Supplemental Table 1 – Randomised controlled trials with robust patient-reported outcomes design (basic study characteristics)
Study*
Internatio
nal
Age of patients
(years) †
Overall
study
sample
size
Baseline
PRO
sample
size
Tannock IF et al,
N Engl J Med;
2004; 351: 15021512.
Armstrong AJ et
al, J Clin Oncol;
2007; 25: 39653970.
Berthold DR et al,
J Clin Oncol;
2008; 26: 242245.
Berthold DR et al,
Ann Oncol; 2008;
19: 1749-1753.
Berthold DR et al,
Clin Cancer Res;
2008; 14: 27632767.
Armstrong AJ et
al, Eur J Cancer,
2010; 46: 517525.
Yes
Median: 68;
Range: 36-92
1006
815
Petrylak DP et al,
N Engl J Med.;
2004; 351: 15131520.
Berry DL et al,
J Clin Oncol,
2006; 24: 28282835.
No
Median: 70;
Range: 43-88
770
629
PRO instruments
used
Primary
endpoint
Treatment outline
Metastatic/Advanced disease stage
FACT-P; Present
Overall
Prednisone (5mg twice
Pain Intensity scale
survival.
day) + mitoxantrone
(PPI) from the
(12mg/m2 every 2
McGill-Melzack
weeks) vs prednisone
questionnaire; diary
(5mg twice day) +
for analgesic use
docetaxel (75mg/m2
reporting.
every 3 weeks) vs
prednisone (5mg twice
day) + docetaxel
(30mg/m2 weekly for 5
of every 6 weeks).
EORTC QLQ-PR25; MPQ-SF.
Overall
survival.
Estramustine (280mg, 3
times daily, day 1 to 5),
docetaxel (60mg/m2 up
to 70mg/m2, day 2),
and dexamethasone
(60mg in 3 doses before
docetaxel) vs
mitoxantrone (12mg/m2
up to 14mg/m2, day 1)
and prednisone (5mg
twice daily). Both arms
given in 21 days cycles
until progression or
unacceptable adverse
event for maximum 12
cycles of docetaxel or
144mg of mitoxantrone.
Summary of main
clinical results
Summary of PRO results/PRO
treatment recommendations
Docetaxel every 3
weeks led to better
overall survival. Both
docetaxel regimens
had better prostatespecific antigen
(PSA) response rates
and pain
improvement.
Adverse events were
more common with
docetaxel.
Docetaxel q3 weeks
associated with better
improvement in pain. Both
docetaxel arms associated
with improved quality of life
versus mitoxantrone. Weekly
docetaxel group had an early
deterioration of quality of life
while on treatment.
Median overall
survival was longer in
docetaxel plus
estramustine arm:
17.5 months vs 15.6
months. Median time
to progression also
favored patients
treated with docetaxel
plus estramustine: 6.3
months vs 3.2 months.
The docetaxel+estramustine
group reported increased
nausea and vomiting
symptoms from baseline to
cycle 4 and cycle 8 compared
to patients treated with
mitoxantrone and prednisone.
Pain and global quality of life
were not different between
treatment arms.
Supplemental Table 1 – Randomised controlled trials with robust patient-reported outcomes design (basic study characteristics)
Study*
Internatio
nal
Age of patients
(years) †
Overall
study
sample
size
Baseline
PRO
sample
size
PRO instruments
used
Primary
endpoint
Treatment outline
Summary of main clinical
results
Summary of PRO results/PRO
treatment recommendations
Metastatic/Advanced disease stage
Saad F et al, J
Natl Cancer Inst ;
2002; 94: 14581468.
Saad F et al, J
Natl Cancer Inst ;
2004; 96: 879882.
Saad F et al,Clin
Prostate Cancer;
2005; 4: 31-37.
Weinfurt KP et
al, Ann Oncol;
2005; 16: 579584.
Saad F et al, Clin
Genitourin
Cancer; 2007; 5:
390-396.
Saad F et al,
Urology , 2010;
76: 1175-1181.
Small EJ et al, J
Clin Oncol; 2002;
20: 3369-3375.
Ahles TA et al,
Cancer, 2004;
101: 2202-2208.
Yes
Median: 72;
Mean: 71.7
643
643
BPI; FACT-G;
EQ-5D.
Proportion of
patients having
at least one
skeletal-related
event.
