Download MP 8.01.11 Brachytherapy for Clinically Localized Prostate Cancer

MP 8.01.11
Brachytherapy for Clinically Localized Prostate Cancer Using Permanently
Implanted Seeds
Medical Policy
Section
Therapy
Original Policy Date
12/2013
Issue
12/2013
Last Review Status/Date
Revised with literature
search/12/20136:2012
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Our medical policies are designed for informational purposes only and are not an authorization,
or an explanation of benefits, or a contract. Receipt of benefits is subject to satisfaction of all
terms and conditions of the coverage. Medical technology is constantly changing, and we
reserve the right to review and update our policies periodically.
Description
Brachytherapy is a procedure in which a radioactive source (e.g., radioisotope "seeds") is
permanently or temporarily implanted to treat localized prostate cancer. The radiation in
brachytherapy penetrates only short distances and is intended to deliver tumoricidal radioactivity
directly to the tumor to improve local control, while sparing surrounding normal tissue. Focal
(subtotal) prostate brachytherapy is a form of organ-preserving therapy for small localized
prostate cancers. This policy only reviews permanent low-dose rate brachytherapy in prostate
cancer.
Brachytherapy is a procedure in which a radioactive source (e.g., radioisotope "seeds") is used
to treat localized prostate cancer. With brachytherapy, the radiation penetrates only short
distances; this procedure is intended to deliver tumoricidal radioactivity directly to the tumor and
improve local control, while sparing surrounding normal tissue. Local tumor control has been
reported to be associated with lower distant metastasis rates and improved patient survival.
Seeds can be permanently or temporarily implanted. Permanent (low-dose rate, LDR)
brachytherapy is generally used for those with low-risk disease; temporary (high-dose rate,
HDR) brachytherapy is typically reserved for intermediate- or high-risk patients. This policy only
reviews permanent LDR brachytherapy in prostate cancer.
The proposed biologic advantages of brachytherapy compared to external-beam radiation
therapy (EBRT) are related to the dose delivered to the target and the dose-delivery rate. The
dose rate of brachytherapy sources is generally in the range of 40-60 centigray per hour,
whereas conventional fractionated EBRT dose rates exceed 200 centigray per minute.
Enhanced normal tissue repair occurs at the LDRs. Repair of tumor cells does not occur as
quickly, and these cells continue to die during continued exposure. Thus, from a radiobiologic
perspective, LDRs cause ongoing tumor destruction in the setting of normal tissue repair. In
addition, brachytherapy is performed as a single procedure in the outpatient setting, which may
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represent a patient preference issue compared to the multiple sessions required to deliver
EBRT. The total doses of radiation therapy that can be delivered may also vary between EBRT
and brachytherapy, especially with newer forms of EBRT such as 3-dimensional conformal
radiation therapy (3D CRT) and intensity-modulated radiation therapy (IMRT).
Brachytherapy, generally, is not indicated for patients with a large prostate or those with a
urethral stricture, as the procedure results in short-term swelling of the prostate, which can lead
to urinary obstruction. As with all forms of radiation therapy, there are concerns regarding the
long-term risk of treatment-related secondary malignancies. There also are reports that suggest
that the clinician’s level of experience with brachytherapy is correlated with disease recurrence
rates.
Studies of permanent brachytherapy have generally used either iodine-125 or palladium-103.
Use of cesium-131 is also being studied. Use of iodine-125 requires more seeds, thus reducing
dosimetric dependence on any single seed. Post-implant dosimetric assessment should be
performed to ensure the quality of the implant and optimal source placement, i.e., the targeted
tumor areas receive the predetermined radiation dosages while nearby structures and tissue are
preserved.
Permanent brachytherapy may be used alone as monotherapy or may be combined with EBRT
(together known as combined modality therapy – CMT) as a way to boost the dose of radiation
therapy delivered to the tumor. Again, CMT can be performed with permanent or temporary
brachytherapy. The brachytherapy boost is typically done 2 to 6 weeks after completion of
EBRT, although the sequence can vary.
Focal or subtotal prostate brachytherapy is a form of more localized, organ-preserving therapy
for small localized prostate cancers. With this approach, brachytherapy “seeds” are placed only
in the areas where the tumor has been identified rather than throughout the whole prostate
gland. This is done in an effort to reduce the occurrence of adverse events that may be
associated with brachytherapy, including urinary, bowel, and sexual dysfunction.
Policy
Brachytherapy using permanent transperineal implantation of radioactive seeds may be
consideredmedically necessary in the treatment of localized prostate cancer when used as
monotherapy or in conjunction with external-beam radiation therapy (EBRT) (see Policy
Guidelines).
Focal or subtotal prostate brachytherapy is considered investigational in the treatment of
prostate cancer.
