Int. J. Radiation Oncology Biol. Phys., Vol. 58, No. 4, pp.

1056 –1062, 2004

Copyright © 2004 Elsevier Inc.
Printed in the USA. All rights reserved
0360-3016/04/$–see front matter

doi:10.1016/j.ijrobp.2003.08.021

CLINICAL INVESTIGATION Prostate

EFFECT OF CIGARETTE SMOKING ON BIOCHEMICAL OUTCOME AFTER

PERMANENT PROSTATE BRACHYTHERAPY

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

ROBERT W. GALBREATH, PH.D.,*† JONATHAN H. LIEF, PH.D.,*† AND EDWARD ADAMOVICH, M.D.§
*Schiffler Cancer Center and §Department of Pathology, Wheeling Hospital; †Wheeling Jesuit University, Wheeling, WV; ‡Puget
Sound Health Care System, Department of Veterans Affairs, Seattle, WA

Purpose: Recent studies have suggested that cigarette smoking may be associated with an increased risk of death
from prostate cancer. In this study, we evaluated the effect of cigarette smoking on the presentation and
biochemical outcome after permanent prostate brachytherapy for prostate cancer.
Methods and Materials: A total of 582 patients underwent brachytherapy with generous periprostatic margins
using either 103Pd or 125I with or without supplemental external beam radiotherapy between April 1995 and
September 2000. Of the 582 patients, 178 (30.6%) had never smoked, 306 (52.6%) were former smokers, and 98
(16.8%) were current smokers. The median patient age was 67.9 years, and the median follow-up was 54.5
months. No patient was lost to follow-up. No patient underwent routine seminal vesicle biopsy or pathologic
lymph node staging. The clinical, treatment, and dosimetric parameters evaluated included tobacco status, age,
clinical stage, Gleason score, pretreatment prostate-specific antigen level, risk group, percentage of positive
biopsies, ultrasound volume, isotope used, planning volume, hormonal status, use of external beam radiotherapy,
and postimplant dosimetry (percentage of target volume receiving 100%, 150%, and 200% of the prescribed dose
and percentage of prescribed dose covering 90% of the target volume). Biochemical outcome was determined
using the American Society for Therapeutic Radiology and Oncology consensus definition.
Results: No differences in the clinical, treatment, or dosimetric parameters were identified, except that current
smokers were statistically younger than those who had never smoked or former smokers (65.9 vs. 67.8 vs. 68.3
years, respectively, p ⴝ 0.016). Specifically, no relationship was discerned between tobacco history and risk
group, supplemental external beam radiotherapy, choice of isotope, or use of hormonal therapy. The overall
biochemical freedom from progression survival rate at 7 years was 96.2%, 95.6%, and 91.6% for patients who
had never smoked, former smokers, and current smokers, respectively (p ⴝ 0.126). When stratified by risk group
and hormonal status, tobacco consumption did not predict outcome, although a trend for poorer biochemical
progression-free survival was noted in current smokers. The median prostate-specific antigen level for hormone-
naive and hormonally manipulated disease-free patients was <0.1 ng/mL. In multivariate Cox regression
analysis, Gleason score, pretreatment prostate-specific antigen level, risk group, and hormonal status were
predictors of biochemical outcome.
Conclusion: In this prostate brachytherapy cohort, tobacco consumption did not predict for risk group strati-
fication or treatment approach. Although no statistically significant difference was found in biochemical
progression-free survival, a trend for poorer biochemical outcome was demonstrated in current smokers.
© 2004 Elsevier Inc.

Prostate, Brachytherapy, Tobacco, Smoking, Survival.

INTRODUCTION Daniell (4) reported that cigarette smokers were more

Although recent studies have suggested that environmental
factors are likely responsible for the promotion of prostate
cancer from a latent state to a clinically evident disease, the
potential causative relationship between tobacco use and
prostate cancer remains unclear (1). Despite the lack of a
clear causal relationship (2), multiple studies have reported
a correlation between cigarette smoking and aggressive
prostate cancer and/or prostate cancer-related death (1– 6).
likely to present with metastatic prostate cancer than non-
smokers, with a 5-year cancer-specific mortality rate of 88%
vs. 63% in favor of nonsmokers. In addition, a review of the
three largest prospective prostate cancer mortality studies
demonstrated a modest association between current ciga-
rette smoking and early death from prostate cancer (5).
Recently, Roberts and colleagues (1) reported that smokers
⬍55 years old who underwent radical prostatectomy had a
greater risk of extracapsular extension or Gleason score 7 or

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

Center, Wheeling Hospital, 1 Medical Park, Wheeling, WV Received Jun 6, 2003, and in revised form Aug 15, 2003.
26003-6300. Tel: (304) 243-3490; Fax: (304) 243-5047; E-mail: Accepted for publication Aug 19, 2003.

