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For Our Fathers
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Nelson
N. Stone, MD
Professor of Urology and Radiation Oncology
Mount Sinai School of Medicine
New York, New York
Welcome
to the Prostate Cancer Education Council's Article
Series: 2000 website.
Below
is the third in a series of six articles by a
select panel of distinguished urologist addressing
a topic related to advancements in prostate cancer
treatment, research, and prevention. Informative
sidebars throughout the article, along with highlighted
technical vocabulary hyperlinked to a prostate
cancer glossary,
create an easily digestible format for consumers.
Article
Series: 2000 is presented on behalf of the Prostate
Cancer Education Council (PCEC). Founded in 1988,
the PCEC is a consortium of physicians, health
educators, scientists, and patient advocates dedicated
to increasing prostate cancer awareness and knowledge.
Here is
a list of currently available and upcoming articles.
The
author of this article is Dr. Nelson Stone. Dr.
Stone is a Professor of Urology and Radiation
Oncology at the Mount Sinai Medical Center in
New York, New York.
Dr.
Stone has authored or co-authored over 200 articles
in numerous medical journals including the Journal
of Urology, the Mt. Sinai Journal of Medicine,
Techniques in Urology, and the International
Journal of Radiation Oncology, Biology, and Physics.
Additional publications produced by Dr. Stone
include several books and book chapters on various
subjects within the urologic field.
Dr.
Stone's main interest lies in prostate cancer,
and specifically, prostate brachytherapy. He is
affiliated with numerous medical groups, including
the American Urological Association, the European
Association of Urology, and the American Association
of Clinical Urologists.
As
a researcher, Dr. Stone has received funding from
numerous biotechnology sources. His current work,
"(The) Study of blood, bone marrow and pelvic
lymph nodes in men with prostate cancer," is made
possible by a grant from NCI. Anna Ferrari PI.
Dr.
Stone invented the real-time method of the seed
implant technique and is responsible for the construction
of over 100 training programs worldwide through
his ProSeed organization. Further information
on this article or the real-time method can be
obtained through Dr. Stone on the net at nproseed@aol.com.
INTRODUCTION
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Prostate
brachytherapy has become an attractive
treatment option due to its relatively
few side effects.
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Prostate
brachytherapy
has recently gained favor as an attractive treatment option
for localized prostate cancer, due to the fewer side effects
caused by the therapy when compared with other standard
approaches. When a patient is diagnosed with prostate
cancer, his usual first thought is "am I going to live?"
Fortunately for most men, this is really not the issue;
most patients are diagnosed with the tumor confined to
the prostate gland. However, every prostate cancer is
not alike and certain types of prostate tumors may be
more aggressive than others.
Types
of Prostate Cancer
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Treatment
for prostate cancer is dependent upon
the assignment of a risk group; the
variables that determine risk group
are PSA level, Gleason score, and
clinical stage.
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Prostate
cancer is usually classified using three separate steps.
First, the urologist examines the gland with his finger
(DRE)
and assigns a number to the stage of disease. Next, the
prostate specific antigen (PSA)
level is categorized, and finally, the pathologist grades
the cancer based on the Gleason
system. The different classifications and their ranking
in terms of the aggressive nature of the lesion are shown
in Table 1. Generally, patients are placed in one of three
categories: low risk, intermediate risk and high risk.
Treatment of a patient's prostate cancer varies dependent
upon the assignment of a risk group. For the purposes
of this discussion, it is assumed that the prostate cancer
has not metastasized.
Table
1
| Type
of Prostate Cancer |
PSA
Level |
Stage |
Gleason
score |
| Low
Risk |
<
10 ng/ml |
T1b-T2a |
<
6 |
| Intermediate
Risk |
10-15
ng/ml |
T2b |
7 |
| High
Risk |
>
15 ng/ml |
T2c-T3 |
8-10 |
Treatment
Options
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Viable
treatment options include watchful
waiting, radical prostatectomy, external
beam radiation, brachytherapy, and,
at some locations, cryotherapy.
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Every
newly diagnosed patient with localized prostate cancer
should have all of the options of treating his cancer
explained to him. These include watchful waiting, radical
prostatectomy, external
beam radiation, and brachytherapy.
Cryotherapy
has also become available in some centers. It is beyond
the scope of this article to describe all of these options
in detail; thus, the remainder of the article will focus
on prostate brachytherapy.
