Prostate Cancer Prostate Cancer Brachytherapy: Brachytherapy: Effects on Quality of Effects on Quality of Life Life & Sexual Function & Sexual Function Dennis de Jong, Helen M Dennis de Jong, Helen M Conaglen Conaglen Leanne Tyrie, & John V Leanne Tyrie, & John V Conaglen Conaglen Sexual Health Research Unit Sexual Health Research Unit Waikato Clinical School, Waikato Clinical School, Hamilton Hamilton
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Prostate Cancer Brachytherapy: Prostate Cancer Brachytherapy:
Effects on Quality of Life Effects on Quality of Life & Sexual Function& Sexual Function
Dennis de Jong, Helen M Conaglen Dennis de Jong, Helen M Conaglen Leanne Tyrie, & John V ConaglenLeanne Tyrie, & John V Conaglen
Sexual Health Research UnitSexual Health Research UnitWaikato Clinical School, HamiltonWaikato Clinical School, Hamilton
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Prostate CancerProstate Cancer
33
Types & GradesTypes & Grades
24 different types of 24 different types of prostate cancer identified prostate cancer identified (Palanisamy et al, 2010)(Palanisamy et al, 2010)
– Many slow growing, but Many slow growing, but some fast and aggressivesome fast and aggressive
On average 7 types of On average 7 types of prostate cancers present prostate cancers present in patients diagnosedin patients diagnosedMost common type of Most common type of prostate cancer is prostate cancer is adenocarcinomaadenocarcinoma
Measures of malignancyMeasures of malignancyLow-grade to high gradeLow-grade to high gradeGleason Scale (1-10)Gleason Scale (1-10)– Cell appearanceCell appearance– Cell arrangementCell arrangement
Cancer tends to become Cancer tends to become more aggressive as it more aggressive as it growsgrows
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Stages Treatments
T1a Low grade cancer - active surveillance, radiation or prostatectomy
T1bAggressive treatment, radiation or prostatectomy
T1cDepends on age, general health, and grade of cancer
T2a/bProstatectomy, radiation, hormone therapy an option for older men
T3a/b/cLarger cancers - radiation, surgery, hormone treatment, or a combination of these
T4a/bUsually spread beyond the prostate and to the lymph nodes. Treatment depends on health and age, but no known cure
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Stages Treatments
T1a Low grade cancer - active surveillance, radiation or prostatectomy
T1bAggressive treatment, radiation or prostatectomy
T1cDepends on age, general health, and grade of cancer
T2a/bProstatectomy, radiation, hormone therapy an option for older men
T3a/b/cLarger cancers - radiation, surgery, hormone treatment, or a combination of these
T4a/bUsually spread beyond the prostate and to the lymph nodes. Treatment depends on health and age, but no known cure
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Brachytherapy for PCaBrachytherapy for PCa Seeds are inserted through the
skin of the perineum
Each seed is placed in a predetermined location
Beams of high-energy radiation are focused on the target area
The radiation attempts to kill cancer cells in the affected area
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AAnnddrrooggeenn
DDeepprriivvaattiioonn
TThheerraappyy
Prevents cancer cells absorbing Prevents cancer cells absorbing testosterone, thereby reducing PSAtestosterone, thereby reducing PSA
Often used along with other measures to Often used along with other measures to prevent aggressive cancers from returningprevent aggressive cancers from returning
Also used prior to surgery as it may Also used prior to surgery as it may reduce the size of the prostate, making reduce the size of the prostate, making surgery easiersurgery easier
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Known Impacts of BrachytherapyKnown Impacts of Brachytherapy
Urinary and bowel issuesUrinary and bowel issues– Include urethritis (irritation) & incontinence, & Include urethritis (irritation) & incontinence, &
minor bowel symptomsminor bowel symptoms
– Often improve over time (usually within months) Often improve over time (usually within months)
– Percentage affected varies across studiesPercentage affected varies across studies(Bottomley et al., 2010; Quek & Penson, 2005)(Bottomley et al., 2010; Quek & Penson, 2005)