Policy Guidelines
Permanent brachytherapy using only implanted seeds is generally used in patients whose
prostate cancer is considered low risk. Active surveillance is generally recommended for very
low-risk prostate cancer. Permanent brachytherapy combined with EBRT (3D-conformal,
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intensity-modulated or proton) is used, sometimes along with androgen deprivation, to treat
higher risk disease. Adequate dose escalation should be achieved with combination permanent
brachytherapy and 3D-CRT. IMRT should be limited only to cases in which 3D-CRT planning is
not able to meet dose volume constraints for normal tissue tolerance.
Prostate cancer risk is often defined using the following criteria:

Low risk: PSA 10 ng/mL or less, Gleason score 6 or less, and clinical stage T1c (very
low risk) or T1-T2a.

Intermediate risk: PSA >10 but 20 ng/mL or less, or Gleason score 7, or clinical stage
T2b-T2c.

High risk: PSA >20 ng/mL or Gleason score 8–10, or clinical stage T3a for clinically
localized disease and T3b-T4 for locally advanced disease.
The procedure is usually performed in two stages: a prostate volume study (CPT code 76873)
followed at a later date by the implant itself, which is performed in the operating room with the
patient under general or epidural anesthesia. Iodine or palladium are the typical isotopes used,
and the selection of isotope is usually based on physician preference. A CT (computed
tomography) scan is usually performed at some stage after the procedure to determine the
quality of the seed placement.
Rationale
This policy was originally created in 1997 and was updated regularly with searches of the
MEDLINE database. The most recent literature search was performed through March 2012. The
following is a summary of the key literature to date.
Evaluating treatment options for clinically localized prostate cancer is difficult because there is
minimal evidence comparing various treatments, including active surveillance (“watchful
waiting”), in terms of improving clinically meaningful patient outcomes. Even assuming that an
intervention can improve outcomes, the variable and often indolent natural history of clinically
localized prostate cancer would require randomized trials with follow-up of 10 to 15 years to
determine if, for example, brachytherapy is associated with equivalent or superior long-term
outcomes compared to alternative therapies including various types of radiation therapy. These
data are not currently available. The lack of these trials makes it difficult to reach strict scientific
conclusions regarding the comparative efficacy of brachytherapy with other treatments for
localized prostate cancer.
The framework often used in analyzing treatments of localized prostate cancer, given the lack of
comparative studies and lack of information regarding impact on survival, is to evaluate the
effect of the treatment on surrogate endpoints (such as biochemical-free survival) and
treatment-related complications.
Brachytherapy has become widely accepted among physicians and its speed and convenience
compared to external-beam radiation are appealing to patients. Therefore, given the baseline
uncertainty regarding long-term outcomes associated with any or no treatment of clinically
localized prostate cancer, decisions regarding any treatment option for prostate cancer are
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frequently reframed as an issue of patient preference, even while acknowledging that the
decision must be made based on incomplete data.
Systematic Reviews
In a 2012 comparative effectiveness report from the international Prostate Cancer Results Study
Group (PCRSG), prostate-specific antigen (PSA)-free survival following various prostate cancer
treatments, including brachytherapy, was noted to be difficult to evaluate, since very few studies
that compared results from treatment options were identified. (1) Additionally, variations in
methods of evaluating outcomes and reporting results complicated the analysis. The PCRSG
only included studies on external-beam radiation therapy (EBRT) that used a minimum 72 Gy
conformal or intensity-modulated radiation therapy (IMRT). The authors concluded, in low-risk
and intermediate-risk prostate cancer, PSA progression-free survival was higher on average
with brachytherapy over radical prostatectomy or EBRT. In intermediate-risk patients, outcomes
were similar with brachytherapy with or without EBRT. With high-risk patients, combined
brachytherapy with EBRT with or without androgen deprivation produced better outcomes than
brachytherapy, surgery, or EBRT alone.
Peinemann and colleagues reported on results from a Cochrane review of brachytherapy in
2011. (2) The authors focused the review on the only identified randomized controlled trial
(RCT), Giberti et al., (3) reported below. The Giberti study compared brachytherapy to radical
prostatectomy and was considered to have a high risk of bias. Peinemann and colleagues also
reported on results from a systematic review of brachytherapy in 2011. (4) In this review, the
Giberti RCT (3) and 30 nonrandomized studies were included; all of which were found to also
have a high risk of bias. Heterogeneity and the poor quality of available studies limited the
interpretation of findings. In both of these reviews, the authors concluded that RCTs are needed
to determine the role of brachytherapy for localized prostate cancer. Similarly, in another 2011
systematic review, Bannuru and colleagues analyzed 75 studies (10 RCTs and 65
nonrandomized comparative studies) on radiation therapy for clinically localized prostate
cancer. (5) Radiation therapies included brachytherapy, high-dose rate (HDR) brachytherapy,
and EBRT (conformal radiation, intensity-modulated radiotherapy, or proton therapy). The
authors found the evidence was insufficient to compare the effectiveness of different forms of
radiation treatments. Additionally, the effects of radiation treatments on patient survival were
unclear compared to no treatment or no initial treatment. However, evidence considered to be of
moderate strength showed higher EBRT dosages were consistently associated with increased
long-term biochemical control rates compared to EBRT delivered at lower dosages.
