Coverage Policy Manual
Policy #: 2006019
Category: Radiology
Initiated: June 2006
Last Review: December 2021
  Brachytherapy, Prostate, High-Dose Rate Temporary

Description: Prostate brachytherapy can be delivered in a variety of ways. Perhaps the most familiar technique is the use of radioactive seeds permanently implanted into prostate tissue. These seeds contain isotopes that slowly emit radiation of relatively low energy. In contrast, temporary prostate brachytherapy involves use of higher energy radioisotopes such as iridium-192. These isotopes deliver radiation at higher dose rates, which may be more effective in destroying rapidly dividing cancer cells. In this technique, needle catheters are placed into the prostate gland using transrectal ultrasound guidance. Once the needles are placed, a dosimetric plan is developed and the radioactive source inserted into each needle using an afterloading device. The radioactive source is left in the needle for a predetermined time, typically ranging from 8 to 12 minutes (called the “dwell” time). The radiation usually is delivered once or twice daily over a course of several days. The dwell time can be altered at various positions along the needle’s length to control dose distribution to the target volume and critical surrounding structures, such as the rectum or urethra. This strategy contrasts with permanent seed implantation in which dosimetry is calculated prior to needle placement and which cannot be altered after seed implantation. The treatment typically consists of 4,000 to 5,000 cGy delivered with external beam radiation therapy (EBRT) to the prostate and periprostatic tissues, while the high-dose rate brachytherapy (HDR BT) is used as the method of dose escalation to the prostate gland. The total boost doses are variable.

It is an accepted premise that increasing doses of radiation therapy are associated with improved biochemical control (i.e., stable levels of PSA), and thus there has been keen interest in exploring different techniques of dose escalation while simultaneously limiting both early and late toxicities in surrounding tissues. In patients with locally advanced disease, it is hypothesized that local failure may be related to the large volume of tumor and radioresistant cell clones, both of which might respond to higher radiation doses. High-dose rate prostate brachytherapy has been primarily investigated as an adjunct to external beam radiotherapy (EBRT) as a technique of dose escalation. Other techniques for dose escalation include EBRT using intensity modulated radiation therapy [IMRT] for treatment planning and delivery, proton beam radiotherapy (which may also use IMRT), or EBRT combined with brachytherapy using interstitial seeds.

The CPT coding for high-dose rate prostate brachytherapy will consist of a series of CPT codes describing the treatment planning, dosimetry, and delivery of radiation therapy. These codes overlap with those describing brachytherapy using permanent seed implantation. However, since the therapy is given over a course of several days, the last 2 CPT codes listed below may be used more than once.

76873: Ultrasound, transrectal; prostate volume study for brachytherapy treatment planning
77326-77328: Brachytherapy isodose calculation; simple, intermediate, or complex
77776-77778: Interstitial radiation source application, simple, intermediate, or complex
77790: Supervision handling, loading of radiation source

High-dose rate brachytherapy for prostate cancer is not a widely disseminated procedure and is provided in only a few specialized centers.

This policy addresses the use of high-dose rate brachytherapy only.  Brachytherapy using permanently implanted interstitial seed is addressed in policy number 1998001.

Policy/
Coverage:
Effective August 1, 2021, for members of plans that utilize a radiation oncology benefits management program, Prior Approval is required for this service and is managed through the radiation oncology benefits management program.
 
EFFECTIVE MAY 24, 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Intermediate risk of recurrence
High dose rate (HDR) brachytherapy meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness and is covered for intermediate risk* prostate cancer when the following condition is met:
      • Used as a boost in combination with external beam radiotherapy (EBRT)
High risk of recurrence
High dose rate (HDR) brachytherapy meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness and is covered for high risk* prostate cancer when the following condition is met:
      • Used in combination with external beam radiotherapy (EBRT)
Local recurrence after radiotherapy
High dose rate (HDR) brachytherapy meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness and is covered to treat recurrent localized disease* with no evidence of distant metastasis
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
High dose rate (HDR) brachytherapy is not covered based on benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the treatment of prostate cancer for any other indication not specifically listed as covered above.
 
For contracts without primary coverage criteria, High dose rate (HDR) brachytherapy is considered investigational for the treatment of prostate cancer for any other indication not specifically listed as covered above Investigational services are an exclusion in the member certificate of coverage.
 
