Int. J. Radiation Oncology Biol. Phys., Vol. 62, No. 2, pp.

437– 447, 2005

Copyright © 2005 Elsevier Inc.
Printed in the USA. All rights reserved
0360-3016/05/$–see front matter

doi:10.1016/j.ijrobp.2004.10.001

CLINICAL INVESTIGATION Prostate

ERECTILE FUNCTION AFTER PROSTATE BRACHYTHERAPY

GREGORY S. MERRICK, M.D.,*† WAYNE M. BUTLER, PH.D.,*† KENT E. WALLNER, M.D.,‡

ROBERT W. GALBREATH, PH.D.,*†§ RICHARD L. ANDERSON, B.S.,* BRIAN S. KURKO, B.S.,*
JONATHAN H. LIEF, PH.D.,*† AND ZACHARIAH A. ALLEN, M.S.*
*Schiffler Cancer Center, Wheeling, WV; †Wheeling Jesuit University, Wheeling, WV; ‡Puget Sound Healthcare Corporation,
Group Health Cooperative and University of Washington, Seattle, WA; §Ohio University Eastern, St. Clairsville, OH

Purpose: To evaluate erectile function after permanent prostate brachytherapy using a validated patient-
administered questionnaire and to determine the effect of multiple clinical, treatment, and dosimetric parameters
on penile erectile function.
Methods and Materials: A total of 226 patients with preimplant erectile function determined by the International
Index of Erectile Function (IIEF) questionnaire underwent permanent prostate brachytherapy in two prospec-
tive randomized trials between February 2001 and January 2003 for clinical Stage T1c-T2c (2002 American Joint
Committee on Cancer) prostate cancer. Of the 226 patients, 132 were potent before treatment and, of those, 128
(97%) completed and returned the IIEF questionnaire after brachytherapy. The median follow-up was 29.1
months. Potency was defined as an IIEF score of >13. The clinical, treatment, and dosimetric parameters
evaluated included patient age; preimplant IIEF score; clinical T stage; pretreatment prostate-specific antigen
level; Gleason score; elapsed time after implantation; preimplant nocturnal erections; body mass index; presence
of hypertension or diabetes mellitus; tobacco consumption; the volume of the prostate gland receiving 100%,
150%, and 200% of the prescribed dose (V100/150/200); the dose delivered to 90% of the prostate gland (D90);
androgen deprivation therapy; supplemental external beam radiotherapy (EBRT); isotope; prostate volume;
planning volume; and radiation dose to the proximal penis.
Results: The 3-year actuarial rate of potency preservation was 50.5%. For patients who maintained adequate
posttreatment erectile function, the preimplant IIEF score was 29, and in patients with brachytherapy-
related ED, the preimplant IIEF score was 25. The median time to the onset of ED was 5.4 months. After
brachytherapy, the median IIEF score was 20 in potent patients and 3 in impotent patients. On univariate
analysis, the preimplant IIEF score, patient age, presence of nocturnal erections, and dose to the proximal
penis predicted for postimplant erectile function. However, in multivariate analysis, only the preimplant
IIEF score and the D50 to the proximal crura were statistically significant predictors of brachytherapy-
related erectile function.
Conclusions: Using a patient-administered validated quality-of-life instrument, brachytherapy-induced ED
occurred in 50% of patients at 3 years. On multivariate analysis, preimplant erectile function and the D50
to the proximal crura were the best predictors of brachytherapy-related erectile function. Because the
proximal penis is the most significant treatment-related predictor of brachytherapy-related ED, techniques
to minimize the radiation dose to the proximal penis may result in improved rates of potency preservation.
© 2005 Elsevier Inc.

Brachytherapy, Erectile function, Prostate, Proximal penis, Quality of life.

INTRODUCTION being, marital discord, loss of self-esteem, decreased inter-

Because of a lack of definitive evidence supporting the
superiority of radical prostatectomy, external beam radio-
therapy (EBRT), or brachytherapy for clinically localized
prostate cancer, quality-of-life (QOL) parameters have as-
sumed greater importance (1– 4). In particular, erectile dys-
function (ED) is a common sequelae of all potentially
curative local approaches and results in deleterious effects
on QOL, including diminished physical and emotional well-
est in sexual relations, and a lesser pleasure from sexual
stimulation (5–11). Accordingly, the selection of a poten-
tially curative treatment by a patient is often preceded by an
exhaustive evaluation of treatment-related morbidity (3).
Although it has been widely asserted that preservation of
erectile function is more likely after brachytherapy, the
incidence of brachytherapy-induced ED is substantially
greater than initially reported (12). Subgroup analyses have
demonstrated ED in 6 –90% of patients undergoing brachy-

Reprint requests to: Gregory S. Merrick, M.D., Schiffler Cancer gmerrick@wheelinghospital.com

Center, Wheeling Hospital, 1 Medical Park, Wheeling, WV Received Jul 6, 2004, and in revised form Sep 29, 2004. Ac-
26003-6300. Tel: (304) 243-3490; Fax: (304) 243-5047; E-mail: cepted for publication Oct 1, 2004.

