelines has generally been
defined according to groups described by Balducci and
Extermann in 2000 [25]. These revised prostate cancer
guidelines classify patients into four groups (the terminol-
ogy now aligns with that in the geriatric literature) along
with the implications for treatment (Figs. 1 and 2).
(1) Healthy or fit: G8 score >14. Patients are expected to
tolerate any form of standard treatment. The choice of a
particular local treatment is then based on the patient’s
wishes and the risk of specific side effects, such as
incontinence (described below), for each modality.
(2) Frail: patients with a G8 score 14 but whose problems,
as established via a simplified geriatric assessment
(CIRS-G, ADL, and malnutrition), are considered revers-
ible. Such problems are: one or two reversible
deficiencies in ADL (apart from incontinence); CISR-G
grade 2 comorbidities (a single grade 3 comorbidity
may also be reversible); and weight loss of 5–10%.
Patients whose problems are reversed can be consid-
ered fit for standard prostate cancer therapies.
(3) Disabled or with severe comorbidities: nonreversible
problems. These include more than two ADL deficien-
cies; multiple grade 3 comorbidities on the CISR-G or
any grade 4 comorbidity; or weight loss >10%. Such
patients should be managed symptomatically. Certain
patients may benefit from geriatric interventions
indicated after CGA and can be given specific adapted
cancer treatments.
(4) Terminally ill: palliation only.
Two additional points should be made. First, in patients
who require a CGA, specific geriatric interventions may be
suggested. Second, if the mini-COG[TM
4_TD$IF] score is abnormal, a
full neuropsychological assessment is recommended.
 EUROPEAN UROLOGY 72 (2017) 521–531 525
[(Fig._1)TD$IG]

Screening with G8 and mini-COG™

Score >14 Score ≤14

No simplified Simplified
geriatric geriatric
evaluaon is evaluaon is
needed mandatory

Reversible = Nonreversible =
- Abnormal ADL: 1 or 2 - Abnormal ADL: ≥ 2
-Weight loss 5–10% -Weight loss >10%
-Comorbidies CISR-G -Comorbidies CISR-G
grades 1–2 grades 3–4

CGA then
geriatric
intervenon

Disabled/severe
Fit Frail
comorbidies
Fig. 1 – Decision tree to determine patient health status. mini-COG[3_TD$IF]TM = mini-COG[4_TD$IF]TM cognitive test; ADL = Activities of Daily Living; CIRS-G = Cumulative
Illness Rating Score-Geriatrics; CGA = Comprehensive Geriatric Assessment.

[(Fig._2)TD$IG]

Geriatric screening with G8 tool and mini-COG™

Then simplified geriatric evaluation if G8 ≤14

Group 1 Group 2 Group 3 Group 4

(healthy) (frail, ie, reversible (disabled/severe (terminal
problems) comorbidities, ie, illness)
nonreversible problems)

Principles = early introduction of palliative care

Standard Standard Symptomatic Only

treatment as treatment as management palliative
for younger for younger including adapted treatments
patients patients specific treatments

