Erectile function after prostate brachytherapy

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Int. J. Radiation Oncology Biol. Phys., Vol. 62, No. 2, pp. 437–447, 2005Copyright © 2005 Elsevier Inc.

Printed in the USA. All rights reserved0360-3016/05/$–see front matter

doi:10.1016/j.ijrobp.2004.10.001

LINICAL 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 parameterson penile erectile function.Methods and Materials: A total of 226 patients with preimplant erectile function determined by the InternationalIndex 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 JointCommittee 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 29.1months. Potency was defined as an IIEF score of >13. The clinical, treatment, and dosimetric parametersevaluated included patient age; preimplant IIEF score; clinical T stage; pretreatment prostate-specific antigenlevel; Gleason score; elapsed time after implantation; preimplant nocturnal erections; body mass index; presenceof 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 adequateposttreatment 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. Afterbrachytherapy, the median IIEF score was 20 in potent patients and 3 in impotent patients. On univariateanalysis, the preimplant IIEF score, patient age, presence of nocturnal erections, and dose to the proximalpenis predicted for postimplant erectile function. However, in multivariate analysis, only the preimplantIIEF 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 EDoccurred 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 theproximal penis is the most significant treatment-related predictor of brachytherapy-related ED, techniquesto 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.

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INTRODUCTION

ecause of a lack of definitive evidence supporting theuperiority of radical prostatectomy, external beam radio-herapy (EBRT), or brachytherapy for clinically localizedrostate cancer, quality-of-life (QOL) parameters have as-umed greater importance (1–4). In particular, erectile dys-unction (ED) is a common sequelae of all potentiallyurative local approaches and results in deleterious effectsn QOL, including diminished physical and emotional well-

Reprint requests to: Gregory S. Merrick, M.D., Schiffler Cancerenter, Wheeling Hospital, 1 Medical Park, Wheeling, WV
6003-6300. Tel: (304) 243-3490; Fax: (304) 243-5047; E-mail: c
437

eing, marital discord, loss of self-esteem, decreased inter-st in sexual relations, and a lesser pleasure from sexualtimulation (5–11). Accordingly, the selection of a poten-ially curative treatment by a patient is often preceded by anxhaustive evaluation of treatment-related morbidity (3).

Although it has been widely asserted that preservation ofrectile function is more likely after brachytherapy, thencidence of brachytherapy-induced ED is substantiallyreater than initially reported (12). Subgroup analyses haveemonstrated ED in 6–90% of patients undergoing brachy-

[email protected] Jul 6, 2004, and in revised form Sep 29, 2004. Ac-

epted for publication Oct 1, 2004.

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

herapy with or without supplemental therapies (i.e., EBRTr androgen deprivation therapy) (12–19). The wide rangesf reported ED likely reflect differences in follow-up, pa-ient selection, implant technique, and the mode of dataollection (12, 20). In general, the series with longest fol-ow-up and/or the use of patient-administered question-aires report lower rates of potency preservation (12). How-ver, most patients with brachytherapy-induced ED respondo erectogenic agents such as sildenafil citrate (21).

The use of patient-administered validated instrumentsuch as the International Index of Erectile Function (IIEF) isssential for the accurate and reliable collection of QOLata (20, 22, 23). The IIEF requires patients to quantifyrectile performance, with a score of �11 and of �6 indic-

Table 1. Demographic, c

Variables

Impotent (n � 59)

Median Mean � SD

ontinuousAge (y) 64.8 64.6 � 7.9Follow-up (mo) 29.0 29.7 � 8.1Gleason score 7.0 6.7 � 0.8

ormones (mo)All patients 0.0 1.0 � 1.8Hormone treated only (n � 32) 4.0 4.0 � 0.0Preimplant PSA 6.0 6.5 � 2.3Preimplant IIEF 25.0 23.3 � 5.6Prostate size (cm3) 35.7 37.2 � 9.1Planning volume 68.8 70.4 � 12.6

ategorical†

HormonesNo 76.3Yes 23.7

StageT1a-T2b 96.6T2c 3.4

Isotope103Pd 83.1125I 16.9

EBXRTImplant only 37.320 Gy 33.944 Gy 28.8

HypertensionNo 50.8Yes 49.2

Tobacco useNever 37.8Former 53.3Current 8.9

BMI�25 20.725–30 55.2�30 24.1

Abbreviations: BMI � body mass index; EBRT � external beamrostate-specific antigen.* Statistically significant.† Data presented as percentage of frequencies, except for p val

tive of moderate and severe ED, respectively (22, 23). At p

rostate cancer diagnosis, ED is present in 30–50% of men9–11, 24).

