Introduction
Approximately 220,000 men will be diagnosed with prostate cancer in 2003.
Early diagnosis, primarily due to more widespread PSA screening, has resulted
in more patients being diagnosed with early stage disease.1,2 For disease
that is likely confined to the prostate and the immediate surrounding area,
surgery, external beam radiation (EBRT) and seed implantation are the primary
treatment options. In recent years, seed implantation has become more popular
as a treatment
option. It has been estimated that up to 50% of patients with early stage
prostate cancer are now receiving ultrasound-guided seed implantation.13
This rise in popularity is most likely due to (1) the fact that five- and
ten-year disease control rates of brachytherapy equal those of the top
surgical and radiation series, (2) the toxicity and side-effects are perceived
to be lower, and (3) the brachytherapy involves
just a single outpatient treatment.7-11,14
Ultrasound-guided transperineal interstitial
permanent prostate brachytherapy
with I-125 or Pd 103 radioactive seeds is a form of radiation therapy in
which radioactive sources, or “seeds”, are permanently inserted
into the prostate. The principal advantage of this technique is that the
seeds can deliver a substantially higher radiation dose to the prostate
and surrounding tissue compared
with external beam irradiation. Because of the low energy of I-125 (Iodine
125) and Pd 103 (Palladium 103) isotopes, the dose falls off quickly with
distance and, therefore, the seeds deliver low doses to the adjacent rectum and bladder.
Historical Background
Seed implantation for prostate cancer was originally suggested by Alexander
Graham Bell as far back as 1903. In 1911, Louis Pasteur suggested that
the insertion of radium into the prostate may eradicate this malignancy.15
Various techniques were subsequently employed with limited success. In
the 1960s, Drs. Scardino and Carlton reintroduced permanent prostate brachytherapy
using 198-Au (gold-198) interstitial implantation combined with external
beam radiation therapy.17 At about the same time, Dr. Whitmore and colleagues
at Memorial Sloan Kettering Cancer Center (MSKCC) also began to insert
I-125 seeds through an open incision as a sole treatment.18 Unfortunately,
these early techniques did not allow for clear visualization of the seeds
as they were being inserted into the prostate and, as a result, there was
often poor dose coverage of the gland.
Despite the limitations of these techniques, some important information
was obtained from the early seed implant approaches. Local cancer control
was better in patients who received high
quality implants and who had low grade and early stage cancer.20,21,26
The group from MSKCC
reported a 60% local control rate in those patients who received prescription
doses of > 140 Gy (Gray) versus 20 % if the dose was less than 140Gy.
The 15-year survival was 70% in patients with stage B1 prostate cancer
treated with I-125 seed brachytherapy.27 These results suggested strongly
that seed placement and proper patient selection were important determinants
of cancer
control. The subsequent development of the transperineal, ultrasound guided
approach provided
a means to more accurately place seeds and thereby improve dose coverage.
Technical Development of the Transperineal Approach
In the 1980s, several investigators were exploring new brachytherapy approaches
to the treatment of prostate cancer.28 Martinez treated patients with EBRT
combined with temporary
seeds inserted using a transperineal approach.29 Drs. Syed and Puthawala
pioneered a temporary seed technique of placing the needles while visualizing
them through an open laparotomy.30 In 1983, Dr. Holm introduced the use
of transrectal ultrasound to visualize the permanent placement of I-125
seeds via needles inserted through the perineum directly into the
prostate.31 The ultrasound-guided transperineal approach resulted in relatively
even distribution
of seeds throughout the prostate; this marked a major advance in prostate
brachytherapy in
that it minimized the need for external beam radiation and allowed more
precise planning of
the implant prior to the procedure. These advances also significantly increased
the accuracy of seed placement and insured that the prostate would receive
the proper number, strength, and positioning of radioactive sources. Derivatives
of this technique are in wide use today. (See Figure 1.)
The first transrectal ultrasound-guided, template-guided I-125 implant
procedure was performed at the Seattle Prostate Institute in late 1985
and is now being used in over 600 centers around the world. The original
Seattle approach has been modified and improved several times since the
original implants. Today, the implant is planned prior to the procedure
either on the day of or several weeks prior to the implant. Typically,
the implant is completed in a 45-90 minute outpatient procedure under spinal
anesthesia or light general anesthesia.32
Technical Advances
As brachytherapy has become more popular, many technical improvements
have been added to improve the consistency and quality of the procedure.31,
33-35 Both Pd-103 and I-125 seeds are now available in continuous strand
form, increasing the likelihood that the seeds will remain in place after
implantation. Compared with loose, or free seeds, these connected seeds
have been demonstrated to substantially lower the incidence of seed migration
to the lung.36 While slight differences in technique are expected to grow
as more and more physicians perform this procedure and as more technical
advances are made, the basic approach is quite similar and it remains to
be determined whether any single technique will prove superior in controlling
the cancer. Fundamentally, most of the active institutions currently use
transrectal ultrasound guidance via a closed template-guided transperineal
technique and a modified uniform seed dispersal pattern. Quality evaluation
is based on postop, CT-based [link to CT-scan] dosimetry. Virtually all
are in
agreement that the keys to successful outcomes are appropriate patient
selection and a high quality implant.43-47
As shown in Figure 2, the entire implantation process consists of several
discrete steps:
•
Patient selection
•
Treatment planning
•
Seed implantation
•
Post-Operative evaluation.
Patient Selection
The three key considerations involved in the selection of patients for
ultrasound-guided implantation are the stage of cancer, technical suitability,
and toxicity issues. Each of these is
carefully evaluated prior to treatment.
Stage and Extent of Cancer
Staging is a means to determine the extent of the cancer prior to treatment.
Patients with a high likelihood of disease in the prostate and immediate
surrounding area can be treated with seeds alone. Patients deemed to have
a higher likelihood of diseases beyond the implant volume are treated initially
with external beam radiation to a region around the prostate after which
they receive an implant “boost.” Patients with distant, metastatic disease
are treated with hormonal
therapy or
other systemic agents.
In early stages, there is a very low risk of disease in the seminal
vesicles or lymph
nodes, and only a modest risk of disease that extends through
the outer wall, or capsule, of the prostate. Fortunately, the disease that
goes through the capsule is almost always within several millimeters of
the prostate and is easily covered by the implant volume.51,52 The risk
of disease outside the prostate can be estimated by looking at the Partin
tables 48,49 which correlate (1) the risk of extra-capsular
penetration (ECP), (2) seminal vesicle involvement (SV), and (3) lymph node involvement
(LN) with the Gleason score, clinical
stage, and pretreatment PSA.50 Note
again, however, that capsule penetration does not mean that disease is
beyond the surgical or implant margin. Typically, surgical and radiation
margins are 4mm – 15mm beyond the prostate. Disease
that is beyond the margin can be roughly estimated from the Partin tables
by the formula LN + SV + ECP (X) (X is 25% if the Gleason score is 6 and
50% if it is 7). This calculation is based on a study that showed that,
for early stage patients with evidence of ECP only, 25% would fail radical
prostatectomy if the Gleason score was 6 or below and approximately 50%
would fail if it was 7 or higher.134
Evidence that patients with early stage (low risk) disease have a high
likelihood of disease confined to the implant margin comes not only from
pathologic studies, but also from clinical
studies showing excellent PSA control with seed implantation alone using
either 103-Pd or I-125.43,54,55,56-61 Some centers combine EBRT with implantation
on all patients, even those with low risk disease, but to date, the long-term
clinical results of combined treatment have not been shown to be superior
to those of implantation as the sole treatment.62,63 For the majority of
patients, implant alone is satisfactory. There are, however, several factors,
such as the number of positive cores, that are considered in determining
whether a patient requires EBRT in addition to implantation.
For intermediate risk patients, the choice of treatment is between implant
alone or EBRT and seeds. A common definition of intermediate-risk is the
presence of one of several unfavorable risk factors:
•
PSA > 10 ng/ml,
•
Gleason > 7, or
•
= cT2c [link to staging] disease by DRE.
This intermediate group is a broad group with a significant range of risk
of disease outside the prostate. Some of the more favorable intermediate-risk
patients (e.g. those with stage T1c, Gleason < 7, a PSA between 10-15ng/ml,
and a low percentage of positive biopsies) have
a relatively low risk of disease beyond the margin and are often treated
with implant alone.
We believe that other intermediate risk patients with worse prognostic
factors are probably
served best by EBRT plus implantation, but further studies are necessary.
High-risk patients are considered as those with two or three of the above
mentioned unfavorable
risk factors.55 Patients in the high-risk group are typically treated with
combined therapy which may also include hormonal therapy. Table 1 shows
the current treatment guidelines recommended by the Seattle Prostate Institute,
which are consistent with those advocated by
the American Brachytherapy Society.
Technical Issues
Prostate Size: In order for an implant to be done well, the physicians
must be able to place the seeds accurately. We have found that if the size
of the prostate is much greater than 60cc, the implant can become technically
challenging since the greater number of needles required causes more swelling
during the procedure. In addition, as the size of the prostate increases,
there is a higher probability that a portion of the gland will be positioned
behind the pubic bone, obstructing the placement of needles.
Prior Prostate Surgery: A prior TURP (Trans-Urethral Resection of the
Prostate) can sometimes prevent a quality implant. TURPs can leave a large
hole in the central portion of the gland (a “TURP defect”)
allowing little room for seed placement. In addition, the early experience
noted higher rates of incontinence when TURP patients were treated with
implantation.44,71,72,73,74 Recent procedural advances that involve placing
seeds further from the TURP defect have decreased this risk of incontinence.
The current consensus, therefore, is that patients with small TURP defects
are eligible for implantation as long as they clearly understand that their
risk of incontinence may be higher than non-TURP patients.
Catheterization: The need for a temporary catheter after implantation
increases as the AUA score increases. The AUA score is a measure of the
blockage present before implantation. Patients with AUA scores above 15
are at higher risk of needing a temporary catheter after seed implantation,
and a few of these may require treatment either before the implant or at
a later date to relieve obstructive problems. For example, some patients
with more severe obstructive symptoms can become candidates for implantation
if their urinary symptoms respond well to alpha-blockers. Others can benefit
from surgical intervention, either a TURP or, preferably, a TUIP (transurethral
incision of the prostate) which is a less complicated and traumatic procedure
that minimizes the risks associated with a TURP.
Also of note is that patients undergoing hormonal therapy to shrink the
prostate may not experience any improvement in their obstructive symptoms.
Moreover, some studies have suggested that pre-treatment with androgen
ablation can slightly increase the risk of requiring a temporary catheter.135,136
Treatment Planning
All implants are planned carefully prior to the procedure either at the
time of the procedure or several weeks prior to the implant. The prescription
dose is determined by the isotope (Pd-103 or I-125) and whether it is to
be used for implant alone (145Gy for I-125, 125 Gy for Pd 103) or in combination
with EBRT (110 Gy for I-125 and 100 Gy Pd 103). This dose is the radiation
dose delivered to an area (target volume) determined by the brachytherapist.
In addition, the brachytherapist also defines ranges of acceptable doses
to the critical nearby structures, including the urethra, rectum, and bladder.
Careful planning is important to avoid areas of high dosage.
The first step in planning an implant is a volume study, which consists
of a series of cross-sectional ultrasound images of the prostate. The volume
study may be performed weeks prior to the procedure or in the operating
room on the day of the procedure. The ultrasound images are then transferred
to a computer planning system, and a skilled team consisting of the treating
physician, physicists, and dosimetrists generates a plan. The plan is actually
a map of the prostate and it describes precisely where each needle needs
to be placed and the number of seeds per needle. The brachytherapy team
follows this map carefully in the operating room, but has the leeway to
add seeds if necessary.
The seeds are generally designed to be approximately 1 cm apart. The size,
shape, and critical structures will modify this overall pattern slightly
within the gland, creating what brachytherapists call a “modified
uniform spacing” pattern to satisfy the dose requirements and to
minimize high dose areas. The vast majority of centers in the USA currently
use a modified uniform seed spacing approach.
Isotope Selection
I-125 and Pd 103 are the primary isotopes used in permanent seed implantation.
I-125 was
introduced into clinical treatment of prostate cancer in 1965, and 103-Pd
was introduced in 1986. The photon energy of 28 Kev for I-125 and 21 Kev
for Pd-103 are nearly identical. The primary difference between the two
isotopes is the rate at which they decay. I-125 has a half-life (the time
it takes to decrease by one half) of 60 days versus 17 days for Pd 103.
The effect is that Pd gives up its energy more quickly. There is no evidence
yet that quicker is better for prostate cancer so selection of the isotope
is at the discretion of the brachytherapist. The American Brachytherapy
Society does not recommend one isotope over the other.43
Dose
The doses prescribed today are the result of initial calculations and
the subsequent experience
from treating thousands of men. The doses delivered by implantation are
significantly higher than those achievable by 3Dconformal/IMRT, external
beam radiation therapy, or HDR brachytherapy. Typical doses for implants
are 125-145 Gy. For EBRT, the doses are 70-80 Gy. In order for EBRT to
deliver a dose equivalent to that of an implant, 120 Gy would have to be
given, a dose far beyond the tolerable range for EBRT.81,92 (EBRT is typically
not given in doses over 80G.)
Implant Procedure
The implant procedure itself is a 45-90 minute outpatient procedure that
can be performed under spinal or general anesthesia. Most centers prophylactically treat with I.V. antibiotics at the time of the implant procedure. Physicians
can use either preloaded needles or a MICK™ apparatus to deposit
the seeds. With preloaded needles, the seeds are placed into the needles
either individually (free seeds) or as part of a connected strand of seeds.
The Mick applicator, shown in Figure 3, uses a cartridge system, and seeds
are inserted into the gland individually. Many centers have published on
these different techniques.35,40,56,66,99
During the procedure, great care is taken with needle and seed placement.
The radiation oncologist’s job is to insure the precise placement
of the seeds and, if necessary, to recommend
additional seeds. The urologist’s job is to place the needles and
to perform necessary urologic
evaluations and procedures. For example, following successful placement
and confirmation
of seed position, a cystoscopy is often performed at the end of the procedure
to remove any blood clots or seeds from the bladder. Typical post-operative
orders include an ice pack to the perineum for 20 minutes and discharge
to home with an alpha-blocker (e.g., Flomax™), an antibiotic, a non-steroidal
anti-inflammatory drug, and an appointment for a CT scan used for post-operative
dosimetry purposes.
The implanted seeds do not represent a significant radiation hazard to
others. The energy of I-125 and 103-Pd is so low that there is minimal
risk of radiation exposure to friends and relatives of the patient. In
one study, the average dose a spouse received during the year following
the implant was determined to be 10 mRem. This is approximately equal to
living in Denver for 3-4 months or taking one round trip airplane flight
from New York to Tokyo.100
Post-Operative Evaluation
The assessment of implant quality can take place, to a certain degree,
during the procedure
through the use of ultrasound, and possibly fluoroscopy, to visualize the
needles and seeds as
they are being placed. Definitive evaluation, however, takes place post-operatively
using CT
scans that identify the position of each seed and allow the brachytherapy
team to calculate the
dose delivered by the seeds to the gland. CT dosimetry shows the radioactive
seeds in cross-sectional images as they lie within the prostate (Figure
4). With the aid of treatment planning
software, the dose is calculated and compared to the pre-plan dosimetry
(Figure 5). CT dosimetry
has allowed brachytherapists to substantially improve the technique.46,108,109
As swelling of the
prostate can sometimes make it difficult to accurately define the gland
and to perform the required calculations, the CT study is usually performed
about four weeks post-op. Most of the
prostate swelling will have resolved by this time.105 However, at centers
where some patients must travel long distances for treatment, practical
considerations often dictate that post-op
dosimetry be done on day 0 or day 1 post-op.
The goal of any implant is to achieve the prescribed dose throughout the
prostate. Several
studies have documented better biochemical
control in the patients treated
with I-125
monotherapy that achieved a dose greater than 130-140 Gy as compared with
patients whose
dose fell below this range.46,47 Research at the Seattle Prostate Institute
has shown that monotherapy patients, treated between 1986-1987 (the first
implants that were performed in the U.S.), achieved significantly worse
biochemical control than did patients treated at the Institute by the same
physicians between 1988-1990.60 The only factor identified as explaining
the difference was the quality of the implant. These studies supported
the hypothesis that higher quality implants result in better cancer control.
Post-op CT dosimetry provides important, immediate feedback on each implant.
If there is an area or areas with significant underdosing, the deficiency
can be addressed in a timely manner with supplemental EBRT, HDR, or a second,
corrective implant. Currently, the American Brachytherapy Society recommends
the use of CT-based, post-op dosimetry on all patients and also recommends
that such findings be included in published reports from clinical research
on implantation.43
Toxicity of Modern Implantation
Major acute operative symptoms and complications are extremely rare. Surgical
events such as (1) bleeding that requires transfusions, (2) admission to
intensive care for any postoperative acute events, or (3) death have not
typically been noted in the literature.30,111 And, it should be noted that
at the Seattle Prostate Institute, where physicians have performed more
than 7,000 implant procedures, no deaths or serious intra-operative or
post-operative morbidity has been observed.
Moderate post-operative side-effects, however, are common, and they primarily
consist of urinary irritative and obstructive symptoms such as increased
urinary frequency, urgency, discomfort during urination, and weakening
of the urinary stream.38,44,55,112 The symptoms are at their worst between
two and six weeks post-op, but they may be bothersome for up to six months
or longer. The need for a temporary catheter occurs in approximately 10%
of patients.38,41,42,66,71,112,113 In one study at the Seattle Prostate
Institute, the average duration of catheterization was 13 days, and 2%
of the patients required a Foley, supra-pubic, or intermittent self-catheterization
for more than six months. No patient has required a permanent catheter.114
In the small percentage of patients who require a catheter for more than
a few weeks, self-catheterization is taught or a
supra-pubic catheter is placed until the swelling and retention resolves.
Increased bowel movement frequency and urgency is uncommon and when it
occurs, the symptoms respond to diet and medications such as Imodium™.
Blood in the urine is to be expected for a few days (and occasionally a
few weeks) after implant. Perhaps half of sexually
active patients will experience some level of discomfort with orgasm, a
problem that generally resolves itself gradually. Although the prostatic
fluid of the ejaculate will decrease dramatically following an implant,
sperm can still be present. Occasionally, blood in the ejaculate will be
seen but it is not harmful or dangerous. Whether the sperm is significantly
damaged by the radiation exposure is unknown; however, to be safe, birth
control measures are recommended for those couples who are still fertile.
Ejaculation of a seed is rarely reported. The Seattle Prostate Institute
team knows of only less than five patients who have noted this event over
the past 15 years.116
Quality of Life (QOL)
With evidence that the various treatments for prostate cancer are likely
to be equally successful
in terms of long-term cancer control, emphasis is now being placed on
the quality of life after treatment. Quality of life can be difficult
to measure, as men can perceive problems after treatment very differently.
Previous attempts to define quality of life have been marred by the fact
that patient reports of problems have differed substantially from physician
reports. Therefore, studies are now incorporating the use of validated
questionnaires that can help decrease, but not totally eliminate bias.
Several recent QOL studies have compared implantation, EBRT, and radical
prostatectomy.
In one study, the analysis showed a decrease in QOL with radical prostatectomy
and implantation at one month post-op, but the overall QOL for both treatments
returned to near the pre-op baseline by the one year mark.117 In another,
the patients treated with radical prostatectomy reported significantly
worse QOL problems in terms of urinary function and sexual function and
bother (Figures 6 and 7). The patients treated with EBRT reported significantly
worse QOL in regard to bowel function (Figure 8) and fear of cancer recurrence.118
More studies in this important area will help compare not only the quality
of life for each of the treatments, but also will
allow comparison of QOL for each of the several brachytherapy techniques
currently in use, as discussed in the following paragraphs.
Rectal bleeding after implants occurs in approximately 2-5% of patients
who receive an implant only, and occurs in approximately 6-10% of those
treated with both EBRT and implantation. It is usually minor and not apparent
until 1-2 years after the implant. Rectal bleeding rarely occurs after
three years.38,42,57,67,68,71 One study demonstrated that careful planning
of the dose to the rectum substantially reduced the risk of rectal bleeding.119
A severe rectal ulcer or fistula is rare in
patients not undergoing electrocautery.19,111 Biopsies or electrocautery
to stop bleeding are to be avoided in all patients with rectal bleeding
after implant because they can increase the risk of a non-healing ulcer
or fistula.