CGA then geriatric CGA then geriatric

intervention intervention

Fig. 2 – Decision-making based on health status assessment. mini-COG[3_TD$IF]TM = mini-COG[4_TD$IF]TM cognitive test; CGA = Comprehensive Geriatric Assessment.
526 EUROPEAN UROLOGY 72 (2017) 521–531
The task force also had a number of specific recommen-
dations. First, prospective studies should be initiated to
validate screening tools in elderly prostate cancer patients.
The G8 in particular should be validated in this specific
population. Second, prospective studies to validate this
pragmatic classification should follow establishment of
consensus among oncogeriatric specialists. Third, nomo-
grams should be developed to predict outcome in older
prostate cancer patients in different settings when using
tools that assess health status (comorbidities through CISR-
G, dependence, and malnutrition).
4. Treatment of elderly prostate cancer patients
We examined standard management of localised and
advanced disease and applied when possible considerations
specific to elderly men.
4.1. Localised disease
Treatment is based on risk [26]. In a large study [27],
mortality at 15 yr was independent of age at diagnosis but
directly linked to risk group, ranging from 10% (low risk) to
20% (intermediate risk) and 35–40% (high risk). Non–
prostate cancer mortality was mainly linked to comorbid-
ities, but the aggressiveness of the disease outweighed
comorbidity in intermediate- and high-risk groups. The aim
in T1–3N0M0 disease is generally curative. Decisions in the
elderly should take into account the risk of dying from
prostate cancer (ie, tumour grade and stage), the risk of
dying from another cause (ie, comorbidities), the risks of
treatment, and patient preferences.
Healthy elderly patients with high-risk prostate cancer
are often undertreated. However, there is also concern
about the overtreatment of many low-risk patients with
comorbidities and limited life expectancy [2]. It is impor-
tant to assess both oncologic outcomes (extracapsular
disease, metastases, lymph node invasion, and cancer-
specific death) and functional outcomes (eg, erectile
dysfunction and incontinence).
4.1.1. Radical prostatectomy (RP)
Older men are more likely to have larger and higher-grade
tumours [28], and thus might benefit more from a local
treatment including RP. For high-risk lesions, cancer-
specific survival is up to 91% after surgery combined with
adjuvant and/or salvage modalities. Survival can be up to
95% with one risk factor (ie, Gleason >7, stage >T2, or
prostate-specific antigen [PSA] >20 ng/ml), and 79% with
three risk factors [29].
We do not know whether surgery should be open or
minimally invasive. A recent review suggested that in older
patients, a minimally invasive approach led to higher rates
of transfusion, postoperative genitourinary complications,
incontinence, and stricture when compared to the same
procedure in younger men [30].
Although 30-d mortality after RP increases with age, it is
only 0.66% in men aged 70–79 yr [31]. Death and
complications following RP depend more on comorbidities.
Conversely, incontinence and erectile dysfunction are
predominantly influenced by age [31]. Even so, continence
rates are still good in older men, with 86% aged 70 yr
regaining continence [31]. Recent data on robotic prosta-
tectomies do not reveal any difference in complications and
continence between patients aged <70 and 70 yr. Only
potency recovery was better among younger patients. An
Australian cohort compared continence after robotic RP in
men <70 and 70 yr and found no difference [32].
4.1.2. Radiation therapy
Image-guided intensity-modulated radiotherapy (RT)is
now standard for external-beam RT. Evidence is accumu-
lating regarding brachytherapy (low and high dose rates) as
a ‘‘boost’’ or as monotherapy.
Combined RT and androgen deprivation therapy (ADT) is
standard for locally advanced or intermediate- to high-risk
T1/T2 disease. The optimum duration of ADT with higher-
dose RT is yet to be determined. Adding ADT to RT confers
no benefit to patients with localised high-risk prostate
cancer and competing moderate to severe comorbidities, as
the latter have a greater impact on survival than the cancer
[33].
Age does not increase acute or late urinary or bowel
toxicity, but does predict reduced sexual function. However,
90% of patients surveyed about their treatment would make
the same decision if asked again [34].
In the CHHIP study, standard RT fractionation (37 frac-
tions over 7.5 wk) was compared to a hypofractionated
regimen (20 fractions over 4 wk). Most patients had
intermediate-risk disease. Acute bowel toxicity was greater
with hypofractionation, but other acute and late toxicities
were comparable. At 5 yr the biochemical control rate was
not inferior to standard fractionation and actually favoured
patients aged >69 yr [35].
4.1.3. Neoadjuvant/adjuvant treatment
The GETUG 12 trial [36] reported on ADT plus docetaxel and
estramustine versus ADT alone in patients (median age 62–
64 yr) with treatment-naive prostate cancer and at least one
risk factor. However no data were presented that relate
specifically to elderly patients.
4.1.4. Minimally invasive therapies
Hemi-gland ablation or ablation of the index lesion(s) may
provide well-tolerated control in the elderly at low to
intermediate risk, but at present remains experimental.
Options include high-intensity focused ultrasound, cryo-
therapy, brachytherapy, photodynamic and laser therapy,
and irreversible electroporation.
4.1.5. Androgen deprivation therapy
In patients with high-risk nonmetastatic prostate cancer
who are too frail to receive curative treatment, immediate
ADT has a very modest role [37]. It improves overall survival
(OS; hazard ratio [HR] 1.21, 95% confidence interval [CI]
1.05–1.39), but not cancer-specific survival. If not initially
treated with ADT, the median time to start ADT on the basis
of symptoms was 7 yr, and 44% of patients in the deferred
 EUROPEAN UROLOGY 72 (2017) 521–531 527

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 [38–40]. 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 [41]. 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 [2].
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
Table 4.
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
[45] 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 [44].
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. Advanced prostate cancer 4.2.2. Metastatic castration-resistant prostate cancer

4.2.1. Metastatic hormone-naive prostate cancer
Until 2014, ADT was the mainstay of treatment. Recently,
three studies (GETUG-AFU-15 [42], CHAARTED [43], and
STAMPEDE [44]) assessed the efficacy and tolerability of
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 [4].