A 2009 review was conducted on both brachytherapy (permanent) and proton-beam therapy. (6)
This report concluded that brachytherapy was at least comparable to intensity-modulated
radiation therapy (IMRT) for localized prostate cancer in terms of clinical effectiveness. This
review also concluded that brachytherapy was a high-value technology compared to IMRT. The
review also mentions that brachytherapy is a more established therapy than IMRT. Despite
identifying 166 studies that met their review criteria for this report, only 1 study involved an
internal comparison of these treatments: a single-center evaluation of toxicity rates in 2 different
case series of brachytherapy or IMRT. Nearly all of the other studies were relatively small
single-center case series of a single modality with evidence further limited by variability in
population demographics, disease risk status, and measures of treatment success and
treatment-related complications. In this review, at 5 years after diagnosis, survival estimates
ranged from 60% to 90% for active surveillance and 77% to 97% for brachytherapy. This review
also estimated acute and late radiation toxicities based on studies identified. This analysis of
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toxicity was based on studies that used standardized scoring criteria and in general involved a
level of severity of 2 or more. For acute gastrointestinal (GI) toxicity, the rate was estimated at
2% for brachytherapy and 18% for IMRT, and for chronic GI toxicity, these rates were 4% and
7%, respectively. For genitourinary (GU) toxicity, acute rates were about 30% for both therapies
and about 15% for chronic toxicity. Erectile dysfunction was 32% in the brachytherapy studies.
Seed migration is a unique risk with permanent brachytherapy. It occurs when one or more
seeds become dislodged and travel to nearby organs such as the bladder or lung. While this
has been reported in 6% to 55% of patients, reports of harm are limited to individual case
studies.
Brachytherapy used as monotherapy
The vast majority of the data on brachytherapy consists of uncontrolled case series, which
typically report results in terms of prostate-specific antigen (PSA) outcomes, as opposed to final
health outcomes.
Permanent low-dose rate (LDR) brachytherapy, as monotherapy, in the treatment of localized
prostate cancer may be best used in men older than 60 years with small volume cancer of lowrisk disease (Gleason sum <7, PSA <10 mg/mL, and stage T1c). (7) Patients in their 50s or
younger may not be considered ideal candidates for brachytherapy based on concerns
regarding the durability of treatment. Ideally, the cancer should be within a prostate with a
volume of less than 60 mL. Patients with locally advanced prostate cancer may be undertreated
by permanent brachytherapy alone.
Randomized, controlled trials
In Giberti et al., 200 low-risk prostate cancer patients were randomized to either radical
retropubic prostatectomy or brachytherapy for low-risk prostate cancer. (3) Biochemical
disease-free survival rates at 5 years were 90% for prostatectomy and 91.7% for brachytherapy.
Both treatment groups experienced decreases in quality of life at 6 months and 1-year posttreatment, although brachytherapy patients reported more urinary disorders but better erectile
function than the prostatectomy group. At 5-year follow-up, functional outcomes did not differ in
either arm of the study. Crook and colleagues also reported on quality-of-life outcomes at 5
years in 168 patients after radical prostatectomy or brachytherapy in the SPIRIT: Surgical
Prostatectomy Versus Interstitial Radiation Intervention Trial. (8) In this study, 34 patients were
randomized, while the other 134 patients were allowed to select a treatment group. SPIRIT was
closed after 2 years due to poor patient accrual. At a median of 5.2 years follow-up, the
brachytherapy patients scored better in patient satisfaction and urinary and sexual function than
prostatectomy.
Non-randomized, comparative studies
Ragde and colleagues report on the 10-year follow-up of patients with prostate cancer treated
with brachytherapy, a duration of follow-up rate that is unusual for any treatment of prostate
cancer. (9) Among low-risk patients, the freedom from increasing PSA levels was approximately
80%. However, without a comparison group, it is difficult to reach conclusions regarding the
relative efficacy of various treatment options.
In a 1:1 matched-pair design, Pickles and colleagues prospectively followed 278 low- and
intermediate-risk, localized prostate cancer patients treated with either brachytherapy or
conformal EBRT (139 patients in each group). (10) The authors reported that biochemical
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control (nadir + 2) at 5 years was 95% in the brachytherapy group versus 85% in the EBRT
group (p<0.001). This rate was unchanged at 7 years in the brachytherapy group but decreased
to 75% in the EBRT group. Brachytherapy patients experienced more urinary complaints while
EBRT patients had more rectal and bowel issues. The authors concluded brachytherapy is
favored over EBRT in these populations of patients. In a nonrandomized study, Martinez and
colleagues compared 454 patients treated with either LDR brachytherapy (206 patients) or highdose rate (HDR) brachytherapy (171 patients) at William Beaumont Hospital (WBH) during the
period of 1993 through 2004. (11) The patients at WBH selected which treatment option they
would receive. Also included in the study analysis were 77 patients who received HDR
brachytherapy at California Endocurietherapy (CET) during the period of 1996 through 2002. All
of the patients selected for this study were low to intermediate risk and had PSA levels equal to
or less than 12 ng/mL, Gleason scores of equal to or less than 7, and clinical stage T1c-T2a
disease. The HDR brachytherapy dosages were 9.5 Gy x 4 at WBH and 7 Gy x 6 at CET.