 
 
NOTES:
 
Disease Definitions
 
Low-risk of recurrence (ALL must be present to qualify as low risk)
    • Stage T1-T2a
    • Gleason score of 6
    • Prostate-specific antigen (PSA) below 10 ng/Ml
Intermediate-risk of recurrence (ANY one characteristic)
    • Stage T2b to T2c
    • Gleason score of 7
    • PSA 10-20 ng/mL
High-risk of recurrence (ANY one characteristic)
    • Stage T3a
    • Gleason score 8-10
    • PSA greater than 20 ng/mL
Localized disease (BOTH must apply)
    • T stage of T1-3a (tumor has spread through the capsule on one or both sides but has not invaded the seminal vesicles or other structures)
    • N0 (no lymph node involvement)
Locally advanced disease (EITHER must apply)
    • Any T status with N1 disease (either no spread to lymph nodes or there has been spread to the regional lymph nodes)
    • T3b and above, no distant metastatic disease beyond local lymph nodes
Distant metastatic disease
    • Beyond the local lymph nodes
 
 
EFFECTIVE Prior to MAY 24, 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Intermediate risk of recurrence
High dose rate (HDR) brachytherapy meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness and is covered for intermediate risk* prostate cancer when EITHER of the following conditions is met:
      • Used as monotherapy; or
      • Used in combination with external beam radiotherapy (EBRT)
 
High risk of recurrence
High dose rate (HDR) brachytherapy meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness and is covered for high risk* prostate cancer when the following condition is met:
      • Used in combination with external beam radiotherapy (EBRT)
 
Local recurrence after radiotherapy
High dose rate (HDR) brachytherapy meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness and is covered to treat recurrent localized disease* with no evidence of distant metastasis
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
High dose rate (HDR) brachytherapy is not covered based on benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the treatment of prostate cancer for any other indication not specifically listed as covered above.
 
For contracts without primary coverage criteria, High dose rate (HDR) brachytherapy is considered investigational for the treatment of prostate cancer for any other indication not specifically listed as covered above Investigational services are an exclusion in the member certificate of coverage.
 
NOTES:
 
Disease Definitions
 
Low-risk of recurrence (ALL must be present to qualify as low risk)
    • Stage T1-T2a
    • Gleason score of 6
    • Prostate-specific antigen (PSA) below 10 ng/Ml
Intermediate-risk of recurrence (ANY one characteristic)
    • Stage T2b to T2c
    • Gleason score of 7
    • PSA 10-20 ng/mL
High-risk of recurrence (ANY one characteristic)
    • Stage T3a
    • Gleason score 8-10
    • PSA greater than 20 ng/mL
Localized disease (BOTH must apply)
    • T stage of T1-3a (tumor has spread through the capsule on one or both sides but has not invaded the seminal vesicles or other structures)
    • N0 (no lymph node involvement)
Locally advanced disease (EITHER must apply)
    • Any T status with N1 disease (either no spread to lymph nodes or there has been spread to the regional lymph nodes)
    • T3b and above, no distant metastatic disease beyond local lymph nodes
Distant metastatic disease
    • Beyond the local lymph nodes
 
Effective Prior to April 01, 2021
High-dose rate brachytherapy in combination with external beam radiotherapy (conventional, 3-D conformal or IMRT) meets member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes for patients with localized prostate cancer.
 
High-dose rate brachytherapy as monotherapy for treatment of prostate cancer does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness due to the lack of data attesting to long-term effectiveness of monotherapy.
 
For members with contracts without primary coverage criteria, high-dose rate brachytherapy as monotherapy for treatment of prostate cancer is considered investigational.  Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
High-dose rate brachytherapy in combination with external beam radiotherapy (conventional, 3-D conformal or IMRT) used for salvage treatment of prostate cancer does not meet member benefit certificate Primary Coverage Criteria of effectiveness in improving health outcomes when used for salvage treatment of prostate cancer.
 
For members with contracts without Primary Coverage Criteria, high-dose rate brachytherapy in combination with external beam radiotherapy (conventional, 3-D conformal or IMRT) used for salvage treatment of prostate cancer is considered investigational.  Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective prior to July 2012
High-dose rate brachytherapy in combination with 3-D conformal radiotherapy meets member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes for patients with localized prostate cancer.
 
High-dose rate brachytherapy in combination with Intensity Modulated Radiotherapy does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes for patients with prostate cancer due to the absence of studies indicating this combination is more effective than, or safer than the combination of HDR brachytherapy and 3-D conformal radiotherapy.
 
High-dose rate brachytherapy as monotherapy for treatment of prostate cancer does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness due to the lack of data attesting to long-term effectiveness of monotherapy, and the fact that this treatment is presently being studied in clinical trials to determine effectiveness.
 
High-dose rate brachytherapy in combination with external beam radiotherapy of any type does not meet member benefit certificate Primary Coverage Criteria of effectiveness in improving health outcomes when used for salvage treatment of prostate cancer.
 