Quality of lifeQuality of life– Reductions in physical well being and role Reductions in physical well being and role
functioning compared to baseline* functioning compared to baseline* (Quek & Penson, 2005)(Quek & Penson, 2005)
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Sexual dysfunctionSexual dysfunction
– Many studies report Many studies report in erectile dysfunction in erectile dysfunction after brachytherapy after brachytherapy (Bottomley et al., 2005; Cesaretti (Bottomley et al., 2005; Cesaretti et al., 2007; Quek & Penson, 2007)et al., 2007; Quek & Penson, 2007)
– High levels of Erectile Function (EF) and High levels of Erectile Function (EF) and younger age before treatment strongly predict younger age before treatment strongly predict maintenance of EF after brachytherapymaintenance of EF after brachytherapy
(Cesaretti et al., 2007)(Cesaretti et al., 2007)
Known Impacts of BrachytherapyKnown Impacts of Brachytherapy
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Known Impacts of BrachytherapyKnown Impacts of Brachytherapy
Probable that issues associated with Probable that issues associated with prostate cancer and brachytherapy are prostate cancer and brachytherapy are multi-factorialmulti-factorial– AgeAge– General healthGeneral health– Lifestyle factorsLifestyle factors
Effects can be described asEffects can be described as– Short term: occurring < 6 months from start of Short term: occurring < 6 months from start of
treatmenttreatment– Long term: occurring after 6 months into treatmentLong term: occurring after 6 months into treatment
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Study AimsStudy Aims
To investigate the impact on the prostate To investigate the impact on the prostate symptoms of brachytherapysymptoms of brachytherapy
To understand the impact on a man’s quality of To understand the impact on a man’s quality of life as result of brachytherapylife as result of brachytherapy
To compare the effect of ADT on all of these To compare the effect of ADT on all of these areas – did QoL, prostate symptoms and sexual areas – did QoL, prostate symptoms and sexual function worsen due to ADT?function worsen due to ADT?
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MethodologyMethodology
Data collected by the Waikato Regional Cancer Data collected by the Waikato Regional Cancer Unit over 5 years - entered but not analysedUnit over 5 years - entered but not analysed
Studentship task to analyse data relating to Studentship task to analyse data relating to quality of lifequality of life
Involved conversion of data to form useable in Involved conversion of data to form useable in statistics package; challenges due to non-return statistics package; challenges due to non-return of questionnaires, and thus intermittent time-of questionnaires, and thus intermittent time-points across grouppoints across group
Dataset describes men with ≥ 3 assessment Dataset describes men with ≥ 3 assessment data points; baseline, mid-point (6-18 months) & data points; baseline, mid-point (6-18 months) & 2 years (22-27 months)2 years (22-27 months)
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Study Sample
Participants161 men aged 48-84 years [Mean 66.4 yrs, SD 6.9]
Cancer Grades T1c to T3c, with a mode of T3a
Gleason ScoresRange: 6 to 10 [Mean 7, SD 0.9]
PSARange: 2.2 to 230 [Mean 17.1, SD 21.8]
Brachytherapy without ADT 89 men
Brachytherapy with ADT 72 men
Short-term effects sub-group (0-3 months)
48 men with age, grades, Gleason Scores, & PSA similar to men above
EORTC-C30: quality of life with cancerEORTC-C30: quality of life with cancer
EORTC-PR25: prostate specific queriesEORTC-PR25: prostate specific queries
ADT data from patient notesADT data from patient notes
IIEF-5: Brief erectile function scaleIIEF-5: Brief erectile function scale
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Analyses Analyses
Repeated measures analysis of variance over Repeated measures analysis of variance over time for each variabletime for each variable– Time: Baseline, 6-18 months, 22-27 monthsTime: Baseline, 6-18 months, 22-27 months
Between subjects factors were:Between subjects factors were:– Age group (3 groups: <60, 60-69, 70+ years) Age group (3 groups: <60, 60-69, 70+ years) – ADT Tx (2 groups – no Tx or ADT Tx)ADT Tx (2 groups – no Tx or ADT Tx)
