Erectile function durability following permanent prostate brachytherapy

CLINICAL INVESTIGATION Prostate

ERECTILE FUNCTION DURABILITY FOLLOWING PERMANENT PROSTATEBRACHYTHERAPY

AL V. TAIRA, M.D.,* GREGORY S. MERRICK, M.D.,y ROBERT W. GALBREATH, PH.D.,y

WAYNE M. BUTLER, PH.D.,y KENT E. WALLNER, M.D.,z BRIAN S. KURKO, C.M.D., M.S.,y

RICHARD ANDERSON, R.T.T.,y AND JONATHAN H. LIEF, PH.D.y

*Department of Radiation Oncology, University of Washington, Seattle, WA; ySchiffler Cancer Center, Wheeling Jesuit University,Wheeling, West Virginia; and zPuget Sound Healthcare Corporation, Group Health Cooperative, University of Washington, Seattle, WA

Purpose: To evaluate long-term changes in erectile function following prostate brachytherapy.Methods and Materials: This study included 226 patients with prostate cancer and preimplant erectile functionassessed by the International Index of Erectile Function-6 (IIEF-6) who underwent brachytherapy in two prospec-tive randomized trials between February 2001 and January 2003. Median follow-up was 6.4 years. Pre- andpostbrachytherapy potency was defined as IIEF-6 $ 13 without pharmacologic or mechanical support. Therelationship among clinical, treatment, and dosimetric parameters and erectile function was examined.Results: The 7-year actuarial rate of potency preservation was 55.6% with median postimplant IIEF of 22 in potentpatients. Potent patients were statistically younger (p = 0.014), had a higher preimplant IIEF (p < 0.001), were lesslikely to be diabetic (p = 0.002), and were more likely to report nocturnal erections (p = 0.008). Potency preservationin men with baseline IIEF scores of 29–30, 24–28, 18–23, and 13–17 were 75.5% vs. 73.6%, 51.7% vs. 44.8%, 48.0%vs. 40.0%, and 23.5% vs. 23.5% in 2004 vs. 2008. In multivariate Cox regression analysis, preimplant IIEF, hyper-tension, diabetes, prostate size, and brachytherapy dose to proximal penis strongly predicted for potency preser-vation. Impact of proximal penile dose was most pronounced for men with IIEF of 18–23 and aged 60–69. Asignificant minority of men who developed postimplant impotence ultimately regained erectile function.Conclusion: Potency preservation and median IIEF scores following brachytherapy are durable. Thoughtful dosesparing of proximal penile structures and early penile rehabilitation may further improve these results. � 2009Elsevier Inc.

Erectile Function, Prostate cancer, Brachytherapy, Proximal penis.

Int. J. Radiation Oncology Biol. Phys., Vol. 75, No. 3, pp. 639–648, 2009Copyright � 2009 Elsevier Inc.

Printed in the USA. All rights reserved0360-3016/09/$–see front matter

doi:10.1016/j.ijrobp.2008.11.058

INTRODUCTION

Radical prostatectomy, external beam radiotherapy, and bra-

chytherapy are effective treatments for clinically localized

prostate cancer, with comparable cause-specific survival

(1). However, the nature and timing of treatment-related mor-

bidity differ significantly by modality (2, 3).

Erectile dysfunction is one of the most common and dis-

tressing sequelae of prostate cancer treatment. Among the

treatment options, brachytherapy offers a somewhat higher

likelihood of preserved potency (2–4). Despite this, most bra-

chytherapy patients experience some subjective and objec-

tive decrease in erectile function after treatment (5, 6).

It is important to identify the patient characteristics and

treatment variables that have the greatest impact on potency

preservation after brachytherapy. With this information, pro-

viders can better inform patients about their expected short-

and long-term sexual function after treatment. These data

63

can also provide guidance in terms of changes to treatment

technique to improve the likelihood of potency preservation.

In this study, we evaluated the temporal changes in erectile

function following permanent prostate brachytherapy with

a minimum follow-up of 5 years using the patient-adminis-

tered International Index of Erectile Function—6 (IIEF-6)

questionnaire (7). The relationship among multiple clinical,

treatment, and dosimetric parameters and erectile function

are examined.

METHODS AND MATERIALS

Between February 2001 and January 2003, 226 patients with

preimplant erectile function determined by IIEF underwent perma-

nent prostate brachytherapy in two prospective randomized trials.

For the low-risk trial (Gleason # 6, prostate-specific antigen

[PSA] # 10 ng/mL, and clinical Stage T1b–T2b), the minimal pe-

ripheral dose was 125 Gy (American Brachytherapy Society,

Address reprint requests to: Gregory S. Merrick, M.D., SchifflerCancer Center, Wheeling Hospital, 1 Medical Park, Wheeling WV26003-6300. Tel: (304) 243-3490; Fax: (304) 243-5047; E-mail:[email protected]

Conflict of interest: none.Received Sept 8, 2008, and in revised form Nov 14, 2008.

Accepted for publication Nov 18, 2008.