Although the etiology of brachytherapy-induced ED isikely multifactorial (25), the available data strongly supporthe proximal penis as an important site-specific structure26–33). Although brachytherapy-related ED is partly de-endent on the radiation dose to the proximal penis, to dateo relationship has been established between brachythera-y-related ED and the radiation dose to the neurovascularundles (13, 34).The documentation of sexual function after brachyther-

py with validated QOL instruments and detailed postim-lant dosimetric evaluation may help elucidate the etiologyf erectile function and refine treatment techniques with the

and treatment variables

Potent (n � 69)

p

Overall (n � 128)

dian Mean � SD Median Mean � SD

0.2 60.9 � 7.2 0.007* 63.4 62.6 � 7.79.2 28.4 � 8.4 0.380 29.1 29.0 � 8.37.0 6.6 � 0.7 0.425 7.0 6.7 � 0.7

0.0 1.4 � 2.7 0.454 0.0 1.2 � 2.30.0 5.7 � 2.6 0.028* 4.0 4.8 � 1.95.5 6.2 � 2.2 0.540 5.9 6.3 � 2.39.0 26.4 � 4.6 0.001* 26.0 25.0 � 5.33.3 34.5 � 7.1 0.069 34.8 35.7 � 8.26.9 67.3 � 10.0 0.118 67.4 68.7 � 11.3

Frequency, %0.839

73.9 75.026.1 25.0

0.78095.7 96.14.3 3.9

0.87884.1 83.615.9 16.4

0.83440.6 39.129.0 31.330.4 29.7

0.33159.4 55.540.6 44.5

0.41645.8 42.340.7 46.213.6 11.5

0.93023.2 22.252.2 53.524.6 24.4

therapy; IIEF � International Index of Erectile Function; PSA �

linical,

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otential for subsequent improvement in potency preserva-

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439Erectile function after prostate brachytherapy ● G. S. MERRICK et al.

ion (32, 33). In this study, erectile function after permanentrostate brachytherapy was evaluated using the IIEF ques-ionnaire with determination of the impact of multiple clin-cal, treatment, and dosimetric parameters on penile erectileunction.

METHODS AND MATERIALS

A total of 226 patients with preimplant erectile function deter-ined by the IIEF underwent permanent prostate brachytherapy in

wo prospective randomized trials between February 2001 andanuary 2003 for clinical Stage T1c-T2c (2002 American Jointommittee on Cancer) prostate cancer (35, 36). Before treatment,ll biopsy slides underwent central pathology review (37).

For the low-risk trial (Gleason score �6, prostate-specific anti-

a.

b.

12 14 16 18 20 22 24 26 28 30

Preimplant IIEF Score

0

5

10

15

20

25

30

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0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30

Postimplant IIEF Score

0

5

10

15

20

25

Nu

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Resp

on

den

ts

Impotent (n = 59) Potent (n = 69)

ig. 1. Histograms of International Index of Erectile FunctionIIEF) score distributions of the 128 patients classified as potentith IIEF score �13. (a) Preimplant scores. (b) Postimplant

cores.

en �10 ng/mL, and clinical Stage T1b-T2b), the minimal periph- 1

ral dose was 125 Gy (American Brachytherapy Society, 2000) for03Pd and 145 Gy (Task Group 43) for 125I. For the higher-risktudy (clinical Stage T1b-T2c with either Gleason score �7 and/orrostate-specific antigen level of 10.1–20.0 ng/mL), the 103Pd doseas 115 Gy and 90 Gy for the 20- and 44-Gy arms, respectively.he calculation algorithms and seed parameters used were those

ecommended by the American Association of Physicists in Med-cine Task Group No. 43 (38).

Both prospective randomized trials used a patient-administeredour-tiered potency scoring system (0, no erections; 1, ability toave erections, but insufficient for vaginal penetration; 2, erectileunction sufficient for vaginal penetration, but considered subop-

0 12 24 36 48

Months since Implant

0

20

40

60

80

100

Po

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Pre

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n (

%)

50.5%

ig. 2. Kaplan-Meier potency preservation curve for 128 patients.ensored patients indicated by plus symbols at time of last follow-p.