Treatment outcomes at 5 years included biochemical control rates of 89% in the LDR group at
WBH, 91% in the HDR group at WBH, and 88% in the HDR group at CET. Overall and causespecific survival rates at 5 years were not statistically different between groups. The HDR
groups experienced statistically significant lower rates of dysuria, urinary frequency/urgency,
and acute rectal pain. Rates of diarrhea, rectal bleeding, and acute urinary incontinence and
retention were similar. Most toxicities were grade 1 in both groups, but more grade 3 acute
genitourinary toxicities were seen in the LDR group. Potency was 30% in the LDR group and
20% in the HDR groups.
Coen and colleagues compared high-dose EBRT (79.2 Gy equivalent) delivered using photons
and protons to permanent LDR in a case-matched analysis of 282 patients (141 matches) with
localized, low- and intermediate-risk prostate cancer. (12) Biochemical failure (nadir + 2) at 8
years was 7.7% in the high-dose EBRT group and 16.1% in the brachytherapy group (p=0.42).
Further study is warranted; since case-matching may not account for important patient
characteristics, the groups may not be similar.
Williams et al. compared data from the United States Surveillance, Epidemiology, and End
Results (SEER) Medicare-linked data on 10,928 patients with localized prostate cancer treated
with primary cryoablation or brachytherapy. (13) Urinary and erectile dysfunction occurred
significantly more frequently with cryoablation than brachytherapy (41.4% and 34.7% vs. 22.2%
and 21%, respectively). The use of androgen deprivation therapy also occurred significantly
more often after cryoablation than brachytherapy, suggesting a higher rate of prostate cancer
recurrence after cryoablation (1.4 vs. 0.5 per 100 person years). Bowel complications, however,
occurred significantly more frequently with brachytherapy (19%) than cryoablation (12.1%).
Brachytherapy combined with external-beam radiation therapy (EBRT)
Permanent brachytherapy has also been combined with EBRT as a way to boost the total
amount of radiation delivered to the prostate cancer; thus increasing the likelihood of increased
patient survival.
Randomized, controlled trials
Merrick and colleagues randomized 247 intermediate- to high-risk prostate cancer patients to
receive brachytherapy with either 20 Gy or 44 Gy EBRT. (14) At a median follow-up of 9 years,
no statistically significant differences were found in biochemical progression-free survival
(BPFS), cause-specific survival, and overall survival (OS) between the 2 groups of
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supplemental EBRT. This suggests outcomes were influenced by quality brachytherapy
implants rather than an increased radiation dosage of EBRT. At 8 and 10 years’ follow-up for
the entire study population, BPFS was 93.2%, the cause-specific survival was 97.7%, and
96.9%, and OS was 80.8% and 75.4%, respectively.
Non-randomized, comparative studies
In 2008, key studies were reviewed by Hurwitz. (15) This summary included results of 2 Phase
II cooperative group studies that were designed to assess toxicity, and participants were
followed up to provide an assessment of treatment efficacy. This subsequent follow-up was to
compare results to prior reports from single-institution studies. Patients in these studies had
intermediate-risk disease and were treated by EBRT followed by permanent brachytherapy. In
the first study (RTOG 0019), 138 patients were treated with 45 Gy of 3D-conformal radiation
therapy followed by iodine-125 brachytherapy. These patients had stage T1-2b disease; if the
Gleason score was less than 7, PSA was between 10 and 20, but if the Gleason score was 7,
then PSA had to be 20 or less. Thus, these patients are in the intermediate-risk group. The 4year rate of biochemical recurrence in this intermediate group was 19% using American Society
for Radiation Oncology (ASTRO) criteria. Grades 3 and 4 late GU toxicity was 13%, and for late
GI toxicity, the rate was 3%. Comments were made that these rates were higher than are often
reported for either treatment alone. However, the total radiation dose was also higher. In this
study, use of androgen deprivation was at the discretion of the treating practitioner. Lee et al.
reported on complication rates in this study at an earlier time. (16) The 18-month estimate of
late grade 3 GU and GI toxicity was 3.3% (confidence interval [CI]: 0.1–6.5%), and no late grade
4 or 5 toxicity had been noted at the time of this earlier report. In the second Phase II study
(CALBG 99809), 68 patients had 45 Gy of EBRT followed by permanent brachytherapy
(radioactive iodine or palladium). All patients in this series received androgen deprivation, and
side effects from the androgen deprivation were noted frequently. At a median follow-up of 38
months, no treatment failures (biochemical failures) were noted. Long-term grades 2 and 3
toxicities were noted in 16% of the patients.