9

mailto:[email protected]

640 I. J. Radiation Oncology d Biology d Physics Volume 75, Number 3, 2009

Table 1. Demographic, clinical and treatment variables

Impotent (n = 55) Potent (n = 69) Overall (n = 124)

Continuous variable Median Mean � SD Median Mean � SD p Median Mean � SD

Age (years) 64.7 64.1 � 7.9 60.2 60.7 � 7.1 0.014 63.1 62.2 � 7.7Follow-up (years) 6.4 6.5 � 0.7 6.4 6.4 � 0.7 0.270 6.4 6.4 � 0.7Gleason score 7.0 6.7 � 0.8 7.0 6.6 � 0.7 0.643 7.0 6.7 � 0.7ADT (months) all patients 0.0 1.9 � 2.7 0.0 1.1 � 1.8 0.211 0.0 1.2 � 2.2ADT treated only (n = 31) 4.0 5.4 � 2.6 4.0 4.0 � 0.0 0.054 4.0 4.7 � 1.8Preimplant PSA 6.1 6.5 � 2.4 5.6 6.2 � 2.2 0.527 5.9 6.3 � 2.3Preimplant IIEF 24.0 23.1 � 5.7 29.0 26.5 � 4.6 <0.001 26.0 24.9 � 5.4Prostate size (cm3) 35.9 37.3 � 9.2 33.3 34.5 � 7.2 0.065 34.8 35.8 � 8.3Planning volume 69.1 70.6 � 12.8 66.8 67.3 � 10.1 0.102 67.4 68.8 � 11.5

% Frequencies

Categorical variable Impotent Potent p Overall

ADTNo 76.8 73.5 0.677 75.0Yes 23.2 26.5 25.0

StageT1a–T2b 96.4 95.6 1.000 * 96.0T2c 3.6 4.4 4.0

IsotopePd-103 82.1 83.8 0.804 83.1I-125 17.9 16.2 16.9

XRTImplant only 39.3 39.5 39.520 Gy 33.9 29.4 0.828 31.544 Gy 26.8 30.9 29.0

HypertensionNo 51.8 60.3 0.342 56.5Yes 48.2 39.7 43.5

DiabetesNo 97.1 85.5 0.022 * 91.9Yes 2.9 14.5 8.1

Nocturnal erections:No 27.5 50.9 0.008 37.9Yes 72.5 49.1 62.1

Tobacco useNever 37.7 44.8 41.6Former 55.8 41.4 0.289 * 47.5Current 7.0 13.8 10.9

BMI# 25 17.9 23.5 21.025–30 57.1 51.5 0.721 54.0$ 30 25.0 25.0 25.0

Abbreviations: ADT = androgen deprivation therapy; BMI = body mass index; IIEF = International Index of Erectile Function; PSA = pros-tate-specific antigen; XRT = radiation therapy.

Bold values indicate that the p value is statistically significant or associated with a statistically significant value.* Fisher exact test used because at least one cell had fewer than five subjects.

2000) for 103Pd and 144 Gy (Task Group 43) for 125I (8). For the

higher risk study (Gleason $ 7, PSA 10.1–20.0, clinical Stage

T1b–T2b), the 103Pd dose was 115 Gy and 90 Gy for the 20- and

44-Gy arms, respectively (9). Additional details regarding the spe-

cifics of treatment are described in a previous publication (5).

Of the 226 patients, 132 (58.4%) were potent before brachyther-

apy (IIEF $ 13) and were eligible for this study. Patients completed

a baseline IIEF survey which was periodically updated during the

follow-up period. Each patient in this study completed a minimum

of three IIEF questionnaires. In addition, at initial consultation,

the presence or absence of nocturnal erections was assessed by phy-

sician interview. On follow-up evaluations, a question was added to

IIEF survey to assess nocturnal erections. Patients were instructed to

complete IIEF questionnaires describing erectile function without

pharmacologic or mechanical assistance. Men who were potent be-

fore therapy but who reported a permanent loss of erectile function

beginning immediately after treatment were assigned a time-to-erec-

tile dysfunction of 1 day.

In 2004, 128 of the total 132 eligible men (97%) completed initial

questionnaires and were included in a previously reported study (5).

From this group of patients, 125 patients were alive in 2008; 124

(99%) completed an IIEF survey in February 2008 and are included

in this report. The clinical, treatment, and dosimetric parameters

evaluated for this study were age at implant; prostate volume;

Erectile function following prostate brachytherapy d A. V. TAIRA et al. 641

planning volume; Gleason score; preimplant PSA; stage; risk; to-

bacco use; diabetes mellitus; supplemental external beam radiation;

androgen deprivation; duration of androgen deprivation; isotope;

values of the minimum dose received by 90% of the prostate gland

(D90); the percent prostate volume receiving 100%, 150%, and

200% of the prescribed dose (V100/150/200); percent dose to the

penile bulb (D95/90/75/70/50/25); percent dose to the proximal

crura (D95/90/75/70/50/25); external beam radiation dose to penile

bulb (D95/90/75/70/50/25); body mass index (BMI); nocturnal

erections; and preimplant IIEF score.

