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Three-dimensional computed tomography-guided monotherapeuticpararectal brachytherapy of prostate cancer with seminal vesicle invasion
Panos Koutrouvelis*, Niko Lailas, Fred Hendricks, Guillermo Gil-Montero,James Sehn, Stuart Katz
Uro-Radiology Prostate Institute, 8320 Old Courthouse Road, #150 Vienna, Virginia 22182, USA
Received 12 July 2000; received in revised form 2 January 2001; accepted 4 April 2001
Abstract
Purpose: To treat patients with prostate cancer and seminal vesicle invasion with monotherapeutic three dimensional computed tomo-
graphy (3-DCT)-guided posterior pararectal brachytherapy.
Methods and materials: Three hundred and sixty two patients with clinical stage T1 a,b or T2 a,b of prostate cancer were referred for 3-
DCT-guided brachytherapy. Each underwent ftirther staging with 3-D CT-guided pararectal biopsy of the seminal vesicles under local
anesthesia during the pre-treatment CT-planning. Forty-three patients (12%) were upstaged to T3 cNoMo disease. In the set of 43 patients,
Eight had Gleason's score#6, 24 Gleason's score� 7, and 11 patients $ 8. Initial PSA was ,10 ng/ml in 14 patients, 10±20 ng/ml in 11
patients, and .20 in 18 patients. Of the 43 patients, 37 patients were treated monotherapeutically with 3-D CT-guided brachytherapy. No
patients received hormone therapy after the implant. The prescribed dosage to the seminal vesicles and prostate is 120 Gy with Pd-103 seeds
and 144 Gy with 1±125 seeds.
Results: The prescribed dosage was achieved in all 37 patient's throughout the seminal vesicles whose range of target radiation extended
5±10 mm outside the target in the adjacent fat as calculated with post-implant CT-dosimetry with Varian Brachy Vision or MMS software.
Prostate Speci®c Antigen (PSA) outcome data were available in 34 patients treated with monotherapy and follow up ranged from 12±56
months (median, 24 months). Decreased PSA levels were strati®ed into six groups based on the presenting Gleason's score and initial PSA. In
the ®rst group (with Gleason's score # 6 and initial PSA ,20 ng/ml), PSA levels decreased to less than 0.5 ng/ml in all seven patients
(100%) after brachytherapy. In the second group (with Gleason's� 7 and initial PSA , 20 ng/ml), PSA levels decreased to less than 1 ng/ml
in 11 of 13 patients (85%); additionally PSA levels decreased to less than 0.5 ng/ml in ten patients (77% in this group). In the third group
(with Gleason's score� 7 and initial PSA . 20 ng/ml), PSA decreased to less than 0.5 ng/ml in four out of eight patients (50%). All of the
patients in the fourth group (with Gleason's score $ 8 and initial PSA , 20 ng/ml) decreased their PSA levels to less than 0.5 ng/ml in three
of three patients. PSA decreased less than 0.5 ng/ml in two out of three patients (67% in the last group with Gleason's score $ 8 and initial
PSA . 20 ng/ml). There were no patients with Gleason's score of 1±6 and greater than 20 ng/ml initial PSA. Patients, irrespective of the
Gleason's score and PSA, had an overall response of decreased PSA (less than 1 ng/ml) of 79%.
Conclusion: 3-D CT-guided brachytherapy delivers adequate dosage to the seminal vesicles. Clinical and biochemical results are
encouraging in patients with low initial PSA levels regardless of their Gleason's scores, but longer-term data in a greater number of patients
is necessary. q 2001 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Prostate; Cancer; Seminal vesicle; Brachytherapy
1. Introduction
The incidence of seminal vesicle invasion with localized
prostate cancer reported after radical prostatectomy is 13-
14% [11,18]. However, clinical staging with biopsy of the
seminal vesicles is not routinely performed in all patients of
prostatic adenocarcinoma during the initial transrectal ultra-
sound-guided biopsy of the prostate or prior to initiation of
any treatment, surgical or radiation therapy.
In our protocol we include biopsy of seminal vesicles for
clinical staging of adenocarcinoma of the prostate in all
patients who are referred for 3-dimensional CT-guided
posterior brachytherapy and have had no transrectal ultra-
sound-guided seminal vesicle biopsy performed prior to
referral. The procedure is performed under local anesthesia
during the pre-treatment CT planning. The 3-dimensional
stereotactic system is adjusted to avoid the coccyx and spare
Radiotherapy and Oncology 60 (2001) 31±35
0167-8140/01/$ - see front matter q 2001 Elsevier Science Ireland Ltd. All rights reserved.
