D de Jong, Prostate cancer brachytherapy

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

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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

2-4 (Low Grade) 2-4 (Low Grade) 5-7 (Intermediate)5-7 (Intermediate)8-10 (High Grade)8-10 (High Grade)

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)


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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

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MeasuresMeasures

IPSS: prostate symptom scaleIPSS: prostate symptom scale

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

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IPS

S-T

OT

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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


Role Function

Time, 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


5

10

15

20

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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


Base line 3-5 months-5

0

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UR

INA

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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


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PR

25

BO

WE

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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

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PR

25

BO

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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



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R 2

5 T

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AT

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NT

-S


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EORTC PR25: Sexual FunctionPR25 Sexua l F unction over T ime by Age G roup - No ADT ; LS Means


Base line 6-18 months 22-27 months-10

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UA

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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

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TIO

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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


20

40

60

80

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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

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IIEF

-5 T

OT

AL

[Ra

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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

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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

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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

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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

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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

D de Jong, Prostate cancer brachytherapy

Health & Medicine

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