Medical Policy

Policy Num:      08.001.010
Policy Name:    High-Dose Rate Temporary Prostate Brachytherapy
Policy ID:          [08.001.010]   [Ac / B / M+ / P+]   [8.01.33]

Last Review:       January 14, 2026
Next Review:       January 20, 2027
 

Related Policies:

07.001.012 - Whole Gland Cryoablation of Prostate Cancer
08.001.012 - Charged-Particle (Proton or Helium Ion) Radiotherapy for Neoplastic Conditions
06.001.016 - Brachytherapy for Clinically Localized Prostate Cancer Using Permanently Implanted Seeds
06.001.056 - Intensity-Modulated Radiotherapy of the Prostate

High-Dose Rate Temporary Prostate Brachytherapy

Summary

Description

High-dose rate (HDR) temporary prostate brachytherapy is a technique for delivering a high-intensity radiation source directly to the prostate gland to treat cancer. The radiation source is administered through hollow catheters or needles inserted precisely into several areas of the prostate gland using ultrasound guidance and treatment planning computed tomography or ultrasound images. Radiation is applied to target areas until the prescribed dose is reached and is then removed. The goal of treatment is to induce direct tumor necrosis and reduce toxicity and surrounding tissue damage.

Summary of Evidence

For individuals who have localized prostate cancer who receive HDR temporary brachytherapy plus external-beam radiotherapy (EBRT), the evidence includes randomized controlled trials (RCTs), observational studies, and two systematic reviews. Relevant outcomes are overall survival (OS), disease-specific survival, and treatment-related morbidity. A systematic review of 73 studies on brachytherapy plus EBRT in individuals with intermediate-risk or high-risk disease found improved biochemical recurrence-free survival (BRFS) with EBRT-BT but no significant differences in disease-specific survival or OS. Twenty-one studies (29%) used HDR brachytherapy. Toxicity risks were similar to EBRT alone. Interpretation was limited due to varied interventions, study designs, and treatment details. One RCT found no statistically significant differences in outcomes between patients treated with HDR brachytherapy plus EBRT and those receiving radical prostatectomy. A second RCT found significantly better biochemical recurrence-free survival, but not better OS, in patients treated with HDR brachytherapy plus EBRT compared with EBRT alone. Another RCT compared HDR and low-dose rate prostate brachytherapy in 195 men, finding better acute urinary and bowel health-related quality of life (HRQOL) with HDR, especially at 6 months, with no significant sexual HRQOL differences over 5 years. Among several controlled observational studies with matched analyses, 1 has reported 5-year OS rates for HDR brachytherapy plus EBRT similar to those of 1 RCT. In another study, 4-year BRFS was significantly higher after HDR brachytherapy plus EBRT than after EBRT alone. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have localized prostate cancer who receive HDR temporary brachytherapy as monotherapy, the evidence includes long-term results based on a single RCT and large observational studies and systematic reviews. Relevant outcomes are OS, disease-specific survival, and treatment-related morbidity. One follow-up study, reporting on the long-term outcomes of a prospective randomized phase II clinical trial, revealed HDR brachytherapy monotherapy (27 Gy/2 fractions) led to higher 8-year BRFS (83%) and lower local failure (11%) compared to 19 Gy/1 fraction (61%, 36%). A number of observational studies, controlled and uncontrolled, have been published. Systematic reviews have found BRFS rates of 80% to 100%. Long-term survival data are available from case series; 1 found an 8-year survival rate of 95% and another found an actutimes 10-year survival rate of 77%. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have treatment-resistant or recurrent prostate cancer and no disseminated disease who receive HDR temporary brachytherapy as salvage treatment with or without EBRT, the evidence includes systematic reviews and meta-analyses of mostly retrospective studies and case series. Relevant outcomes are OS, disease-specific survival, and treatment-related morbidity. No RCTs were identified on the use of HDR temporary brachytherapy as salvage treatment. A systematic review and meta-analysis of 16 prospective and retrospective trials on HDR brachytherapy in patients with locally recurrent prostate cancer found 2-year and 5-year recurrence-free survival of 77% and 60%. The odds ratio for 2-year and 5-year recurrence-free survival for HDR brachytherapy compared to radical prostatectomy (RP) was 1.26 (95% confidence interval [CI], 0.77 to 2.09) and 1.25 (95% CI, 0.88 to 1.78), respectively. The pooled rates for the RP comparator groups were not reported. The rates of severe gastrointestinal and genitourinary toxicities were lower than rates with RP. However, the meta-analysis was primarily an indirect comparison involving mostly non-comparative, retrospective studies, and OS was not reported. Another meta-analysis of 21 trials found 2-year and 5-year BRFS of 54% (95% CI, 39% to 68%) and 23% (95% CI, 8% to 51%), respectively. However, most of the trials included in the meta-analysis were retrospective. Recent observational studies report manageable toxicity and moderate efficacy. One cohort study of 59 patients found limited severe adverse effects and a 3-year BRFS of 54%, with 82% of cases avoiding androgen deprivation or repeat salvage therapy. A retrospective analysis of 17 patients observed mostly low-grade urinary toxicity (6% to 59%) and no severe bowel events. Higher urethral dose and worse baseline function predict increased urinary symptoms in a third series of 100 patients. Ongoing trials aim to further clarify the acute and late toxicity and efficacy outcomes of focal salvage HDR prostate brachytherapy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Additional Information

2025 Input

Clinical input was sought to help determine whether the use of high-dose rate temporary brachytherapy as salvage treatment with or without external-beam radiotherapy for individuals with treatment-resistant or recurrent prostate cancer and no disseminated disease would provide a clinically meaningful improvement in net health outcome and represents generally accepted medical practice in selected patients. In response to requests, clinical input was received from 8 respondents, include 3 specialty society-level response(s) including physicians with academic medical center affiliation; 3 physician-level responses identified through a specialty society; 2 physician-level responses identified through an academic medical center.