Prostate
Brachytherapy
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The
most common type of prostate brachytherapy
is known as permanent seed implantation;
the other is called temporary implantation.
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There
are two types of prostate brachytherapy
being performed today. The procedure more familiar to
most patients is called permanent seed implantation (tiny
seeds or "grains of rice" permanently placed inside the
prostate gland). The second form of prostate brachytherapy
is called temporary implantation (radioactive wires temporarily
placed inside the gland and removed after radiation is
delivered). As only a small fraction of the brachytherapy
cases being performed are done with this method, comments
will be limited to permanent implantation.
Radioactive
Isotopes used in Permanent Prostate Brachytherapy
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External
beam radiation must travel through
the body to reach the prostate, while
with prostate brachytherapy, the radiation
is placed directly inside the prostate
gland.
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Prostate
brachytherapy
is a form of radiation treatment similar but not identical
to external
beam radiation. The difference: external
beam radiation travels through the body to reach the
prostate, potentially damaging surrounding tissues (bowel
and bladder) while trying to eradicate the tumor. With
prostate brachytherapy,
the radiation is placed directly inside the gland where
the cancer is located.
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Iodine-125
has a half-life of 60 days, and is
used in patients who have Gleason
scores of 2 to 6. Palladium-103 has
a half-life of 17 days; it is normally
used for tumors with Gleason scores
of 7 or higher.
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The
radiation is contained in small (4.5mm by 0.8mm) titanium
bullet-shaped shells. The hollow shell contains a radioactive
isotope
of either iodine-125 (I-125) or palladium-103 (Pd-103).
I-125 has a half-life
of 60 days, and is generally used in patients with Gleason
scores of 2 to 6 on prostate biopsy. Almost all the radiation
will be delivered over one year following the implant.
The half-life
of Pd-103 is 17 days; it is usually chosen for tumors
with Gleason
scores of 7 or greater
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Choice
of isotope should depend on the physician's
comfort in handling it for a given
tumor.
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The
isotope
choice depends on the physician's comfort level in treating
the prostate cancer with a particular substance. In addition,
both I-125 and Pd-103 may be combined with external
beam radiation, in which the seeds act as a "boost"
to the total radiation dose delivered.
Types
of Procedures
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The
"Seattle Method," whereby the probe
partitions the prostate into 5mm images,
was developed in the early 1980s.
The newer method, known as "The Real
Time Method," relies on imaging performed
in the operating room.
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There
are currently two types of procedures available for permanent
seed implantation. The first was developed in the early
1980's using a probe with unidirectional capabilities.
When inserted in the anus, the probe partitions the prostate
into 5mm images. Using the sonograms, physicians can plan
where to introduce the seeds prior to surgery for optimal
placement. This technique has also been referred to as
the "Seattle Method".1,2,3,4
The newer method relies on imaging performed within the
operating room to plan and place the seeds, and uses two
planes of view rather than one. This technique has also
been called "The Real Time Method."4,5,6,7,8
Both techniques have been shown to provide excellent long-term
results.
Results
of Treatment
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It
is important that the proper doses
of radiation be delivered to the prostate
and surrounding tissue.
A
recent study shows a 92% cure rate
with radiation dose of 140 Gy and
higher for I-125, compared with less
than 50% if the delivered dose is
less than 140 Gy.
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The
primary concern for patients is that they be treated by
a team of physicians (usually a urologist, a radiation
oncologist, and a physicist) who have the experience to
deliver proper doses of radiation to the prostate and
surrounding tissue. Stock9
has shown that with radiation doses of 140 Gy
and higher for I-125, more than 92% of patients are cured.
This contrasts with less than a 50% success rate if the
delivered dose is less than 140 Gy.
Similar results were found for Pd-103, where doses greater
than 100 Gy
to 120 Gy10,11
needed to be delivered. Patients should ask their physicians
about success rates using the above parameters. A suitable
facility should be in the 95% to 100% range for delivery
of these doses.
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A
recent study indicated that when properly
trained, physicians achieved high-quality
implants in over 95% of their patients.
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In
a study published last year, Stone12
evaluated implant outcomes in 16 centers that had gone
through a formal training program. The results showed
that when properly trained, physicians achieved high-quality
implants in over 95% of their patients.
Treatment
of Low Risk Patients
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A
low risk prostate cancer (PSA <
10ng/ml, Gleason score < 6, clinical
stage <T2) has a low
likelihood of metastases and high
likelihood of cure. At this risk state,
it does not appear that one treatment
had an advantage to any of the others,
though patients at low risk should
consider brachytherapy alone without
addition of hormonal or external beam
radiation.