1056
 Cigarette smoking and prostate cancer ● G. S. MERRICK et al. 1057

Table 1. Clinical treatment and dosimetric values for patient population stratified by tobacco smoking status

Never smoked Former smoker Current smoker

(n ⫽ 178) (n ⫽ 306) (n ⫽ 98) Overall (n ⫽ 582)

Variable Median Mean ⫾ SD Median Mean ⫾ SD Median Mean ⫾ SD P* Median Mean ⫾ SD

Age at implant (y) 67.8 67.3 ⫾ 6.6 68.3 67.2 ⫾ 6.9 65.9 65.1 ⫾ 6.9 †
0.016 ‡
67.9 66.9 ⫾ 6.9
Follow-up (mo) 55.6 58.5 ⫾ 17.8 53.9 55.6 ⫾ 18.1 52.4 54.3 ⫾ 21.3 0.130 54.5 54.3 ⫾ 18.6
Pretreatment PSA
(ng/ml) 7.1 8.7 ⫾ 5.2 7.4 9.3 ⫾ 6.6 7.6 9.6 ⫾ 6.9 0.442 7.4 9.1 ⫾ 6.3
Gleason score 7.0 6.6 ⫾ 1.0 7.0 6.6 ⫾ 1.0 6.5 6.4 ⫾ 0.9 0.357 7.0 6.6 ⫾ 1.0
Clinical stage§ T2a 3.7 ⫾ 0.8 T2a 3.7 ⫾ 0.8 T2a 3.7 ⫾ 0.8 0.977 T2a 3.7 ⫾ 0.8
Prostate volume
(cm3) 36.3 37.3 ⫾ 10.0 35.0 35.7 ⫾ 9.6 34.9 34.6 ⫾ 9.8 0.066 35.4 36.0 ⫾ 9.8
Planning volume
(cm3) 63.1 62.2 ⫾ 13.9 59.8 60.5 ⫾ 12.5 59.2 60.2 ⫾ 13.2 0.389 60.6 60.9 ⫾ 13.0
V100 95.3 93.5 ⫾ 5.7 95.5 94.1 ⫾ 5.4 94.9 93.7 ⫾ 4.2 0.750 95.1 93.8 ⫾ 5.3
V150 54.7 55.3 ⫾ 11.1 52.6 54.8 ⫾ 12.9 50.4 52.1 ⫾ 9.6 0.382 53.0 54.5 ⫾ 11.9
V200 26.2 26.9 ⫾ 7.4 25.8 27.4 ⫾ 9.6 23.2 24.9 ⫾ 6.0 0.310 25.8 26.8 ⫾ 8.5
D90 (% mPD) 111 111 ⫾ 11 109 112 ⫾ 14 107 108 ⫾ 9.0 0.290 109 111 ⫾ 12
% positive biopsies 33.3 41.2 ⫾ 24.9 33.3 40.7 ⫾ 24.7 33.3 42.5 ⫾ 26.4 0.825 33.3 41.1 ⫾ 25.0
Hormone use (mo) 0.0 2.5 ⫾ 3.9 0.0 3.0 ⫾ 6.5 0.0 2.8 ⫾ 5.9 0.694 0.0 2.8 ⫾ 5.7
Risk group (n)
Low 70 (39.3) 111 (36.3) 38 (38.8) 0.936㛳 219 (37.6)
Intermediate 71 (39.9) 122 (39.9) 38 (38.8) 231 (39.7)
High 37 (20.8) 73 (23.9) 22 (22.4) 132 (22.7)
Isotope (n)
125
I 72 (59.6) 119 (61.1) 42 (57.1) 0.777㛳 233 (60.0)
103
Pd 106 (40.4) 187 (38.9) 56 (42.9) 349 (40.0)
Hormones (n)
None 91 (53.5) 168 (58.9) 51 (57.3) 0.830㛳 310 (57.0)
ⱕ6 mo 61 (35.9) 90 (31.6) 28 (31.5) 179 (32.9)
⬎6 mo 18 (10.6) 27 (9.5) 10 (11.2) 55 (10.1)
EBRT (n) 97 (54.5) 176 (57.5) 49 (50.0) 0.413㛳 322 (55.3)