For individuals who have treatment-resistant or recurrent prostate cancer with no disseminated disease, clinical input supports that use of high-dose rate temporary brachytherapy as salvage treatment with or without external-beam radiotherapy is consistent with generally accepted medical practice and that its clinical use is expected to provide a clinically meaningful improvement in net health outcome.

Further details from clinical input are included in the Appendix.

Objective

The objective of this evidence review is to determine whether temporary high-dose rate brachytherapy alone or in combination with external-beam radiotherapy improves the net health outcome in individuals with localized, treatment-resistant, or recurrent prostate cancer.

Policy Statements

High-dose rate temporary prostate brachytherapy may be considered medically necessary as monotherapy or in conjunction with external-beam radiotherapy in the treatment of localized prostate cancer.

High-dose rate temporary prostate brachytherapy may be considered medically necessary as salvage therapy for localized prostate cancer in individuals who have biopsy-confirmed recurrence following definitive radiation treatment. (see Policy Guidelines)

High-dose rate temporary prostate brachytherapy is considered investigational when the above criteria are not met.

Policy Guidelines

High-dose rate (HDR) brachytherapy as monotherapy is being used in low- and intermediate-risk individuals with localized prostate cancer. HDR brachytherapy combined with external-beam radiotherapy (3-dimensional conformal radiotherapy [3D-CRT], intensity-modulated radiotherapy, or proton beam therapy) may be used for more advanced or aggressive prostate cancers. Adequate dose escalation should be achieved with combination HDR temporary brachytherapy and 3D-CRT. Intensity-modulated radiotherapy should be limited only to cases in which 3D-CRT planning is not able to meet dose-volume constraints for normal tissue tolerance. Permanent low-dose rate brachytherapy using only implanted seeds is generally used in individuals whose prostate cancer is considered low risk. Active surveillance is generally recommended for very low risk prostate cancer. Permanent brachytherapy combined with external-beam radiotherapy is used (sometimes along with androgen deprivation therapy) to treat higher-risk disease.

Prostate cancer risk is often defined using the following criteria (American Cancer Society):

• Low risk: prostate-specific antigen (PSA) level of 10 ng/mL or less, Gleason score of 6 or less, and clinical stage T1c (very low risk) or T1 to T2a.

• Intermediate risk: PSA level greater than 10 but 20 ng/mL or less, or Gleason score of 7, or clinical stage T2b to T2c.

• High risk: PSA level greater than 20 ng/mL or Gleason score of 8 to 10, or clinical stage T3a for clinically localized disease and T3b to T4 (very high risk) for locally advanced disease.

Clinical input from 8 respondents across four specialty societies and 2 academic centers strongly supports the NCCN’s latest guidance (v3.2026), which states that brachytherapy can be considered in patients with biochemical recurrence after external-beam radiotherapy. The joint 2024 guidelines on prostate cancer salvage therapy from the American Urological Association (AUA), American Society for Radiation Oncology (ASTRO), and Society of Urologic Oncology (SUO) also recommend reirradiation, including HDR brachytherapy. The consensus across studies and guidelines from organizations including the AUA and ASTRO consistently emphasizes that salvage therapies for recurrent prostate cancer require specialized expertise and careful patient selection due to a higher risk of severe toxicities compared to primary treatments. Emphasis is placed on specialized expertise, multidisciplinary care, use of advanced imaging techniques, and complication management which supports performing these procedures in experienced high-volume centers. Further details from clinical input are included in the Appendix.

Coding

See the Codes table for details.

Benefit Application

BlueCard/National Account Issues

State or federal mandates (eg, Federal Employee Program) may dictate that certain U.S. Food and Drug Administration-approved devices, drugs, or biologics may not be considered investigational, and thus these devices may be assessed only by their medical necessity.

High-dose rate brachytherapy is not a widely disseminated procedure, and thus patients seeking this therapy may request access to an out-of-network facility.

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

Background

Prostate Brachytherapy

Brachytherapy for prostate cancer can be delivered in a variety of ways. Perhaps the most common technique uses radioactive seeds permanently implanted into the prostate tissue. These seeds contain isotopes that slowly emit radiation of relatively low energy. In contrast, temporary prostate brachytherapy involves the use of higher energy radioisotopes such as iridium 192. The latter isotopes deliver radiation at higher dose rates than permanent seeds and may be more effective in destroying rapidly dividing cancer cells. For implantation, needle catheters are placed into the prostate gland using transrectal ultrasound guidance. Once placed, a dosimetric plan is developed, and the radioactive source is inserted into each needle using an after-loading device. The radioactive source is left in the needle for a predetermined time, called the "dwell" time. The radiation usually is delivered once or twice daily over 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 (eg, rectum, urethra). This strategy contrasts with permanent seed implantation in which dosimetry is calculated before needle placement and which cannot be altered after seed implantation. Treatment typically consists of delivering a dose of 4000 to 5000 centigray with external-beam radiotherapy (EBRT) to the prostate and periprostatic tissues, while high-dose rate (HDR) brachytherapy is used as the method of dose escalation to the prostate gland. Total boost doses vary. Additionally, studies are also being conducted using HDR brachytherapy as the sole treatment modality (monotherapy) for prostate cancer.