Contouring of penile bulb and proximal crura was performed on

axial CT imaging at 0.5-cm intervals, using previously reported

methodology (5, 10, 11). Briefly, the penile bulb was identified on

Day 0 postimplant CT scan as the soft tissue structure bounded by

the paired crura laterally, the corpora spongiosum anteriorly, and

the levator ani posteriorly. Using this methodology results in penile

bulb volumes typically in the range of 6–10 cm3 (11). The proximal

crura was defined as the proximal most 1.0-cm segment of the crura.

Patients were stratified by preimplant IIEF scores, and then 2004

and 2008 IIEF scores were compared descriptively. Also, using

a one-way analysis of variance and chi-squared analysis, select con-

tinuous and categorical variables were analyzed respectively for sig-

nificance across the groups defined as ‘‘always potent,’’ ‘‘potent

(2004), then impotent (2008),’’ ‘‘impotent (2004), then potent

(2008),’’ ‘‘always (2004 and 2008) impotent.’’

Kaplan-Meier analyses were used to compare potency preserva-

tion among patients of different preimplant ages, IIEF scores, and

nocturnal erection status, as well as type of isotope used and the

use or nonuse of supplemental external beam radiotherapy. Univar-

iate Cox regression analysis was used to determine univariate predic-

tors of potency preservation for the IIEF obtained in 2008. Variables

with a p value # 0.10 were then included in a multivariate model of

a Cox regression as a means of identifying multiple predictors. For all

tests, a p value of # 0.05 was considered significant. Statistical anal-

ysis was performed with the Statistical Package for the Social Sci-

ences (SPSS) version 14.0 software (SPSS, Chicago, IL).

RESULTS

Table 1 summarizes the clinical and treatment characteris-

tics for the 124 of 132 patients (94%) who were potent before

Years Since Implant

876543210

Po

ten

cy P

reservatio

n (%

)

100

80

60

40

20

0

55.6%

Fig. 1. Kaplan-Meier potency preservation curve for 124 patients.

treatment and completed the IIEF-6 survey in 2004 and again

in February 2008. The 7-year actuarial potency preservation

rate for the group as a whole was 55.6% (Fig. 1). Median time

to onset of erectile dysfunction was 6.4 months. On average,

men who retained potency were younger (p = 0.014), had

higher pretreatment IIEF scores (p < 0.001), were more likely

to experience pretreatment nocturnal erections (p = 0.008),

and were less likely to be diabetic (p = 0.022).

Figure 2 displays the distribution of preimplant and most

recent IIEF scores for patients considered potent before treat-

ment. Median IIEF score at most recent follow-up for men

who remained potent was 22. Men who lost potency had

a most recent median IIEF score of 3. Figure 3 presents

the Kaplan-Meier potency preservation rate, stratified by

preimplant IIEF score. Seven-year potency preservation

for patients with preimplant IIEF score of 24–30, 18–23,

and 13–17 was 67.1%, 40.0%, and 23.5%, respectively

(p < 0.001). Patients with a preimplant IIEF score of 29

or 30 had a 75.5% rate of potency preservation at 7 years,

with a median IIEF of 24.

Younger men had a greater likelihood of potency preserva-

tion than older men (Fig. 4). Men younger than 60 had

Nu

mb

er o

f R

es

po

ns

es

35

30

25

20

15

10

5

0

Pre-implant IIEF Score

30282624222018161412a.

b. Most Recent IIEF Score

302826242220181614121086420

Nu

mb

er o

f R

es

po

nd

en

ts

25

20

15

10

5

Potent (n = 69)Impotent (n=55)

Fig. 2. Histograms of international index of erectile function (IIEF)score distributions with potency defined as an IIEF $ 13. (a) Preim-plant IIEF. (b) Postimplant IIEF.


a 73.5% 7-year potency preservation compared with 48.1%

and 33.3% for men aged 60–69 and $ 70 (p = 0.001). Men

with pretreatment nocturnal erections also had better long-

term potency (p = 0.005; Fig. 5).

Twenty-four men (19% of all men who were potent before

treatment) were immediately impotent after brachytherapy.

Seven of 17 men (41%) with pretreatment IIEF of 13–17, 9

of 25 men (36%) with IIEF 18–23, 6 of 29 men (21%) with

IIEF 23–28, and 2 of 53 men (4%) with IIEF 29–30 reported

immediate impotency. None of these patients regained po-

tency.

Forty-six percent of men never lost potency after treat-

ment. Their mean pretreatment and most recent IIEF scores

were 26.7 and 22.2. Forty-four percent of men became impo-

tent at some point after treatment and never regained potency.

Years Since Implant

876543210

Po

ten

cy P

reservatio

n (%

)

100

80

60

40

20

0

Ages ≤ 59, 73.5%

Ages 60-69, 48.1%

Ages ≥ 70, 33.3%

p = 0.001

Fig. 4. Kaplan-Meier potency preservation, stratified by patient ageat implant.