0 12 24 36 48


0

20

40

60

80

100

Po

ten

cy P

res

erv

ati

on

(%

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O = IIEF 13–17, 22.1%

+ = IIEF 18–23, 48.0%

∆ = IIEF 24–30, 57.6%

p = 0.001

ig. 3. Kaplan-Meier potency preservation stratified by preimplantnternational Index of Erectile Function (IIEF) score: IIEF 24–30,� 86 (open triangles); IIEF 18–23, n � 25 (plus signs); and IIEF
3–17, n � 17 (open circles).

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imal; and 3, normal erectile function). In addition, at the Schifflerancer Center, patients also completed the IIEF at baseline anderiodically during the follow-up period. Each of the patients inhis study completed two or three IIEF questionnaires. Follow-upas calculated from the completion of the last IIEF. The onset of

mpotency was determined by review of the four-tiered potencyssessment score and by chart review.

For supplemental EBRT, the target volume consisted of therostate gland and seminal vesicles, with 2.0-cm margins superi-rly, inferiorly, anteriorly, and laterally and a 1.0-cm posteriorargin. Patients were irradiated in 2.0-Gy fractions using a four-eld conformal technique calculated to the 95% isodose line. Forach patient, the penile bulb was identified and the EBRT doseistribution calculated.

0 12 24 36 48


0

20

40

60

80

100

Po

ten

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Pre

serv

ati

on

(%

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Ages 60–69, 48.6%

Ages ≥ 70, 32.0%

Ages < 60, 60.8%

p = 0.002

ig. 4. Kaplan-Meier potency preservation stratified by patient aget implant: �60 years, n � 49 (plus signs); 60–69 years, n � 54open circles); and �70 years, n � 25 (open triangles).

0 12 24 36 48


0

20

40

60

80

100

Po

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res

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(%

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O = No nocturnal erection, 39.4%

+ = Nocturnal erection, 57.4%

p = 0.018

ig. 5. Kaplan-Meier potency preservation stratified by preimplantocturnal erection status. Patients with (n � 80) and without (n �8) preimplant nocturnal erections indicated by plus signs and
pen circles, respectively. 1
Of the 226 patients, 132 (58.4%) were potent before brachytherapyy IIEF criteria (22). In addition, at the initial consultation, theresence or absence of nocturnal erections was assessed by physiciannterview. After brachytherapy, each of the 132 patients was mailed aelf-addressed, stamped, return envelope along with the IIEF ques-ionnaire. Before and after brachytherapy, the IIEF instructions in-luded a sentence that specified that erectile function needed to beuantified without pharmacologic or mechanical erectogenic assis-ance. Of the 132 patients, 128 (97%) completed and returned theost-implant IIEF questionnaire. Pre- and postimplant potency wasefined as an IIEF score �13. The mean and median patient fol-ow-up was 29.0 � 8.3 months and 29.1 months, respectively (range3.1–42.8).

The brachytherapy planning target volume consisted of the

0 12 24 36 48


0

20

40

60

80

100

Po

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res

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ati

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(%

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O = Implant only, 50.0%

+ = Supplemental XRT, 50.9%

p = 0.624

ig. 6. Kaplan-Meier potency preservation stratified by use ofupplemental external beam radiotherapy (EBRT): EBRT plusrachytherapy (n � 78, plus signs) vs. implant only (n � 50, openircles).

0 12 24 36 48


0

20

40

60

80

100

Po

ten

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rese

rvati

on

(%

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O = I-125, 45.2%

+ = Pd-103, 52.7%

p = 0.829

ig. 7. Kaplan-Meier potency preservation stratified by isotope:
25I (n � 21, open circles) vs. 103Pd (n � 107, plus signs).