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

Regulatory Status

A number of devices have been cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process to deliver HDR brachytherapy to the prostate. The Martinez Prostate Template Set and the Photon Technologies HDR Prostate Template and Accessories are examples of radiation application devices. These devices are intended as accessories to commercially available HDR remote afterloader systems for prostate brachytherapy. FDA product code: JAQ.

Rationale

This evidence review was created in April 2000 and has been updated regularly with searches of the PubMed database. The most recent literature update was performed through July 16, 2025.

Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life, and ability to function-including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, 2 domains are examined: the relevance, and the quality and credibility. To be relevant, studies must represent 1 or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Population Reference No. 1 

High-Dose Rate Brachytherapy Plus External-Beam Radiotherapy

Clinical Context and Therapy Purpose

The purpose of high-dose rate (HDR) temporary brachytherapy plus external-beam radiotherapy (EBRT) in individuals who have localized prostate cancer is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The following PICO was used to select literature to inform this review.

Populations

The relevant population of interest is individuals with localized prostate cancer.

Interventions

The therapy being considered is HDR temporary brachytherapy plus EBRT.

Comparators

The following therapies are currently being used to make decisions about localized prostate cancer: EBRT alone, surgery, and cryoablation.

Outcomes

The general outcomes of interest are locoregional recurrence, overall survival (OS), and adverse events. Regular follow-up (every 6 to 12 months) is suggested for the first 5 years posttreatment.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials studies were sought, with a preference for RCTs;

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

• Consistent with a 'best available evidence approach,' within each category of study design, studies with larger sample sizes and longer durations were sought.

• Studies with duplicative or overlapping populations were excluded.

Review of Evidence

Systematic Reviews

Slevin et al. (2024) conducted a systematic review of studies, published between January 2000 and June 2022, to examine the benefits and harms of EBRT plus brachytherapy (EBRT-BT).^1,The primary outcomes assessed were biochemical recurrence-free survival (BRFS), severe late genitourinary (GU) and gastrointestinal (GI) toxicity, metastasis-free survival (MFS), cancer-specific survival (CSS), and OS, at or beyond 5 years. Risk of bias and confounding assessments were performed, and a meta-analysis was conducted for RCTs. A total of 73 studies were included, encompassing 2 RCTs, 7 prospective studies, and 64 retrospective studies. Most studies involved patients with intermediate-risk or high-risk disease, and the majority, including both RCTs, utilized androgen deprivation therapy with EBRT-BT. Of the 2 RCTs, one compared HDR EBRT-BT against EBRT alone. Among the 7 prospective studies, 3 compared HDR EBRT-BT with EBRT alone. In the 64 retrospective studies, 17 used HDR boosts, 11 used low-dose rate (LDR) boosts, and 11 used both HDR and LDR boosts. The type of BT boost was not recorded in the remaining studies. The findings suggested that EBRT-BT generally resulted in improved BRFS compared to EBRT alone, but there were no significant differences in MFS, CSS, or OS. The meta-analysis of the RCTs demonstrated superior BRFS with EBRT-BT, with an estimated fixed-effect hazard ratio (HR) of 0.54 (95% confidence interval [CI], 0.40 to 0.72, p<.001), and absolute improvements in BRFS at 5 to 6 years ranging from 4.9% to 16%. However, no significant difference was observed for MFS (HR 0.84, 95% CI 0.53 to 1.28, p=0.4) or OS (HR 0.87, 95% CI, 0.63 to 1.19, p=0.4). Regarding toxicity, there was no significant increase in the risk of severe late GU toxicity in the 6-year actutimes incidence for HDR EBRT-BT versus EBRT (30% vs. 29%, p=0.6) based on findings from a single RCT. Similarly, no significant differences were observed in late GI toxicity, with the 6-year actutimes incidence of severe toxicity being 7% for HDR EBRT-BT and 6% for EBRT (p=0.9). Interpretation of the results of this systematic review are limited given the mix of interventions, different study designs, minimal treatment-related information, potential for differences in radiotherapy technique, dose and volume, and androgen deprivation therapy use and duration.

Zaorsky et al (2014) reviewed 38 prospective and retrospective studies (N=8008) reporting on HDR brachytherapy boost with EBRT for prostate cancer.^2, Five-year freedom from biochemical failure rates were 85% to 100% for low-risk, 80% to 98% for intermediate-risk, 59% to 96% for high-risk patients, and 34% to 85% for locally advanced patients. In all risk groups, 5-year rates of cancer-specific survival, OS, local recurrence, and distant metastases were 99% to 100%, 85% to 100%, 0% to 8%, and 2% to 12%, respectively. Late Radiation Therapy Oncology Group (RTOG) grade 3 or 4 genitourinary (GU) or gastrointestinal (GI) toxicities occurred in less than 6% of patients. Comparisons of HDR brachytherapy with other radiation techniques were inconclusive. Interpretation of the results of this systematic review was limited by the number of reports from single-institution studies, the lack of comparative studies, and insufficient reporting on toxicity and quality of life.