Years Since Implant

876543210

Po

te

nc

y P

re

se

rv

atio

n (%

)

100

80

60

40

20

0

IIEF 24-30, 67.1%

IIEF 18-23, 40.0%

IIEF 13-17, 23.5%

p < 0.001

Fig. 3. Kaplan-Meier potency preservation stratified by preimplantindex of erectile function (IIEF) scores.

Their mean pretreatment and most recent IIEF scores were

22.8 and 3.2. Finally, 9.6% of men developed posttreatment

impotence but later regained potency. Their mean pretreat-

ment and most recent IIEF scores were 26.5 and 21.3, respec-

tively. Men who become impotent and subsequently regained

potency had younger age and higher preimplant IIEF scores,

similar to men who never lost potency (Table 2).

Table 3 examines factors that predicted subsequent erectile

function for men who at some point became impotent. Higher

pretreatment IIEF score was the factor most strongly associ-

ated with an increased likelihood of regaining potency at

some future point.

Table 4 displays the Day 0 dosimetry parameters of men

who retained potency vs. those who did not. None of the eval-

uated measures of dose to the prostate itself was associated

with increased level of erectile dysfunction. In contrast, for

nearly all of the dosimetry parameters examined, impotent

men received statistically significantly higher doses to the pe-

nile bulb and crura than men who retained potency.

Analysis of factors predicting potency is presented in

Table 5. On univariate analysis, nearly all of the dosimetric

measures describing brachytherapy proximal penile dose

were significant. Dose to the prostate itself, the use of supple-

mental beam radiation, and supplemental beam radiation

dose to the penile bulb were not significant. On multivariate

analysis, preimplant IIEF, diabetes, and dose to penile bulb

and distal crura were the most significant factors predicting

for preserved potency.

Figure 6 presents the Kaplan-Meier potency preservation

rate, stratified by dose to the penile bulb. Men with a D25

< 50% of the prescribed dose had a 7-year actuarial potency

rate of 70.6% compared with 45.2% for those with D25 $

50% (p = 0.003). Figure 7 displays potency preservation

stratified by dose to the proximal crura. Men with a D50 #

50% of the prescribed dose had a 7-year actuarial potency

Months Since Implant

876543210

Po

te

nc

y P

re

se

rv

atio

n (%

)

100

80

60

40

20

0

Nocturnal Erection, 64.9%

No Nocturnal Erection, 40.4%

p = 0.005

Fig. 5. Kaplan-Meier potency preservation, stratified by pre-im-plant nocturnal erection status.


Table 2. Demographic data, stratified by time-related changes in IIEF

Continuous variablesAlways potent Potent, then impotent Impotent, then potent Always impotent

Mean � SD Mean � SD Mean � SD Mean � SD p

Age at implant 60.3 � 7.0 62.8 � 8.0 61.0 � 7.5 65.0 � 7.9 0.021Follow-up 6.4 � 0.7 6.2 � 0.8 6.4 � 0.7 6.5 � 0.6 0.475Gleason score 6.6 � 0.7 6.6 � 0.5 6.4 � 0.7 6.8 � 0.8 0.508ADT months all patients 1.1 � 1.8 1.1 � 1.9 0.3 � 1.2 1.6 � 2.9 0.371ADT treated only (n = 31) 4.0 � 0.0 4.0 � 0.0 4.0 � - 5.7 � 2.7 0.096Preimplant PSA 6.0 � 2.2 7.2 � 2.5 6.0 � 1.8 6.6 � 2.5 0.296Preimplant IIEF 26.7 � 4.5 25.2 � 5.3 26.5 � 4.5 22.2 � 5.7 <0.001Prostate size 35.0 � 6.8 31.9 � 8.7 34.0 � 5.5 38.2 � 9.9 0.065Planning volume 67.8 � 9.6 64.5 � 12.5 66.2 � 8.9 71.8 � 13.5 0.126

% Frequency

Categorical variables Always potent Potent, then impotent Impotent, then potent Always impotent p

ADTNo 73.7 72.7 91.7 72.7 0.634Yes 26.3 27.3 8.3 27.3

StageT1a–T2b 94.7 100 100 95.5 1.000T2c 5.3 0.0 0.0 4.5

IsotopePd-103 86.0 72.7 66.7 86.4 0.237I-125 14.0 27.3 33.3 13.6

XRTImplant only 40.4 36.4 50.0 36.4 0.65220 Gy 26.3 45.5 16.7 38.644 Gy 33.3 18.2 33.3 25.0

HypertensionNo 63.2 45.5 75.0 45.5 0.151Yes 36.8 54.5 25.0 54.5

Tobacco useNever 42.9 55.6 25.0 40.0 0.558Former 40.8 44.4 75.0 51.4Current 16.3 0.0 0.0 8.6

BMI# 25 22.8 27.3 33.3 13.6 0.61025–30 52.6 45.5 58.3 56.8$ 30 24.6 27.3 8.3 19.5

Abbreviations: ADT = androgen deprivation therapy; BMI = body mass index; IIEF = International Index of Erectile Function; PSA = pros-tate-specific antigen; XRT = radiation therapy

Bold values indicate that the p value is statistically significant or associated with a statistically significant value.

rate of 65.7% compared with 42.6% for those with D50 >

50% (p = 0.004).