Long-term results from the RTOG 0019 study were published in 2012, with data from 131
patients followed for a median of 8.3 years. (17) Late genitourinary (GU) and/or gastrointestinal
(GI) tract toxicity greater than grade 3 was estimated to be 15% and most commonly included
urinary frequency, dysuria, and proctitis. Grade 3 impotence was reported in 42% of patients. As
noted above, these adverse effects rates with combined modality therapy (CMT) were higher
than are often reported for either brachytherapy or EBRT treatment alone. Estimates of
biochemical failure were 18% by the Phoenix definition and 21% by ASTRO’s definition and
were similar to either treatment alone.
Long-term results are also available from large cohorts treated at single institutions. For
example, Sylvester et al. reported on results of treatment with 45 Gy of EBRT followed by
permanent brachytherapy. In this series, no androgen deprivation therapy was used. (18) This
report was based on a series of 223 consecutive patients treated between 1987 and 1993 at the
Seattle Prostate Institute; patients had stage T1–T3 disease. Permanent brachytherapy was
performed with radioactive palladium or iodine 4 weeks after EBRT. In this series, the authors
reported 15-year biochemical relapse-free survival (BRFS) in the low-risk group of 88%, 80% in
the intermediate-risk group, and 53% in the high-risk group. In addition, while this was a case
series, long-term outcomes were compared to those of two institutions that had results for
radical prostatectomy. Results were similar across Gleason score categories, e.g., the relapsefree survival was 25% to 30% for those with Gleason score 7 for the 3 series of patients but
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were variable for other prognostic factors such as PSA. The authors noted that when they
initiated their study, they included low-risk patients but that they now would not use combined
modality therapy (CMT) in low-risk patients. In another report from one center, results were
summarized for CMT using 3D-conformal radiation therapy followed by permanent (palladium)
brachytherapy. (19) This study involved 282 consecutive patients; 119 were intermediate risk
and 124 were high risk. Patients were treated from 1992 to 1996. In this series, 14-year freedom
from biochemical progression in the intermediate-risk group was 87% and 72% in the high-risk
group.
In a retrospective analysis by Koontz and colleagues, 199 patients with low- to high-risk prostate
cancer were treated with LDR brachytherapy and 46 Gy EBRT during the period of June 1997
through August 2007. (20) Overall BRFS and PSA control at 5 years were 87% and 92%,
respectively. In the high-risk group of 66 patients, overall BRFS and PSA control at 5 years
were 81% and 86%, respectively. The authors concluded EBRT plus LDR brachytherapy
provides excellent results even in high-risk cancer patients with acceptable morbidity.
Focal (subtotal) prostate brachytherapy
There is limited data in the published literature on focal prostate brachytherapy. Available
reports have focused on methods for delineating and evaluating tumor areas to identify
appropriate candidates for focal prostate therapy and treatment-planning approaches. Reports
on patient outcomes after focal brachytherapy have not been published. Many questions remain
including treatment effectiveness, patient selection criteria, and post-treatment monitoring
approaches.
In 2012, Langley and colleagues reported on a consensus meeting convened to address issues
on focal low-dose rate (LDR) brachytherapy for prostate cancer including “optimal patient
selection, disease characterization and localization, treatment protocols and outcome
measures.” (21) The consensus criteria developed for patient selection included life expectancy
greater than 10 years, PSA 15 ng/mL or less, unilateral disease 0.5 mL or less, Gleason score
6-7, and tumor stage T2b or less.
Ongoing Trials
An April 2012 search of online site ClinicalTrials.gov identified several active studies on
brachytherapy for prostate cancer treatment. In a randomized Phase III trial, the effectiveness of
brachytherapy with or without EBRT will be evaluated in intermediate-risk prostate cancer
patients (NCT00063882). Brachytherapy used alone in the treatment of intermediate-risk
prostate cancer patients is being studied in NCT00525720. In a Phase II, prospective trial,
brachytherapy will be evaluated for patients with locally recurrent prostate cancer after EBRT
(NCT00450411).
A randomized Phase III study of patients with intermediate- and high-risk localized prostate
cancer will compare androgen suppression and elective pelvic nodal irradiation followed by
high-dose 3-D conformal boost versus androgen suppression and elective pelvic nodal
irradiation followed by Iodine-125 brachytherapy implant boost (NCT00175396). In a
randomized controlled trial, radical prostatectomy will be compared to brachytherapy in patients
with low-risk prostate cancer (NCT01098331). A prospective, randomized, multicenter, Phase III
trial to compare radical prostatectomy and radiotherapy (EBRT, HDR, and LDR brachytherapy)
to active surveillance in the Study of Active Surveillance Therapy Against Radical Treatment in
Patients Diagnosed With Favorable Risk Prostate Cancer [START] trial (NCT00499174) was
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terminated. The study was unable to meet its target for patient accrual. Finally, in a Phase II
study, focal prostate brachytherapy will be studied in patients with early stage, low-volume
prostate cancer (NCT01354951).