Where apparently significant ANOVAs found, Where apparently significant ANOVAs found, post hoc analyses were not always significant post hoc analyses were not always significant because of uneven group sizes etcbecause of uneven group sizes etcReporting today on significant findingsReporting today on significant findings
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IPSS: TotalIPSS-T ota l over T ime by ADT T x; LS MeansCurren t e ffect: F (2 , 120)=4 .2682 , p=.01619
Vertica l ba rs: +/- 0 .95 con fidence
Base line 6-18 months 22-27 months1
2
3
4
5
6
7
8
9
10
11
12
IPS
S-T
OT
AL
No ADT ADT T x
83% with symptoms at baseline 69% with symptoms at 22-27 monthsIPSS did not worsen over time with therapy, but ADT Tx effect was significant, p<.05Men on ADT Tx sig worse:– at baseline than non-ADT men at 6-8 months, p<.01, – and 22-27 months, p<.05
EORTC-30: EORTC-30:
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ScaleMain Effect
Post hoc
General QoL
Time, p <.05
Sig worse at two years than baseline, p <.05
Physical Function
Time, p <.01
Sig worse at two years than baseline, p <.05
Role Function
Time, p <.05
Sig worse at two years than baseline, p <.05
Social Function
Time, p <.01
Sig worse at mid-point than baseline, p <.05, and two years than baseline, p <.001
However, all NZ levels significantly better than general EORTC norms taken across all treatment options
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EORTC PR25: Urinary
PR25 Urina ry Sca le over T ime by ADT T x; LS MeansVertica l ba rs: +/- 0 .95 con fidence
Base line 6-18 months 22-27 months0
5
10
15
20
25
30
EO
RT
C P
R25 - U
RIN
AR
Y
No ADT ADT T x
15% men had no symptoms at baseline
5% men had no symptoms at 22-27 mths
Sig main effect of Time, p <.0001
Post hoc: Baseline values sig lower than 6-18 months, p <.01 or 22-27 months, p <.0001
Sig interaction with ADT Tx, p <.05
PR25: Urinary – short term
Significant interaction between age group and time effect on urinary symptoms, p <.05
Effect o f T ime on Urinary Symptoms by Age G roup ; LS MeansCurren t e ffect: F (2 , 39)=4 .4434, p=.01826
Vertica l ba rs: +/- 0 .95 con fidence
Base line 3-5 months-5
0
5
10
15
20
25
30
35
40
45
UR
INA
RY
SY
MP
TO
MS
<60 years 60-69 years 70+ years
PR25: BowelPR25: Bowel
Baseline: 75% men had no Baseline: 75% men had no symptomssymptoms6-18 mths: 44% men had 6-18 mths: 44% men had no symptomsno symptoms22-27 mths: 57% men had 22-27 mths: 57% men had no symptomsno symptomsMain effect of Time, Main effect of Time, p p <.01, <.01, worse at 22-27 months than worse at 22-27 months than baselinebaselineShort term sig more Short term sig more symptoms at 3 months, symptoms at 3 months,
pp<.01<.01
Bowe l Symptoms O ver T ime; LS MeansCurren t e ffect: F (2 , 128)=5 .2286 , p=.00656
Vertica l ba rs:+/- 0 .95 con fidence
Base line 6-18 months 22-27 months0
1
2
3
4
5
6
7
8
9
10
11
12
PR
25
BO
WE
L
Short-te rm Bowe l Symptoms; LS MeansCurren t e ffect: F (1 , 38)=6 .1160 , p=.01798
Vertica l ba rs:+/- 0 .95 con fidence
Base line 3-5 months0
2
4
6
8
10
12
PR
25
BO
WE
L
2020
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PR25: Treatment side effects
Main effect of Time, p <.0001. – Post hoc: More side effects
at 6-18 months, p < .0001 & 22-27 months, p < .0001 than baseline
Sig interaction with Age Group, p < .05– Younger men had more
side effects than two older groups at 6-18 & 22-27 months
Short term analysis showed this impact present at 3 months also
EO RT C PR25-T rea tmentS over T ime by Age G roup; LS MeansCurren t e ffect: F (4 , 126)=3 .4194 , p=.01086
Vertica l ba rs: +/- 0 .95 con fidence
Base line 6-18 months 22-27 months0
5
10
15
20
25
30
EO
RT
C P
R 2
5 T
RE
AT
ME
NT
-S
<60 years 60-69 years 70+ years
2222
EORTC PR25: Sexual FunctionPR25 Sexua l F unction over T ime by Age G roup - No ADT ; LS Means
Vertica l ba rs: +/- 0 .95 con fidence
Base line 6-18 months 22-27 months-10
0
10
20
30
40
50
60
70
80
90
100
EO
RT
C P
R2
5: S
EX
UA
L F
UN
CT
ION
<60 years 60-69 years 70+ years
EO RT C PR25: Sex F unction over T ime by Age G roup - ADT T x; LS MeansVertica l ba rs: +/- 0 .95 con fidence
Base line 6-18 months 22-27 months-10
0
10
20
30
40
50
60
70
80
90
100
EO
RT
C P
R2
5: S
EX
FU
NC
TIO
N
<60 years 60-69 years 70+ years
Sig main effect of Time, p <.0001
Function at baseline better than at mid-pt, p <.01 or 22-27 months, p <.0001