Abbreviations: PSA ⫽ prostate-specific antigen; V100/150/200 ⫽ percentage of target volume receiving 100%, 150%, 200% of prescribed
dose; D90 ⫽ percentage of prescribed dose covering 90% of target volume; MPD ⫽ minimal peripheral dose; EBRT ⫽ external beam
radiotherapy
Data in parentheses are percentages.
* Determined using analysis of variance.
†
Significantly younger than the never and former smokers.
‡
Statistically significant.
§
Mean clinical stage determined by scaling T1a–T3c from 1 to 9.
㛳
Determined using chi-square.

greater histologic features and extraprostatic extension than
did nonsmokers, with former smokers possessing an inter-
mediate risk.
After permanent prostate brachytherapy, most studies
have reported long-term biochemical outcomes that com-
pare favorably with radical prostatectomy and external
beam radiotherapy (EBRT), with low rates of urinary in-
continence and rectal injury and acceptable rates of sexual
dysfunction (7, 8). Cigarette smoking has not been evalu-
ated as a risk factor for biochemical progression after
brachytherapy. Accordingly, we evaluated the effect of cig-
arette smoking on the presentation and biochemical out-
come after permanent prostate brachytherapy.
METHODS AND MATERIALS
A total of 582 consecutive patients at the Schiffler Cancer
Center underwent brachytherapy with generous peripros-
tatic margins using either 103Pd or 125I with or without
supplemental EBRT between April 1995 and September
2000 for clinical Stage T1b-T3a (1997 American Joint
Committee on Cancer) prostate cancer. The mean and me-
dian follow-up was 54.3 ⫾ 18.6 months and 54.5 months,
respectively (range, 30 –97 months). No patient was lost to
follow-up. Patients underwent clinical staging by medical
history, physical examination, including digital rectal exam-
ination, and serum prostate-specific antigen (PSA) measure-
ment. Bone scans, CT of the pelvis, and prostatic acid
phosphatase levels were obtained as clinically indicated. No
patient underwent seminal vesicle biopsy or pathologic
lymph node staging.
Because of well-documented inaccuracies in Gleason
grading, all cases originating from outside institutions were
reviewed by a single pathologist (E.A.) with a special in-
terest in urologic malignancies (9). The calculation algo-
rithms and seed parameters used in preplanning and post-
1058 I. J. Radiation Oncology ● Biology ● Physics Volume 58, Number 4, 2004

Table 2. Most recent PSA level in patients free of biochemical progression, stratified by risk and months of hormone use and
smoking status

Never smoked Former smoker Current smoker

(n ⫽ 172*) (n ⫽ 293*) (n ⫽ 90*) Overall (n ⫽ 555*)