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A low
risk prostate cancer has a low likelihood of metastases
and a high likelihood of cure with any of the treatment
choices. Low risk disease is usually encountered when
a patient has a PSA<
10 ng/ml,
a Gleason
score < 6 and a clinical stage
< T2. D'Amico13
has shown success rates of 87% to 97% using brachytherapy,
radical
prostatectomy, or external
beam radiation. In this study, it did not appear that
one treatment had an advantage over another. Several other
published studies on brachytherapy
have shown success rates of 92% at 4 years, 90% at 5 years,
85% at 7 years and 66% at 10 years.1,2,3,4,5,6,7,8,14,15,16,17
Again, these results appear to be similar to radical
prostatectomy. Patients with low risk prostate cancer
should consider brachytherapy
alone (either I-125 or Pd-103) without the addition of
hormonal
therapy or external
beam radiation.
Treatment
of Intermediate Risk Patients
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Intermediate
risk patients (PSA >10 ng/ml and Gleason
score of 7 or a T3 lesion) should
not be treated with implant alone.
If brachytherapy is chosen, the resulting
options are implant with hormonal
therapy, implant plus external beam
radiation, or all three.
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Intermediate
risk patients are those who present with one of the follow
features: a PSA
> 10 ng/ml,
a Gleason
score of 7, or a T3
lesion. Such patients should not be treated with implant
alone, owing to the high recurrence rate.18
If brachytherapy
is chosen, the resulting options are implant with hormonal
therapy, implant plus external
beam radiation, or all three. Stone6
has shown significant improvement in outcomes when 5 to
6 months of leuprolide acetate and flutamide
was used in conjunction with the implant.
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Patients
who presented with an initial PSA
> 10 had only a 43% remission rate
if they received implant alone, compared
with a 90% remission if they received
hormones in addition to implant.
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Patients
who presented with an initial PSA
> 10 had a 90% likelihood of remission if they received
hormones with the implant compared to 43% if they received
implant alone (Figure 1). Biopsy results showed similar
findings. Prostate biopsies were done two years after
implantation to determine if the cancer was eradicated.
In those intermediate risk patients receiving hormones
plus seeds, only 3.2% had evidence of persistent disease,
versus 31.4% in those treated with implant alone.6
Figure
1: Percent free from PSA failure for patients with
intermediate risk prostate cancer treated by seed implant
with hormones (HT) versus no hormones (p=0.01).6
Treatment
of High Risk Patients
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Options
for treating high-risk patients (PSA
> 15 ng/ml, Gleason > 8, or clinical
T3 lesion) include the combination
of hormonal therapy with a high dose
of conformal beam radiation and the
use of a combination of seed implantation
with external beam radiation with
or without the addition of hormonal
therapy.
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Men
who present with a PSA
> 15 ng/ml,
Gleason
> 8, or a clinical T3
lesion are at high risk for metastases
and will most likely fail if treated by radical
prostatectomy, by external
beam radiation, or by brachytherapy
alone. The options for treating this difficult situation
include the combination of hormonal
therapy with high dose conformal external
beam radiation and the use of a combination of seed
implantation with external
beam radiation with or without the addition of hormonal
therapy. In the case of combining the seeds and external
beam radiation, the actual dose to the prostate is
higher than what can be achieved with even the best conformal
external beam.
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An
aggressive approach to high-risk prostate
cancer includes nine months of hormonal
therapy with seed implantation and
conformal external beam radiation.
Initial data indicate a 71% success
rate.
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A more
aggressive approach with this type of disease is to combine
nine months of hormonal
therapy with seed implantation and conformal external
beam radiation. The hormones, given as leuprolide
acetate plus flutamide,
are used for three months prior to and six months after
the implant. The patient receives an implant with two-thirds
of the total dose of radiation; after a two-month break,
conformal external beam is given for 5 weeks. The initial
data published on this treatment plan showed 71% free
of disease (almost 100% higher than conventional therapy).6
Conclusions
This
article has discussed the various treatment options
for prostate cancer. The indications for prostate brachytherapy
have been presented along with the proper selection
of the different treatments based upon the aggressive
nature of the disease. It is hoped that the patient
will be able to use this information as a means to further
educate himself and to help him make the best decision
along with his own physician about how to best proceed
with his treatment.