For contracts without Primary Coverage Criteria, all of the following indications are considered investigational and are not covered:
        • High-dose rate brachytherapy in combination with Intensity Modulated Radiotherapy for patients with prostate cancer.
        • High-dose rate brachytherapy as monotherapy for treatment of prostate cancer.
        • High-dose rate brachytherapy in combination with external beam radiotherapy of any type.
Investigational services are exclusions in the member benefit certificate of coverage.
 
Effective prior to August 2009
High-dose rate prostate brachytherapy is not covered based on benefit certificate primary coverage criteria as this treatment is the subject of ongoing clinical trials.  
 
For contracts without primary coverage criteria, high-dose rate prostate brachytherapy is considered investigational and is not covered.  Investigational services are exclusions in the member benefit contract.
 
 

Rationale:
An evidence-based approach to the analysis of data on the various treatment options for prostate cancer is problematic for the following reasons:
    • The lack of controlled clinical trials comparing various different treatment options in homogeneous groups of patients. Thus far, the only randomized comparison of alternatives for managing early stage prostate cancer compared watchful waiting with radical prostatectomy.
    • Similar trials are lacking to compare surgery with radiation or to compare different methods of radiation. In a recent review of 2,991 consecutive patients receiving a variety of therapies for localized prostate cancer, the authors concluded that it is still not possible to determine which of the treatment options leads to the best metastasis free or overall survival. Therefore, at the present time, there is no evidence-based gold standard of treatment, which limits the ability to assess emerging approaches.  
    • The numerous patient variables, including tumor stage, size of tumor (i.e., percent positive biopsy score), Gleason score, and PSA level.
    • The indolent natural history of many early stage prostate cancers, requiring prolonged follow-up to determine final patient outcomes.
    • A variety of intermediate outcomes have been used, most commonly biochemical failure as evidenced by rising PSA levels.
    • The evolving nature of radiation therapy.
Over the last 10 years, there have been major advances in the planning and delivery of radiation therapy, including conformal therapy and intensity modulated radiation therapy (IMRT), both of which permit dose escalation. There are variables in the total dosage of radiation therapy, variations in the planning and delivery of radiation therapy, and multiple different combinations of therapy (i.e., EBRT plus brachytherapy). Fractionation of doses is another treatment variable that intends to balance the treatment effectiveness with both early and late morbidities to surrounding normal tissues.
 
The role of dose escalation in radiation therapy of prostate cancer
A dose-response relationship in the treatment of prostate cancer is generally accepted among clinicians and physicists, and in fact serves as the scientific rationale of high-dose rate brachytherapy, as well as other recent techniques for radiation planning and delivery (i.e., IMRT). While a few randomized controlled trials have examined this issue, the data suggest that dose escalation is associated with improved biochemical control.  However, data regarding the impact of total radiation dose on survival among patients with different prognostic factors are minimal. In addition, the optimal radiation therapy dose is unknown.
 
Given these significant limitations, the following results have been reported for HDR as an adjunct to EBRT. The largest case series has been reported by researchers at the William Beaumont Hospital in Royal Oak, Mich. This group reported on the outcomes of a series of 207 patients treated between 1991 and 2000 (Martinez , 2003).  All patients had poor prognostic factors, which included tumor stage T2B, a Gleason score of 7 or a PSA greater than 10 nl/mL. External beam radiation therapy was alternated with high-dose rate radiation therapy as a boost. At a mean follow-up of 4.7 years, overall biochemical control rate was 74%, but was 85% if one poor prognostic factor was present, 75% if 2 were present, and 50% if all 3 were present. Late toxicity was minimal. The authors suggest that these results are similar or better to other treatment alternatives for prostate cancer with poor prognostic features. In another analysis, the authors performed a matched-pair analysis of high-dose rate brachytherapy boost versus external beam radiation therapy alone.  A total of 161 patients received a high-dose rate boost; they were randomly matched with a unique patient who received EBRT alone (Kestin , 2000).  Patients were matched according to PSA level, Gleason score, T stage, and follow-up of duration. Those who received the HDR boost reported a 5-year biochemical control rate of 67% compared to 44% in those receiving EBRT alone. In a review article, Vicini and colleagues summarized the experience reported in 8 other case series of locally advanced prostate cancer totaling just over 1,000 patients (Vicini et al, 2003) .  The biochemical control rate ranged from 74% to 97% with median follow-ups ranging from 11 to 74 months.
 