As mentioned earlier, men with higher pretreatment IIEF

scores, younger age, and presence of nocturnal erections

had better chance of retaining potency. Table 6 explores the

impact of dose to the penile bulb for these specific patient sub-

groups. For each of the subgroups examined, men with penile

bulb D25 < 50% had higher rates of long-term potency.

The most significant impact of penile bulb dose on subse-

quent erectile function was found in men with pretreatment

IIEF of 18–23. In this group, men whose penile bulb D25

was limited to less than 50% of prescription dose had potency

preservation rates of 72.7%, almost identical to potency pres-

ervation in men with pretreatment IIEF of 24–30. In contrast,

men with pretreatment IIEF of 18–23 who received high pe-

nile bulb doses had potency preservation of only 14.3%, sim-

ilar to potency preservation of men with pretreatment IIEF of

13–17 who received high penile bulb doses.

Men with the highest pretreatment IIEF scores tolerated

higher penile bulb doses without a significantly lower rate of

potency preservation (63.0% vs. 72.2%, p = 0.29). However,

long-term erectile function of men in this group with high pe-

nile doses was not as good as men with slightly lower pretreat-

ment IIEF scores who had a relatively spared penile bulb.

Younger men (aged # 59) tolerated higher penile bulb

doses without significant impairment in potency (70.0% vs.

78.3%, p = 0.48). The effect of penile bulb dose was most no-

table in men in our middle-age category. Men aged 60–69 had

significantly lower potency preservation (28.6% vs. 73.7%,

p = 0.001) with high penile bulb dose. Men in this middle-

age category with high penile bulb exposure experienced

potency preservation as low as that of the oldest men who


Table 3. Univariate and multivariate linear regressionanalysis: predicting recent IIEF scores of those who

previously were impotent

Univariate analysis Multivariate analysis

Variable p r p Part r

Age (years) 0.029 -0.292 0.084Follow-up (years) 0.441Gleason score 0.133ADT (months) all

patients0.117

Preimplant PSA 0.435Preimplant IIEF 0.004 0.381 <0.001 0.496Prostate size (cm3) 0.087 0.010 -0.300Stage* 0.201Isotope 0.062 0.239EBXRT* 0.193Hypertension* 0.194Tobacco use* 0.674Diabetes* 0.083 0.001 -0.385Nocturnal erections* 0.411BMI 0.132Prostate

V200 0.796V150 0.548V100 0.723%D90 0.234

Penile bulbD95 0.794D90 0.710D75 0.622D70 0.571D50 0.490D25 0.502

Proximal cruraD95 0.353D90 0.335D75 0.438D70 0.514D50 0.564D25 0.540

Distal cruraD95 0.644D90 0.600D75 0.624D70 0.609D50 0.597D25 0.613

XRT penile bulby

D95 0.495D90 0.568D75 0.666D70 0.709D50 0.973D25 0.601

Abbreviations: ADT = androgen deprivation therapy; BMI = bodymass index; EBXRT = external-beam radiation therapy; IIEF = Inter-national Index of Erectile Function; PSA = prostate-specific antigen;XRT = radiation therapy.

Those variables that had probability values of 0.10 or less duringthe univariate analysis were included in the multivariate analysis.

Bold values indicate that the p value is statistically significant orassociated with a statistically significant value.

* Data entered as a categorical variable.y Only those with XRT (n = 24) were included.

received high bulb doses. However, men aged 60–69 with pe-

nile bulb sparing had similar potency preservation to younger

men.

DISCUSSION

Erectile dysfunction is a common sequelae of all definitive

treatments for prostate cancer. The etiology of posttreatment

erectile dysfunction is felt to be multifactorial (12, 13). In

men treated with radiotherapy, arteriogenic dysfunction

seems to play a prominent role in posttreatment ED (14).

Cavernosal dysfunction with disruption of venoocclusive

mechanism has also been implicated (13, 14). Although spar-

ing of the neurovascular bundle appears to have a significant

impact in preserving potency in men undergoing prostatec-

tomy (15), this does not appear to be the case for radiotherapy

patients (16–18).

Dose to proximal penile structures in men treated with ra-

diotherapy has been implicated as a risk factor for posttreat-

ment erectile dysfunction in some studies (5, 10, 18–21) but

not others (16, 22–24). We currently report long-term follow-

up of a relatively large cohort of brachytherapy patients, all of

whom had pre- and posttreatment patient-reported assess-

ment of erectile function. For this patient population, dose

to proximal penile structures was strongly associated with

subsequent erectile function.