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$IF] every 3 wk is suitable for both fit and ‘‘frail’’ senior adults, while the biweekly regimen should be considered in those who
are disabled or have severe comorbidities
 In mCRPC, abiraterone and enzalutamide are suitable first-line options
 In patients who have received docetaxel, options include cabazitaxel, abiraterone, and enzalutamide
 The optimum sequencing of therapies is subject to research. After failure of a novel endocrine agent, agents with another mechanism of action including
taxanes or radium-223 should be the preferred option because of cross-resistance between androgen receptor–targeted agents
 Careful evaluation of drug-drug interactions and proactive management of adverse events is needed in senior adults
 Patients (with no visceral or bulky lymph node metastases) receiving first-line treatment for mCRPC, and after failure to docetaxel, are eligible for
radium-223
 Palliative treatments include radiotherapy, radiopharmaceuticals, bone-targeted therapies, palliative surgery, and medical treatments for pain and
symptoms
 Early palliation should be implemented
 Management of the patient and family should include a multidisciplinary approach ([8_TD$IF]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.
528 EUROPEAN UROLOGY 72 (2017) 521–531
4.2.2.1. Cytotoxic chemotherapy. There is increasing evidence
that older age per se is not a contraindication to
chemotherapy. Docetaxel 75 mg/m2[9_TD$IF] every 3 wk plus daily
prednisone is the standard of care in CRPC [4], improving OS
while reducing pain and improving quality of life when
compared to mitoxantrone plus prednisone. The OS benefit
for men aged 75 yr was similar to that for younger
patients, but there were more G3/4 toxicities and dose
reductions [4]. A two-weekly docetaxel regimen was
associated with an increase in OS of 2
5 mo, and fewer
cases of grade 3–4 neutropenia compared with a three-
weekly regimen [46]. In a prospective registry study in
patients aged 70 yr, those with frailty related to cancer
also benefited from a taxane-based therapy (regimen
adapted in 52%) [47].
Cabazitaxel is combined with prednisone in patients
progressing during or after a docetaxel-based regimen
[4]. Safety was analysed by age (<70, 70–74, and 75 yr)
among 746 men [48]. The number of cabazitaxel cycles,
dose reductions for any cause, dose delays possibly related
to cabazitaxel adverse events, and tolerability were similar
in the three age groups. Prophylactic granulocyte colony-
stimulating factor (G-CSF) use was more common in men
aged 70 yr. In multivariate analysis, age 75 yr, first
treatment cycle, and baseline neutrophil count <4000/mm3
were associated with higher risk of grade 3 neutropenia
and/or neutropenic complications. Prophylactic G-CSF
reduced this risk by 30% (odds ratio 0.70; p = 0.04). A
recent phase 3 study comparing cabazitaxel 20 mg/m2
versus 25 mg/m2 every 3 wk plus daily prednisone in
mCRPC patients progressing after docetaxel concluded that
20 mg/m2 was noninferior in terms of OS and was better
tolerated [49].
The toxicity of chemotherapy in older patients can be
predicted. Two published models use somewhat different
criteria, but geriatric, chemotherapy, and biological char-
acteristics are predictive in both [4]. Severe toxicity rates
were relatively high with both models, indicating that older
patients should be monitored closely. There is strong
evidence to support primary prophylaxis with G-CSF in this
setting [4]. Alternatively, the chemotherapy regimen could
be adapted.
4.2.2.2. Endocrine therapies. Abiraterone in combination with
prednisone is effective in both chemotherapy-treated and
chemotherapy-naive mCRPC patients [4,50]. In chemother-
apy-naive mCRPC, median OS was significantly longer in the
abiraterone plus prednisone group than for placebo plus
prednisone (34.7 vs 30.3 mo; HR 0.81; p = 0.0033)
[50]. Elderly patients in both treatment arms had higher
rates of fluid retention and cardiac disorders than younger
patients, although dose reductions or treatment interrup-
tions due to adverse events were few in both groups.
Abiraterone demonstrated clinical benefit and was well
tolerated in elderly men with chemotherapy-naive mCRPC.