Summary
Brachytherapy is a procedure in which a radioactive source (e.g., radioisotope "seeds") is
permanently or temporarily implanted to treat localized prostate cancer. The radiation in
brachytherapy penetrates only short distances and is intended to deliver tumoricidal radioactivity
directly to the tumor to improve local control, while sparing surrounding normal tissue. Focal
(subtotal) prostate brachytherapy is a form of organ-preserving therapy for small localized
prostate cancers.
Permanent brachytherapy provides freedom from biochemical recurrence at acceptable risk
and, based on many case series and single-institution studies with long-term follow-up, may be
considered as an option in the treatment of localized prostate cancer; while brachytherapy
combined with EBRT is considered an option in patients with intermediate- and high-risk
prostate cancer. This treatment approach provides radiation dose to the prostate and
extraprostatic coverage as well. While quality studies differentiating superiority of any type of
radiation technique are not available, the available evidence for permanent brachytherapy in the
treatment of localized prostate cancer when used as monotherapy or in conjunction with EBRT
is sufficient to demonstrate improvements in net health outcomes and may be considered
medically necessary.
There are limited data in published literature on focal brachytherapy. Available reports have
focused on methods for delineating and evaluating tumor areas to identify appropriate
candidates for focal prostate therapy. Reports on patient outcomes after focal brachytherapy
have not been published. Given the lack of available studies and evidence, focal or subtotal
prostate brachytherapy is considered investigational.
Practice Guidelines and Position Statements
The National Comprehensive Cancer Network (NCCN) guidelines for prostate cancer (v.3.2012)
note that the cancer-control rates for brachytherapy appear comparable to surgery for low-risk
tumors with medium-term follow up. (22) The guidelines also add that for intermediate-risk
cancer, brachytherapy may be combined with external-beam radiation therapy (40–50 Gy) with
or without androgen deprivation, but the complication rate increases. The guidelines state that
patients with very large or very small prostates, symptoms of bladder outlet obstruction, or
previous transurethral resection of the prostate (TURP) are more difficult to implant and may
suffer increased risk of side effects. In cases of enlarged prostate, neoadjuvant androgen
deprivation therapy may be used to shrink the prostate.
The American Brachytherapy Society (ABS) Prostate Low-Dose Rate Task Group provides the
following patient selection criteria for monotherapy: clinical stage T1b-T2b and Gleason score
equal to or less than 6, and PSA equal to or less than 10 ng/mL. (23) The ABS guidelines also
indicate monotherapy may be used in select higher risk patients and for salvage of select
radiation therapy failures. For boost, patient selection criteria includes: clinical stage T2c or
greater and/or Gleason score equal to or greater than 7 and/or PSA greater than 10 ng/mL.
These guidelines also note inadequate information exists to recommend supplemental EBRTbased on perineural invasion, percent positive biopsies, and/or magnetic resonance imaging
[MRI]-detected extracapsular penetration.
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In an Institute for Clinical and Economic Review (ICER) report, it is noted a gold standard
treatment approach for the management of low-risk prostate cancer is not available. (24) This
report found there are no randomized controlled trials comparing brachytherapy to other
treatment approaches and limited high-quality data available, making it difficult to compare the
effectiveness of treatment options. The report concluded rates of survival and tumor recurrence
are similar in each of the following treatment options for low-risk prostate cancer: active
surveillance, brachytherapy, intensity-modulated radiation therapy, robot-assisted laparoscopic
prostatectomy, and proton beam therapy.
The American College of Radiology (ACR) and American Society for Therapeutic Radiation
Oncology (ASTRO) guidelines on permanent brachytherapy indicate permanent LDR
brachytherapy is appropriate in low- to intermediate-risk patients. (25) These guidelines also
note EBRT may be added to permanent brachytherapy in high-risk protocols. ACR/ASTRO
exclusion criteria for permanent brachytherapy include: life expectancy less than 5 years;
unacceptable operative risk; poor anatomy that prevents a quality implant; positive lymph nodes
by pathology; significant obstructive uropathy, and distant metastases. ACR-ASTRO also notes
IMRT is a widely used treatment option for many indications including prostate tumors. (26)
The ACR also developed appropriateness criteria for permanent brachytherapy. (27) The ACR
found brachytherapy offers “favorable morbidity profiles and durable biochemical control rates
for patients with low-, intermediate-, and high-risk features.” Favorable outcomes are noted as
being dependent upon having a quality implant. The role of EBRT in addition to permanent
brachytherapy for higher risk patients is uncertain.
Medicare National Coverage
Brachytherapy sources and services for administration and delivery of brachytherapy are
covered by Medicare.
References:
1. Grimm P, Billiet I, Bostwick D et al. Comparative analysis of prostate-specific antigen
free survival outcomes for patients with low, intermediate and high risk prostate cancer
treatment by radical therapy. Results from the Prostate Cancer Results Study Group.
BJU Int 2012; 109 Suppl 1:22-9.
2. Peinemann F, Grouven U, Hemkens LG et al. Low-dose rate brachytherapy for men with
localized prostate cancer. Cochrane Database Syst Rev 2011; (7):CD008871.