Randomized Controlled Trials

Crook et al (2024) conducted a randomized trial at a single Canadian center, investigating acute and late urinary, bowel, and sexual health-related quality of life (HRQOL) following a combination of EBRT with either LDR or HDR prostate brachytherapy.^3, The study enrolled 195 men diagnosed with intermediate or high-risk prostate cancer, who were treated with combined pelvic EBRT and brachytherapy. Patients were randomly assigned to receive either an HDR boost (n=108, 15 Gy) or an LDR boost (n=87, 110 Gy). The study population consisted of patients with NCCN unfavorable intermediate-risk disease (43%) and high-risk disease (57%). Androgen deprivation therapy was administered to 75% of the patients for a median duration of 12 months. The findings revealed that better acute urinary HRQOL was maintained in the HDR arm through the 6-month assessment, compared to the LDR arm (84 vs 77; p=.001). By 12 months post-radiation, urinary domain scores between the two arms were comparable and remained consistent until the final evaluation at 5 years. In terms of bowel HRQOL, the HDR group exhibited better outcomes, with higher bowel domain scores at 6 months (89 vs 83; p=.023). The HDR patients consistently maintained higher scores than their LDR counterparts throughout the follow-up period, with statistically significant differences observed at 18 and 24 months, and trends toward significance at 3 to 5 years (p=.06 and p=.07). There were no significant differences in acute or late sexual domain scores between the two groups over the 5-year period. A series of ongoing trials, led by the same team of investigators, aim to assess primary efficacy endpoints including OS, disease-free survival, and BRFS (See Table 4: Summary of Key Trials).

In a multicenter open-label RCT in Sweden, Lennernäs et al (2015) allocated patients with localized and locally advanced (T1b to T3a, N0, M0) prostate cancer to open radical prostatectomy (RP; n=45) or to combined EBRT (3-dimensional conformal radiotherapy, 25´2 Gray [Gy]) and HDR brachytherapy (2´10 Gy) between 1996 and 2001 (n=44).^4, All patients received total androgen blockade that comprised a combination of leuprorelin and flutamide for 6 months. Follow-up assessments included digital rectal examinations if serum prostate-specific antigen (PSA) levels exceeded 10 ng/mL. Quality of life changes were assessed using the European Organization of Research and Treatment of Cancer Quality of Life Questionnaire C33.^5, Patients completed the RTOG/European Organization of Research and Treatment of Cancer Toxicity Scale at 12, 24, and 60 months posttreatment. No statistically significant between-group differences were reported for any of the European Organization of Research and Treatment of Cancer Quality of Life Questionnaire C33 variables or treatment-associated toxicities. Sixty-eight (76%) patients were alive at 10-year follow-up; 8 patients (6 in the RP group, 2 in the 3-dimensional conformal radiotherapy group; 9% total) died of prostate cancer, 13 (n=6 in the RP group, n=7 in the 3-dimensional conformal radiotherapy group) died of other causes.

Hoskin et al (2007) 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.^6, With a median follow-up of 30 months, an improvement was reported in BRFS, as well as a lower incidence of acute rectal discharge. Hoskin et al (2012) later reported on the longer-term follow-up of 218 patients from this phase 3 trial.^7, 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 (2021) 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.^8,

Observational Studies

Boehm et al (2016) published a single-center retrospective analysis of 5619 patients with clinically localized prostate cancer who were treated between 1999 and 2009 with HDR brachytherapy plus EBRT (n=419) or RP (n=5200).^9, Eligibility criteria included stage cT1 or cT2 prostate cancer, a prostate volume of 60 mL or less, no neoadjuvant androgen suppression therapy, and no urinary retention symptoms. HDR brachytherapy treatment (18 Gy in 2 fractions) preceded EBRT (50.4 Gy, 1.8 Gy per fraction with 5 fractions per week). In an unmatched analysis of the overall cohort (N=5619), 5-year OS rates were 97.1% in the RP group and 92.4% in the HDR brachytherapy plus EBRT group (p<.01). An analysis was also conducted after matching the 2 groups on a number of variables including age, cardiovascular disease, diabetes, PSA level, Gleason score, clinical stage, and years of treatment. Five-year OS rates in the matched cohort (n=1257) did not differ significantly between groups. Rates were 95.7% after RP and 92.4% after HDR brachytherapy plus EBRT (p=.5).

Khor et al (2013) reported on a matched pair analysis that compared 344 patients who received EBRT (46 Gy in 23 fractions) plus HDR brachytherapy (19.5 Gy in 3 fractions) with 344 patients who received only EBRT (74 Gy in 37 fractions) for intermediate- or high-risk prostate cancer.^10, Median biochemical follow-up was 60.5 months. Freedom from biochemical failure at 5 years was 79.8% (95% confidence interval [CI], 74.3% to 85.0%) for the HDR brachytherapy plus EBRT group and 70.9% (95% CI, 65.4% to 76.0%) for the EBRT-only group. However, significantly more grade 3 urethral strictures occurred with HDR brachytherapy (11.8%) than with EBRT (0.3%; p<.001).

Long-term outcomes of treatment with HDR brachytherapy and EBRT were reported by Yaxley et al (2017).^11, 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 actutimes 10-year OS rate was 85%, and the actutimes 10-year disease-specific survival rate was 90%. The overall urethral stricture rate was 28.9% (28.9% for men treated before 2005 vs. 4.2% for men treated after 2005).

