Sat 31st Aug 2013
Session 1 / Talk 1
09:20 – 09:46
BROOKLYN 2
RADIOTHERAPY
Patries HERST
ABSTRACT
Purpose. Acute radiation-induced cystitis is a common side effect of radiation therapy to the
pelvis, with up to 40% of prostate cancer patients suffering from cystitis to some extent.
Currently there is no effective treatment for radiation cystitis. Here we investigate the effect
of cranberry capsules on the extent of radiation-induced cystitis in prostate cancer patients in
a double blinded RCT.
Methods and materials. A total of 40 men receiving radiation therapy for prostate cancer at
the Department of Radiation Therapy in Dunedin Hospital participated in this trial; 20 men
were randomized to the cranberry arm and 20 were randomized to the placebo arm. The
men took one capsule a day during breakfast from the first day of treatment for 70 days.
Patients, clinicians and research assistants were blinded to the content of the capsules.
Severity of cystitis was assessed using the modified urinary domain of the Expanded
Prostate Cancer Index Composite (EPIC) scale. Items include severity of symptoms (pain,
blood in urine, urinary frequency during day or night, leakage, use of pads and URAL
sachets) as well as their effect on daily life.
Results. Cranberry capsules significantly decreased the level of pain associated with acute
radiation cystitis but did not affect the other EPIC measures.
Cranberry capsules
for Radiation cystitis: a pilot RCT
Katelin Hamilton, Noelle Bennett, Patries Herst*
August 2013
Background
 Radiation cystitis in 60-90% of prostate patients
 Damage to the lining of the bladder wall
 seepage of acidic urine into the underlying tissues
 inflammation, compromised detrussor muscle
functioning
 Symptoms similar to UTIs without infection:




Pain/Burning
Weak stream, incomplete emptying
Poor control, leakage, dripping
Urgency
Treatment
 Currently no standard treatment to prevent or
decrease the severity of radiation cystitis
 URAL treats the symptoms but not the
inflammation
 Cranberries reduce the incidence of UTIs in young
women (Cochrane review in 2009)
 Anecdotally, cranberry capsules seemed to
reduce radiation cystitis in Dunedin patients
Hypothesis
Cranberry capsules are superior to placebo in
decreasing the severity of radiation cystitis.
Campbell et al (2003)
 randomized unblinded comparison between cranberry juice
and apple juice in 112 men with prostate cancer
 No significant difference between study arms
Cowan et al (2012)
 placebo-controlled, double blinded trial of cranberry juice
and placebo in 128 women with uterine/bladder cancer.
 Trend for decrease in urinary symptoms but not significant
Bonetta and Pierro (2012)
 standardized enteric coated cranberry tablets against
nothing on radiation cystitis in 370 prostate cancer patients
 Decreased levels of pain, urgency and day and night time
frequencies (p<0.01)
 Not blinded, randomization unclear
Take home message
 Use standardized capsules
 Use placebo capsules for double blinding
 Be aware of compliance issues
Protocol: Stage II RCT: 40 patients
Eligibility
•
•
•
•
CT Scan
IMRT for prostate cancer
No previous RT to pelvis
No systemic disease
Karnofski score>70
Informed Consent
Randomization
Cranberry Capsules
Assessment
Modified EPIC: 2x week
during and 1x week for 4
weeks after tmt
Start RT
Placebo Capsules
1 Capsule a day for 10 weeks
1. Severity of cystitis
2. URAL usage
2 weeks after RT completion
Measurements: EPIC
 Expanded Prostate Index Composite: Urinary
Domain: both symptoms AND effect on QoL
 Scores were taken 2x a week, subtracted from
baseline score and averaged over the number of
assessments to give average increase in EPIC
scores for each patient
 Patients scores are averaged to give average
increase in EPIC scores for each cohort
Randomized
41
Cranberry Capsules
21
Placebo Capsules
20
Non-Compliance
1
Non-Compliance
1
Cranberry Completed
20
Placebo Completed
19
Participants for Analysis
39
Symptoms
In the last few days have you had:






Pain:
Leakage:
Control:
Pads:
URAL:
Blood:
how often: “never” to “more than once a day”
how often: “never” to “more than once a day”
total to none whatsoever
how many: “none” to “more than 2”
how often: “rarely” to “more than once a day”
how often: “rarely” to “more than once a day”
Average Increase in EPIC Score
n=20
n=19
Symptoms
P value
0.03
pain
0.03
leakage
0.14
control
0.94
pads
0.49
URAL
0.54
blood
0.85
No cystitis : 10/39 (26%)
Cranberries: 7/20 (35%)
Placebos:
3/19 (16%)
Quality of Life
From “no bother at all” to “big problem”,
how much bother have the following been:







Pain/burning upon urination
Dripping/leaking
Weak stream/incomplete emptying
Day time frequency
Night time frequency (nocturia)
Blood in urine
Overall
Average Increase in EPIC Score
Quality of Life
n=20
n=19
0.04
P value
pain
0.04
leakage
0.67
weak stream
0.68
frequency
0.49
nocturia
0.12
blood
0.72
overall
0.64
No bother: 4/39 (10%)
Cranberries: 4/20 (20%)
Placebos: 0/19 (0%)
Major Confounder
Over-hydration (‘full bladder syndrome”)
14 patients had high hydration levels (8 cranberries, 6
controls)
25 patients had low hydration levels (12 cranberries,
13 controls)
Average Increase in EPIC Score
0.01
n=14
n=25
Symptoms
P value
Inconsistent
advice
pain
0.52
leakage
0.31
control
0.33
pads
0.25
URAL
0.01
blood
0.10
Average Increase in EPIC Score
n=14
n=25
Quality of Life
P value
pain
0.93
leakage
0.22
weak stream
0.56
frequency
0.31
nocturia
0.27
blood
0.27
overall
0.08
Other possible confounders
High baseline cystitis scores
19/39 (49%) men had baseline scores >1 for at least one
of the measures
 Increase from baseline is highest if baseline is 0 (0-4),
compared with 1 (0-3) or 2 (0-2) or 3 (0-1) or 4 (0)
 12 men on placebo capsules and 7 men on cranberry
capsules had high baseline scores. Placebo results
likely to be artificially low.
Inconsistent advice regarding URAL usage
Conclusion
Cranberry capsules may decrease certain aspects
of radiation cystitis.
Next
 Large multicentre RCT in NZ
 Standardized capsules, placebo capsules
 Exclude men with high baseline scores
 Consistent hydration levels
 URAL given only when symptoms reach 2
Acknowledgements
 Trial
Participants
 Staff
from Southern DHB
Funding: