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Permanent Prostate Brachytherapy: Lessons Learned, Lessons to Learn

Permanent Prostate Brachytherapy: Lessons Learned, Lessons to Learn

ABSTRACT: Current techniques for permanent prostate brachytherapy are associated with excellent biochemical control in patients with localized prostate cancer. Data now available confirm 5- to 10-year results with this treatment modality that are comparable to those with external-beam irradiation or radical prostatectomy. Nonetheless, treatment protocols and techniques for prostate brachytherapy vary from center to center. Controversy exists regarding the selection of patients for brachytherapy alone or in combination with external-beam irradiation. The role of neoadjuvant androgen deprivation also remains undefined in patients with localized prostate cancer. Matched-pair analysis studies performed at Memorial Sloan-Kettering Cancer Center have examined the role of isotope selection, the addition of external-beam irradiation, and the use of neoadjuvant androgen deprivation. These studies provide insights into the use of permanent brachytherapy in patients with localized prostate cancer. In addition, postimplant dosimetry needs to be a requirement for centers performing seed implants. Data now appear to support specific computed tomography–based criteria to evaluate implant quality and delivered dose to the prostate. Unfortunately, prostate edema and poor imaging techniques limit the evaluation of implant dosimetry. Treatment planning techniques that utilize new imaging modalities, coupled with computerized treatment planning, may help improve the implant procedure and dosimetry. [ONCOLOGY 14(7):981-991, 2000]

Introduction

Localized prostate cancer
may be treated with permanent isotope implants, used either as
monotherapy or combined with external-beam irradiation as curative
therapy. Permanent source brachytherapy has evolved from a surgically
based retropubic technique to today’s closed, ultrasound-guided,
interstitial transperineal approach using either iodine-125 (125I)
or palladium-103 (103Pd).

The therapeutic goal in patients with localized prostate cancer is to
achieve local control and disease-free survival, defined as
prostate-specific antigen (PSA) relapse-free survival. Therefore,
prostate brachytherapy is a therapeutic alternative to three-dimensional
high-dose external-beam radiation or radical prostatectomy for
patients with localized prostate cancer.

Recent data with follow-up of 9 and 10 years confirm that
transperineal implantation offers excellent PSA relapse-free survival
rates,[1,2] however, as with any treatment modality, there is
considerable variation in how brachytherapy is being performed. A
recent review of prostate brachytherapy series confirms that there is
no consistency in the implant technique used or how the data are
reported.[3] To help standardize this procedure, the American
Brachytherapy Society has published clinical and dosimetric
guidelines, which, when adhered to, will provide uniform treatment
parameters and methods for reporting data.[4,5] This article
describes current state-of-the-art permanent prostate brachytherapy.

Retropubic 125I Brachytherapy: Lessons Learned

Experience with retropubic 125I brachytherapy as
monotherapy was gained between 1970 and approximately 1988. Thus,
these data were obtained prior to the PSA era, and both the staging
and grading systems used are now considered to be obsolete. In
addition, the definitions of local control and treatment success at
that time differ considerably from today’s more stringent
American Society for Therapeutic Radiology (ASTRO) consensus
definitions using consecutive PSA values.[6] The clinical definition
of “local control” varied considerably in publications from
that era, but grade and stage were consistently identified as
significant predictors of local control.

For early-stage, low-grade tumors, local control rates reported at
the time for retropubic prostate brachytherapy were similar to those
for external-beam irradiation.[7] In patients with disease of higher
grade and stage, the outcomes with prostate brachytherapy were
inferior to those achieved with external-beam radiation therapy.[8]
Nonetheless, much information can be extrapolated from these series,
which can provide guidance for the current technique of transperineal
prostate brachytherapy.

Dose-Response or Implant Quality

An advantage of brachytherapy is its ability to provide a prescribed
conformal radiation dose to a defined target volume. Postimplant
dosimetry can be performed as a means of measuring the dose-response,
or quality of the implant. However, the technology of the time did
not permit accurate delineation of the prostate volume relative to
the implanted volume, and, therefore, these early series did not
provide clear-cut dose-response data. Several series that attempted
to analyze the dose delivered by an implant confirmed that local
control is a function of dose. Inferior local control rates were
associated with doses to the prostate below 100 to 140 Gy.[9-12]

A recent analysis of 110 patients from the original Yale series of
retropubic brachytherapy was carried out using modern,
three-dimensional CT-based dosimetric parameters; this analysis
provides new insights into the retropubic experience.[13] Several
dosimetric parameters were evaluated to determine cutoff points that
statistically separated the parameters according to local
recurrence-free survival. This analysis demonstrated a twofold
increase in 10-year recurrence-free survival between the favorable
and unfavorable dosimetry parameters. More importantly, a comparison
of Yale’s “inadequate” implants identified a group of
patients with local control rates similar to those of other series
from this era that reported poor outcomes.[7,14]

One of the main reasons for poor implant dosimetry during this time
period was inadequate imaging technology for the volume-averaging
technique of determining 125I activity. Other factors
include a poor delivery system, resulting in the bunching together of
individual seeds centrally within the prostate; poor patient
selection; and differences in technique among institutions and physicians.[8]

Conclusions From the Retropubic 125I Experience

Although these variables cannot be evaluated readily from published
data from the retropubic era, certain conclusions can be drawn from
this experience. First, implant dosimetry, reported either as implant
quality or delivered dose, clearly has an impact on local control.
Second, stage and tumor grade also affect local control and
disease-free survival rates. An understanding of the retropubic data
within this context provided the foundation for the evolution of
prostate brachytherapy in the late 1980s and ’90s.

Transperineal Permanent Isotope Brachytherapy

With the advent of the transrectal ultrasound probe as a means for
visualizing the prostate, Holm et al developed the transperineal
approach to prostate brachytherapy.[15] This closed technique allows
for placement of needles into the prostate, guided by real-time
ultrasound imaging, while the patient is in the lithotomy position.
The isotope is then introduced through the needles directly into the prostate.

In the United States, Drs. Blasko and Ragde from Seattle pioneered
this approach to brachytherapy in the early 1990s.[16] A conceptually
similar approach using computed tomographic (CT) scans instead of
ultrasonography was developed at Memorial Sloan-Kettering Cancer
Center (MSKCC) around the same time.[17] In the intervening 10 years,
the number of patients treated with ultrasound-guided transperineal
interstitial permanent prostate brachytherapy (TIPPB) has grown
exponentially; an estimated 35,000 implants were performed in 1999.[5]

Some believe that TIPPB with advanced biplane-transrectal
ultrasonography, perineal guidance systems, treatment planning
computers, and postimplant CT scanning has enhanced our ability to
perform an “adequate” implant. As such, permanent
brachytherapy yields associated biochemical control rates that are
comparable to those of radical prostatectomy or high-dose
three-dimensional external-beam irradiation in appropriately selected
patients. However, an American Brachytherapy Society review of the
practices of physicians who perform prostate brachytherapy uncovered
tremendous variation in indications, technique, treatment regimens,
and dosimetry.[4]

The main areas of controversy include the selection of patients for
monotherapy or combined therapy with external-beam irradiation, the
role of neoadjuvant androgen deprivation, the selection of 125I
or 103Pd, the type of preimplant planning and technique,
and the type and timing of postimplant dosimetry.

Despite these controversies, several published studies have assessed
outcomes following TIPPB at institutions reporting biochemical
control rates (Table 1). According
to these studies, 4- to 10-year biochemical control rates range from
63% to 92%.[1,2,18-26] Because of differences among the studies with
respect to patient characteristics, median follow-up, and the methods
of defining outcomes, a meta-analysis of these data cannot be performed.

Potters et al reported risk-profile outcomes of a cohort of 717
patients treated with TIPPB. Patients were grouped based on a
pretreatment PSA £ 10 ng/mL and
Gleason score £ 6.[22] Patients who
met both criteria were classified as a favorable-risk group (N = 303)
and had a 93% 5-year PSA relapse-free survival rate (ASTRO
definition[6]; see Figure 1).
Individuals who fulfilled one criterion were considered at
intermediate risk (N = 268), with a 5-year PSA relapse-free survival
of 77%. Those who did not satisfy either criterion were classified as
unfavorable risk (N = 146) and had a 62% 5-year PSA relapse-free
survival rate.

Using identical risk definitions and a modification of the ASTRO
definition of PSA relapse-free survival (two consecutive rises),
Blasko et al reported outcomes in 230 patients treated with 103Pd
monotherapy.[1] Favorable-risk patients had a 94% 5-year PSA
relapse-free survival rate, while the intermediate- and
unfavorable-risk patients had PSA relapse-free survival rates of 82%
and 65%, respectively (P = .04; see Table
2
).

Prestidge et al have reported that biochemical control rates
correlate with postbrachytherapy biopsy rates. Their data indicate a
close correlation between PSA control and biopsy results, with 80% of
biopsied patients having a negative result.[27] However, the
significance of a negative or positive postimplant biopsy result
remains controversial.

Currently, a multi-institutional trial is underway, with strict
reporting methodology, to assess TIPPB in early-stage prostate
cancer. In addition, the Radiation Therapy Oncology Group (RTOG) is
conducting a feasibility trial of this modality, also with strict
quality control parameters. Until prospective data become available,
variations in treatment techniques for TIPPB will appear in the literature.

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