Hormone deprivation therapy analysis, ns
NO ADT ADT Tx
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EORTC PR25: Sex Cond Fn
Questions men about sexual function if sexually active– 16% reported 100% sexual
function at baseline– 0% @ 22-27 months
Too few men in each age group to analyse with age & hormone factors over time1-way ANOVA shows oldest men sig less functional at baseline, p < .01 <60 yrs: M=82.9 ± 15.3 [n=19]60-9 yrs: M=74.8 ± 24.3 [n=39]70+ yrs: M=52.5 ± 25.5 [n=17]
No sig diffs at other times
EO RT C PR25: Mean SexCondF n Scores by Age G roup
Base line 6-18 months 22-27 months0
20
40
60
80
100
<60 years 60-69 years 70+ years
IIEF-5 Sexual FunctionIIEF-5 Sexual FunctionChange to IIEF -5 over T ime
Curren t e ffect: F (2 , 62)=11.221, p=.00007Vertica l ba rs denote 0 .95 con fidence in te rva ls
Base line 12 months 24 months
T IME
0
5
10
15
20
25
IIEF
-5 T
OT
AL
[Ra
ng
e 5
-25
]
Effect of Time & ADT on IIEF-5Effect of Time & ADT on IIEF-5
Sig effect of time: F(2, 60)=10.888, p=.00009 No effect of ADT, nor interaction.
IIEF-5 sub-scales over TimeIIEF-5 sub-scales over TimeEffect o f T ime on IIEF -5 Sub-sca les
W ilks lambda=.24950 , F (10 , 13 )=3 .9105 , p=.01215Vertica l ba rs denote 0 .95 con fidence in te rva ls
Base line 12 months 24 months
T IME
1
2
3
4
5
Confidence Hardness Post-pene tra tion Ma in ta in Sa tisfaction
Short or Long Term Effects?Short or Long Term Effects?Short- & Longer- T erm Effects on IIEF -5
Mean; W h isker: Mean±SD
Base line 3 months 12 months 24 months
T IME
0
5
10
15
20
25
IIEF
-5 S
core
s [Ra
ng
e 5
-25
]
Mean Mean±SD
Sig change from baseline to 3 months: t(15) = 2.96, p < .01
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ConclusionsConclusions
IPSS symptoms did not significantly worsen over time IPSS symptoms did not significantly worsen over time Impact was affected by ADT and the age of the menImpact was affected by ADT and the age of the men
Men undergoing brachytherapy reported worsening Men undergoing brachytherapy reported worsening urinary prostate symptoms initially and these continued urinary prostate symptoms initially and these continued to get worse to get worse
Men undergoing brachytherapy reported negative Men undergoing brachytherapy reported negative impacts on general quality of life, physical function, role impacts on general quality of life, physical function, role function and social function over the two year time-framefunction and social function over the two year time-frame
Impacts on QoL less in NZ study than in EORTC dataImpacts on QoL less in NZ study than in EORTC data
2929
ConclusionsConclusions
Sexual Function from EORTC-PR25, was reduced in the Sexual Function from EORTC-PR25, was reduced in the short term and did not improve with timeshort term and did not improve with time
Sexual function from IIEF-5 worsened at each time pointSexual function from IIEF-5 worsened at each time point Short-term impact found at 3 months was ongoingShort-term impact found at 3 months was ongoing
What is impact over longer time-frame?What is impact over longer time-frame? At ~ 2 years, nothing appears to return to normal functioningAt ~ 2 years, nothing appears to return to normal functioning
However, other studies show many functions and symptoms do However, other studies show many functions and symptoms do appear to stabilize, and claim improvement, over longer time appear to stabilize, and claim improvement, over longer time periodsperiods
What is impact on partners of these men, and their What is impact on partners of these men, and their relationships?relationships?– Seeking funding for studies, pilot just underwaySeeking funding for studies, pilot just underway
3030
AcknowledgementsAcknowledgements
Thanks go to:Thanks go to:
The men who have completed all the paperwork The men who have completed all the paperwork over the years the data has been collectedover the years the data has been collected
Those who have entered the data at various Those who have entered the data at various times – special mention of Ali Gisler, who times – special mention of Ali Gisler, who managed the data collectionmanaged the data collection
The Waikato Clinical School for the Summer The Waikato Clinical School for the Summer Studentship opportunity to analyse the dataStudentship opportunity to analyse the data