437
438 I. J. Radiation Oncology ● Biology ● Physics Volume 62, Number 2, 2005

Table 1. Demographic, clinical, and treatment variables

Impotent (n ⫽ 59) Potent (n ⫽ 69) Overall (n ⫽ 128)

Variables Median Mean ⫾ SD Median Mean ⫾ SD p Median Mean ⫾ SD

Continuous
Age (y) 64.8 64.6 ⫾ 7.9 60.2 60.9 ⫾ 7.2 0.007* 63.4 62.6 ⫾ 7.7
Follow-up (mo) 29.0 29.7 ⫾ 8.1 29.2 28.4 ⫾ 8.4 0.380 29.1 29.0 ⫾ 8.3
Gleason score 7.0 6.7 ⫾ 0.8 7.0 6.6 ⫾ 0.7 0.425 7.0 6.7 ⫾ 0.7
Hormones (mo)
All patients 0.0 1.0 ⫾ 1.8 0.0 1.4 ⫾ 2.7 0.454 0.0 1.2 ⫾ 2.3
Hormone treated only (n ⫽ 32) 4.0 4.0 ⫾ 0.0 0.0 5.7 ⫾ 2.6 0.028* 4.0 4.8 ⫾ 1.9
Preimplant PSA 6.0 6.5 ⫾ 2.3 5.5 6.2 ⫾ 2.2 0.540 5.9 6.3 ⫾ 2.3
Preimplant IIEF 25.0 23.3 ⫾ 5.6 29.0 26.4 ⫾ 4.6 0.001* 26.0 25.0 ⫾ 5.3
Prostate size (cm3) 35.7 37.2 ⫾ 9.1 33.3 34.5 ⫾ 7.1 0.069 34.8 35.7 ⫾ 8.2
Planning volume 68.8 70.4 ⫾ 12.6 66.9 67.3 ⫾ 10.0 0.118 67.4 68.7 ⫾ 11.3
Categorical† Frequency, %
Hormones 0.839
No 76.3 73.9 75.0
Yes 23.7 26.1 25.0
Stage 0.780
T1a-T2b 96.6 95.7 96.1
T2c 3.4 4.3 3.9
Isotope 0.878
103
Pd 83.1 84.1 83.6
125
I 16.9 15.9 16.4
EBXRT 0.834
Implant only 37.3 40.6 39.1
20 Gy 33.9 29.0 31.3
44 Gy 28.8 30.4 29.7
Hypertension 0.331
No 50.8 59.4 55.5
Yes 49.2 40.6 44.5
Tobacco use 0.416
Never 37.8 45.8 42.3
Former 53.3 40.7 46.2
Current 8.9 13.6 11.5
BMI 0.930
ⱕ25 20.7 23.2 22.2
25–30 55.2 52.2 53.5
ⱖ30 24.1 24.6 24.4

Abbreviations: BMI ⫽ body mass index; EBRT ⫽ external beam radiotherapy; IIEF ⫽ International Index of Erectile Function; PSA ⫽
Prostate-specific antigen.
* Statistically significant.
†
Data presented as percentage of frequencies, except for p value.

therapy with or without supplemental therapies (i.e., EBRT
or androgen deprivation therapy) (12–19). The wide ranges
of reported ED likely reflect differences in follow-up, pa-
tient selection, implant technique, and the mode of data
collection (12, 20). In general, the series with longest fol-
low-up and/or the use of patient-administered question-
naires report lower rates of potency preservation (12). How-
ever, most patients with brachytherapy-induced ED respond
to erectogenic agents such as sildenafil citrate (21).
The use of patient-administered validated instruments
such as the International Index of Erectile Function (IIEF) is
essential for the accurate and reliable collection of QOL
data (20, 22, 23). The IIEF requires patients to quantify
erectile performance, with a score of ⬍11 and of ⬍6 indic-
ative of moderate and severe ED, respectively (22, 23). At
prostate cancer diagnosis, ED is present in 30 –50% of men
(9 –11, 24).
Although the etiology of brachytherapy-induced ED is
likely multifactorial (25), the available data strongly support
the proximal penis as an important site-specific structure
(26 –33). Although brachytherapy-related ED is partly de-
pendent on the radiation dose to the proximal penis, to date
no relationship has been established between brachythera-
py-related ED and the radiation dose to the neurovascular
bundles (13, 34).
The documentation of sexual function after brachyther-
apy with validated QOL instruments and detailed postim-
plant dosimetric evaluation may help elucidate the etiology
of erectile function and refine treatment techniques with the
potential for subsequent improvement in potency preserva-
 Erectile function after prostate brachytherapy ● G. S. MERRICK et al. 439

35 100

Potence Preservation (%)

30
80

25
Number of Responses

60
20
50.5%
15 40

10
20

0
0
a. 12 14 16 18 20 22 24 26 28 30 0 12 24 36 48
Preimplant IIEF Score
Months since Implant
Fig. 2. Kaplan-Meier potency preservation curve for 128 patients.
25
Censored patients indicated by plus symbols at time of last follow-
Impotent (n = 59) Potent (n = 69) up.