Most reports in the literature note that long-term urinary morbidity and/or
incontinence is rare following implantation. In patients (1) without severe
obstructive urinary symptoms, (2) with significant benign prostatic hypertrophy,
and (3) without a prior TURP, the risk of chronic urinary irritation or
incontinence following implantation is less than 3%.19,111
Sexual functioning and impotency are more challenging to evaluate due
to differences in patient perceptions, the definition of potency, age differences,
baseline functioning, comorbid diseases, and, in addition, the sexual functioning
and interest of the patient’s partner. A Seattle Prostate Institute
team has reported the results of a patient self-reported questionnaire.
Of those seed
monotherapy patients who noted full normal erection ability prior to implantation,
80% maintained the ability to obtain an erection “adequate for intercourse”,
as compared to 69% of patients who were treated with EBRT plus implantation.65,97,121
In other studies, 75% of implant patients maintained erection function
at one year post-implant. At three years, 81% reported the ability to maintain
an erection ability.57,68 Of interest is the fact that several studies
may have identified the cause of impotence in some men. The dose to the
bulb of the penis may correlate to erectile dysfunction. In a small series
of retrospectively reviewed patients, Dr. Merrick noted that 19 of 23 patients
lost erectile function when the dose to the bulb of the penis was greater
than 40% of the minimal peripheral dose, whereas 19 of 23 maintained erectile
function if the dose at the bulb of the penis was less than 40% of the
minimal peripheral dose.110 These findings are likely to change the planning
of dose to this area in the future.
Clinical Results
There remains considerable debate as to how best to define PSA control
following surgery, EBRT, or implantation, particularly in the urological
literature.122 This is because PSA levels fall at different rates after
each of these treatments. PSA falls rapidly after surgery but more slowly
after implantation or EBRT. For example, following an implant with Pd-103,
the PSA level, on average, will fall by 50% in approximately 90 days. After
surgery, conversely, the 50% reduction takes only 3.8 days.120,123 To allow
meaningful comparisons of cancer control rates between surgery and implantation,
the American Society for Therapeutic Radiation and Oncology (ASTRO) adopted
a definition of PSA failure as being three consecutive increases in PSA
level following an implant. Treatment success, therefore, is described
as being “PSA Progression-Free.” PSA Progression-Free data
is used today for most of the comparison studies. In addition, most experts
agree that ten years is
necessary before meaningful comparisons can be made between the treatments.
By that time, almost all of the failures will have occurred. Using a fixed
PSA value to define failure (such as 0.5 ng/ml as used in some studies)
is inappropriate, since some implant patients may take as long as eight
years to reach this level. The different definitions of cancer control
will continue to spark debate between the radiation oncology and urology
communities.
Five-Year Results
As stated earlier, ten years is considered the benchmark for evaluating
the results of therapy. Because many centers have not reached this mark,
five-year results are reported. Five-year results for radical prostatectomy
and high dose 3D conformal EBRT are shown in Table 2 for
low, intermediate, and high-risk patients.
Table 3 displays the five-year results for patients treated with implantation
alone or implant plus EBRT. The five-year PSA Progression-Free rate is
88-95% for the low-risk patients, 58%-96% for intermediate risk patients,
and 54-79% for high-risk patients.14,61,63,120,129 A Seattle Prostate Institute
study found no significant difference in five-year results between patients
treated with implant alone versus implant plus EBRT for either low or intermediate
risk groups.130 While implant alone appears to be appropriate for the majority
of low-risk patients, more research needs to be done with respect to what
patients in the intermediate risk group can truly benefit from the addition
of EBRT.
Ten-Year Results
Long-term results have been reported from the Seattle group. For Pd 103,
seed monotherapy, patients, 83.5% were PSA Progression-Free at nine years.137
With I-125, a ten-year PSA Progression Free rate of 87% was reported. The
local control rate was 97%, and the metastatic disease-free survival rate
was 97%. While 50% of the patients had died of other causes by the end
of ten years, none of these patients died of prostate cancer.138
The ten-year results of 634 consecutively treated patients treated at
the Seattle Prostate Institute with I-125/Pd-103 (both with and without
EBRT) between the years 1987-1993 were reported at the 2001 annual ASTRO
meeting. PSA Progression Free rates for low, intermediate, and high-risk
groups were 87%, 74%, and 45%, respectively, at 10 years (Table 4). The
long-term Seattle Prostate Institute results are very similar to those
achieved with radical prostatectomy as reported by Han, Walsh, and colleagues
from the Johns Hopkins series (Figure 9). Both patient groups had comparable
stage and PSA characteristics (Figure 10).