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rostate gland with a 5-mm anterior and lateral margin on eachltrasound slice and was approximately 1.75 times the ultrasound-etermined prostate volume (39). The minimal peripheral dosemPD) was prescribed to the planning target volume with a mar-in. At implantation, the prostate gland, periprostatic region, andase of the seminal vesicles were implanted. Specifically, therachytherapy procedure was performed with transverse and sag-ttal ultrasonography and fluoroscopy. On average, approximately5% of seeds were placed in periprostatic locations (40).Within 2 hours of implantation, spiral CT was obtained at 3–5m thickness and 3–5 mm spacing. The dose distribution to the

rostate gland, urethra, and proximal penis was generated by aedicated treatment planning computer (Variseed; Varian, Char-ottesville, VA). The CT-determined proximal penile anatomy wasefined as previously described (41). All CT-determined structuresnd seed locations were determined by one of us (G.S.M. and.L.A., respectively). The crura was subdivided into a proximal.0-cm segment and a subsequent 3.0-cm segment. After EBRTnd brachytherapy, the most proximal centimeter of the cruraeceived the greatest doses of radiation (30, 32). Dosimetric cal-

Table 2. Day 0 dosimetry para

Variable

Impotent (n � 59)

Median Mean � SD Med

rostateV200 39.7 41.1 � 10.1 41V150 70.2 70.9 � 10.6 73V100 98.4 97.2 � 3.4 98D90 119.2 120.7 � 12.7 122

enile bulbD95 17.6 17.7 � 10.1 9D90 19.9 21.9 � 11.9 10D75 26.5 30.1 � 16.4 16D70 29.6 33.5 � 17.9 17D50 45.7 48.7 � 24.2 27D25 74.2 76.6 � 34.7 45

roximal cruraD95 19.1 22.1 � 13.5 11D90 22.1 24.9 � 15.3 12D75 33.0 35.6 � 22.1 16D70 39.1 40.2 � 25.1 18D50 65.6 65.5 � 38.8 28D25 112.7 112.2 � 57.9 56

istal cruraD95 12.3 13.8 � 10.7 6D90 14.5 16.2 � 12.6 7D75 20.6 22.3 � 17.4 10D70 22.4 24.6 � 19.1 12D50 33.0 38.9 � 31.6 16D25 59.0 69.2 � 47.6 32

BRT to penile bulbD95 20.3 22.1 � 13.9 10D90 22.9 25.9 � 16.2 11D75 31.7 35.5 � 21.9 16D70 34.9 39.3 � 23.7 18D50 52.0 56.8 � 31.4 28D25 89.8 88.6 � 43.3 49

Abbreviations: D95/90/75/70/50/25 � dose delivered to 95%, 90%adiotherapy; V200/150/100 � volume of prostate receiving 200%,

* Statistically significant.

ulations consisted of the values of the minimal dose received by t

0% of the prostate gland (D90) and the percentage of the prostateolume receiving 100%, 150%, and 200% of the prescribed mPDV100/150/200). For the bulb of the penis and the two arbitrarilyefined components of the crura, the radiation dose was defined inerms of the minimal dose delivered to 25%, 50%, 70%, 75%,0%, and 95% of the bulb and the crural components (D25/50/70/

5/90/95).The clinical, treatment, and dosimetric parameters evaluated for

rectile function included patient age, preimplant IIEF score, clin-cal T stage, pretreatment prostate-specific antigen level, Gleasoncore, elapsed time after implantation, presence of preimplantocturnal erections, body mass index, the presence of hypertensionr diabetes mellitus, tobacco consumption, prostate V100/150/200,rostate D90, radiation dose to the bulb of the penis, radiation doseo the proximal and distal crura, use of androgen deprivationherapy, supplemental EBRT, isotope, prostate volume, planningolume, and radiation dose to the proximal penis.A 2 � 2 analysis of variance was conducted between the factors

f group and potency to evaluate differences in continuous demo-raphic data. Categorical data were analyzed using two-way con-

: Potent vs. impotent patients

t (n � 69)

p

Overall (n � 128)

Mean � SD Median Mean � SD

42.9 � 9.7 0.328 40.6 42.1 � 9.973.2 � 8.6 0.176 72.5 72.2 � 9.697.7 � 2.5 0.364 98.4 97.5 � 2.9

121.4 � 11.0 0.763 120.7 121.1 � 11.8

12.8 � 9.2 0.001* 12.8 15.5 � 10.015.6 � 13.0 0.005* 15.8 18.5 � 12.820.5 � 15.1 0.001* 22.4 25.0 � 16.422.1 � 15.9 �0.001* 24.7 27.3 � 17.732.1 � 21.5 �0.001* 35.8 39.7 � 24.251.8 � 31.8 �0.001* 59.3 63.3 � 35.3