3. Giberti C, Chiono L, Gallo F et al. Radical retropubic prostatectomy versus
brachytherapy for low-risk prostatic cancer: a prospective study. World J Urol 2009;
27(5):607-12.
4. Peinemann F, Grouven U, Bartel C et al. Permanent interstitial low-dose-rate
brachytherapy for patients with localised prostate cancer: a systematic review of
randomised and nonrandomised controlled clinical trials. Eur Urol 2011; 60(5):881-93.
5. Bannuru RR, Dvorak T, Obadan N et al. Comparative evaluation of radiation treatments
for clinically localized prostate cancer: an updated systematic review. Ann Intern Med
2011; 155(3):171-8.
42 Memorial Drive  Suite 1  Pinehurst, N.C. 28374 Phone (910) 715-8100  Fax (910) 715-8101
FirstCarolinaCare Insurance Company, Inc. is a wholly-owned subsidiary of
6. Institute for Clinical and Economic Review (ICER). Brachytherapy/proton beam therapy
for clinically localized, low-risk prostate cancer. Available online at: http://www.icerreview.org/index.php/bt-pbt.html. Last accessed April 2012.
7. Zietman AL. Localized prostate cancer: brachytherapy. Curr Treat Options Oncol 2002;
3(5):429-36.
8. Crook JM, Gomez-Iturriaga A, Wallace K et al. Comparison of health-related quality of
life 5 years after SPIRIT: Surgical Prostatectomy Versus Interstitial Radiation
Intervention Trial. J Clin Oncol 2011; 29(4):362-8.
9. 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
irradiation in the treatment of patients with clinically localized, low to high Gleason grade
prostate carcinoma. Cancer 1998; 83(5):989-1001.
10. Pickles T, Keyes M, Morris WJ. Brachytherapy or conformal external radiotherapy for
prostate cancer: a single-institution matched-pair analysis. Int J Radiat Oncol Biol Phys
2010; 76(1):43-9.
11. Martinez AA, Demanes J, Vargas C et al. High-dose-rate prostate brachytherapy: an
excellent accelerated-hypofractionated treatment for favorable prostate cancer. Am J
Clin Oncol 2010; 33(5):481-8.
12. Coen JJ, Zietman AL, Rossi CJ et al. Comparison of high-dose proton radiotherapy and
brachytherapy in localized prostate cancer: a case-matched analysis. Int J Radiat Oncol
Biol Phys 2012; 82(1):e25-31.
13. Williams SB, Lei Y, Nguyen PL et al. Comparative effectiveness of cryotherapy vs
brachytherapy for localised prostate cancer. BJU Int 2011 [Epub ahead of print].
14. Merrick GS, Wallner KE, Butler WM et al. 20 Gy versus 44 Gy of supplemental external
beam radiotherapy with palladium-103 for patients with greater risk disease: results of a
prospective randomized trial. Int J Radiat Oncol Biol Phys 2012; 82(3):e449-55.
15. Hurwitz MD. Technology Insight: Combined external-beam radiation therapy and
brachytherapy in the management of prostate cancer. Nat Clin Pract Oncol 2008;
5(11):668-76.
16. Lee WR, DeSilvio M, Lawton C et al. A phase II study of external beam radiotherapy
combined with permanent source brachytherapy for intermediate-risk, clinically localized
adenocarcinoma of the prostate: preliminary results of RTOG P-0019. Int J Radiat Oncol
Biol Phys 2006; 64(3):804-9.
17. Lawton CA, Yan Y, Lee WR et al. Long-term results of an RTOG phase II trial (00-19) of
external-beam radiation therapy combined with permanent source brachytherapy for
intermediate-risk clinically localized adenocarcinoma of the prostate. Int J Radiat Oncol
Biol Phys 2012; 82(5):e795-801.
18. Sylvester JE, Grimm PD, Blasko JC et al. 15-Year biochemical relapse free survival in
clinical Stage T1-T3 prostate cancer following combined external beam radiotherapy and
brachytherapy; Seattle experience. Int J Radiat Oncol Biol Phys 2007; 67(1):57-64.
42 Memorial Drive  Suite 1  Pinehurst, N.C. 28374 Phone (910) 715-8100  Fax (910) 715-8101
FirstCarolinaCare Insurance Company, Inc. is a wholly-owned subsidiary of
19. Dattoli M, Wallner K, True L et al. Long-term outcomes after treatment with
brachytherapy and supplemental conformal radiation for prostate cancer patients having
intermediate and high-risk features. Cancer 2007; 110(3):551-5.
20. Koontz BF, Chino J, Lee WR et al. Morbidity and prostate-specific antigen control of
external beam radiation therapy plus low-dose-rate brachytherapy boost for low,
intermediate, and high-risk prostate cancer. Brachytherapy 2009; 8(2):191-6.
21. Langley S, Ahmed HU, Al-Qaisieh B et al. Report of a consensus meeting on focal low
dose rate brachytherapy for prostate cancer. BJU Int 2012; 109 Suppl 1:7-16.
22. National Comprehensive Cancer Network. Prostate cancer. Clinical Practice Guidelines
in Oncology, v.3.2012. Available online at:
http://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf. Last accessed April
2012.