Thus, abiraterone is also an option for patients who may not
tolerate therapies with higher toxicity.
Enzalutamide increased OS compared to placebo in the
postchemotherapy setting in mCRPC (AFFIRM trial)
[4,51]. The effect in elderly patients was similar to that in
the total study population, but some side effects were more
common [52]. In the PREVAIL trial, oral enzalutamide
160 mg/d was compared to placebo in chemotherapy-naive
mCRPC [53]. Some 72% of men in the enzalutamide group
but only 63% in the placebo group were alive at cutoff (29%
reduction in risk of death; HR 0.71; p < 0.001). Fatigue and
hypertension were the most common adverse events
associated with enzalutamide. Among patients aged >75
yr (35% of the total), the median treatment duration was
16.6 and 5.0 mo in the enzalutamide and placebo arms,
respectively [54]. In the elderly subgroup, OS was greater
for enzalutamide than for placebo (32.4 vs 25.1 mo; HR
0.61; p = 0.0001), that is, elderly men benefited from
enzalutamide, which was generally well tolerated, but
fatigue and falls may be related side effects. Since
enzalutamide is a strong CYP3A4 inducer, drug interactions
should be carefully checked.
4.2.2.3. Treatment sequencing. Progression on one of the novel
hormonal agents is usually associated with poor response to
subsequent use of another one. The optimum sequencing of
life-extending therapies has not been determined [55].
Symptomatic patients with mCRPC—both fit and frail—
should receive first-line docetaxel, while those who are
disabled or have severe comorbidities or are reluctant to
receive chemotherapy should receive novel endocrine
agents. At progression after docetaxel, cabazitaxel and
novel endocrine agents are appropriate for fit patients.
Chemotherapy-naive fit patients who have experienced
failure on a novel endocrine agent should receive second-
line taxane chemotherapy since cross resistance means they
are unlikely to respond to a second endocrine agent.
Patients need to be fully informed of the benefits and side
effects so that they can indicate a preference.
4.2.2.4. RT/radiopharmaceuticals and bone-targeted therapy. RT is
the first-choice treatment for localised painful metastasis in
elderly men with prostate cancer. A phase 3 study of patients
with painful metastases and no visceral metastases who had
progressed after docetaxel or who were unfit for or unwilling
to have chemotherapy compared Ra-223 with placebo
[4]. Ra-223 extended OS, delayed skeletal-related events,
and improved quality of life in older and younger patients.
Therefore, patients without visceral or bulky lymph node
metastases who are receiving first-line treatment for mCRPC
after failure of docetaxel are eligible to receive Ra-223.
In patients with newly diagnosed metastatic or nonmet-
astatic prostate cancer, adding zoledronic acid to ADT did
not benefit failure-free survival, skeletal-related events, or
OS [44]. In CRPC and bone metastases, zoledronic acid (4 mg
intravenously) or denosumab (120 mg subcutaneously)
every 4 wk is recommended to decrease the risk of
disease-related skeletal complications such as pathologic
fractures. Both drugs have been approved by the US Food
and Drugs Administration and the European Medicines
Agency in this setting [4]. Preventive measures (calcium
and vitamin D supplementation, and an initial dental check)
are of utmost importance [4].
 EUROPEAN UROLOGY 72 (2017) 521–531
4.2.2.5. Immunotherapy. New therapies for mCRPC include
immunotherapy [4]. None is currently available outside
the USA.
4.2.2.6. Palliative care. Life expectancy of <1 yr defines a
patient who might benefit from a palliative care approach
[56]. Temel et al [57] deserve credit for demonstrating that
it is possible to include early specialized palliative care in
the management of advanced cancer and that patients are
best served by management that combines cancer and
palliative care specialists. The major benefits were lower
anxiety and depression, better quality (and quantity) of life,
and less time spent in hospital. These studies were in lung
cancer, and similar research should be conducted in
prostate cancer, for which the burden of symptoms,
especially in the elderly, can be very high.