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

Low risk
No hormones ⬍0.1 0.18 ⫾ 0.37 ⬍0.1 0.11 ⫾ 0.20 0.06 0.20 ⫾ 0.36 ⬍0.1 0.15 ⫾ 0.29
Hormones ⱕ6 mo ⬍0.1 0.12 ⫾ 0.22 ⬍0.1 0.08 ⫾ 0.11 ⬍0.1 0.09 ⫾ 0.07 ⬍0.1 0.10 ⫾ 0.16
Hormones ⬎6 mo 0.20 0.17 ⫾ 0.15 ⬍0.1 0.01 ⫾ 0.00 ⬍0.1 0.16 ⫾ 0.30 ⬍0.1 0.11 ⫾ 0.14
Intermediate risk
No hormones ⬍0.1 0.08 ⫾ 0.13 ⬍0.1 0.12 ⫾ 0.20 ⬍0.1 0.13 ⫾ 0.29 ⬍0.1 0.11 ⫾ 0.20
Hormones ⱕ6 mo ⬍0.1 0.08 ⫾ 0.09 ⬍0.1 0.05 ⫾ 0.09 ⬍0.1 0.04 ⫾ 0.08 ⬍0.1 0.05 ⫾ 0.09
Hormones ⬎6 mo ⬍0.1 0.01 ⫾ 0.00 ⬍0.1 0.01 ⫾ 0.01 ⬍0.1 0.01 ⫾ 0.00 ⬍0.1 0.01 ⫾ 0.00
High risk
No hormones ⬍0.1 0.06 ⫾ 0.16 ⬍0.1 0.10 ⫾ 0.22 0.10 0.11 ⫾ 0.20 ⬍0.1 0.09 ⫾ 0.19
Hormones ⱕ6 mo ⬍0.1 0.02 ⫾ 0.03 ⬍0.1 0.04 ⫾ 0.09 0.30† 0.30 ⫾ 0.00 ⬍0.1 0.05 ⫾ 0.09
Hormones ⬎6 mo ⬍0.1 0.05 ⫾ 0.13 ⬍0.1 0.02 ⫾ 0.04 0.10 0.03 ⫾ 0.04 ⬍0.1 0.03 ⫾ 0.06
All risks
No hormones ⬍0.1 0.11 ⫾ 0.25 ⬍0.1 0.11 ⫾ 0.20 ⬍0.1 0.16 ⫾ 0.31 ⬍0.1 0.12 ⫾ 0.24
Hormones ⱕ6 mo ⬍0.1 0.09 ⫾ 0.17 ⬍0.1 0.06 ⫾ 0.10 ⬍0.1 0.07 ⫾ 0.09 ⬍0.1 0.07 ⫾ 0.13
Hormones ⬎6 mo ⬍0.1 0.06 ⫾ 0.10 ⬍0.1 0.02 ⫾ 0.04 ⬍0.1 0.02 ⫾ 0.03 ⬍0.1 0.03 ⫾ 0.07

Abbreviation: PSA ⫽ prostate-specific antigen.

Main effects: Tobacco use, p ⫽ 0.401; risk p ⫽ 0.364; hormones, p ⫽ 0.080.
* Not including patients with failure (overall failures, n ⫽ 27).
†
n ⫽ 1.

operative dosimetry were those recommended by the
American Association of Physicists in Medicine Task
Group No. 43 (10). The monotherapeutic brachytherapy
dose was 125 Gy minimal peripheral dose for 103Pd (78
patients) and 145 Gy for 125I (182 patients). The brachy-
therapy boost dose was 90 Gy for 103Pd (271 patients) and
110 Gy for 125I (51 patients).
Our patient selection, preplanning, and intraoperative
philosophy and dosimetric evaluation method have been
previously described (11–16). The brachytherapy planning
target volume consisted of a 3– 8-mm enlargement of the
prostate gland on each ultrasound slice, with a resultant
planning volume approximately 1.75 times the ultrasound-
determined prostate volume (13, 14). The minimal periph-
eral dose was prescribed to the planning target volume with
margin. At the time of implantation, the prostate gland,
periprostatic region, and base of the seminal vesicles were
implanted. On average, approximately 40% of the seeds
were placed in periprostatic locations (11). The brachyther-
apy procedure was performed with preloaded 18-gauge nee-
dles using transverse and sagittal ultrasonography, along
with fluoroscopy.
Of the 582 patients, 322 received supplemental EBRT
before brachytherapy. In general, EBRT consisted of 45 Gy
to the prostate, periprostatic region, seminal vesicles, and
first echelon lymph nodes in 1.8-Gy fractions using 15–
18-MV photons delivered by a multifield technique with
shielding of the posterior half of the rectum via the lateral
portals. Of the 582 patients, 234 (40.2%) received hormonal
manipulation for either cytoreduction or multiple poor prog-
nosticators. Hormonal therapy consisted of a luteinizing
hormone-releasing hormone agonist and an antiandrogen.
The mean and median duration of hormonal manipulation in
this subgroup was 7.0 ⫾ 7.2 and 4 months, respectively
(range, 1–36 months). For all 582 patients, the mean and
median duration of hormonal therapy was 2.8 ⫾ 5.7 and
0.0 months, respectively.
Patients were monitored by physical examination, includ-
ing digital rectal examination and PSA determination at
3– 6-month intervals. The end point of the analysis was
biochemical progression-free survival as defined by the
American Society of Therapeutic Radiology and Oncology
consensus definition (17). Although in this series, all pa-
tients with treatment failure presented with PSA progres-
sion, abnormal digital rectal examination findings or the
development of distant metastases in the absence of PSA
progression also would have been scored as a treatment
failure. No patient underwent routine postimplant prostate
biopsy.
The clinical, treatment, and dosimetric parameters eval-
uated for biochemical progression-free survival included
cigarette consumption (never, former, or current), age, clin-
ical T stage, Gleason score, pretreatment PSA level, isotope,
hormonal status, supplemental EBRT, risk group (low risk,
Gleason score 6 or less, PSA level ⱕ10 ng/mL, clinical
Stage T1c-T2a; intermediate risk, Gleason score 7 or greater
or PSA ⬍10 ng/mL or clinical Stage T2b or greater; and
high risk, two or three of the intermediate-risk criteria),
percentage of positive biopsies, prostate volume, percentage
of the target volume receiving 100%, 150%, and 200% of
the prescribed dose, and the percentage of the prescribed
dose covering 90% of the target volume.
 Cigarette smoking and prostate cancer ● G. S. MERRICK et al. 1059