An update on conventional brachytherapy (using permanently implanted seeds) noted that while final health outcomes are not available, thus limiting scientific conclusions, conventional brachytherapy had become widely accepted by patients and physicians and may be considered a reasonable treatment option. Large case series of conventional brachytherapy have reported data on both morbidity and the intermediate outcome of biochemical relapse-free survival (i.e., survival-free from increasing PSA levels). These studies show that conventional brachytherapy is associated with similar outcomes when compared with the alternative (EBRT). Therefore, given the uncertainty for choosing between the established treatment options of watchful waiting, radical prostatectomy, EBRT, or conventional brachytherapy, some may consider patient preference to be particularly appropriate in selecting conventional brachytherapy.
 
In contrast, the data regarding outcomes of high-dose rate brachytherapy remain relatively sparse compared to conventional brachytherapy. At this stage in its evolution, based on the volume and quality of the published literature, high-dose rate brachytherapy cannot be considered an established treatment option of prostate cancer.
 
A review of the literature for the period of 2004 through April 2005 did not identify any additional literature that would address the limitations noted above. An international group of investigators reported on the use of HDR as an adjunct to EBRT with or without androgen-deprivation therapy in a case series of 611 patients (Galale et al, 2004).  A total of 209 patients were treated at William Beaumont Hospital, and thus it is likely that there are overlapping patients with the studies reviewed above. While the authors reported that adjunctive HDR was associated with excellent long-term outcomes in terms of biochemical control, disease-free survival and cause-specific survival, interpretation of the findings is extremely limited due to the absence of a control group.
 
2007 Update
HDR brachytherapy as treatment for clinically localized prostate cancer is presently in phase III trials.  Several papers reporting phase II trials indicate effectiveness of this therapy in the short term but long term effectiveness has yet to be reported.
 
Dec 2007
NCCN Clinical Practice Guidelines for Prostate Cancer make several recommendations about brachytherapy for prostate cancer but none of them refer to high dose rate therapy.  
 
In their 2007 Update of Guideline for the Management of Clinically Localized Prostate Cancer, the American Urological Association makes the following statement:  "Minimal data currently are available for the following interventions: high-intensity focused ultrasound, cyrotherapy, high-dose rate interstitial prostate brachytherapy, and primary hormonal therapy.  Conclusions regarding outcomes of these treatments cannot be made."
 
2009 Update
A randomized phase III trial of 220 patients with histologically confirmed prostate cancer compared external beam radiotherapy alone with a dose escalated schedule using high dose rate brachytherapy (Hoskin et al, 2007).  Patients were randomized to receive either standard radiotherapy 55 Gy in 20 fractions over 4 weeks or a combined schedule comprising external beam treatment delivering 35.75 Gy in 13 fractions treating daily over 2.5 weeks followed by a temporary high dose rate afterloading implant delivering 17 Gy in two fractions over 24h.  Median follow-up was 30 months (range 3 to 90 months).  There was an improved biochemical relapse free survival and less acute rectal toxicity in the combined EBRT-HDR treated group.
 
Demanes reported on a study of 209 consecutive patients treated with HDR brachytherapy plus EBRT.  Median follow-up in this trial was 7.25 years.  The overall survival rate was 79% with cause-specific survival rate = 97% (Demanes et al, 2005).
 
An uncontrolled study using HDR brachytherapy after EBRT in 309 patients reported an overall survival rate of 91%. In this study, some of the patients also received hormonal therapy.  The median followup was 59 months with a 5-year cause specific survival of 98% (Phan et al, 2007).
 
In a review article, the author states, “External beam radiation therapy combined with brachytherapy is an attractive treatment option for selected patients with clinically localized prostate cancer…Either low-dose-rate (LDR) permanent brachytherapy or high-dose-rate (HDR) temporary brachytherapy can be combined with EBRT; such combined-modality therapy (CMT) is typically used to treat patients with intermediate-risk to high-risk, clinically localized disease.  Controversy persists with regard to indications for CMT, choice of LDR or HDR boost, isotope selection for LDR, and integration of EBRT and brachytherapy.  Initial findings from prospective, multicenter trials of CMT support the feasibility of this strategy.  Updated results from these trials as well as those ongoing and new phase III trials should help to define the role of CMT in the management of prostate cancer.  In the meantime, long-term expectations for outcomes of CMT are based largely on the experience of single institutions, which demonstrate that CMT with EBRT and either LDR or HDR brachytherapy can provide freedom from disease recurrence with acceptable toxicity” (Hurwitz, 2008).
 
Studies have also been conducted using HDR Brachytherapy as monotherapy.
 