14.6 � 12.7 0.002* 15.1 18.0 � 13.616.3 � 14.4 0.001* 16.6 20.2 � 15.422.0 � 19.1 �0.001* 23.3 28.3 � 21.624.3 � 20.6 �0.001* 27.2 31.6 � 24.138.0 � 30.6 �0.001* 40.5 50.7 � 37.171.2 � 52.0 �0.001* 79.8 90.1 � 58.3

9.6 � 6.7 0.007* 9.3 11.6 � 9.011.0 � 7.6 0.005* 10.8 13.4 � 10.514.8 � 10.2 0.003* 15.4 18.3 � 14.416.1 � 11.2 0.002* 17.5 20.0 � 15.923.6 � 16.5 0.001* 26.6 30.7 � 25.743.3 � 31.6 0.001* 45.5 55.3 � 41.7

15.2 � 12.5 0.003* 14.5 18.4 � 13.618.4 � 16.9 0.012* 17.6 21.9 � 16.924.2 � 20.3 0.003* 24.4 29.5 � 21.726.0 � 21.3 0.001* 26.7 32.1 � 23.337.6 � 28.5 �0.001* 38.9 46.5 � 31.360.3 � 41.4 �0.001* 62.1 73.4 � 44.4

70%, 50%, and 25% of prostate gland; EBRT � external beamand 100% of prescribed dose.

meters

Poten

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ingency tables and were compared for the factors of group and

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otency. Associations among categorical variables were testedsing a Pearson chi-square test. The correlation between age atmplantation and the dose to the proximal penis was analyzedsing a Pearson correlation coefficient. Doses to the prostate,enile bulb, and proximal and distal crura were compared betweenhose who were and were not potent using independent t-tests.otency preservation curves were determined by the Kaplan-Meierethod, with the log–rank test used for comparison among the

evels of the various factors of interest. Univariate Cox regressionnalysis was used to determine the univariate predictors of erectileunction, and all variables with p �0.10 were included as covari-tes in a multivariate model of Cox regression as a means ofdentifying independent predictors of erectile function. For allests, p �0.05 was considered statistically significant. Statisticalnalysis was performed with Statistical Package for Social Sci-nces, version 11.0, software (SPSS, Chicago, IL).

RESULTS

Table 1 summarizes the clinical and treatment parametersor the 128 (97%) of the 132 patients who were potentefore brachytherapy and who completed the postbrachy-herapy IIEF survey. On average, patients who maintainedotency after brachytherapy were 3.7 years younger thanhose who became impotent and presented with a statisti-ally greater preimplant IIEF score (p � 0.001), with a trendor smaller prostate size (p � 0.069). None of the othervaluated clinical or treatment parameters approached sta-istical significance.

Figure 1a illustrates the distribution of the preimplantIEF scores for patients considered potent, and Fig. 1bisplays the distribution of the postimplant IIEF scores. Ofhe 69 patients who maintained adequate erectile function,he median preimplant IIEF score was 29, and patients whoeveloped brachytherapy-related ED had a median preim-lant IIEF score of 25 (p � 0.001). The mean and medianime to the onset of brachytherapy-related ED was 2.6 and

Table 3. Day 0 dosimetry: 103

Variable

103Pd (n � 29) 1

Median Mean � SD Median

enile bulbD95 10.7 13.2 � 10.1 24.8D90 12.2 15.8 � 12.9 29.0D75 17.9 22.6 � 18.5 38.2D70 20.2 24.6 � 19.6 41.0D50 31.6 37.1 � 26.4 53.6D25 57.2 61.0 � 39.5 74.9

roximal cruraD95 12.6 16.4 � 16.4 26.4D90 14.0 18.7 � 18.7 29.6D75 22.2 26.5 � 25.0 37.4D70 25.6 29.8 � 27.0 41.8D50 48.6 49.0 � 38.0 64.0D25 101.4 91.0 � 58.2 95.8

Abbreviations as in Table 2.