Fig. 1. Clinical and biochemical outcomes for 582 study patients.

Comparisons of the continuous variables across the three
levels of smoking were made using analysis of variance. The
three levels of risk were compared across the three levels of
smoking using two-way analysis of variance. A Tukey posthoc
analysis was made when significance was found to cross the
levels of a given factor. Associations between categorical vari-
ables and levels of smoking were tested with Pearson’s chi-
square test. Survival curves were analyzed using the Kaplan-
Meier method, and the log–rank test was used for comparison
among the three levels of smoking. Univariate Cox regression
analysis was used to determine the univariate predictors of
biochemical disease-free survival, and all variables with p
ⱕ0.10 were included as covariates in a multivariate Cox re-
gression model to identify independent predictors of biochem-
ical disease-free survival. For all tests, p ⱕ0.05 was considered
to be statistically significant. Statistical analysis was performed
with Statistical Package for Social Sciences, version 11.0,
software (SPSS, Chicago, IL).
1060 I. J. Radiation Oncology ● Biology ● Physics Volume 58, Number 4, 2004

Fig. 2. Seven-year overall biochemical progression-free (bNED)
survival stratified by tobacco status. Symbols indicate follow-up
time for censored patients. Open circles indicate never smoked;
open triangles, former smokers; plus signs, current smokers.
Fig. 3. Seven-year biochemical progression-free (bNED) survival
for hormone-naı̈ve, low-risk patients stratified by tobacco status.
Symbols indicate follow-up time for censored patients. Open cir-
cles indicate never smoked; open triangles, former smokers; plus
signs, current smokers.

RESULTS
manipulated patients were stratified by risk group, no sta-
Table 1 summarizes the mean clinical, treatment, and tistically significant difference in biochemical outcome was
dosimetric variables of the patients stratified by tobacco demonstrated among the three tobacco cohorts.
status. The mean and median follow-up for the entire cohort In multivariate Cox regression analysis, pretreatment
was 54.3 ⫾ 18.6 and 54.5 months, respectively. The three PSA level, Gleason score, hormonal status, and risk group
patient cohorts were well-matched, except that current predicted for biochemical failure (Table 3). Additional clin-
smokers were statistically younger (p ⫽ 0.016), with a trend ical, treatment, and dosimetric parameters, including to-
for smaller prostate glands. Tobacco status did not predict bacco status, failed to predict for biochemical outcome.
for pretreatment PSA level, Gleason score, clinical stage,
risk group, percentage of positive biopsies, or the addition
DISCUSSION
of supplemental EBRT or hormonal therapy.
Table 2 displays the most recent posttreatment PSA level In the current brachytherapy study, tobacco consumption
in patients free of biochemical progression for the three did not predict a more aggressive presentation, as deter-
tobacco cohorts stratified by risk group. In the biochemi-
cally disease-free patients, neither tobacco status nor risk
group predicted for the absolute posttreatment PSA level,
and a trend for lower posttreatment PSA levels was noted in
patients who had received hormonal therapy (p ⫽ 0.080).
Figure 1 diagrams the clinical and biochemical outcomes
for all 582 patients. Tobacco did not influence the overall
prostate cancer death rate; however, current and former
smokers were more likely to die of other causes than those
who had never smoked (p ⫽ 0.006).
Figure 2 displays the freedom from biochemical progres-
sion for all three tobacco cohorts. A trend was noted for
poorer outcome in current smokers vs. those who had never
smoked or former smokers (p ⫽ 0.126). Patients who had
never smoked and former smokers had nearly equivalent
biochemical outcomes (96.2% vs. 95.6%, respectively).
Figures 3–5 illustrate the freedom from biochemical pro-
gression in hormone-naive low-risk, intermediate-risk, and
high-risk patients. In the low-risk and high-risk, but not Fig. 4. Seven-year biochemical progression-free (bNED) survival
for hormone-naı̈ve, intermediate-risk patients stratified by tobacco
intermediate-risk groups, those who had never smoked and status. Symbols indicate follow-up time for censored patients.
former smokers had nearly identical outcomes, with a trend Open circles indicate never smoked; open triangles, former smok-
for poorer outcomes in current smokers. When hormonally ers; plus signs, current smokers.
 Cigarette smoking and prostate cancer ● G. S. MERRICK et al. 1061