It is clear from prior studies that the better erectile function

a man has before treatment, the greater likelihood of retaining

function after treatment (5, 15). In this study, men with pre-

treatment IIEF of 29–30 had a 75.5% 7-year potency preser-

vation rate, compared with 23.5% for men with pretreatment

IIEF of 13–17. As well, younger men had significantly higher

potency preservation rates than older men.

Dose to the proximal penis affected erectile function more

significantly in certain subgroups of men. Younger men and

men with higher pretreatment IIEF scores appeared to tolerate

high penile bulb doses, without a significant decrease in likeli-

hood of preserved potency. Men aged 60–69 and those with

IIEF scores of 18–23 appeared to receive the biggest benefit

from limiting proximal penile dose. For this subset of men,

those with penile bulb D25 < 50% had potency preservation

rates similar to that of younger men and men with higher pre-

treatment IIEF. However, in those who did not have this level

of penile bulb sparing, potency preservation rates fell to a level

comparable with the oldest cohort of men in the study and men

with the lowest pretreatment IIEF scores.

We did not identify a statistically significant benefit to pe-

nile bulb sparing in men $ 70 years old or those with the low-

est IIEF scores. It is likely that our sample size in these

subgroups was too small to identify a modest difference, if

it existed. Nonetheless, even with penile bulb sparing, our

data suggest that these patients’ prospect for preserved po-

tency will be worse than that for younger men and for those

with better pretreatment erectile function. It also is possible

that the proximal penile sparing required to avoid erectile

dysfunction in this already tenuous group may be at such


Table 4. Day 0 dosimetry parameters: potent vs. impotent patients

Impotent (n = 55) Potent (n = 69) Overall

Variable Median Mean � SD Median Mean � SD p Median Mean � SD

ProstateV200 39.8 41.1 � 10.8 41.5 42.9 � 9.2 0.350 40.6 42.1 � 9.9V150 70.2 70.8 � 10.4 73.9 73.3 � 8.8 0.164 67.0 72.2 � 9.6V100 98.3 97.2 � 3.1 98.6 97.7 � 2.9 0.470 98.4 97.5 � 3.0D90 118.3 119.6 � 11.5 123.5 122.5 � 12.1 0.228 120.9 121.2 � 11.9

Penile BulbD95 16.8 17.5 � 10.1 10.6 13.8 � 9.9 0.042 12.7 15.5 � 10.1D90 19.2 20.6 � 11.8 12.5 16.8 � 13.7 0.103 15.5 18.5 � 13.0D75 25.8 28.4 �16.4 17.2 22.0 � 16.2 0.035 22.1 24.9 � 16.5D70 29.1 31.5 � 18.0 18.8 23.8 � 17.1 0.017 24.1 27.2 � 17.9D50 42.5 45.8 � 24.9 27.9 34.5 � 22.8 0.010 35.3 39.5 � 24.3D25 65.9 72.5 � 36.9 48.4 55.2 � 32.7 0.007 57.7 62.9 � 35.6

Proximal cruraD95 18.3 21.0 � 13.7 11.5 15.5 � 13.3 0.026 14.9 18.0 13.7�D90 20.7 23.7 � 15.6 12.6 17.3 � 15.0 0.022 16.5 20.2 � 15.6D75 29.3 33.3 � 22.4 18.2 24.0 � 20.5 0.017 22.3 28.1 � 21.8D70 32.8 37.3 � 25.3 20.3 26.8 � 22.5 0.016 26.4 31.4 � 24.3D50 55.8 59.1 � 39.1 35.7 42.7 � 33.6 0.013 39.4 50.0 � 36.9D25 101.4 100.8 � 58.9 61.6 78.7 � 55.4 0.034 79.4 88.5 � 57.8

Distal cruraD95 11.7 13.2 � 11.1 7.7 10.2 � 6.8 0.054 9.2 11.5 � 9.1D90 14.0 15.4 � 13.0 8.8 11.6 � 7.8 0.046 10.5 13.3 � 10.6D75 19.7 21.0 � 17.9 11.3 15.8 � 10.8 0.045 14.9 18.1 � 14.5D70 21.9 23.1 � 19.6 12.2 17.3 � 11.9 0.042 16.8 19.9 16.0�D50 29.2 36.4 � 32.4 18.0 25.5 � 17.8 0.018 25.5 30.3 � 25.8D25 53.7 62.6 � 45.9 36.0 47.6 � 36.1 0.044 43.5 54.3 � 41.3

XRT penile bulbD95 18.9 20.9 � 13.6 10.6 16.4 � 13.7 0.074 14.3 18.4 � 13.8D90 21.2 24.5 � 15.8 12.3 19.9 � 18.0 0.141 17.5 21.9 � 17.2D75 29.7 33.6 � 21.5 17.0 26.2 � 22.0 0.065 24.4 29.5 � 22.0D70 32.2 37.2 � 23.3 18.8 28.2 � 23.2 0.035 26.7 32.2 � 32.2D50 45.3 53.7 � 31.5 31.4 40.7 � 30.9 0.023 38.9 46.4 � 31.7D25 75.7 84.3 � 45.0 50.2 64.5 � 43.4 0.015 62.1 73.3 � 45.0

Abbreviation: XRT = radiation therapy.Bold values indicate that the p value is statistically significant or associated with a statistically significant value.

a level that unacceptable underdosing of the prostate apex

would frequently be required.