Task force recommendations for the management of
advanced prostate cancer in elderly patients are sum-
marised in Table 4.
5. Conclusions
A SIOG prostate cancer task force has updated recommen-
dations for the management of elderly men with prostate
cancer. Overall, the urologic approach in the fit elderly
should be the same as in younger patients and based on
existing international recommendations. Individual elderly
patients should be managed according to their health status
and not according to age.
Evaluation of health status should include a validated
screening tool (the G8) and the assessment of comorbid
conditions (CISR-G scale), degree of dependence (ADL), and
nutritional status (weight loss estimation). When patients
are frail or disabled or have severe comorbidities, a CGA is
needed. This may indicate the need for additional geriatric
interventions. Screening for cognitive impairment is man-
datory when making treatment decisions and should be
part of the initial patient assessment.
Author contributions: Jean-Pierre Droz had full access to all the data in the
study and takes responsibility for the integrity of the data and the accuracy
of the data analysis.
Study concept and design: Droz, Aapro.
Acquisition of data: Droz, Albrand, Hughes, Mottet, Oudard, Payne, Puts,
Zulian.
Analysis and interpretation of data: Droz, Albrand, Gillessen, Hughes,
Mottet, Oudard, Payne, Puts, Zulian.
Drafting of the manuscript: Droz, Albrand, Gillessen, Hughes, Mottet,
Oudard, Payne, Puts, Zulian, Balducci.
Critical revision of the manuscript for important intellectual content: Droz,
Albrand, Gillessen, Hughes, Mottet, Oudard, Payne, Puts, Zulian, Balducci,
Aapro.
Statistical analysis: None.
Obtaining funding: Aapro.
Administrative, technical, or material support: None.
Supervision: Droz, Balducci, Aapro.
Other: None.
Financial disclosures: Jean-Pierre Droz certifies that all conflicts of
interest, including specific financial interests and relationships and
affiliations relevant to the subject matter or materials discussed in the
529
manuscript (eg, employment/affiliation, grants or funding, consultan-
cies, honoraria, stock ownership or options, expert testimony, royalties,
or patents filed, received, or pending), are the following: Jean-Pierre Droz
has received consultancy fees from Sanofi. Silke Gillessen has received
advisory board compensation from AAA International, Active Biotech,
Astellas, Bristol-Myers Squibb, Curevac, Dendreon, Ferring, Janssen Cilag,
MaxiVAX, Millennium Pharmaceuticals, Orion, Roche, and Sanofi
Aventis; has participated in advisory boards without compensation
for Astellas, Bayer, ESSA, Nectar, ProteoMediX, and Sanofi; has received
speaker fees from Janssen and Novartis; has participated in a speaker
bureau without compensation for Astellas, Janssen, and Sanofi Aventis;
and has a pending patent application for a method for a biomarker (WO
2009138392 A1). Simon Hughes has received honoraria from Sanofi and
Bayer and consultancy fees from Astellas and Janssen. Nicolas Mottet has
received grant funding from Takeda Pharmaceutical/Millenium, Astellas,
Pierre Fabre, Sanofi, and Pasteur; and consultancy fees from Takeda
Pharmaceutical/Millenium, Janssen, Astellas, BMS, Bayer, IPSEN, Ferring,
Novartis, Nuclétron, Pierre Fabre, Sanofi, and AstraZeneca. Stéphane
Oudard has received consultancy fees from Sanofi, Bayer, Astellas, and
Janssen. Heather Payne has received grant funding from Astellas;
consultancy fees from Astellas, Janssen, Sanofi, Ferring, and AstraZeneca;
and honoraria from Ipsen, Bayer, and Novartis. Lodovico Balducci has
received honoraria from Astellas, Johnson & Johnson, Teva, and Amgen.
Matti Aapro has received honoraria from Astellas, and consultancy fees
from Sanofi, Janssen, Novartis, and Amgen. Gilles Albrand, Martine Puts,
and Gilbert Zulian have nothing to disclose.
Funding/Support and role of the sponsor: This work was supported by
funding from the International Society of Geriatric Oncology. The
sponsor played a role in manuscript preparation via editorial support
provided by Adelphi Communications and Rob Stepney (medical writer,
Charlbury, UK).
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