PII: S0167-8140(01)00372-3
www.elsevier.com/locate/radonline
* Corresponding author.
needle penetration of the rectum. Veri®cation of needle
position with CT is made prior to biopsy. Three biopsies
of each seminal vesicle are performed: one near the junction
of each seminal vesicle with the base of the prostate (S1),
one in the mid-portion of each seminal vesicle (S2) and
®nally, the distal portion of each seminal vesicle (S3).
Seminal vesicle invasion of prostate adenocarcinoma
occurs through direct extension of the tumor through the
ejaculatory ducts, through invasion of the capsule in the
prostate base or through the perineural invasion in the peri-
prostatic fat tissue (more often in the distal portion of semi-
nal vesicles). Forty-three out of 362 patients (12%) had
seminal vesicle invasion upstaged with 3-dimensional para-
rectal biopsy (T3cNoMo). Pathological seminal vesicle
invasion has been reported after radical prostatectomy in
63 out of 375 patients (13%) T3cNoMo [18].
Seminal vesicle involvement is a poor prognostic feature
in patients who have undergone radical prostatectomy in 3±
5 years, particularly in patients with high grade tumor Glea-
son's score $ 7, PSA . 10, and/or distal portion of seminal
vesicle involvement [2,3,4,18]. The range of success after
radical prostatectomy with seminal vesicle invasion at eight
large centers is reported to be 5±60% [13].
External beam radiation (EBRT) has been used to treat
patients with prostatic cancer and seminal vesicle invasion
(T3cNoMo). Although EBRT may not be suf®cient to
provide long term control of stage T3c prostate cancer
[1,5], large radiation ®eld with EBRT to include seminal
vesicles increases the dose to the rectum by 40±50% [6].
Because of the low risk of invasion of the seminal vesicles
in the low risk patients (6% of 192 patients with
PSA , 10ng/ml and Gleason's score # 6) and because of
the high dosage to the rectum with a large radiation ®eld,
monotherapeutic EBRT has not been recommended [6].
Furthermore, the Clinical Research Committee of the Amer-
ican Brachytherapy Society considers ultrasound guided,
transperineal brachytherapy alone a relative contraindica-
tion for patients with poor prognosis prostate cancer
(Stage T3, prostate .60 gm, previous transurethral resec-
tion, PSA . 10 ng/ml, Gleason's score . 6, extensive
intraprostatic calci®cation) [12].
The combined method of EBRT and booster with
brachytherapy covering only the portion of seminal vesicles
near the base of the prostate has been performed with trans-
rectal ultrasound-guided transperineal approach [16].
Dosage of the seminal vesicles using combined treatment
as calculated with dose volume histograms was not adequate
[16]. We report 37 patients with prostate cancer and seminal
vesicle invasion treated with monotherapeutic 3-dimen-
sional stereotactic CT-guided pararectal brachytherapy
with excellent coverage of the entire seminal vesicles.
2. Methods and materials
Three-hundred and sixty-two patients staged at T1 a,b or
T2 a,b prostate cancer were referred for 3-DCT-guided
brachytherapy. Each underwent further staging with 3-
DCT-guided pararectal biopsy of the seminal vesicles.
Three biopsies were performed of each seminal vesicle.
The position of the needles during biopsy was veri®ed
with CT. (Fig. 1). Pathologists reported 98% of the speci-
mens included seminal vesicle wall or epithelium. Forty-
three patients (12%) were found to have seminal vesicle
involvement and were upstaged to T3c disease. Of these
43 patients, eight patients had Gleason's score # 6, 24
patients� 7, and 11 patients had Gleason's score $ 8.
Initial PSA was ,10 ng/ml in 14 patients, 10±20 ng/ml in
11 patients, and .20 ng/ml in 18 patients. The age of
patients ranged from 52 to 82 years (median, 70; mean,
68). Initial PSA ranged from 1.4 to 80 ng/ml (median,
14.5; mean, 20.5). Initial volume ranged from 24 to 110
cm3 (median,55; mean, 59.3).