gression was evident in current smokers compared with

Fig. 5. Seven-year biochemical progression-free (bNED) survival
for hormone-naı̈ve, high-risk patients stratified by tobacco status.
Symbols indicate follow-up time for censored patients. Open cir-
cles indicate never smoked; open triangles, former smokers; plus
signs, current smokers.
mined by pretreatment PSA level, Gleason score, clinical
stage, percentage of positive biopsies, or risk group. Al-
though a trend for poorer biochemical freedom from pro-
those who had never smoked or were former smokers, the
trend did not reach statistical significance in univariate
analysis. In addition, tobacco consumption was not associ-
ated with an increased death rate from prostate cancer.
However, current and former smokers were more likely to
die of other causes compared with nonsmokers (Fig. 1).
However, because a trend for increased biochemical failure
was related to tobacco consumption, it is possible that with
longer follow-up of more patients, tobacco consumption
would result in an increased incidence of prostate cancer-
related death. As such, our current results are not necessar-
ily contradictory to the previously published literature. A
review (5) of the three largest prospective prostate cancer
mortality studies demonstrated a modest association be-
tween current cigarette smoking and early death from pros-
tate cancer, and Daniell (4) reported that cigarette smokers
were more likely to present with metastatic prostate cancer
with a decreased 5-year cancer-specific mortality rate.
Using patient-administered quality-of-life instruments, to-
bacco consumption has been correlated with deleterious effects
on brachytherapy-related late urinary and bowel function (18,
19). Using the Expanded Prostate Cancer Index, tobacco con-
sumption was the strongest predictor of late urinary function,
with statistically significant differences in all urinary-specific
domains, including function, incontinence, irritation/obstruc-

Table 3. Univariate and multivariate Cox regression analysis for biochemical failure

Univariate Cox regression Multivariate Cox regression

Variable RR p* RR p

Gleason score 2.12 ⬍0.001* 2.45 0.001*

PSA 1.06 0.001* 1.05 0.029*
Hormone use 0.079* 0.006*
None vs. ⱕ6 mo 0.26 0.029* 0.36 0.101
None vs. ⬎6 mo 0.57 0.450 0.08 0.005*
ⱕ6 mo vs. ⬎6 mo 2.20 0.388 0.22 0.158
Risk ⬍0.001* 0.028*
Low vs. intermediate 1.17 0.814 0.36 0.193
Low vs. high 7.77 ⬍0.001* 1.53 0.575
Intermediate vs. high 6.62 ⬍0.001* 4.26 0.008*
Percent positive biopsies 1.03 ⬍0.001* 0.101
Stage (T1a-T2a vs. T2b-T3c) 3.38 0.003* 0.675
EBRT (no vs. yes) 3.58 0.010* 0.787
Prostate volume 1.03 0.100
Tobacco use 0.140
Never vs. former 1.31 0.586
Never vs. current 2.69 0.067
Former vs. current 2.05 0.110
Isotope (125I vs. 103Pd) 1.66 0.231
Hypertension (no vs. yes) 0.55 0.152
Diabetes (no vs. yes) 1.20 0.808
Age 1.04 0.237
V100 0.02 0.303
V150 0.01 0.208
V200 0.01 0.348
%D90 2.92 0.653