Section Summary: High-Dose Rate Brachytherapy Plus External-Beam Radiotherapy

A systematic review of 73 studies on brachytherapy plus EBRT in individuals with intermediate-risk or high-risk disease found improved BRFS with EBRT-BT but no significant differences in disease-specific survival or OS. Twenty-one studies (29%) used HDR brachytherapy. Toxicity risks were similar to EBRT alone. Interpretation was limited due to varied interventions, study designs, and treatment details. One RCT found no statistically significant differences in outcomes between patients treated with HDR brachytherapy plus EBRT and those receiving radical prostatectomy. A second RCT found significantly better BRFS, but not better OS, in patients treated with HDR brachytherapy plus EBRT compared with EBRT alone. Another RCT compared HDR and low-dose rate prostate brachytherapy in 195 men, finding better acute urinary and bowel HRQOL with HDR, especially at 6 months, with no significant sexual HRQOL differences over 5 years. Among several controlled observational studies with matched analyses, 1 has reported 5-year OS rates for HDR brachytherapy plus EBRT similar to those of 1 RCT. In another study, 4-year BRFS was significantly higher after HDR brachytherapy plus EBRT than after EBRT alone.

For individuals who have localized prostate cancer who receive HDR temporary brachytherapy plus external-beam radiotherapy (EBRT), the evidence includes randomized controlled trials (RCTs), observational studies, and two systematic reviews. Relevant outcomes are overall survival (OS), disease-specific survival, and treatment-related morbidity. A systematic review of 73 studies on brachytherapy plus EBRT in individuals with intermediate-risk or high-risk disease found improved biochemical recurrence-free survival (BRFS) with EBRT-BT but no significant differences in disease-specific survival or OS. Twenty-one studies (29%) used HDR brachytherapy. Toxicity risks were similar to EBRT alone. Interpretation was limited due to varied interventions, study designs, and treatment details. One RCT found no statistically significant differences in outcomes between patients treated with HDR brachytherapy plus EBRT and those receiving radical prostatectomy. A second RCT found significantly better biochemical recurrence-free survival, but not better OS, in patients treated with HDR brachytherapy plus EBRT compared with EBRT alone. Another RCT compared HDR and low-dose rate prostate brachytherapy in 195 men, finding better acute urinary and bowel health-related quality of life (HRQOL) with HDR, especially at 6 months, with no significant sexual HRQOL differences over 5 years. Among several controlled observational studies with matched analyses, 1 has reported 5-year OS rates for HDR brachytherapy plus EBRT similar to those of 1 RCT. In another study, 4-year BRFS was significantly higher after HDR brachytherapy plus EBRT than after EBRT alone. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

Population Reference No. 2 

High-Dose Rate Brachytherapy as Monotherapy

Clinical Context and Therapy Purpose

The purpose of HDR temporary brachytherapy as monotherapy in individuals who have localized prostate cancer is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The following PICO was used to select literature to inform this review.

Populations

The relevant population of interest is individuals with localized prostate cancer.

Interventions

The therapy being considered is HDR temporary brachytherapy as monotherapy.

Comparators

The following therapies are currently being used to make decisions about localized prostate cancer: EBRT, surgery, and cryoablation.

Outcomes

The general outcomes of interest are locoregional recurrence, OS, and adverse events. Regular follow-up (every 6 to 12 months) is suggested for the first 5 years posttreatment.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

• Consistent with a 'best available evidence approach,' within each category of study design, studies with larger sample sizes and longer durations were sought.

• Studies with duplicative or overlapping populations were excluded.

Review of Evidence

Systematic Reviews

Anderson et al (2021) published a systematic review analyzing the evidence on HDR brachytherapy as monotherapy for prostate cancer.^12, The review included 7 studies (N=2123); all studies had at least 5 years of follow-up, a minimum of 80 patients, and BRFS outcomes. The median follow-up was 74 months. The 5-year BRFS rate was 95% (95% CI, 93% to 96%). Grade 3 or 4 GU and GI toxicity rates were low (2% and 0.3%, respectively).

Zaorsky et al (2015), in a comparative effectiveness review, assessed the relative clinical effectiveness of HDR brachytherapy as monotherapy and robotic arm stereotactic body radiotherapy (SBRT).^13, This review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses conventions. Studies selected enrolled 35 or more men with localized (T1 to T2, N0 to Nx, M0) and locally advanced (T3 to T4, N0 to Nx, M0) prostate cancer who underwent either therapy and were followed for 12 or more months. To be included, studies had to report disease-related outcomes such as BRFS, PSA kinetics, and late GU or GI tract toxicities. For SBRT, BRFS rates were generally 90% or greater at up to 5 years; for HDR brachytherapy as monotherapy, rates were generally 85% or greater at up to 5 years. Median follow-up was 2.9 years, and the longest reported actutimes outcomes were at 8 years. For SBRT, late GU RTOG grade 3 or 4 toxicity rates ranged from 0% to 12%; RTOG late grade 3 or 4 GI toxicity rates ranged from 0% to 5%; for HDR brachytherapy, these rates were 0% to 26% and 0% to 16%, respectively.

Demanes and Ghilezan (2014) published a systematic review analyzing evidence on HDR brachytherapy as monotherapy for prostate cancer.^14, Thirteen studies met selection criteria; they presented clinical outcomes and toxicity data with follow-up ranging from 1.5 to 8.0 years. All risk groups (low, intermediate, high) were represented in selected articles, and a variety of dose and fractionation schedules were reported. Information on study designs, study quality, and other study and patient characteristics were very limited in this review. BRFS rates reported among the studies ranged from 79% to 100%, and local control rates ranged from 97% to 100%. Grade 3 GU toxicity rates, mainly related to urinary urgency or frequency, ranged from 0% to 16%; grade 3 GI tract toxicity rates ranged from 0% to 2%. Erectile functional preservation rates ranged from 67% to 89%.

Randomized Controlled Trials

Hudson et al. (2024) presented the long-term outcomes of a prospective randomized phase II Canadian clinical trial (published by Morton et al, 2020 and included in the above Anderson systematic review).^15,This study compared HDR brachytherapy monotherapy delivered as 27 Gy in 2 fractions (n=83) against 19 Gy in 1 fraction (n=87). The study enrolled patients with NCCN low-risk disease (19%), favorable intermediate-risk disease (51%), and unfavorable intermediate-risk disease (30%). At 8-year follow-up, the biochemical disease-free survival (BDFS) rate was observed to be 83% (95% CI, 75% to 92%) in the 2-fraction arm compared to 61% (95% CI, 52% to 73%) in the single-fraction arm (p=.001). Further analysis showed that the cumulative incidence of local failure at 8 years was significantly lower in the 2-fraction arm (11%) than in the single-fraction arm (36%) (p<.001). However, the incidence of distant failure at 8 years showed no significant difference, being 3.8% in the 2-fraction arm and 2.5% in the single-fraction arm (p=.6). Multivariate analysis revealed two significant predictive factors for distant failure: baseline PSA levels over 10 ng/mL (HR 6.14, p=.017) and the presence of perineural invasion (HR 8.15, p=.004). These findings underscore that HDR brachytherapy monotherapy delivered in two fractions of 13.5 Gy maintains a persistent cancer control rate at 8 years and is well-tolerated compared to single-fraction monotherapy.

Observational Studies

Hegde et al (2018) reported on 437 patients with intermediate-risk prostate cancer who were treated with HDR brachytherapy (n=137) or SBRT (n=300).^16, 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=.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 study by Chiang and Liu (2016) 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).^17, The study included patients with clinically localized prostate cancer (stage T3a or lower). The mean follow-up was approximately 3 years. In an unadjusted analysis, the length of PSA BRFS differed significantly across the 4 groups (p<.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 (94.8% in the RP group, 99.1% in the cryotherapy group, 99.2% in the HIFU group; p<.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.

Strom et al (2015) published a nonrandomized comparative study assessing 413 men who had low- or intermediate-risk prostate cancer.^18, Patients received HDR brachytherapy (n=85), low-dose rate brachytherapy (n=249), or intensity-modulated radiotherapy (n=79). The median follow-up was 32 months. Primary outcomes were patient-reported and validated HRQOL measures obtained before treatment and at 1, 3, 5, 12, and 18 months posttreatment. Sixty-percent of patients completed pre-and posttreatment HRQOL questionnaires. HRQOL outcomes were mixed. At 1 and 3 months posttreatment, HDR brachytherapy patients reported significantly less deterioration in urinary HRQOL than low-dose rate brachytherapy patients (p=.005). However, HDR brachytherapy patients had significantly worse sexual HRQOL than low-dose rate brachytherapy at 1, 6, 9, and 18 months after irradiation (p=.02, p=.003, p=.006, p=.02, respectively). At 18 months, the intensity-modulated radiotherapy group had significantly worse bowel HRQOL scores than either brachytherapy group (p=.007 for both comparisons).

Long-term survival data have also been reported in uncontrolled series. For example, Demanes et al (2011) reported on 298 patients with previously untreated low- to intermediate-risk localized prostate cancer (median PSA, 6.0 ng/mL) treated with HDR brachytherapy as monotherapy between 1996 and 2005, using 2 treatment protocols.^19, Forty-two Gy units in 6, 7-Gy fractions were delivered using computed tomography for treatment planning in 1 protocol; the other treatment planning delivered 38 Gy units in 4, 9.5-Gy fractions using ultrasonography. At 8-year follow-up, outcomes included 99% local control, 97% biochemical control (using the Phoenix definition of PSA nadir plus 2 ng/mL), 99% distant metastasis-free survival, 99% cause-specific survival, and 95% OS rate. Grade 2 urinary frequency or urgency was transient in 10% of patients, whereas grade 3 urinary retention was experienced in 3% of patients. GI toxicity was reported in less than 1% of patients.

Hauswald et al (2016) reported on 448 previously untreated men with low- to intermediate-risk localized prostate cancer patients treated with HDR brachytherapy.^20, Median follow-up was 78 months (range, 3 to 216 months). The actutimes 10-year OS rate was 76.7% (95% CI, 69.9% to 82.2%) and the actutimes 10-year BRFS rate was 97.8% (95% CI, 95.5% to 98.9%) The incidence of grade 3 or 4 GU toxicity during follow-up was 4.9%. No grade 3 or 4 GI toxicity occurred.