20
eral dose was 125 Gy (American Brachytherapy Society, 2000) for
Number of Respondents

103
Pd and 145 Gy (Task Group 43) for 125I. For the higher-risk
study (clinical Stage T1b-T2c with either Gleason score ⱖ7 and/or
15
prostate-specific antigen level of 10.1–20.0 ng/mL), the 103Pd dose
was 115 Gy and 90 Gy for the 20- and 44-Gy arms, respectively.
The calculation algorithms and seed parameters used were those
10
recommended by the American Association of Physicists in Med-
icine Task Group No. 43 (38).
Both prospective randomized trials used a patient-administered
5 four-tiered potency scoring system (0, no erections; 1, ability to
have erections, but insufficient for vaginal penetration; 2, erectile
function sufficient for vaginal penetration, but considered subop-
b. 0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30
Postimplant IIEF Score
100
Fig. 1. Histograms of International Index of Erectile Function
(IIEF) score distributions of the 128 patients classified as potent
Potency Preservation (%)

with IIEF score ⱖ13. (a) Preimplant scores. (b) Postimplant

80
scores.
∆ = IIEF 24–30, 57.6%

60
tion (32, 33). In this study, erectile function after permanent
prostate brachytherapy was evaluated using the IIEF ques-
tionnaire with determination of the impact of multiple clin- 40
+ = IIEF 18–23, 48.0%
ical, treatment, and dosimetric parameters on penile erectile
function.
20
O = IIEF 13–17, 22.1%
p = 0.001
METHODS AND MATERIALS
A total of 226 patients with preimplant erectile function deter- 0

mined by the IIEF underwent permanent prostate brachytherapy in 0 12 24 36 48

two prospective randomized trials between February 2001 and
January 2003 for clinical Stage T1c-T2c (2002 American Joint
Committee on Cancer) prostate cancer (35, 36). Before treatment,
all biopsy slides underwent central pathology review (37).
For the low-risk trial (Gleason score ⱕ6, prostate-specific anti-
gen ⱕ10 ng/mL, and clinical Stage T1b-T2b), the minimal periph-
Months since Implant
Fig. 3. Kaplan-Meier potency preservation stratified by preimplant
International Index of Erectile Function (IIEF) score: IIEF 24 –30,
n ⫽ 86 (open triangles); IIEF 18 –23, n ⫽ 25 (plus signs); and IIEF
13–17, n ⫽ 17 (open circles).
440 I. J. Radiation Oncology ● Biology ● Physics Volume 62, Number 2, 2005

100 100

Potency Preservation (%)

Potenct Preservation (%)

80 80
Ages < 60, 60.8%
O = Implant only, 50.0%
60 60

40
Ages 60–69, 48.6%
40 + = Supplemental XRT, 50.9%

Ages ≥ 70, 32.0%

20 20 p = 0.624

p = 0.002
0 0

0 12 24 36 48 0 12 24 36 48

Months since Implant Months since Implant

Fig. 4. Kaplan-Meier potency preservation stratified by patient age Fig. 6. Kaplan-Meier potency preservation stratified by use of
at implant: ⬍60 years, n ⫽ 49 (plus signs); 60 – 69 years, n ⫽ 54 supplemental external beam radiotherapy (EBRT): EBRT plus
(open circles); and ⱖ70 years, n ⫽ 25 (open triangles). brachytherapy (n ⫽ 78, plus signs) vs. implant only (n ⫽ 50, open
circles).

timal; and 3, normal erectile function). In addition, at the Schiffler

Cancer Center, patients also completed the IIEF at baseline and
periodically during the follow-up period. Each of the patients in
this study completed two or three IIEF questionnaires. Follow-up
was calculated from the completion of the last IIEF. The onset of
impotency was determined by review of the four-tiered potency
assessment score and by chart review.
For supplemental EBRT, the target volume consisted of the
prostate gland and seminal vesicles, with 2.0-cm margins superi-
orly, inferiorly, anteriorly, and laterally and a 1.0-cm posterior
margin. Patients were irradiated in 2.0-Gy fractions using a four-
field conformal technique calculated to the 95% isodose line. For
each patient, the penile bulb was identified and the EBRT dose
distribution calculated.
Of the 226 patients, 132 (58.4%) were potent before brachytherapy
by IIEF criteria (22). In addition, at the initial consultation, the
presence or absence of nocturnal erections was assessed by physician
interview. After brachytherapy, each of the 132 patients was mailed a
self-addressed, stamped, return envelope along with the IIEF ques-
tionnaire. Before and after brachytherapy, the IIEF instructions in-
cluded a sentence that specified that erectile function needed to be
quantified without pharmacologic or mechanical erectogenic assis-
tance. Of the 132 patients, 128 (97%) completed and returned the
post-implant IIEF questionnaire. Pre- and postimplant potency was
defined as an IIEF score ⱖ13. The mean and median patient fol-
low-up was 29.0 ⫾ 8.3 months and 29.1 months, respectively (range
13.1– 42.8).
The brachytherapy planning target volume consisted of the

100
100
Potency Preservation (%)

Potency Preservation (%)