.4 months, respectively. In patients maintaining adequate

rectile function after brachytherapy, the median IIEF scoreas 20 (range, 13–30), and the median IIEF score in impo-

ent patients was 3 (range, 1–12).Figure 2 presents the Kaplan-Meier 3-year overall po-

ency preservation rate (50.5%) for the 128 patients. Ofote, 12% of patients developed impotency immediatelyfter the implant procedure, with nearly 40% of the patientopulation developing ED within the first 12 months. Figure

stratifies potency preservation by the preimplant IIEFcore. The 3-year rate of potency preservation for patientsith a preimplant IIEF score of 24–30, 18–23, and 13–17as 57.6%, 48.0%, and 22.1%, respectively (p � 0.001). Inatients with a preimplant IIEF score of 29 or 30, a 78.8%ate of potency preservation was noted, with a medianostimplant IIEF score of 24.When stratified by age, younger patients were more likely

o maintain erections sufficient for vaginal penetration afterrachytherapy (Fig. 4). The 3-year actuarial rate of potencyreservation was 60.8%, 48.6%, and 32.0% for patients60, 60–69, and �70 years of age, respectively (p �

.002).Figure 5 evaluates the impact of preimplant nocturnal

rections on brachytherapy-related ED. The presence ofrebrachytherapy nocturnal erections resulted in a signifi-antly greater rate of potency preservation (p � 0.018). These of neoadjuvant androgen deprivation therapy (49.1% vs.6.3%, p � 0.828), supplemental EBRT (Fig. 6, p � 0.624),sotope (Fig. 7, p � 0.829), tobacco status (p � 0.382),ypertension (p � 0.315), or body mass index (p � 0.943)id not affect the 3-year rate of potency preservation. Inddition, the stratification of supplemental EBRT into 20-s. 44-Gy arms did not affect potency preservation (47.5%s. 55.0%, p � 0.778). Finally, a trend for a greater rate ofD was identified in diabetic patients; however, it did not

each statistical significance (30.0% vs. 52.2%, p � 0.100).

125I (lower-risk patient trial)

� 21)

p

Overall (n � 50)

Mean � SD Median Mean � SD

25.5 � 8.0 �0.001 17.7 18.4 � 11.129.1 � 9.3 �0.001 21.3 21.4 � 13.237.9 � 12.7 �0.001 28.3 29.0 � 17.940.7 � 14.0 �0.001 30.9 31.4 � 19.054.8 � 18.9 �0.001 43.6 44.5 � 24.978.8 � 24.8 �0.001 67.1 68.5 � 35.0

28.4 � 11.0 0.036 19.4 21.5 � 15.531.2 � 12.7 0.037 21.2 23.9 � 17.541.2 � 19.5 0.016 29.0 32.7 � 23.845.3 � 22.7 0.008 32.4 36.3 � 26.263.8 � 30.7 0.001 55.1 55.3 � 35.596.3 � 39.7 �0.001 97.8 93.2 � 50.9

Pd vs.

25I (n

Table 2 summarizes the Day 0 postimplant dosimetry for

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he prostate, bulb of the penis, and proximal and distal crura.one of the evaluated prostate dosimetric parameters pre-icted for brachytherapy-related ED. In contrast, for everyose level examined for the proximal penis (i.e., penileulb, proximal crura, and distal crura), impotent patientseceived statistically greater doses than patients who main-ained adequate erectile capability. Despite the absence of aorrelation between brachytherapy-related ED and isotopeFig. 7), patients implanted with 125I received statisticallyreater doses to the proximal penis (Table 3).Figure 8 illustrates the mean minimal doses delivered to

5%, 90%, 75%, 70%, 50%, and 25% of the penile bulb androximal crura stratified by potency status. Receiver oper-ting characteristics curves were plotted for potency vs. thearious Dxx values of the proximal penis. The greatest areasnder the receiver operating characteristics curve were

a.

b.

D25 D50 D70 D75 D90 D95

0

20

40

60

80

Mea

n P

en

ile

Bu

lb D

os

e (

% m

PD

) impotent

potent

D25 D50 D70 D75 D90 D95

0

20

40

60

80

100

120

Me

an

Pro

xim

al C

rura

Do

se

(%

mP

D)

impotent

potent

ig. 8. Mean dose for various Dxx levels as %mPD for impotentlight bars) and potent (dark bars) patients. (a) Penile bulb. (b)roximal crura.

ound for the penile bulb D50 (area � 0.725) and the 7

roximal crura D50 (area � 0.737). Coordinates of theeceiver operating characteristics curves indicated that theptimal cutpoints were 30% mPD for the penile bulb D50

sensitivity 0.797, specificity 0.623) or an mPD of 50% forhe proximal crura D50 (sensitivity 0.678, specificity 0.739).otency preservation stratified by the penile bulb D50 cut-oint of 30% mPD is plotted in Fig. 9, and potency pres-rvation stratified by the proximal crura D50 cutpoint of0% mPD is plotted in Fig. 10. In both, the differenceetween the lower-dose cohort and the higher-dose cohortas substantially statistically significant (p � 0.001). Figure1 displays a lack of correlation between patient age and theose to the bulb of the penis for dose levels D50 and D25.