Section Summary: High-Dose Rate Brachytherapy as Monotherapy

One follow-up study, reporting on the long-term outcomes of a prospective randomized phase II clinical trial, revealed HDR brachytherapy monotherapy (27 Gy/2 fractions) led to higher 8-year BRFS (83%) and lower local failure (11%) compared to 19 Gy/1 fraction (61%, 36%). A number of observational studies, controlled and uncontrolled, have been published. Systematic reviews have found BRFS rates of 80% to 100%. Long-term survival data are available from case series; 1 found an 8-year survival rate of 95% and another found an actutimes 10-year survival rate of 77%. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have localized prostate cancer who receive HDR temporary brachytherapy as monotherapy, the evidence includes long-term results based on a single RCT and large observational studies and systematic reviews. Relevant outcomes are OS, disease-specific survival, and treatment-related morbidity. One follow-up study, reporting on the long-term outcomes of a prospective randomized phase II clinical trial, revealed HDR brachytherapy monotherapy (27 Gy/2 fractions) led to higher 8-year BRFS (83%) and lower local failure (11%) compared to 19 Gy/1 fraction (61%, 36%). A number of observational studies, controlled and uncontrolled, have been published. Systematic reviews have found BRFS rates of 80% to 100%. Long-term survival data are available from case series; 1 found an 8-year survival rate of 95% and another found an actutimes 10-year survival rate of 77%. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

Population Reference No. 3 

High-Dose Rate Brachytherapy as Salvage Treatment

Clinical Context and Therapy Purpose

The purpose of HDR temporary brachytherapy as salvage treatment with or without EBRT in individuals who have treatment-resistant or recurrent prostate cancer and no disseminated disease is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The following PICO was used to select literature to inform this review.

Populations

The relevant population of interest is individuals with treatment-resistant or recurrent prostate cancer and no disseminated disease.

Interventions

The therapy being considered is HDR temporary brachytherapy as salvage treatment with or without EBRT.

Comparators

The following therapies are currently being used to make decisions about localized prostate cancer: active surveillance, surgery, and cryoablation.

Outcomes

The general outcomes of interest are locoregional recurrence, OS, and adverse events. Regular follow-up (every 6 to 12 months) is suggested for the first 5 years posttreatment.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

• Consistent with a 'best available evidence approach,' within each category of study design, studies with larger sample sizes and longer durations were sought.

• Studies with duplicative or overlapping populations were excluded.

Review of Evidence

Systematic Review

Valle et al (2021 ) published a systematic review and meta-analysis on the use of local salvage therapies after radiotherapy for prostate cancer.^21, Radical prostatectomy was compared to HDR brachytherapy plus other therapies including HIFU, 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 (Table 1). Characteristics of the meta-analysis are summarized in Table 2. 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 (Table 3). 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.

Zhong et al (2021) published a similar systematic review and meta-analysis on salvage reirradiation options for locally recurrent prostate cancer.^22, The review included outcomes for low-dose brachytherapy, HDR brachytherapy, and EBRT. Only the HDR brachytherapy information is included in this review. Details are described in Tables 1 to 3.

Yang et al (2024) conducted a systematic review and meta-analysis of nonsurgical salvage options for locally recurrent prostate cancer after primary definitive radiotherapy.^23, The review included outcomes for cryotherapy, high-intensity focused ultrasound, HDR brachytherapy, LDR brachytherapy, and stereotactic body radiotherapy. Only the HDR brachytherapy information is included in this review. Details are described in Tables 1 to 3.

Morgan et al (2024) conducted a systematic review to support the development of joint guidelines on salvage therapy for prostate cancer by the American Urological Association (AUA), together with the American Society for Radiation Oncology (ASTRO) and the Society of Urologic Oncology (SUO).^24, This review included studies published up to July 2023. Recommendations regarding salvage reradiation (using LDR brachytherapy, HDR brachytherapy, or SBRT) were primarily informed by the above Valle et al (2021) meta-analysis.

Table 1. Studies Included in Systematic Review

Table 2. Systematic Review Characteristics

 NR: not reported.

Table 3. Systematic Review Results

 CI: confidence interval; GI: gastrointestinal; GU: genitourinary; HDR: high-dose rate; NA: not applicable; NR: not reported; RP: radical prostatectomy. aAcute toxicity/late toxicity bLate toxicity cBiochemical recurrence-free survival dGrade ≥3

Observational Studies

Data on HDR brachytherapy as salvage treatment after failed prior radiotherapy are limited; there are no RCTs or nonrandomized comparative studies. Most of the existing evidence comes from retrospective case series that have been included in previous meta-analyses. Additionally, a small number of new studies have been published since the above meta-analyses.

Paulin et al. (2025) reported on updated results of the final cohort of patients (NCT01583920) examining toxicities, HRQOL, and efficacy of focal salvage HDR brachytherapy.^25, The study included 59 patients (enrolled between 2012 and 2021) with biopsy-confirmed, MRI-visible local recurrent prostate cancer following prior external beam radiotherapy and/or brachytherapy. Patients received MR-assisted, ultrasound-based focal HDR brachytherapy, with a total prescription dose of 27 Gy administered in two fractions separated by one to two weeks. No adjuvant androgen deprivation therapy was used. The median age of patients before salvage therapy was 72 years (range, 66-76). Over a median follow-up of 54 months (range, 11 to 132), only one patient experienced grade 3-5 toxicity (late grade 3 GU toxicity), and a single patient required temporary urinary catheterization. The 3-year biochemical failure-free survival rate was 54%, and 82% of patients avoided androgen deprivation or repeat salvage therapy. Post-HDR MRI (n=55 patients; median 464 days) showed a complete response in 84% of patients, and nine patients had persistent disease. Eight patients (15%) experienced recurrence elsewhere in the prostate.