REFERENCES
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Ragde H, Elgamal AA, Snow PB, et al. Ten-year
disease free survival after transperineal sonography-guided
Iodine-125 brachytherapy with or without 45-Gray external
beam radiation in the treatment of patients with clinically
localized, low to high Gleason grade prostate carcinoma.
Cancer. 1998;83(5):989-1001.
-
Blasko JC, Radge H, Schumacher D. Transperineal percutaneous
Iodine-125 implantation for prostatic carcinoma using
transrectal ultrasound and template guidance. Endocurie
Hypertherm Oncol. 1987;3:131-139.
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Blasko JC, Ragde H, Luse RW, Sylvester JE, Cavanagh
W, Grimm PD. Should
brachytherapy be considered a therapeutic option in
localized prostate cancer? Urol Clin North
Amer. 1996;23(4):633-650.
-
Ragde H, Blasko JC, Grimm PD, et al. Interstitial
Iodine-125 radiation without adjuvant therapy in the
treatment of clinically localized prostate carcinoma.
Cancer. 1997;80(3):442-453.
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Stock RG, Stone NN, Wesson MF, DeWyngaert JK. A
modified technique allowing interactive ultrasound-guided
three-dimensional transperineal prostate implantation.
Int J Radiat Oncol Biol Phys. 1995;32(1):219-225.
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Stone NN, Stock RG. Prostate
brachytherapy: treatment strategies. J Urol.
1999;162(2):421-426.
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Stone NN, Ramin SA, Wesson MF, Stock R, Unger P, Klein
G. Laparoscopic
pelvic lymph node dissection combined with real-time
interactive transrectal ultrasound guided transperineal
radioactive seed implantation of the prostate.
J Urol. 1995;153(5):1555-1560.
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Stone NN, Stock RG, DeWyngaert JK, Tabert A. Prostate
brachytherapy: improvements in prostate volume measurements
and dose distribution using interactive ultrasound
guided implantation and three-dimensional dosimetry.
Radiat Oncol Investig. 1995;3:185-195.
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Stock RG, Stone NN, Tabert A, Iannuzzi C, DeWyngaert
JK. A
dose-response study for I-125 prostate implants.
Int J Radiat Oncol Biol Phys. 1998;41(1):101-108.
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Iannuzzi CM, Stock RG, Stone NN. PSA
kinetics following I-125 radioactive seed implantation
in the treatment of T1-T2 prostate cancer. Rad
Ocol Invest. 1999;7(1):30-35.
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Stone NN, Stock RG, Kao J, Unger P. Prostate biopsy
results following brachytherapy: factors affecting
a positive outcome. J Urol. 2000;163:1274a.
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Stone NN, Stock RG, Pressor J, Chircus JH, et al.
Can prostate brachytherapy be taught? Dosimetric evaluation
of implant quality following training. Int J Rad
Oncol Biol Phys. 1999.
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D'Amico AV, Whittington R, Malkowicz SB, et al. Biochemical
outcome after radical prostatectomy, external beam
radiation therapy, or interstitial radiation therapy
for clinically localized prostate cancer. JAMA.
1998;280(11):969-974.
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Grado GL, Larson TR, Balch CS, et al. Actuarial
disease-free survival after prostate cancer brachytherapy
using interactive techniques with biplane ultrasound
and fluoroscopic guidance. Int J Radiat Oncol
Biol Phys. 1998;42(2):289-298.
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Blasko JC, Wallner K, Grimm PD, Ragde H. Prostate
specific antigen based disease control following ultrasound
guided 125-iodine implantation for stage T1/T2 prostatic
carcinoma. J Urol. 1995;154(3):1096-1099.
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Stokes SH, Real JD, Adams PW, Clements JC, Wuertzer
S, Kan W. Transperineal
ultrasound-guided radioactive seed implantation for
organ-confined carcinoma of the prostate. Int
J Radiat Oncol Biol Phys. 1997;37(2):337-341.
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Storey MR, Landgren RC, Cottone JL, et al. Transperineal
125-iodine implantation for the treatment of clinically
localized prostate cancer: 5-year tumor control and
morbidity. Int J Radiat Oncol Biol Phys.
1999;43(3):565-570.
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Stock RG, Stone NN. The
effect of prognostic factors on therapeutic outcome
following transperineal prostate brachytherapy.
Seminars in Surgical Oncology. 1997;13(6):454-460.
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