0 12 24 36 48


0

20

40

60

80

100

Po

ten

cy P

reserv

ati

on

(%

)

O = D50 ≤ 30% mPD, 76.2%

O = D50 > 30% mPD, 31.5%

p = < 0.001

Penile Bulb

ig. 9. Kaplan-Meier potency preservation stratified by penile bulbosimetric D50 cutpoint of 30% mPD: D50 �30% mPD (n � 55,pen circles) vs. D50 �30% mPD (n � 73, plus signs).


0

20

40

60

80

100

Po

ten

cy P

reserv

ati

on

(%

)

O = D50 ≤ 50% mPD, 70.1%

+ = D50 > 50% mPD, 27.4%

p = < 0.001

Proximal Crura

0 12 24 36 84

ig. 10. Kaplan-Meier potency preservation stratified by proximalrura dosimetric D cutpoint of 50% mPD: D �50% mPD (n �
50 50
1, open circles) vs. D50 �50% mPD (n � 57, plus signs).

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In univariate t-test analysis (Table 4), preimplant IIEFcore, age, nocturnal erections, and radiation dose to theroximal penis (bulb and crura) correlated with the devel-pment of brachytherapy-related ED and prostate size ap-roached statistical significance (p � 0.051). Determininghether or not the patient had nocturnal erections factored

nto whether the patient developed brachytherapy-relatedD; absence predicted ED; presence predicted potencyaintenance. However, in multivariate analysis, only the

reimplant IIEF score (p �0.001) and D50 to the proximalrura (p �0.001) were statistically significant predictors ofrachytherapy-induced ED, without any additional factorspproaching statistical significance, except for patient age

a.

b.

40 50 60 70 80

Age at Implant

0

40

80

120

160

200P

en

ile B

ulb

D25 (

%m

PD

)r = 0.040, p = 0.656

40 50 60 70 80

Age at Implant

0

20

40

60

80

100

120

140

Pen

ile B

ulb

D50 (

%m

PD

)

r = 0.027, p = 0.760

ig. 11. Correlation between patient age and (a) D50 or (b) D25

ose to penile bulb. p value compared patients with brachytherapy-elated erectile dysfunction (ED) (open circles) and patients with-ut ED (filled triangles). Linear regression line and correlationoefficient (r) was for overall population (n � 128).

p � 0.100). w

DISCUSSION

Since the mid-1980s, prostate brachytherapy has beensed increasingly as definitive treatment for early-stagerostate cancer, with most studies reporting favorable bio-hemical outcomes (19). However, because of a lack ofefinitive evidence demonstrating the superiority in cureates of one local treatment compared with another, QOLarameters have assumed greater importance (1–4). Previ-us studies have documented multiple deleterious effects ofD on overall QOL, including diminished physical andmotional well-being, marital discord, loss of self-esteem,ecreased interest in sexual relations, and less pleasure fromexual stimulation (5–11).

Erectile dysfunction is a common sequelae of all poten-ially curative local treatments (19). After brachytherapy,ide ranges of ED have been reported, probably a result ofifferences in follow-up, patient selection, implant tech-ique, and the mode of data collection (12, 20). The mech-nism of ED after definitive treatment likely represents aultifactorial process. After brachytherapy, the proximal

enis appears to be an important site-specific structure (26–3). Compared with our previous study (32), the radiationose to the penile bulb was comparable; however, the radi-tion dose to the proximal crura was slightly greater. Thislight increase in the proximal crural dose may explain themergence of the proximal crura (together with the preim-lant IIEF score) as one of the two strongest predictors ofrachytherapy-related ED. In our prior study, the penileulb was of greater statistical consequence; however, theose to the proximal crura approached statistical signifi-ance (p � 0.052). Mulhall and colleagues have emphasizedhat radiation doses to the crura may be more importantecause the corpora cavernosa are true erectile tissuehereas corpora spongiosum plays little role in erectile