Zoledronic acid 4mg
IV versus zoledronic
acid 8mg
(subsequently reduced
to 4mg) IV versus
placebo every 3
weeks for 15 months
duration extended to
24 months.
Zoledronic acid
decreased skeletal
related events at 15 and
24 months, prolonged
median time to the first
event and decreased
urinary markers of bone
resorption compared
with placebo arm.
Patients who received the
high dose of zoledronic acid
(4mg) had, compared with
placebo arm, a significant
reduction of pain at 3, 9, 21
and 24 months.
No
Median: 70.5;
Range: 40-85
390
385
FACT-P; CES-D;
BPI.
Objective
Response Rate
including PSA
response rate.
Low dose suramin
(3.192g/m2) vs
intermediate dose (
5.320g/m2) vs high
dose (7.661g/m2)
with incremental
decreasing of doses
over 10 weeks.
Dose-response
relationship between
dose and toxicity.
Patients treated with the
lowest dose of suramin had
better quality of life outcomes
and low depression than those
treated with intermediate or
high dosages of suramin. Pain
was not different amongst
treatment arms.
Supplemental Table 1 – Randomised controlled trials with robust patient-reported outcomes design (basic study characteristics)
Study*
Internatio
nal
Age of patients
(years) †
Overall
study
sample
size
Baseline
PRO
sample
size
PRO instruments
used
Primary
endpoint
Treatment outline
Summary of main clinical
results
Summary of PRO results/PRO
treatment recommendations
Metastatic/Advanced disease stage
Arai Y et al, J
Cancer Res Clin
Oncol; 2008; 134:
1385-1396.
Akaza H et al,
Cancer; 2009;
115: 3437-3445.
Akaza H et al,
2009; 115: 34373445. Jpn J Clin
Oncol.;2004; 34:
20-28.
Usami M et al,
Prostate Cancer
Prostatic Dis.
2007; 10: 194201.
No
Maximum androgen
blockade (MAB),
bicalutamide arm:
53 patients (52%)
< 75 years, 49
patients (48%) ≥ 75
years; luteinizing
hormone-releasing
hormone agonist
(LHRH-a),
monotherapy arm:
50 patients (50%)
< 75 years, 51
patients (51%) ≥ 75
years.
205
203
FACT-P.
Objective
Response
Rate PSA
normalization
(≤ 4) rate and
tumor
response rate
at 12 weeks
and the rate of
withdrawals at
the time of
study cut-off.
LHRH-a with
bicalutamide 80mg
daily or placebo.
Bicalutamide arm was
superior in terms of
antitumor response,
time to treatment failure
and progression at 12
weeks. Overall survival
difference favoring
bicalutamide arm was
significant at 5.2 years
follow up.
MAB associated with better
emotional well-being,
prostate cancer specific issues
including micturation
disorder-related QOL. MAB
had higher incomplete
improvement rates in pain and
micturation disorder item.
Erectile dysfunction worsened
less in this arm.
Caffo O et al,
BJU Int;2008;
102: 1080-1085.
No
Median:69;
Range: 48-86
95
73
EORTC QLQ-C30;
short form of BPI;
amount of pain
relief on a 0-100
scale; use of
analgesic reports.
PSA response.
Docetaxel 70mg/m2 on
day 1 versus docetaxel
70mg/m2 on day 2 plus
3 times daily
estramustine total dose
840mg on days 1-5.
Docetaxel+estramustine
resulted in higher
proportion of PSA
responders and longer
median time to
progression but groups
were not statistically
compared (phase II
study).
Docetaxel+estramustine
associated with significant
decrease in pain (EORTC
QLQ-C30 pain scales).
No
Mean: 64
52
50
BDI; FSS.
Percent
change in
bone mineral
density in
posterioranterior
lumbar spine
and percent
change in
thigh muscle
area from
baseline to 12
months.
Leuprolide 3 mo depot
every 3 months versus
bicalutamide 150mg
daily for 12 months.
Leuprolide patients
received bicalutamide
50mg daily for 1rst
month.
Bicalutamide resulted in
increased bone mineral
density and lessened fat
accumulation. Breast
enlargement and
tenderness more
common with
bicalutamide. Fatigue,
loss of libido and
vasomotor flushing
more common with
leuprolide.
Fatigue increased over time in
this population (overall) while
depression did not. Treatment
group comparisons revealed
that leuprolide group had
greater fatigue than the
bicalutamide group at
baseline and at 12 months.