80

+ = Nocturnal erection, 57.4% 80

60

60 + = Pd-103, 52.7%

40
O = No nocturnal erection, 39.4%
40
O = I-125, 45.2%
20

p = 0.018
20
p = 0.829
0

0 12 24 36 48 0
Months since Implant
0 12 24 36 48
Fig. 5. Kaplan-Meier potency preservation stratified by preimplant Months since Implant
nocturnal erection status. Patients with (n ⫽ 80) and without (n ⫽
48) preimplant nocturnal erections indicated by plus signs and Fig. 7. Kaplan-Meier potency preservation stratified by isotope:
open circles, respectively. 125
I (n ⫽ 21, open circles) vs. 103Pd (n ⫽ 107, plus signs).
 Erectile function after prostate brachytherapy ● G. S. MERRICK et al. 441

Table 2. Day 0 dosimetry parameters: Potent vs. impotent patients

Impotent (n ⫽ 59) Potent (n ⫽ 69) Overall (n ⫽ 128)

Variable Median Mean ⫾ SD Median Mean ⫾ SD p Median Mean ⫾ SD

Prostate
V200 39.7 41.1 ⫾ 10.1 41.5 42.9 ⫾ 9.7 0.328 40.6 42.1 ⫾ 9.9
V150 70.2 70.9 ⫾ 10.6 73.7 73.2 ⫾ 8.6 0.176 72.5 72.2 ⫾ 9.6
V100 98.4 97.2 ⫾ 3.4 98.5 97.7 ⫾ 2.5 0.364 98.4 97.5 ⫾ 2.9
D90 119.2 120.7 ⫾ 12.7 122.9 121.4 ⫾ 11.0 0.763 120.7 121.1 ⫾ 11.8
Penile bulb
D95 17.6 17.7 ⫾ 10.1 9.5 12.8 ⫾ 9.2 0.001* 12.8 15.5 ⫾ 10.0
D90 19.9 21.9 ⫾ 11.9 10.7 15.6 ⫾ 13.0 0.005* 15.8 18.5 ⫾ 12.8
D75 26.5 30.1 ⫾ 16.4 16.1 20.5 ⫾ 15.1 0.001* 22.4 25.0 ⫾ 16.4
D70 29.6 33.5 ⫾ 17.9 17.7 22.1 ⫾ 15.9 ⬍0.001* 24.7 27.3 ⫾ 17.7
D50 45.7 48.7 ⫾ 24.2 27.4 32.1 ⫾ 21.5 ⬍0.001* 35.8 39.7 ⫾ 24.2
D25 74.2 76.6 ⫾ 34.7 45.6 51.8 ⫾ 31.8 ⬍0.001* 59.3 63.3 ⫾ 35.3
Proximal crura
D95 19.1 22.1 ⫾ 13.5 11.1 14.6 ⫾ 12.7 0.002* 15.1 18.0 ⫾ 13.6
D90 22.1 24.9 ⫾ 15.3 12.4 16.3 ⫾ 14.4 0.001* 16.6 20.2 ⫾ 15.4
D75 33.0 35.6 ⫾ 22.1 16.3 22.0 ⫾ 19.1 ⬍0.001* 23.3 28.3 ⫾ 21.6
D70 39.1 40.2 ⫾ 25.1 18.4 24.3 ⫾ 20.6 ⬍0.001* 27.2 31.6 ⫾ 24.1
D50 65.6 65.5 ⫾ 38.8 28.5 38.0 ⫾ 30.6 ⬍0.001* 40.5 50.7 ⫾ 37.1
D25 112.7 112.2 ⫾ 57.9 56.4 71.2 ⫾ 52.0 ⬍0.001* 79.8 90.1 ⫾ 58.3
Distal crura
D95 12.3 13.8 ⫾ 10.7 6.5 9.6 ⫾ 6.7 0.007* 9.3 11.6 ⫾ 9.0
D90 14.5 16.2 ⫾ 12.6 7.7 11.0 ⫾ 7.6 0.005* 10.8 13.4 ⫾ 10.5
D75 20.6 22.3 ⫾ 17.4 10.9 14.8 ⫾ 10.2 0.003* 15.4 18.3 ⫾ 14.4
D70 22.4 24.6 ⫾ 19.1 12.0 16.1 ⫾ 11.2 0.002* 17.5 20.0 ⫾ 15.9
D50 33.0 38.9 ⫾ 31.6 16.5 23.6 ⫾ 16.5 0.001* 26.6 30.7 ⫾ 25.7
D25 59.0 69.2 ⫾ 47.6 32.8 43.3 ⫾ 31.6 0.001* 45.5 55.3 ⫾ 41.7
EBRT to penile bulb
D95 20.3 22.1 ⫾ 13.9 10.1 15.2 ⫾ 12.5 0.003* 14.5 18.4 ⫾ 13.6
D90 22.9 25.9 ⫾ 16.2 11.9 18.4 ⫾ 16.9 0.012* 17.6 21.9 ⫾ 16.9
D75 31.7 35.5 ⫾ 21.9 16.7 24.2 ⫾ 20.3 0.003* 24.4 29.5 ⫾ 21.7
D70 34.9 39.3 ⫾ 23.7 18.3 26.0 ⫾ 21.3 0.001* 26.7 32.1 ⫾ 23.3
D50 52.0 56.8 ⫾ 31.4 28.9 37.6 ⫾ 28.5 ⬍0.001* 38.9 46.5 ⫾ 31.3
D25 89.8 88.6 ⫾ 43.3 49.1 60.3 ⫾ 41.4 ⬍0.001* 62.1 73.4 ⫾ 44.4