igidity (29–31).Although the results of the current study did not defini-

ively clarify the site-specific structure in the proximal pe-is, they further substantiated the impact of the radiationose to the proximal penis as a prime culprit in the devel-pment of brachytherapy-related ED and emphasize themportance of refinements in implant technique, includingreplanning and intraoperative seed placement, to decreasehe radiation dose to the proximal penis. Refinements inmplant technique, including careful planning to avoid over-ggressive periapical implantation, along with extensive usef sagittal ultrasonography during the implant procedure,hould lower the radiation dose to the proximal penis andmprove potency preservation. Because previous prospec-ive and retrospective analyses have not suggested a rela-ionship between the radiation dose to the neurovascularundles and potency (13, 34), the neurovascular bundleoses were not calculated in the current study.Consistent with previous studies (14, 15), preimplant

rectile function remains the best clinical predictor for po-ency preservation (p �0.001). In our previous study (15),
e reported that supplemental EBRT predicted for brachy-

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herapy-related ED. In the current study (Fig. 6), supple-ental EBRT did not affect brachytherapy-related erectile

unction. This was probably a result of EBRT planningechniques designed to limit the dose to the proximal penis.n our earlier brachytherapy experience, no attempt wasade to either limit or calculate the dose to the proximal

enis. Compared with our 2001 study, the overall potencyreservation rate increased from 38.9% to 50.4% (Fig. 12).

Table 4. Univariate and multivariate C

Variable

Univariate analy

p

ollow-up 0.845leason score 0.307SA 0.437reimplant IIEF �0.001*rostate size 0.051lanning volume 0.085sotope† 0.837ge at implant 0.004*ypertension† 0.340iabetes† 0.126ormones† 0.837onths of hormones 0.148

obacco use† 0.426tage group† 0.743isk† 0.869Positive biopsies 0.787

octurnal erection† 0.027*BRT 0.797MI 0.451200 0.400150 0.170100 0.219D90 0.607

enile bulbD95 0.002*D90 0.010*D75 0.002*D70 0.001*D50 �0.001*D25 �0.001*

roximal cruraD95 0.003*D90 0.003*D75 0.001*D70 �0.001*D50 �0.001*D25 �0.001*

istal cruraD95 0.005*D90 0.003*D75 0.001*D70 0.001*D50 �0.001*D25 �0.001*

Abbreviations as in Tables 1 and 2.* Statistically significant.† Data entered as a categorical variable.

his apparent improvement in overall potency was exclu- a

ively a result of better erectile function in patients under-oing supplemental EBRT. Monotherapy potency preserva-ion outcomes have remained virtually unchanged overime. Recently, our brachytherapy doses to the proximalenis have decreased substantially (unpublished data), ande hope this will translate to additional improvements inrachytherapy-related potency preservation.To the best of our knowledge, this is the first brachyther-

gression analysis: Predicting potency

Multivariate analysis

ve risk p Relative risk

18 �0.001* 0.917

55 0.100

60 0.354

34 0.53113 �0.23620 0.39521 0.72517 0.66013 0.278

22 0.17519 0.18015 0.19115 0.22012 �0.001* 1.01207 0.659

30 0.54926 0.55515 0.51118 0.52313 0.75209 0.678

ox re

sis

Relati

0.9

1.0

0.5

1.01.01.01.01.00.0

1.01.01.01.01.01.0

1.01.01.01.01.01.0

py study to evaluate the effect of preimplant nocturnal

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REFEREN

1

1

1

52–62.

1

1

1

1

1

1

1

2

2

2

2

2

F2spenile bulb-sparing techniques.


rections on brachytherapy-related ED. A potential short-oming of our nocturnal erection evaluation was the ab-ence of formal nocturnal penile tumescence testing. How-ver, although subjective, physician interview represents anccepted mode of evaluation (42). The presence of preim-lant nocturnal erections predicted for a greater chance ofotency preservation in univariate, but not multivariate,nalysis and could potentially be a predictor of early vas-ular compromise.

CONCLUSION

Using a patient-administered validated QOL instrument,rachytherapy-induced ED occurred in 50% of patients at 3ears. In multivariate analysis, preimplant erectile functionnd the D50 to the proximal crura were the best predictors ofrachytherapy-related erectile function. Because the proxi-al penis was the most significant treatment-related predic-

or of brachytherapy-related ED, techniques to minimize theadiation dose to the proximal penis may result in improved
ates of potency preservation.
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Erectile function after prostate brachytherapy

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