However, no difference were
shown with regard to
depression between treatment
groups.
Caffo O et al,
BJU Int, 2011;
108: 1825-1832.
Pirl WF et al,
Psychooncology,
2008; 17: 148153.
Smith MR et al, J
Clin Oncol, 2004;
22: 2546-2553.
Supplemental Table 1 – Randomised controlled trials with robust patient-reported outcomes design (basic study characteristics)
Study*
International
Age of patients
(years) †
Overall
study
sample size
Baseline
PRO
sample
size
PRO instruments used
Primary
endpoint
Treatment outline
Summary of main
clinical results
Summary of PRO results/PRO
treatment recommendations
Non-metastatic disease stage
Warde P et al,
Lancet, 2011;
378: 2104-2111.
Yes
Median: 69.7
1205
1031
EORTC QLQ-C30 +
PR13 prostate specific
module; FACT-P.
Overall
survival.
Lifelong androgen
deprivation therapy
(ADT) and radiotherapy,
RT, 65-69 Gy to the
prostate and seminal
vesicles, 54 Gy to the
pelvic nodes) vs ADT
alone (patients chose
before randomization
between bilateral
orchiectomy or LHRH-a).
Time to
progression,
prostate-cancer
and overall
mortality were
better for
radiotherapy plus
ADT versus ADT
alone.
Radiotherapy group had
worse EORTC bowel and
rectum and diarrhea scores
and FACT-P urinary scores at
6 months. No differences at
36 months.
Fransson P et al,
Lancet Oncol;
2009; 10: 370380.
Yes
Mean: 66;
Range: 48-75
875
836
EORTC QLQ-C30;
PCSS.
Prostate
cancer
specific
survival.
Leuprorelin depot plus
flutamide 250mg three
times daily for 3 months.
Patients then randomized
to continuous endocrine
treatment with flutamide
alone versus flutamide
plus 70Gy or higher 3D
conformal radiotherapy to
prostate.
10-year prostate
cancer specific
mortality and
overall mortality
decreased in the
group that
received
radiotherapy in
addition to
endocrine therapy.
At 4 years, patients who
received endocrine treatment
plus radiotherapy had
decreased social functioning
(EORTC QLQ-C30). Also
more treatment related
symptoms were reported by
this group including: urinary
bother, pain while urinating,
bother from all bowel
symptoms and sexual
functions. No differences
existed with regard to other
functioning scales and
symptoms measured by the
EORTC QLQ-C30 between
treatment groups.
Widmark A et al,
Lancet, 2009;
373: 301-308.
Supplemental Table 1 – Randomised controlled trials with robust patient-reported outcomes design (basic study characteristics)
Study*
Internatio
nal
Age of patients
(years) †
Overall
study
sample size
Baseline
PRO sample
size
PRO instruments used
Primary
endpoint
Treatment outline
Summary of main
clinical results
Summary of PRO results/PRO
treatment recommendations
Non-metastatic disease stage
Thompson IM et
al, J Urol, 2009;
181: 956-962.
No
Median: 65;
425
217
SWOG Quality of
Life questionnaire
including SF-20; SF36 and GHRQOL.
Metastatic
free
survival.
60-64Gy adjuvant
radiotherapy versus
observation and usual
care after radical
prostatectomy.
Adjuvant
radiotherapy
associated with
improved
metastasis -free
and overall
survival.
Adjuvant radiotherapy to radical
prostatectomy produce worse
bowel symptoms and urinary
symptoms mainly at the
beginning of therapy (during the
fist 2 years). Erectile dysfunction
is not different between treatment
arms. However higher short-term
morbidity for patients treated with
radiotherapy does not translate
into a major impact on patient’s
overall quality of life. While
long-term quality of life (at 5
years) is better for patients treated
with additional radiotherapy.
244
231
EORTC QLQ-C30;
UCLA PCI.
Proportion
of patients
with disease
progression
at 36
months.
LHRH agonist for 3-6
months then
randomized to 6873.5Gy external beam
radiation therapy
(EBRT) or cryotherapy
with 2 freeze-thaw
cycles using thirdgeneration technology.
If cryotherapy was
repeated within 6
months for early PSA
failure the patient was
not considered a
treatment failure.