Conclusion
Modern transrectal ultrasound-guided, interstitial permanent brachytherapy
is a 45-minute, single outpatient treatment for the majority of men with
early-stage prostate cancer. It has documented five- and ten-year biochemical,
overall, and disease-specific relapse-free survival rates that equal the
best that radical prostatectomy has thus far achieved. These favorable
findings have established permanent prostate brachytherapy as a primary
treatment option for early stage prostate cancer.
Quality assurance is an important part of seed implantation. Many centers
are participating in quality assurance programs (e.g., ProQura.com). The
learning curve that practitioners typically experience before they can
perform high quality implants on a consistent basis can be formidable.
Fortunately, careful intraoperative evaluation and post-implant CT dosimetry
can identify any under-dosed areas, or cold spots, that may exist, allowing
corrective treatment to take place in a timely manner. In this regard,
developments in the field of implant dosimetry that should bring significant
progress in the future are underway.
At present, it is possible to carry out pretreatment dosimetry planning
either weeks before the procedure or in the OR just before the implant.
Efforts are also underway to develop “real-time dosimetry” that
will permit determining the accuracy of seed placement and the resulting
dose to the prostate during the procedure itself. To date, however, the
developmental work on instantaneous dosimetry evaluation has not yielded
reliable methodologies. Finally, clinicians are continually looking to
identify specific procedural techniques and seed distribution patterns
that will reduce both the short- and long-term side-effects of implantation
while maintaining the excellent long-term cancer control rates that have
been observed to date.
About the Authors
Peter Grimm, D.O., currently the Seattle Prostate Institute’s (SPI)
Director of Research, was instrumental in the establishment of SPI and
the shaping of its clinical, educational, and research activities. Since
his involvement in establishing the first transperineal prostate implantation
program in the United States, Dr. Grimm has devoted considerable effort
to bringing about improvements in technical aspects of the implant procedure.
He was the principal developer of the I-125 Rapid Strand designed to eliminate
movement of seeds inside the prostate and he has recently been granted
a patent for an advanced design of the needles used in implant procedures.
Dr. Grimm received his medical education at the Chicago College of Osteopathic
Medicine and his graduate training in radiation oncologist at UCLA. He
currently chairs the Prostate Brachytherapy Quality Assurance Group of
the American Brachytherapy Society.
John Blasko, M.D., the Seattle Prostate Institute’s Medical Director
and Clinical Professor of Radiation Oncology at the University of Washington,
is recognized internationally for the quality of the clinical research
he has conducted on the SPI implant series, by far the world’s largest.
He was a member of the medical team that performed the first transperineal
prostate implant in the U.S. in 1985. Since that time, he has developed
data collection and analysis protocols that have permitted meaningful research
on the long-term effectiveness of this procedure. Dr. Blasko received his
medical education at the University of Maryland and his graduate training
in radiation oncology at the University of Washington. Dr. Blasko is a
past president and current board member of the American Brachytherapy Society.
John Sylvester, M.D., is SPI’s President and Director of Education
and Training, overseeing
SPI’s clinical education program that includes intensive training
workshops offered on a monthly basis and larger annual scientific meetings
covering a wide range of topics related the diagnosis and treatment of
prostate cancer. In addition to directing the Institute’s educational
program, Dr Sylvester’s innovative work has included a the development
of a technique that allows more accurate ultrasound visualization of the
urethra and less distortion of the prostate during implantation. Dr Sylvester
received both his medical education and radiation oncology training at
UCLA. In addition to his work at SPI, Dr. Sylvester established and directs
the prostate implantation program of Stevens Hospital north of Seattle.
He is a director of the Puget Sound Tumor Institute and the president of
SPI
Charles Heaney, Ph.D. is the Clinical Projects Director at SPI where his
is responsible for
overseeing SPI’s research activities, managing the institute’s
website, providing technical assistance to area physicians affiliated with
SPI’s research and training programs, and other
special projects. He joined Drs. Blasko and Grimm in the mid-1980s when
the implant program was first established and developed the clinical training
courses and scientific conferences for which the Seattle team is internationally
recognized. Dr. Heaney received his undergraduate and graduate business
and health administration training at New York University and Yale University
respectively and his doctorate in Health Policy and Administration at the
London School of Economics.
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