Two out of 43 patients were not treated with brachyther-
apy. One of the two had brachytherapy performed elsewhere
3 years prior and developed a prostatourethrorectal ®stula
and was treated with systemic therapy. The other one had a
Gleason's score of 8 and failed external radiation therapy
and was treated with systemic therapy. Four patients out of
the remaining 41 patients had combined method of treat-
ment or salvage brachytherapy and are excluded from the
analysis of this report. Three patients of the remaining 37
patients treated with monotherapeutic 3-DCT-guided para-
rectal brachytherapy were excluded from this report (two
patients expired from other causes within 1 year post-
brachytherapy and one patient was treated for a second
primary). The remaining 34 patients treated with 3-DCT-
guided method of brachytherapy are included in the analysis
of this report.
The 3-DCT-guided method has been reported [7±10]. The
senior author developed the 3-dimesional CT-guided poster-
ior method in 1994. CT is used for pretreatment planning,
the execution of the implant procedure in conjunction with
the 3-dimensional stereotactic system and for post-implant
dosimetry. Precise placement of the afterloading needles is
achieved with the 3-dimensional stereotactic system. The
correct position of the needles is veri®ed with CT prior to
implant. The template is large enough to cover a large target
and has perforations that are 2.5 mm apart in either direction
for ®ne needle correction if needed. The procedure is
performed under epidural anesthesia. The patient is able to
return home the same day. A Mick applicator is used for
loose seeds. An attachment to the 3-D stereotactic template
is used for instant loading and implant of seeds in rapid
strand and/or loose seeds with spacers. The afterloading
needles are not preloaded to avoid seed placement in vessels
and reduce seed migration to a minimum. Post-implant CT
dosimetry is performed immediately after the procedure.
Dosage to the prostate and seminal vesicles under the mono-
therapeutic method, is 120 Gy with Palldium-103 and 144
Gy with iodine-125, includes 5±10 mm outside the target.
Three-dimensional CT-guided planning and dosimetry is
P. Koutrouvelis et al. / Radiotherapy and Oncology 60 (2001) 31±3532
performed with Varian Brachy Vision, and post-implant CT
dosimetry is performed with Varian/MIVIS or Varian
BrachyVision (Figs. 2 and 3).
3. Results
Follow-up was determined by of®ce visits every 3 months
during the ®rst year, every 6 months during the second year,
and yearly thereafter. In addition, data were collected from
direct telephone contact and patient responses to written
annual questionnaires.
Prescribed dosage (120 Gy using Palladium-103 seeds
and 144 Gy using Iodine-125 seeds) to the entire seminal
vesicles was achieved in all 37 patients treated with mono-
therapeutic 3-D stereotactic CT-guided brachytherapy as
calculated with postimplant CT-dosimetry with Varian
Brachytherapy or Varian MMS. Follow-up PSA results
were available 12±56 months (median, 24 months) in 34
patients treated with brachytherapy. We have established a
PSA level less than 1 ng/ml as a nadir. PSA levels were
strati®ed into six groups based on the presenting Gleason's
score and initial PSA. In the group (with Gleason's score~6
and initial PSA ,20 ng/ml), PSA levels decreased to less
than 0.5 ng/ml in all seven patients (100%) after brachyther-
apy. In the group with Gleason's� 7 and initial PSA ,20
ng/ml, PSA levels decreased to less than 1 ng/ml in 11 of 13
patients (85%) and PSA , 0.5 ng/ml in ten patients (77%).
In the group with Gleason's score� 7 and initial PSA . 20
ng/ml, PSA decreased to less than 0.5 ng/ml in four out of
eight patients (50%). In the group with Gleason's score $ 8
and initial PSA , 20 ng/ml PSA levels decreased to less
than 0.5 ng/ml in three of three patients. PSA decreased
less than 0.5 ng/ml in two out of three patients in the last
group 67% with Gleason's score $ 8 and initial PSA . 20
nglml. There were no patients with a Gleason score of 1±6
and greater then 20 nglml initial PSA. (Table 1). Patients
(n � 34), irrespective of the Gleason's score and PSA, had
an overall response from CT guided brachytherapy of 79%
(decreased PSA less than 1 ng/ml).