The null
hypothesis that
cryotherapy is
inferior to
external beam
radiotherapy was
not rejected. The
rate of positive
biopsy at 36
months was
higher after
radiotherapy
compared to
cryotherapy:
28.9% vs 7.7%.
Cryoablation was associated with
poorer sexual functioning
(UCLA-PCI) over time. No
statistically or clinically
meaningful differences existed
with regard to other functioning
scales and symptoms measured
by the EORTC QLQ-C30
between treatment groups at 3
years. Patients who wish to
increase their odds of retaining
sexual functioning might be
informed that EBRT is
recommended over cryoablation.
Range: 43.879.2
Moinpour CM et;
J Clin Oncol,
2008; 26: 112120.
Thompson IM Jr
et al, JAMA,
2006; 296: 23292335.
Donnelly BJ et al,
Cancer, 2010;
116: 323-330.
Robinson JW et
al, Cancer, 2009;
115: 4695-4704.
No
Median: 69;
Range: 52.881.4
Supplemental Table 1 – Randomised controlled trials with robust patient-reported outcomes design (basic study characteristics)
Study*
International
Age of patients
(years) †
Overall
study
sample size
Baseline
PRO
sample
size
PRO instruments used
Primary
endpoint
Treatment outline
Summary of main
clinical results
Summary of PRO results/PRO
treatment recommendations
Mixed disease stage (loco-regional disease and metastatic disease)
Salonen AJ et al,
J Urol, 2008; 180:
915-919;
discussion 919920.
No
Mean: 71.5;
Range: 46-95
554
554
30-item HRQOL
questionnaire for
prostate cancer patients
developed by Cleary et
al ‡
Time to
Treatment
Failure
(including
disease
progression,
treatment
toxicity,
death).
Gosorelin IM monthly
for 24 weeks with
cyproterone 100 mg
twice daily for first
12.5 days then groups
with PSA response
randomized to
continue gosorelin
versus intermittent
gosorelin for 24
weeks if PSA
progression.
No statistically
significance results.
Intermittent therapy
associated with better activity,
physical and sexual
functioning. Erectile
dysfunction and depressed
mood more common in the
intermittent arm.
No
Mean: 72.6
311
309
EORTC QLQ-C30; A
validated Mayo Clinic
hot-flush Diary.
PRO (hot
flushes)
Six months of
leuprorelin then
symptomatic patients
randomized to
venlafaxine 75mg
daily vs
medroxyprogesterone
acetate 20mg daily vs
cyproterone acetate
100mg daily for 6
months.
Not applicable (see
next box on PRO
results)
All 3 treatment resulted in
decrease of median daily hot
flush score. Cyproterone and
medroxyprogesterone were
significantly better than
venlafaxine in decreasing hot
flushes. Venlafaxine had
better emotional functioning
( EORTC QLQ-C30 scale)
and less dyspnea at 4 and 8
weeks.
Salonen AJ et al,
J Urol,2012;187:
2074-2081.
Salonen AJ et al,
Eur Urol, 2013;
63: 111-120.
Irani J et al,
Lancet Oncol,
2010; 11: 147154.
Legend: * No ranking was made based on level or reporting in this table. Studies are ordered by overall number of patients recruited in the study. † Data are reported so as available in the paper. ‡ This measure, specifically
validated on advanced metastatic prostate patients, consists of 30 questions addressing 10 relevant domains including physical capacity, sexual functioning, sexual interest, bed disability and pain (Cleary PD, et al, Qual Life Res
1995;4:207-20).
Abbreviations: FACT-P: Functional Assessment of Cancer Therapy-Prostate; EORTC QLQ-PR-25: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Prostate Module-25; MPQ-SF:
McGill Pain Questionnaire Short Form ; BPI: Brief Pain Inventory; FACT-G: Functional Assessment of Cancer Therapy - General; EQ-5D: European Quality of Life-5 Dimensions; CES-D: Center for Epidemiological studiesdepression scale; EORTC QLQ-C30: Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30; BDI: Beck Depression Inventory; FSS: Fatigue Severity Scale; PCSS: Prostate Cancer Symptom
Scale; UCLA PCI: University of California Los Angeles Prostate Cancer Index; SF-36: Rand Medical Outcomes Study (MOS) Short Form-36 scale; SF-20: Rand Medical Outcomes Study Short Form-20 scale; SWOG: The
Southwest Oncology Group; GHRQOL: General Health-Related Quality of Life; PRO: Patient-Reported Outcomes.