Abbreviations: D95/90/75/70/50/25 ⫽ dose delivered to 95%, 90%, 75%, 70%, 50%, and 25% of prostate gland; EBRT ⫽ external beam
radiotherapy; V200/150/100 ⫽ volume of prostate receiving 200%, 150%, and 100% of prescribed dose.
* Statistically significant.

prostate gland with a 5-mm anterior and lateral margin on each
ultrasound slice and was approximately 1.75 times the ultrasound-
determined prostate volume (39). The minimal peripheral dose
(mPD) was prescribed to the planning target volume with a mar-
gin. At implantation, the prostate gland, periprostatic region, and
base of the seminal vesicles were implanted. Specifically, the
brachytherapy procedure was performed with transverse and sag-
ittal ultrasonography and fluoroscopy. On average, approximately
35% of seeds were placed in periprostatic locations (40).
Within 2 hours of implantation, spiral CT was obtained at 3–5
mm thickness and 3–5 mm spacing. The dose distribution to the
prostate gland, urethra, and proximal penis was generated by a
dedicated treatment planning computer (Variseed; Varian, Char-
lottesville, VA). The CT-determined proximal penile anatomy was
defined as previously described (41). All CT-determined structures
and seed locations were determined by one of us (G.S.M. and
R.L.A., respectively). The crura was subdivided into a proximal
1.0-cm segment and a subsequent 3.0-cm segment. After EBRT
and brachytherapy, the most proximal centimeter of the crura
received the greatest doses of radiation (30, 32). Dosimetric cal-
culations consisted of the values of the minimal dose received by
90% of the prostate gland (D90) and the percentage of the prostate
volume receiving 100%, 150%, and 200% of the prescribed mPD
(V100/150/200). For the bulb of the penis and the two arbitrarily
defined components of the crura, the radiation dose was defined in
terms of the minimal dose delivered to 25%, 50%, 70%, 75%,
90%, and 95% of the bulb and the crural components (D25/50/70/
75/90/95).
The clinical, treatment, and dosimetric parameters evaluated for
erectile function included patient age, preimplant IIEF score, clin-
ical T stage, pretreatment prostate-specific antigen level, Gleason
score, elapsed time after implantation, presence of preimplant
nocturnal erections, body mass index, the presence of hypertension
or diabetes mellitus, tobacco consumption, prostate V100/150/200,
prostate D90, radiation dose to the bulb of the penis, radiation dose
to the proximal and distal crura, use of androgen deprivation
therapy, supplemental EBRT, isotope, prostate volume, planning
volume, and radiation dose to the proximal penis.
A 2 ⫻ 2 analysis of variance was conducted between the factors
of group and potency to evaluate differences in continuous demo-
graphic data. Categorical data were analyzed using two-way con-
tingency tables and were compared for the factors of group and
442 I. J. Radiation Oncology ● Biology ● Physics Volume 62, Number 2, 2005

103 125
Table 3. Day 0 dosimetry: Pd vs. I (lower-risk patient trial)
103
Pd (n ⫽ 29) 125
I (n ⫽ 21) Overall (n ⫽ 50)

Variable Median Mean ⫾ SD Median Mean ⫾ SD p Median Mean ⫾ SD

Penile bulb
D95 10.7 13.2 ⫾ 10.1 24.8 25.5 ⫾ 8.0 ⬍0.001 17.7 18.4 ⫾ 11.1
D90 12.2 15.8 ⫾ 12.9 29.0 29.1 ⫾ 9.3 ⬍0.001 21.3 21.4 ⫾ 13.2
D75 17.9 22.6 ⫾ 18.5 38.2 37.9 ⫾ 12.7 ⬍0.001 28.3 29.0 ⫾ 17.9
D70 20.2 24.6 ⫾ 19.6 41.0 40.7 ⫾ 14.0 ⬍0.001 30.9 31.4 ⫾ 19.0
D50 31.6 37.1 ⫾ 26.4 53.6 54.8 ⫾ 18.9 ⬍0.001 43.6 44.5 ⫾ 24.9
D25 57.2 61.0 ⫾ 39.5 74.9 78.8 ⫾ 24.8 ⬍0.001 67.1 68.5 ⫾ 35.0
Proximal crura
D95 12.6 16.4 ⫾ 16.4 26.4 28.4 ⫾ 11.0 0.036 19.4 21.5 ⫾ 15.5
D90 14.0 18.7 ⫾ 18.7 29.6 31.2 ⫾ 12.7 0.037 21.2 23.9 ⫾ 17.5
D75 22.2 26.5 ⫾ 25.0 37.4 41.2 ⫾ 19.5 0.016 29.0 32.7 ⫾ 23.8
D70 25.6 29.8 ⫾ 27.0 41.8 45.3 ⫾ 22.7 0.008 32.4 36.3 ⫾ 26.2
D50 48.6 49.0 ⫾ 38.0 64.0 63.8 ⫾ 30.7 0.001 55.1 55.3 ⫾ 35.5
D25 101.4 91.0 ⫾ 58.2 95.8 96.3 ⫾ 39.7 ⬍0.001 97.8 93.2 ⫾ 50.9