Twenty percent of patients treated with brachytherapy
experience transient treatment-related symptoms of
frequency of urination and burning sensation lasting 2±4
weeks and were treated with alpha-blockers and Pyridium
and/or steroids. None of the 37 patients treated for seminal
vesicle involvement required a catheter after the implant
procedure. One patient of the 37 patients, who had transur-
ethral prostatectomy (TURP) prior to implant, developed
P. Koutrouvelis et al. / Radiotherapy and Oncology 60 (2001) 31±35 33
Fig. 1. CT image of 3-D CT-guided stereotactic pararectal biopsy needle placement into the seminal vesicles. The rectum and coccyx is spared.
lower urinary-tract infection 2 years after the implant and
his urologist performed a TURP resulting in grade 2 incon-
tinence. Transient rectal symptoms of diarrhea and/or
constipation occurred after implant in 20% of the patients
lasting 1±4 weeks. Two patients experienced post-implant
delayed effect of radiation with grade 3 rectal complications
12 months after the implant with rectal bleeding and pain.
4. Discussion
Under the 3-D CT-guided pararectal approach,
brachytherapy delivers adequate dosage to the entire semi-
nal vesicles as well to the adjacent fat tissue. Under
combined ultrasound-guided transperineal brachytherapy
and external beam radiation, the dosage to the seminal vesi-
cles has been reported to be inadequate [16]. In addition,
with CT-guided monotherapeutic brachytherapy, the dosage
to the adjacent organs (bladder and rectum) is 20±40% of
the prescribed dose. This is less than the dosage given under
combined methods of treatment or radical EBRT.
Studies have reported extra capsular extension to range
from 15±60% in patients with clinically organ-con®ned
disease and may have local recurrence after radical prosta-
tectomy [14,15,17]. Furthermore, patients who underwent
radical prostatectomy with negative surgical margins and
negative lymph nodes have a better prognosis in spite of
seminal vesicle invasion. PSA of . 10 ng/ml and Gleason's
score . 7 had adverse prognostic failure [17].
P. Koutrouvelis et al. / Radiotherapy and Oncology 60 (2001) 31±3534
Table 1
Post Treatment PSA (12±56 months, median 24 months) by combined Gleason's and initial PSA (n� 34)
N PSA ,1 ng/mI % PSA , 0.5 ng/ml %
Gleason's, 1Ð6 & initial PSA, ,20 ng/ml 7 7 100 7 100
Gleason's, 1Ð6 & Initial PSA, .20 ng/ml 0 NA NA NA NA
Gleason's,� 7 Initial PSA ,20 ng/ml 13 11 85 10 77
Gleason's, � 7 Initial PSA .20 ng/ml 8 4 50 4 50
Gleason's, $ 8 Initial PSA ,20 ng/ml 3 3 100 3 100
Gleason's, $ 8 Initial PSA .20 ng/ml 3 2 67 2 67
Fig. 3. Dose volume histogram for patient in Fig. 2. One hundred per cent of
the target volume of the prostate and seminal vesicles are shown to have
received the prescribed dose of 120 Gy. The urethra received 100% of the
target dose. The rectum and urinary bladder received in the range of 20±
50% of the target dose.
Fig. 2. Post-implant CT dosimetry (Varian Brachy Vision) of the seminal
vesicles with Pd-103 seeds. Seminal vesicles are colored in pink. The 100%
isodose level of the prescribed dose of 120 Gy is outlined in blue and
extends 5±10 mm outside the seminal vesicles. The 50% isodose level of
the prescribed dose of 120 Gy is outlined in yellow. Anterior rectal wall is
outlined in blue and urinary bladder in yellow at bottom.
The afterloading needles are not preloaded. If bleeding
results from placement of any of the needles, then adjust-
ments to the needles are made to avoid seed placement in
the venous plexus; therefore, little, if any, seed migration
occurs. There is no signi®cant seed migration with loose
seeds outside the capsule of the prostate, however we prefer
seeds in rapid strand. This is con®rmed with CT of the pelvis
and chest radiographs taken 3±6 months after implant in all
patients.
In the absence of infection, high initial PSA (greater than
20) is a poor prognostic indicator without and with seminal
vesicle invasion. Although these patients may have negative
bone scan, negative CT and negative MRI of the upper and
lower abdomen, they may have microscopic systemic
disease. We perform pelvic lymph node resection and/or
nuclear Prostascint scan for patients with seminal vesicle
invasion and high PSA. If positive we recommend EBRT
and hormone therapy rather than monotherapy with
brachytherapy. However, high-risk patients with Gleason's
score $ 7 and PSA ,20 have had good results and have
good coverage with radioactive seeds.
5. Conclusions
3-DCT-guided monotherapeutic brachytherapy delivers
adequate dosage to the seminal vesicles. Clinical and
biochemical results are encouraging in patients with low
initial PSAs regardless of their Gleason's scores, but
longer-term data in a greater number of patients is necessary.
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