We plan to update this data in 2012. With longer follow-up,

we will be interested to see whether penile bulb sparing ulti-

mately affects potency preservation in our subset of younger

men and those with the best pretreatment erectile function.

With our current follow-up, there is a nonsignificantly higher

level of potency preservation in younger men and those with

higher IIEF scores who had penile bulb spared. We hypothe-

size that this difference may widen as the erectile reserve of

this most potent group naturally diminishes over time and

the impact of radiation becomes more apparent.

Nearly one fifth of the men who developed impotency after

treatment eventually recovered potency. The men who recov-

ered potency did not have initially mild erectile dysfunction;

in fact, they had a mean nadir posttreatment IIEF of 5.5.

However, men who regained potency tended to have above

average preimplant IIEF, with mean score of 26.5. When

we examined factors predicting for improvement in posttreat-

ment erectile function, pretreatment IIEF was not surpris-

ingly the most significant.

There are no randomized studies validating the benefit of

penile rehabilitation for brachytherapy patients who experi-

ence erectile dysfunction. However, there is emerging evi-

dence of a potential benefit in the postprostatectomy

setting. Early use of PDE5 inhibitors has been shown to pre-

serve and enhance cavernosal smooth muscle content after

prostatectomy (25). Further, in several small studies, PDE5

inhibitors after surgery has led to increases in nocturnal erec-

tions (26), improvements in IIEF scores (27), and shorter

time to recovery of erectile function (27, 28).

All of the men in our study were encouraged to begin a pe-

nile rehabilitative regimen including use of PDE5 inhibitors

and/or mechanical support as necessary to obtain at least

four erections per week. We hypothesize that a focus on erec-

tile rehabilitation contributed to improved outcomes, but this

was not formally evaluated. Encouragingly, among men who

lost potency after treatment and then subsequently regained

erectile function, the mean IIEF score was 21.3 at time of

last response. This suggests that, particularly for men with rel-

atively good pretreatment erectile function, even individuals

who experience a dramatic reduction in erectile function after


Table 5. Univariate and multivariate Cox regressionanalysis: predicting potency

Univariate Analysis Multivariate Analysis

Variable pHazardRatio p

HazardRatio

Age (year) 0.002 1.061 0.410Follow-up (years) 0.520Gleason score 0.286ADT (months)

all patients0.456

Preimplant PSA 0.077Preimplant IIEF <0.001 0.902 <0.001 0.872Prostate size (cm3) 0.081 0.047 1.031Stage* 0.896Isotope 0.724EBXRT* 0.508Hypertension* 0.047 1.716 0.011 2.061Tobacco use* 0.333Diabetes* 0.014 2.569 0.001 3.973Nocturnal erections 0.009 0.464 0.279BMI 0.192Prostate

V200 0.364V150 0.145V100 0.347%D90 0.239

Penile bulbD95 0.070 0.729D90 0.142 0.513D75 0.028 1.015 0.622D70 0.012 1.016 0.782D50 0.007 1.013 0.896D25 0.005 1.010 0.008 1.012

Proximal cruraD95 0.022 1.018 0.709D90 0.019 1.016 0.679D75 0.014 1.012 0.622D70 0.012 1.011 0.778D50 0.007 1.008 0.384D25 0.018 1.005 0.907

Distal cruraD95 0.024 1.027 0.898D90 0.016 1.023 0.491D75 0.015 1.017 0.005 0.952D70 0.014 1.016 0.537D50 0.003 1.012 0.002 1.029D25 0.019 1.006 0.666

XRT penilebulby

D95 0.484D90 0.384D75 0.308D70 0.265D50 0.206D25 0.128

Abbreviations: ADT = androgen deprivation therapy; BMI = bodymass index; EBXRT = external-beam radiation therapy; IIEF = Inter-national Index of Erectile Function; PSA = prostate-specific antigen;XRT = radiation therapy.

Those variables that had probability values of 0.10 or less duringthe univariate analysis were included in the multivariate analysis.

Bold values indicate that the p value is statistically significant orassociated with a statistically significant value.

* Data entered as a categorical variable.y Only those with XRT (n = 55) were included.

treatment have a reasonable hope for recovery of potency and

may be the group best suited for penile rehabilitation.

Overall, 19% of men in the study were impotent immedi-

ately after brachytherapy. None of these men regained po-

tency. Men with more fragile pretreatment erectile function

were at greatest risk of developing immediate impotency.

Among men with pretreatment IIEF of 13–17, the rate of im-

mediate impotence was 41%. Whether the mechanism for im-

mediate impotence differs from gradual onset impotence is

unclear. Men with penile bulb D25 < 50% had less immediate

impotence than those with higher proximal doses. However,

even with penile bulb sparing, roughly 10% of men lost po-

tency immediately.