Abbreviations as in Table 2.

potency. Associations among categorical variables were tested
using a Pearson chi-square test. The correlation between age at
implantation and the dose to the proximal penis was analyzed
using a Pearson correlation coefficient. Doses to the prostate,
penile bulb, and proximal and distal crura were compared between
those who were and were not potent using independent t-tests.
Potency preservation curves were determined by the Kaplan-Meier
method, with the log–rank test used for comparison among the
levels of the various factors of interest. Univariate Cox regression
analysis was used to determine the univariate predictors of erectile
function, and all variables with p ⱕ0.10 were included as covari-
ates in a multivariate model of Cox regression as a means of
identifying independent predictors of erectile function. For all
tests, p ⱕ0.05 was considered statistically significant. Statistical
analysis was performed with Statistical Package for Social Sci-
ences, version 11.0, software (SPSS, Chicago, IL).
RESULTS
Table 1 summarizes the clinical and treatment parameters
for the 128 (97%) of the 132 patients who were potent
before brachytherapy and who completed the postbrachy-
therapy IIEF survey. On average, patients who maintained
potency after brachytherapy were 3.7 years younger than
those who became impotent and presented with a statisti-
cally greater preimplant IIEF score (p ⫽ 0.001), with a trend
for smaller prostate size (p ⫽ 0.069). None of the other
evaluated clinical or treatment parameters approached sta-
tistical significance.
Figure 1a illustrates the distribution of the preimplant
IIEF scores for patients considered potent, and Fig. 1b
displays the distribution of the postimplant IIEF scores. Of
the 69 patients who maintained adequate erectile function,
the median preimplant IIEF score was 29, and patients who
developed brachytherapy-related ED had a median preim-
plant IIEF score of 25 (p ⫽ 0.001). The mean and median
time to the onset of brachytherapy-related ED was 2.6 and
5.4 months, respectively. In patients maintaining adequate
erectile function after brachytherapy, the median IIEF score
was 20 (range, 13–30), and the median IIEF score in impo-
tent patients was 3 (range, 1–12).
Figure 2 presents the Kaplan-Meier 3-year overall po-
tency preservation rate (50.5%) for the 128 patients. Of
note, 12% of patients developed impotency immediately
after the implant procedure, with nearly 40% of the patient
population developing ED within the first 12 months. Figure
3 stratifies potency preservation by the preimplant IIEF
score. The 3-year rate of potency preservation for patients
with a preimplant IIEF score of 24 –30, 18 –23, and 13–17
was 57.6%, 48.0%, and 22.1%, respectively (p ⫽ 0.001). In
patients with a preimplant IIEF score of 29 or 30, a 78.8%
rate of potency preservation was noted, with a median
postimplant IIEF score of 24.
When stratified by age, younger patients were more likely
to maintain erections sufficient for vaginal penetration after
brachytherapy (Fig. 4). The 3-year actuarial rate of potency
preservation was 60.8%, 48.6%, and 32.0% for patients
⬍60, 60 – 69, and ⱖ70 years of age, respectively (p ⫽
0.002).
Figure 5 evaluates the impact of preimplant nocturnal
erections on brachytherapy-related ED. The presence of
prebrachytherapy nocturnal erections resulted in a signifi-
cantly greater rate of potency preservation (p ⫽ 0.018). The
use of neoadjuvant androgen deprivation therapy (49.1% vs.
56.3%, p ⫽ 0.828), supplemental EBRT (Fig. 6, p ⫽ 0.624),
isotope (Fig. 7, p ⫽ 0.829), tobacco status (p ⫽ 0.382),
hypertension (p ⫽ 0.315), or body mass index (p ⫽ 0.943)
did not affect the 3-year rate of potency preservation. In
addition, the stratification of supplemental EBRT into 20-
vs. 44-Gy arms did not affect potency preservation (47.5%
vs. 55.0%, p ⫽ 0.778). Finally, a trend for a greater rate of
ED was identified in diabetic patients; however, it did not
reach statistical significance (30.0% vs. 52.2%, p ⫽ 0.100).
Table 2 summarizes the Day 0 postimplant dosimetry for
 Erectile function after prostate brachytherapy ● G. S. MERRICK et al. 443

80 100

Potency Preservation (%)

impotent O = D50 ≤ 30% mPD, 76.2%
Mean Penile Bulb Dose (% mPD)

potent
80
60

60 Penile Bulb

40
40

O = D50 > 30% mPD, 31.5%

20
20
p = < 0.001

0 0 12 24 36 48
D25 D50 D70 D75 D90 D95 a.
Months since Implant
Fig. 9. Kaplan-Meier potency preservation stratified by penile bulb
120 dosimetric D50 cutpoint of 30% mPD: D50 ⱕ30% mPD (n ⫽ 55,
impotent open circles) vs. D50 ⬎30% mPD (n ⫽ 73, plus signs).
Mean Proximal Crura Dose (%mPD)

potent
100
proximal crura D50 (area ⫽ 0.737). Coordinates of the
receiver operating characteristics curves indicated that the
80
optimal cutpoints were 30% mPD for the penile bulb D50
(sensitivity 0.797, specificity 0.623) or an mPD of 50% for
60 the proximal crura D50 (sensitivity 0.678, specificity 0.739).
Potency preservation stratified by the penile bulb D50 cut-
point of 30% mPD is plotted in Fig. 9, and potency pres-
40
ervation stratified by the proximal crura D50 cutpoint of
50% mPD is plotted in Fig. 10. In both, the difference
20 between the lower-dose cohort and the higher-dose cohort
was substantially statistically significant (p ⫽ 0.001). Figure
11 displays a lack of correlation between patient age and the
0
D25 D50 D70 D75 D90 D95 b. dose to the bulb of the penis for dose levels D50 and D25.