Yoshioka and colleagues conducted an uncontrolled study of 111 patients treated with HDR brachytherapy alone without EBRT with a median follow-up time of 27 months (Yoshioka et al, 2006).  The prescribed dose was 48Gy in 8 fractions over 5 days or 54 Gy in 9 fractions over 5 days.  The 3- and 5-year PSA failure-free rates were 83% and 70%.  The authors concluded: “HDR-BT without EBI was feasible and its toxicity acceptable.  Short-term tumor control was promising, even for locally advanced cases.  More patient accrual and longer follow-up are needed to confirm the efficacy of this novel approach.”
 
Corner reported results of a phase II study of 110 patients with locally advanced prostate cancer who received only HDR brachytherapy (34 Gy in 4 fractions, 36 Gy in four fractions, and 31.5 Gy in 3 fractions) (Corner et al, 2008).  The median follow-up was 30 months (34 Gy), 18 months (36 Gy), and 11.8 months (31.5 Gy).  The authors concluded: “the results from this study show equivalent low rates of acute and late urinary and rectal toxicity across the three dose groups.  Initial biochemical disease control is excellent and appears equivalent among the three groups when stratified for androgen deprivation therapy and no androgen deprivation therapy treated patients; however, longer follow-up is required to evaluate this further.  The toxicity seen with this approach suggests further dose escalation could be possible, although longer term follow-up to confirm late toxicity events is required before proceeding in this way.”
 
A non-randomized cohort study conducted at William Beaumont Hospital compared HDR temporary brachytherapy (iridium) versus LDR brachytherapy (permanent palladium seeds) (Grills et al, 2004).  HDR was given at 38 Gy delivered in 4 fractions.  The LDR dose was 120 Gy.  Median follow-up was 35 months.  PSA control was the same in both groups but HDR resulted in lower toxicity.  
 
The National Institute for Health and Clinical Excellence (NICE) published provisional recommendations that HDR brachytherapy in combination with EBRT offers “improved biochemical and overall survival, and reduced side effects compared to other treatments”.  There was no mention of HDR brachytherapy as monotherapy in these recommendations. The 2009 National Comprehensive Cancer Network (NCCN) guidelines make no mention of either HDR brachytherapy with EBRT or as monotherapy.
 
HDR Brachytherapy as monotherapy and as salvage therapy is currently being conducted in clinical trials.  
 
In summary, results from published literature on HDR brachytherapy as monotherapy are limited by the number of patients studied, the length of follow-up, and/or lack of a comparable control group.  In an opinion article, the author states, “HDR monotherapy will require much longer followup and more published data to prove that it is as efficacious and safe as LDR brachytherapy.  Even if it proves itself in the long term in these areas, it will ultimately fall short in terms of patient convenience” (Stock, 2006).   Therefore, the policy has been changed to reflect the lack of scientific evidence to establish effectiveness of HDR brachytherapy as monotherapy or in combination with Intensity Modulated Radiotherapy for treatment of prostate cancer.  In addition, the policy coverage statement has been changed to include non-coverage for HDR brachytherapy in combination with EBRT of any type when used for salvage treatment of prostate cancer.
 
2012 Update
In 2011, Bannuru and colleagues analyzed 75 studies (10 RCTs and 65 nonrandomized comparative studies) on radiation therapy for clinically localized prostate cancer (Bannuru, 2011). (7) 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. Yamada and colleagues conducted a review of the literature and published consensus guidelines for HDR brachytherapy for the American Brachytherapy Society in 2012 (Yamada, 2012).  The authors reported dosing schedule differences and heterogeneous studies make HDR brachytherapy difficult to evaluate systematically. However, HDR brachytherapy was found to have favorable 5-year biochemical disease control ranging from 85-100% for low-risk, 83-98% for intermediate-risk, and 51-96% for high-risk prostate cancer.
 
High-dose rate brachytherapy as monotherapy
Publications on use of high-dose rate (HDR) as monotherapy for treatment of prostate cancer are fewer than those that report its use as combined modality therapy (CMT) with EBRT. The National Comprehensive Cancer Network (NCCN) guidelines (v.3.2012) for the treatment of prostate cancer do not give mention HDR brachytherapy as monotherapy.
 
Salvage HDR brachytherapy
Data on using HDR in the salvage treatment following failed prior radiation therapy are limited. In 2012, Jo and colleagues reported on 11 patients with radiorecurrent local prostate cancer who received salvage high-dose rate brachytherapy with EBRT (n=10) or proton beam (n=1) (Jo, 2012). During mean follow-up of 29 months (range 18-41 months) PSA levels remained low in 7 patients but rose in 4 patients. No grade 3 adverse events were reported.
 