23. Grills IS, Martinez AA, Hollander M et al. High dose rate brachytherapy as prostate
cancer monotherapy reduces toxicity compared to low dose rate palladium seeds. J Urol
2004; 171(3):1098-104.
24. Ollendorf DA, Hayes J, McMahon P et al. Management options for low-risk prostate
cancer: a report on comparative effectiveness and value. Boston, MA: Institute for
Clinical and Economic Review, December 2009. Available online at: http://www.icerreview.org/index.php/mgmtoptionlrpc.html. Last accessed April 2012.
25. Rosenthal SA, Bittner NH, Beyer DC et al. American Society for Radiation Oncology
(ASTRO) and American College of Radiology (ACR) practice guideline for the
transperineal permanent brachytherapy of prostate cancer. Int J Radiat Oncol Biol Phys
2011; 79(2):335-41.
26. ACR-ASTRO Practice Guideline for Intensity Modulated Radiation Therapy (IMRT).
2011. Available online at:
http://www.acr.org/SecondaryMainMenuCategories/quality_safety/guidelines/ro/imrt.asp
x. Last accessed May 2012.
27. Frank SJ, Arterbery VE, Hsu IC et al. American College of Radiology Appropriateness
Criteria permanent source brachytherapy for prostate cancer. Brachytherapy 2011;
10(5):357-62.
Codes
CPT
Number
55875
76873
77326 - 77328
77402 - 77406
Description
Transperineal placement of needles or
catheters into prostate for interstitial
radioelement application, with or without
cystoscopy
Ultrasound, prostate volume study for
brachytherapy treatment planning (separate
procedure)
Brachytherapy isodose calculation, code range
Radiation treatment delivery, single treatment
42 Memorial Drive  Suite 1  Pinehurst, N.C. 28374 Phone (910) 715-8100  Fax (910) 715-8101
FirstCarolinaCare Insurance Company, Inc. is a wholly-owned subsidiary of
ICD-9 Procedure
ICD-9 Diagnosis
HCPCS
77776 - 77778
92.27
185
C1715
C1728
C2634
C2635
C2636
C2637
C2638
C2639
C2640
C2641
C2642
C2643
C2698
C2699
Q3001
ICD-10-CM
(effective 10/1/13)
ICD-10 PCS
(effective 10/1/13)
C61
DV1097Z, DV1098Z,
DV1099Z, DV109BZ,
DV109CZ, DV109YZ
DV10B7Z, DV10B8Z,
area, code range (used for EBRT)
Interstitial radioelement application, code range
Implantation/insertion of radioactive elements
Malignant neoplasm of the prostate
Brachytherapy needle
Catheter, brachytherapy seed administration
Brachytherapy source, nonstranded, high
activity, iodine-125, greater than 1.01 mCi
(NIST), per source
Brachytherapy source, nonstranded, high
activity, palladium-103, greater than 2.2. mCi
(NIST), per source
Brachytherapy linear source, nonstranded,
palladium-103, per 1 mm
Brachytherapy source, nonstranded, ytterbium169
Brachytherapy source, stranded, iodine-125,
per source
Brachytherapy source, non-stranded, iodine125, per source
Brachytherapy source, stranded, palladium103, per source
Brachytherapy source, non-stranded,
palladium-103, per source
Brachytherapy source, stranded, cesium-131,
per source
Brachytherapy source, nonstanded, cesium131, per source
Brachytherapy source, stranded, not otherwise
specified, per source
Brachytherapy source, nonstranded, not
otherwise specified, per source
Radioelements for brachytherapy, any type,
each
Malignant neoplasm of prostate
ICD-10-PCS codes are only used for inpatient
services.
Radiation oncology, male reproductive system,
brachytherapy, prostate, high dose rate, code
by isotope (cesium 137, iridium 192, iodine
125, palladium 103, californium 252, other
isotope)
Radiation oncology, male reproductive system,
42 Memorial Drive  Suite 1  Pinehurst, N.C. 28374 Phone (910) 715-8100  Fax (910) 715-8101
FirstCarolinaCare Insurance Company, Inc. is a wholly-owned subsidiary of
DV10B9Z, DV10BBZ,
DV10BCZ, DV10BYZ
Type of Service
Place of Service
0VH001Z, 0VH031Z,
0VH041Z, 0VH071Z,
0VH081Z
Oncology
Outpatient
brachytherapy, prostate, low dose rate, code by
isotope (cesium 137, iridium 192, iodine 125,
palladium 103, californium 252, other isotope)
Surgical, male reproductive system, insertion,
prostate, radioactive element, code by
approach
Index
Brachytherapy for Prostate Cancer
Prostate Cancer, Brachytherapy
Radioactive Seeds
42 Memorial Drive  Suite 1  Pinehurst, N.C. 28374 Phone (910) 715-8100  Fax (910) 715-8101
FirstCarolinaCare Insurance Company, Inc. is a wholly-owned subsidiary of