Fig. 8. Mean dose for various Dxx levels as %mPD for impotent
(light bars) and potent (dark bars) patients. (a) Penile bulb. (b)
100
Proximal crura.
Potency Preservation (%)

the prostate, bulb of the penis, and proximal and distal crura. 80 O = D50 ≤ 50% mPD, 70.1%
None of the evaluated prostate dosimetric parameters pre-
dicted for brachytherapy-related ED. In contrast, for every 60
dose level examined for the proximal penis (i.e., penile Proximal Crura
bulb, proximal crura, and distal crura), impotent patients
received statistically greater doses than patients who main- 40
tained adequate erectile capability. Despite the absence of a
correlation between brachytherapy-related ED and isotope
+ = D50 > 50% mPD, 27.4%
(Fig. 7), patients implanted with 125I received statistically 20

greater doses to the proximal penis (Table 3). p = < 0.001

Figure 8 illustrates the mean minimal doses delivered to
0
95%, 90%, 75%, 70%, 50%, and 25% of the penile bulb and
proximal crura stratified by potency status. Receiver oper- 0 12 24 36 48

ating characteristics curves were plotted for potency vs. the Months since Implant
various Dxx values of the proximal penis. The greatest areas Fig. 10. Kaplan-Meier potency preservation stratified by proximal
under the receiver operating characteristics curve were crura dosimetric D50 cutpoint of 50% mPD: D50 ⱕ50% mPD (n ⫽
found for the penile bulb D50 (area ⫽ 0.725) and the 71, open circles) vs. D50 ⬎50% mPD (n ⫽ 57, plus signs).
444 I. J. Radiation Oncology ● Biology ● Physics Volume 62, Number 2, 2005

DISCUSSION
200 r = 0.040, p = 0.656
Since the mid-1980s, prostate brachytherapy has been
160
used increasingly as definitive treatment for early-stage
prostate cancer, with most studies reporting favorable bio-
Penile Bulb D25 (%mPD)

chemical outcomes (19). However, because of a lack of

120 definitive evidence demonstrating the superiority in cure
rates of one local treatment compared with another, QOL
parameters have assumed greater importance (1– 4). Previ-
80 ous studies have documented multiple deleterious effects of
ED on overall QOL, including diminished physical and
emotional well-being, marital discord, loss of self-esteem,
40
decreased interest in sexual relations, and less pleasure from
sexual stimulation (5–11).
0 Erectile dysfunction is a common sequelae of all poten-
a.
tially curative local treatments (19). After brachytherapy,
40 50 60 70 80
wide ranges of ED have been reported, probably a result of
Age at Implant
differences in follow-up, patient selection, implant tech-
nique, and the mode of data collection (12, 20). The mech-
140 r = 0.027, p = 0.760
anism of ED after definitive treatment likely represents a
multifactorial process. After brachytherapy, the proximal
120 penis appears to be an important site-specific structure (26 –
33). Compared with our previous study (32), the radiation
Penile Bulb D50 (%mPD)

100
80
60
40
20
b. 0 because the corpora cavernosa are true erectile tissue
40 50 60
Age at Implant
Fig. 11. Correlation between patient age and (a) D50 or (b) D25
dose to penile bulb. p value compared patients with brachytherapy-
related erectile dysfunction (ED) (open circles) and patients with-
out ED (filled triangles). Linear regression line and correlation
coefficient (r) was for overall population (n ⫽ 128).
In univariate t-test analysis (Table 4), preimplant IIEF
score, age, nocturnal erections, and radiation dose to the
proximal penis (bulb and crura) correlated with the devel-
opment of brachytherapy-related ED and prostate size ap-
proached statistical significance (p ⫽ 0.051). Determining
whether or not the patient had nocturnal erections factored
into whether the patient developed brachytherapy-related
ED; absence predicted ED; presence predicted potency
maintenance. However, in multivariate analysis, only the
preimplant IIEF score (p ⬍0.001) and D50 to the proximal
crura (p ⬍0.001) were statistically significant predictors of
brachytherapy-induced ED, without any additional factors
approaching statistical significance, except for patient age
(p ⫽ 0.100).
dose to the penile bulb was comparable; however, the radi-
ation dose to the proximal crura was slightly greater. This
slight increase in the proximal crural dose may explain the
emergence of the proximal crura (together with the preim-
plant IIEF score) as one of the two strongest predictors of
brachytherapy-related ED. In our prior study, the penile
bulb was of greater statistical consequence; however, the
dose to the proximal crura approached statistical signifi-
cance (p ⫽ 0.052). Mulhall and colleagues have emphasized
that radiation doses to the crura may be more important
70 80 whereas corpora spongiosum plays little role in erectile
rigidity (29 –31).
Although the results of the current study did not defini-
tively clarify the site-specific structure in the proximal pe-
nis, they further substantiated the impact of the radiation
dose to the proximal penis as a prime culprit in the devel-
opment of brachytherapy-related ED and emphasize the
importance of refinements in implant technique, including
preplanning and intraoperative seed placement, to decrease
the radiation dose to the proximal penis. Refinements in
implant technique, including careful planning to avoid over-
aggressive periapical implantation, along with extensive use
of sagittal ultrasonography during the implant procedure,
should lower the radiation dose to the proximal penis and
improve potency preservation. Because previous prospec-
tive and retrospective analyses have not suggested a rela-
tionship between the radiation dose to the neurovascular
bundles and potency (13, 34), the neurovascular bundle
doses were not calculated in the current study.
Consistent with previous studies (14, 15), preimplant
erectile function remains the best clinical predictor for po-
tency preservation (p ⬍0.001). In our previous study (15),
we reported that supplemental EBRT predicted for brachy-
 Erectile function after prostate brachytherapy ● G. S. MERRICK et al. 445