Practice Guidelines and Position Statements
The National Comprehensive Cancer Network (NCCN) guidelines (v.3.2012) for the treatment of prostate cancer indicate HDR brachytherapy combined with EBRT (45 40-50 Gy) may be used instead of LDR brachytherapy to increase the dose of radiation for intermediate- to high-risk patients. (21) Boost regimens commonly used include 9.5-10.5 Gy x 2 fractions, 5.5–7.5 Gy x 3 fractions, and 4.0-6.0 Gy x 4 fractions.  The coverage statement has been changed to allow HDR brachytherapy combined with EBRT, based on this guideline and the available scientific evidence.
 
The American Brachytherapy Society (ABS) Prostate High-Dose Rate Task Group provides the following patient selection criteria for monotherapy: clinical stage T1b-T2b and Gleason score equal to or less than 7, and/or PSA equal to or less than 10 ng/mL. For HDR boost, ABS patient selection criteria includes: patients with high-risk features such as T3-T4, Gleason score 7-10, and/or PSA greater than 10 ng/mL or patients with bulky T1-2b tumor. The ABS published a review of the literature and consensus guidelines for HDR brachytherapy in 2012 as noted above (Yamada, 2012). The ABS recommends HDR brachytherapy with or without EBRT for various risk levels of localized prostate cancer especially for intermediate- or high-risk patients as a boost with EBRT. The ABS guidelines note HDR brachytherapy is contraindicated in patients who have a preexisting rectal fistula, are unable to tolerate anesthesia and/or have no proof of malignancy. HDR monotherapy is considered investigational for high-risk patients by the ABS. HDR monotherapy as salvage treatment is only recommended for use in specialty centers or Institutional Review Board-approved protocols.
 
2013 Update
A literature search using the MEDLINE database was conducted through June 2013. There was no new information identified that would prompt a change in the coverage statement.   
 
2014 Update
A literature search conducted through June 2014 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
In 2014, Zaorsky reviewed 38 prospective and retrospective studies reporting on a total of 8008 patients treated with high-dose rate (HDR) brachytherapy for prostate cancer (Zaorsky, 2014). Five-year freedom from biochemical failure rates were 85-100% for low-risk, 80-98% for intermediate-risk, 59-96% for high-risk and 34-85% for locally advanced patients. In all risk groups, 5-year rates of cancer-specific survival, overall survival, local recurrence and distant metastases were 99-100%, 85-100%, 0-8%, and 2-12%, respectively. Late Radiation Therapy Oncology Group Grade 3-4 genitourinary or gastrointestinal toxicities occurred in less than 6% of patients. Comparisons of HDR brachytherapy to other radiation techniques were inconclusive. Interpretation of results from the review is limited by reports from single-institution studies, the lack of comparative studies and insufficient reporting on toxicity and quality of life.
 
In 2013, Tselis et al reported on short-term outcomes of 351 patients with clinically localized prostate cancer treated with HDR brachytherapy as monotherapy (Tselis, 2013). At 36- and 60-months, biochemical control rates were 98% and 94% and metastasis-free survival rates were 99 and 98%, respectively. No acute Grade 3 gastrointestinal toxicity occurred and acute Grade 3 genitourinary events were 4.8%. Late Grade 3 genitourinary toxicity events were 3.4% and gastrointestinal toxicity events were 1.4%. There were no Grade 4 or greater acute or late adverse events reported.
 
Practice Guidelines and Position Statements
The National Comprehensive Cancer Network (NCCN) guidelines (v.2.2014) for the treatment of prostate cancer indicate HDR brachytherapy alone or combined with EBRT (40-50 Gy) may be used instead of LDR brachytherapy to increase the dose of radiation for intermediate- to high-risk patients. Boost regimens commonly used include 9.5-11.5 Gy x 2 fractions, 5.5–7.5 Gy x 3 fractions, and 4.0-6.0 Gy x 4 fractions. For HDR brachytherapy alone, 13.5 x 2 fractions is a commonly used regimen. HDR brachytherapy may also be considered to treat local recurrence after EBRT or primary brachytherapy. HDR dosages for recurrence range from 9-12 Gy x 2 fractions, depending on the primary radiation dosage delivered.
 
American College of Radiology (ACR) Appropriateness Criteria for high-dose-rate brachytherapy for prostate cancer were issued in 2014 (ACR, 2014). The ACR indicates HDR monotherapy, HDR with EBRT and HDR as salvage treatment may be appropriate treatment options.
 
2017 Update
A literature search was conducted using the MEDLINE database through November 2017. There was no information identified that would prompt a change in the coverage statement. The key identified literature is summarized below.  
 