Abbreviations: EBRT ⫽ external beam radiotherapy; PSA ⫽ prostate specific antigen; RR ⫽ relative risk.
* Only those variables with p ⬍ 0.10 in univariate Cox regression analysis included in multivariate Cox regression analysis.
1062 I. J. Radiation Oncology ● Biology ● Physics
tion, and bother scores (18). The International Prostate Symp-
tom Scores were also significantly greater in current smokers.
An evaluation of late bowel function using the Rectal Function
Assessment Score demonstrated that the number of preimplant
bowel movements, tobacco status, and median rectal dose
correlated with late bowel function (19).
A potential shortcoming of our study was that the pack-
year history was not available. Rodriguez and colleagues
(5), however, reported that “no trend in risk was observed
with the number of cigarettes per day or with the duration of
smoking among current smokers and no increased risk was
found among former smokers.” In contrast, Giovannucci et
al. (6) reported that men who had smoked ⱖ15 pack years
of cigarettes within the preceding 10 years were at a greater
risk of distant metastatic disease and fatal prostate cancer
relative to nonsmokers, with the excess risk among smokers
eliminated within 10 years of stopping tobacco use.
Consistent with a previous report, smokers in the current
study were diagnosed with prostate cancer at a younger age
than were nonsmokers, with no relationship between Gleason
score and tobacco consumption (1, 4). The trend for smaller
prostate glands in current smokers (Table 1) is consistent with
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Volume 58, Number 4, 2004
the observation that the development of benign prostatic hy-
perplasia is inhibited by cigarette smoking (20).
The data reported here are not necessarily in contradiction
with the findings of increased extraprostatic extension in smok-
ers (1). Mayo and Cleveland Clinic studies have shown that the
vast majority of extraprostatic extension is limited to within 5
mm of the prostatic capsule (21, 22). Our implant philosophy,
which includes the use of multiple periprostatic seeds with or
without supplemental EBRT (11–16), results in a Day 0 CT-
determined extracapsular treatment margin of 6.5 mm and 9.6
mm at the 100% and 75% isodose line, respectively (12). As
such, generous periprostatic treatment margins might neutral-
ize the adverse effect of a greater incidence of extraprostatic
extension in smokers (23).
CONCLUSION
In this prostate brachytherapy cohort, tobacco consumption
did not predict for risk group stratification or treatment ap-
proach. Although no statistically significant difference was
found in biochemical progression-free survival, a trend for
poorer biochemical outcome was demonstrated in current
smokers.
13. Butler WM, Merrick GS, Lief JH, et al. Comparison of seed
loading approaches in prostate brachytherapy. Med Phys
2000;27:381–392.
14. Merrick GS, Butler WM. Modified uniform seed loading for
prostate brachytherapy: Rationale, design, and evaluation.
Tech Urol 2000;6:78–84.
15. Merrick GS, Butler WM, Dorsey AT, et al. Potential role of
various dosimetric quality indicators in prostate brachyther-
apy. Int J Radiat Oncol Biol Phys 1999;44:717–724.
16. Merrick GS, Butler WM, Dorsey AT, et al. The effect of
prostate size and isotope selection on dosimetric quality fol-
lowing permanent seed implantation. Tech Urol 2001;7:233–
240.
17. American Society for Therapeutic Radiology and Oncology
Consensus Panel. Consensus Statement: Guidelines for PSA
following radiation therapy. Int J Radiat Oncol Biol Phys
1997;37:1035–1041.
18. Merrick GS, Butler WM, Wallner KE, et al. Long-term uri-
nary quality of life after permanent prostate brachytherapy. Int
J Radiat Oncol Biol Phys 2003;56:454–461.
19. Merrick GS, Butler WM, Wallner KE, et al. Late rectal
function following prostate brachytherapy. Int J Radiat Oncol
Biol Phys 2003;57:42–48.
20. Daniell H. More stage A prostatic cancers, less surgery for
benign hypertrophy in smokers. J Urol 1993;149:68–72.
21. Davis BJ, Pisansky TM, Wilson TM, et al. The radial distance
of extraprostatic extension of prostate carcinoma: Implications
for prostate brachytherapy. Cancer 1999;85:2630–2637.
22. Sohayda C, Kupelian PA, Levin HS, et al. Extent of extra-
capsular extension in localized prostate cancer. Urology 2000;
55:382–386.
23. Wallner KE, Merrick GS, Butler WM, et al. Treatment mar-
gins predict two-year PSA response after Pd-103 prostate
brachytherapy. Submitted.