Years Since Implant

876543210

Po

te

nc

y P

re

se

rv

atio

n (%

)

100

80

60

40

20

0

Penile Bulb D25 ≥ 50%, 45.2%

p = 0.003

Penile Bulb D25 < 50%, 70.6%

Fig. 6. Kaplan-Meier potency preservation stratified by percentdose (< 50% vs. $ 50%) delivered to 25% of the penile bulb (PenileBulb D25).

Months Since Implant

876543210

Po

te

nc

y P

re

se

rv

atio

n (%

)

100

80

60

40

20

0

D50 ≤ 50% mPD, 65.7%

D50> 50% mPD, 42.6%

p = 0.004

Proximal Crura

Fig. 7. Kaplan-Meier potency preservation, stratified by proximalcrura dosimetric D50 cutpoint of 50% minimum peripheral dose(mPD).


Table 6. Impact of dose to the penile bulb, stratified by preimplant erectile function, patient age, and nocturnal erections

Kaplan-Meier Survival (%), given a specific % of the prescribed dose to 25% of the penile bulb (Penile Bulb D25)

< 100 $ 100 p < 75 $ 75 p < 50 $ 50 p < 25 $25 p

Pre-IIEF13–17 21.4 33.3 0.880 27.3 16.7 0.523 50.0 15.4 0.140 0.0 25.0 0.79318–23 45.0 20.0 0.324 60.0 10.0 0.016 72.7 14.3 0.005 66.7 36.4 0.36124–30 67.6 63.6 0.718 70.0 59.1 0.312 72.2 63.0 0.290 91.7 62.9 0.064

Age# 59 75.6 62.5 0.317 77.1 64.3 0.328 78.3 70.0 0.482 90.0 69.7 0.22060–69 48.9 44.4 0.878 58.8 30.0 0.026 73.7 28.6 0.001 66.7 45.5 0.450$ 70 36.8 0.0 0.128 41.2 0.0 0.023 44.4 22.2 0.242 50.0 3313 0.485

Nocturnal ErectionsYes 64.2 70.0 0.795 67.9 57.1 0.469 75.0 56.1 0.072 90.9 60.6 0.072No 44.7 22.2 0.187 53.3 17.6 0.004 60.0 31.3 0.037 50.0 39.5 0.535

Abbreviation: IIEF = International Index of Erectile Function.Bold values indicate that the p value is statistically significant or associated with a statistically significant value.

We conjectured that the trauma of needle insertion, in the

periimplant time frame, might contribute to sudden onset

erectile dysfunction in some men. Although this is possible,

in a landmark study examining the etiology of radiotherapy

associated erectile dysfunction, Zelefsky (14) found a 22%

rate of sudden onset impotence in men receiving external

beam treatment only. This suggests that needle trauma alone

is unlikely to account for the relatively high rate of sudden

postbrachytherapy impotence. As well, a recent study evalu-

ating morbidity after extensive transperineal biopsies (24

prostatic regions sampled with a median of 56 biopsies)

found no significant decrease in erectile function after needle

trauma, with needle trauma similar to that associated with

transperineal brachytherapy (29).

Not all studies that have examined radiation dose to the

proximal penis have found a significant impact. However,

these negative studies may have been limited by small num-

bers (16) and shorter follow-up (16, 22). Patient selection

also likely plays a role in assessing importance of proximal

penile dose. As we demonstrated earlier, the impact of penile

bulb sparing was difficult to identify in the youngest men

with excellent pretreatment erectile function and in the oldest

men or those with the lowest IIEF scores.

We intentionally collected data on erectile function with-

out pharmacologic or mechanical support to ensure compara-

bility of data collected before treatment with the data

collected at subsequent points in time. This also increased

our sensitivity for identifying the potentially modifiable fac-

tors that influenced posttreatment potency. A strength of the

study is also the length of follow-up. We are aware of only

one other brachytherapy series (Mount Sinai) (30) with min-

imum 5-year follow-up, and that series did not evaluate the

impact of dose parameters on potency.

Our results suggest that limiting dose to the proximal penis

may decrease posttreatment erectile dysfunction. However,

although the data was collected prospectively, this is not

a randomized study evaluating the benefit of limiting penile

bulb dose. In the absence of such a trial, we encourage other

researchers to report their experience, particularly with an

emphasis on the impact of relevant dosimetric parameters

for patients stratified by pretreatment erectile function score.

CONCLUSION

Potency preservation and median IIEF scores following

brachytherapy are durable. The early institution of penile re-

habilitative strategies may be responsible for these results. In

addition, paying careful attention to periapical doses to min-

imize dose to proximal penis may further improve potency

rates. Younger men and men with better pretreatment erectile

function appear to tolerate higher proximal penile doses with

less adverse impact. However, for slightly older men and men

with more limited pretreatment erectile function, limiting

proximal penile dose appears to make a significant difference

in their long-term potency preservation.

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Erectile function durability following permanent prostate brachytherapy

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