High-Dose Rate Brachytherapy Plus External-Beam Radiotherapy
Long-term outcomes of treatment with HDR brachytherapy and EBRT were reported by Yaxley et al in 2017 (Yaxley, 2017).  The analysis included 507 patients with localized prostate cancer who were followed for at least 6 years; the median follow-up was 10.3 years. For 271 men with a minimum follow-up of 10 years, the actuarial 10-year OS rate was 85%, and the actual 10-year disease-specific survival rate was 90%. The overall urethral stricture rate was 28.9% (28.9% for men treated before 2005, 4.2% for men treated after 2005).
 
Hdr Brachytherapy As Monotherapy
In 2016, Hegde et al reported on 437 patients with intermediate-risk prostate cancer who were treated with HDR brachytherapy (n=137) or SBRT (n=300) (Hegde, 2016).  After a median follow-up of 4 years, the BRFS rate was 98.5% in the HDR brachytherapy group and 95.3% in the SBRT group (p=0.17). There were no statistically significant differences in subgroup analyses (eg, comparing patients with a PSA level <10 and 10 ng/mL or clinical stage T1 with T2). OS and disease-specific survival were not reported.
 
A 2016 study by Chiang and Liu reported on a nonrandomized comparison of outcomes after HDR brachytherapy (n=161), RP (n=97), cryoablation (n=114), or high-intensity focused ultrasound (HIFU; n=12) (Chiang, 2016).  The study included patients with clinically localized prostate cancer (stage T3a or lower). Mean follow-up was approximately 3 years. In an unadjusted analysis, the length of PSA BRFS differed significantly across the 4 groups (p<0.001). The mean number of months of BRFS was 21.2 in the HDR group, 22.1 in the RP group, 26.4 in the cryotherapy group, and 27.7 in the HIFU group. There was a longer duration of BRFS in the HDR brachytherapy group than in the other 3 groups. Moreover, patients treated with HDR brachytherapy had a significantly lower metastasis-free rate (90.7%) than those who received other treatments. The percentage of patients who were metastasis-free was 90.7% in the HDR brachytherapy group, 94.8% in the RP group, 99.1% in the cryotherapy group, and 99.2% in the HIFU group (p<0.001). OS and disease-specific survival were not reported. The study was not randomized, and baseline differences across groups might have affected outcomes. For example, patients differed at baseline in a number of characteristics, including age, preoperative prostate volume, and Gleason score. The authors did not report adjusted analyses.
 
Hdr Brachytherapy As Salvage Treatment
In 2017, Jiang et al published a retrospective series of 29 patients with local failure after EBRT who received HDR brachytherapy as salvage therapy (Jiang, 2017). The minimum length of follow-up was 60 months. Five-year OS was 95.5%, and 5-year biochemical control was 45%. There were no grade 3 or 4 late GI toxicities, but 2 patients experienced grade 2 late GI toxicity. Two patients also experienced urinary incontinence and another experienced urinary tract obstruction.
 
American Society of Clinical Oncology and Cancer Care Ontario
In 2017, the American Society of Clinical Oncology and Cancer Care Ontario issued joint guidelines on brachytherapy for prostate cancer that included the following statement (Chin, 2017):
 
“For patients with intermediate-risk prostate cancer choosing EBRT with or without androgendeprivation therapy, brachytherapy boost (LDR [low-dose rate] or high–dose rate [HDR]) should be offered to eligible patients. For low-intermediate risk prostate cancer (Gleason 7, prostate-specific antigen, <10 ng/mL or Gleason 6, prostate-specific antigen, 10 to 20 ng/mL) LDR brachytherapy alone may be offered as monotherapy. For patients with high-risk prostate cancer receiving EBRT and androgen-deprivation therapy, brachytherapy boost (LDR or HDR) should be offered to eligible patients.”
 
The guidelines did not address HDR brachytherapy as salvage treatment.
 