Table 4. Univariate and multivariate Cox regression analysis: Predicting potency

Univariate analysis Multivariate analysis

Variable p Relative risk p Relative risk

Follow-up 0.845
Gleason score 0.307
PSA 0.437
Preimplant IIEF ⬍0.001* 0.918 ⬍0.001* 0.917
Prostate size 0.051
Planning volume 0.085
Isotope† 0.837
Age at implant 0.004* 1.055 0.100
Hypertension† 0.340
Diabetes† 0.126
Hormones† 0.837
Months of hormones 0.148
Tobacco use† 0.426
Stage group† 0.743
Risk† 0.869
% Positive biopsies 0.787
Nocturnal erection† 0.027* 0.560 0.354
EBRT 0.797
BMI 0.451
V200 0.400
V150 0.170
V100 0.219
%D90 0.607
Penile bulb
D95 0.002* 1.034 0.531
D90 0.010* 1.013 ⬎0.236
D75 0.002* 1.020 0.395
D70 0.001* 1.021 0.725
D50 ⬍0.001* 1.017 0.660
D25 ⬍0.001* 0.013 0.278
Proximal crura
D95 0.003* 1.022 0.175
D90 0.003* 1.019 0.180
D75 0.001* 1.015 0.191
D70 ⬍0.001* 1.015 0.220
D50 ⬍0.001* 1.012 ⬍0.001* 1.012
D25 ⬍0.001* 1.007 0.659
Distal crura
D95 0.005* 1.030 0.549
D90 0.003* 1.026 0.555
D75 0.001* 1.015 0.511
D70 0.001* 1.018 0.523
D50 ⬍0.001* 1.013 0.752
D25 ⬍0.001* 1.009 0.678

Abbreviations as in Tables 1 and 2.

* Statistically significant.
†
Data entered as a categorical variable.

therapy-related ED. In the current study (Fig. 6), supple-
mental EBRT did not affect brachytherapy-related erectile
function. This was probably a result of EBRT planning
techniques designed to limit the dose to the proximal penis.
In our earlier brachytherapy experience, no attempt was
made to either limit or calculate the dose to the proximal
penis. Compared with our 2001 study, the overall potency
preservation rate increased from 38.9% to 50.4% (Fig. 12).
This apparent improvement in overall potency was exclu-
sively a result of better erectile function in patients under-
going supplemental EBRT. Monotherapy potency preserva-
tion outcomes have remained virtually unchanged over
time. Recently, our brachytherapy doses to the proximal
penis have decreased substantially (unpublished data), and
we hope this will translate to additional improvements in
brachytherapy-related potency preservation.
To the best of our knowledge, this is the first brachyther-
apy study to evaluate the effect of preimplant nocturnal
446 I. J. Radiation Oncology
100
Potency Preservation (%)
80
60
2004 study, 50.5%
40
2001 study, 38.9%
20
p = 0.355
0
0 12 24 36 48
Months since Implant
Fig. 12. Comparison of potency preservation rates reported in our
2001 survey (15) with current (2004) survey. Patients in 2004
survey underwent implantation after 2001 and were treated with
penile bulb-sparing techniques.
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● Biology ● Physics Volume 62, Number 2, 2005
erections on brachytherapy-related ED. A potential short-
coming of our nocturnal erection evaluation was the ab-
sence of formal nocturnal penile tumescence testing. How-
ever, although subjective, physician interview represents an
accepted mode of evaluation (42). The presence of preim-
plant nocturnal erections predicted for a greater chance of
potency preservation in univariate, but not multivariate,
analysis and could potentially be a predictor of early vas-
cular compromise.
CONCLUSION
Using a patient-administered validated QOL instrument,
brachytherapy-induced ED occurred in 50% of patients at 3
60 72 years. In multivariate analysis, preimplant erectile function
and the D50 to the proximal crura were the best predictors of
brachytherapy-related erectile function. Because the proxi-
mal penis was the most significant treatment-related predic-
tor of brachytherapy-related ED, techniques to minimize the
radiation dose to the proximal penis may result in improved
rates of potency preservation.
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