2018 Update
A literature search was conducted through November 2018.  There was no new information identified that would prompt a change in the coverage statement.  
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through November 2021. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Hoskin et al reported on a European single-center randomized trial of 220 patients conducted between 1997 and 2005. It compared EBRT at 55 Gy with EBRT at 35.75 Gy plus HDR brachytherapy in patients with prostate cancer (Hoskin, 2007). With a median follow-up of 30 months, an improvement was reported in actutimes biochemical recurrence-free survival (BRFS), as well as a lower incidence of acute rectal discharge. Hoskin et al later reported on the longer-term follow-up of 218 patients from this phase 3 trial (Hoskin, 2012). Seventy-six percent of the patients also received androgen-deprivation therapy. BRFS was greater in the combination treatment group after 4 years (median time to relapse, 116 months) than in the EBRT-only treatment group (median time to relapse, 74 months). Estimates of BRFS rates for the combination group at 5, 7, and 10 years were 75%, 66%, and 46% compared with 61%, 48%, and 39% for the EBRT-only group, all respectively (p=.04). However, OS did not differ significantly between treatment arms. Estimates of OS rates for the combination group at 5, 7, and 10 years were 88%, 81%, and 67% compared with 89%, 88%, and 79% for the EBRT-only group, all respectively (p=.2). Severe urinary symptoms (26% to 31%) and bowel events (6% to 7%) did not differ significantly between groups at 5 years or 7 years. Erectile dysfunction rates were not reported. Hoskin et al reported similar results at 12 years, with a higher rate of relapse-free survival in the combination group compared to EBRT-alone, but no difference between groups in OS (Hoskin, 2021).
 
Valle et al published a systematic review and meta-analysis on use of local salvage therapies after radiotherapy for prostate cancer (Valle, 2020). Radical prostatectomy was compared to HDR brachytherapy plus other therapies including high-intensity focused ultrasound, cryotherapy, SBRT, and low-dose-rate brachytherapy. Only the comparison of RP to HDR brachytherapy is included in this review. The meta-analysis reported 2-year and 5-year recurrence-free survival rates and incidences of severe GU and GI toxicity. Sixteen studies evaluated HDR brachytherapy, and 4 of these were prospective studies. The covariate-adjusted estimates of 2-year and 5-year recurrence-free survival with HDR brachytherapy were 77% (95% CI, 70 to 83%; 14 studies; n=456) and 60% (95% CI, 52 to 67%; 7 studies; n=350), respectively. Severe GU toxicity occurred in 8% of patients (95% CI, 5.1 to 11; 16 studies; n=586) and severe GI toxicity occurred in 0% of patients (95% CI, 0 to 0.2; 15 studies; n=571). The authors also conducted a meta-regression to compare HDR brachytherapy to RP. There was no difference between HDR brachytherapy and RP in 2-year recurrence-free survival and 5-year recurrence-free survival. However, severe GU toxicity and severe GI toxicity were lower with HDR brachytherapy versus RP. The results of the meta-analysis were limited by including mostly non-comparative, retrospective studies. In addition, OS was not reported.
 
A 2020 practice parameter by the American College of Radiology, the American Brachytherapy Society, and the American Society for Radiation Oncology on radionuclide-based HDR brachytherapy also recommended that HDR monotherapy, HDR plus external beam radiotherapy, and HDR as salvage treatment are appropriate options for specific patients (ACR, 2020).

CPT/HCPCS:
76873Ultrasound, transrectal; prostate volume study for brachytherapy treatment planning (separate procedure)
77316Brachytherapy isodose plan; simple (calculation[s] made from 1 to 4 sources, or remote afterloading brachytherapy, 1 channel), includes basic dosimetry calculation(s)
77317Brachytherapy isodose plan; intermediate (calculation[s] made from 5 to 10 sources, or remote afterloading brachytherapy, 2 12 channels), includes basic dosimetry calculation(s)
77318Brachytherapy isodose plan; complex (calculation[s] made from over 10 sources, or remote afterloading brachytherapy, over 12 channels), includes basic dosimetry calculation(s)
77770Remote afterloading high dose rate radionuclide interstitial or intracavitary brachytherapy, includes basic dosimetry, when performed; 1 channel
77771Remote afterloading high dose rate radionuclide interstitial or intracavitary brachytherapy, includes basic dosimetry, when performed; 2 12 channels
77772Remote afterloading high dose rate radionuclide interstitial or intracavitary brachytherapy, includes basic dosimetry, when performed; over 12 channels
77778Interstitial radiation source application, complex, includes supervision, handling, loading of radiation source, when performed
77790Supervision, handling, loading of radiation source
Q3001Radioelements for brachytherapy, any type, each

References: ACR-ABS-ASTRO(2020) Practice Parameter for the performance of radionuclide-based high-dose-rate brachytherapy. Revised 2020. https://www.acr.org/-/media/ACR/Files/Practice-Parameters/HDR-BrachyRO.pdf. Accessed May 24, 2021.

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Chin J, Rumble RB, Kollmeier M, et al.(2017) Brachytherapy for patients with prostate cancer: American Society of Clinical Oncology/Cancer Care Ontario Joint Guideline Update. J Clin Oncol. May 20 2017;35(15):1737-1743

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