Fang et al. (2024) conducted a retrospective study on acute toxicity following salvage HDR brachytherapy in locally recurrent prostate cancer.^26, Seventeen patients, enrolled between 2019 and 2022, were included, all of whom previously received curative prostate radiotherapy but experienced new biochemical failure. The median age before salvage therapy was 68 years (range, 66-74), and patients were followed for a median of 20 months (range, 13 to 24). At baseline, 47% reported significant lower urinary tract symptoms, with a median AUA score of 7 (range, 3 to 18). Additionally, 18% had irregular bowel function and 12% experienced hematochezia. One month after treatment, the median AUA score rose to 13, though this was not statistically significant (p =.21). No patients experienced grade 2 or higher bowel/rectal toxicity or grade 3 or higher urinary toxicity. Temporary grade 2 urinary toxicities included bladder spasms (59%), incontinence (12%), urinary obstruction (6%), and urgency (24%).

van Son et al (2020), in a study of 100 patients treated with ultrafocal salvage HDR brachytherapy, found that a worse baseline score and a higher urethral dose (≥16 Gy) were significant predictors of increased urinary symptoms (p <.01 and p =.03).^27, Conversely, a better baseline score was linked to improved sexual function outcomes (p <.01). These findings highlight the need to carefully monitor patients' baseline function and manage urethral dose constraints to minimize adverse effects during HDR brachytherapy.

Further studies are underway to assess the acute and late toxicity and efficacy outcomes of focal salvage HDR prostate brachytherapy. For example, the F-SHARP trial (Focal Salvage High-dose-rate BRachytherapy for Locally Recurrent Prostate Cancer in Patients Treated With Prior Radiotherapy, NCT03312972), is a multi-center Phase I/II study currently recruiting 50 patients with locally recurrent prostate cancer across three U.S. centers. The trial is expected to conclude in July 2026, as outlined in Table 4, which provides a summary of key ongoing studies.

Section Summary: High-Dose Rate Brachytherapy as Salvage Treatment

No RCTs are available on the use of HDR brachytherapy as salvage treatment. A meta-analysis of 16 prospective and retrospective trials on HDR brachytherapy in patients with locally recurrent prostate cancer found 2-year and 5-year recurrence-free survival of 77% (95% CI, 70% to 83%) and 60% (95% CI, 52% to 67%). Rates of severe GI and GU toxicities were lower than rates with RP. However, the meta-analysis was primarily an indirect comparison involving mostly non-comparative, retrospective studies, and OS was not reported. An additional meta-analysis of 15 trials found 2-year and 5-year BRFS of 74% (95% CI, 63% to 89%) and 51% (95% CI, 45% to 65%), respectively. Another meta-analysis of 21 trials found 2-year and 5-year BRFS of 54% (95%CI, 39% to 68%) and 23% (95% CI, 8% to 51%), respectively. Recent observational studies report manageable toxicity and moderate efficacy. One cohort study of 59 patients found limited severe adverse effects and a 3-year BRFS of 54%, with 82% of cases avoiding androgen deprivation or repeat salvage therapy. A retrospective analysis of 17 patients observed mostly low-grade urinary toxicity (6% to 59%) and no severe bowel events. Higher urethral dose and worse baseline function predict increased urinary symptoms in a third series of 100 patients. Ongoing trials aim to further clarify the acute and late toxicity and efficacy outcomes of focal salvage HDR prostate brachytherapy.

For individuals who have treatment-resistant or recurrent prostate cancer and no disseminated disease who receive HDR temporary brachytherapy as salvage treatment with or without EBRT, the evidence includes systematic reviews and meta-analyses of mostly retrospective studies and case series. Relevant outcomes are OS, disease-specific survival, and treatment-related morbidity. No RCTs were identified on the use of HDR temporary brachytherapy as salvage treatment. A systematic review and meta-analysis of 16 prospective and retrospective trials on HDR brachytherapy in patients with locally recurrent prostate cancer found 2-year and 5-year recurrence-free survival of 77% and 60%. The odds ratio for 2-year and 5-year recurrence-free survival for HDR brachytherapy compared to radical prostatectomy (RP) was 1.26 (95% confidence interval [CI], 0.77 to 2.09) and 1.25 (95% CI, 0.88 to 1.78), respectively. The pooled rates for the RP comparator groups were not reported. The rates of severe gastrointestinal and genitourinary toxicities were lower than rates with RP. However, the meta-analysis was primarily an indirect comparison involving mostly non-comparative, retrospective studies, and OS was not reported. Another meta-analysis of 21 trials found 2-year and 5-year BRFS of 54% (95% CI, 39% to 68%) and 23% (95% CI, 8% to 51%), respectively. However, most of the trials included in the meta-analysis were retrospective. Recent observational studies report manageable toxicity and moderate efficacy. One cohort study of 59 patients found limited severe adverse effects and a 3-year BRFS of 54%, with 82% of cases avoiding androgen deprivation or repeat salvage therapy. A retrospective analysis of 17 patients observed mostly low-grade urinary toxicity (6% to 59%) and no severe bowel events. Higher urethral dose and worse baseline function predict increased urinary symptoms in a third series of 100 patients. Ongoing trials aim to further clarify the acute and late toxicity and efficacy outcomes of focal salvage HDR prostate brachytherapy. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

SUPPLEMENTAL INFORMATION

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

Clinical Input From Physician Specialty Societies and Academic Medical Centers

While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

2025 Input

Clinical input was sought to help determine whether the use of high-dose rate temporary brachytherapy as salvage treatment with or without external-beam radiotherapy for individuals with treatment-resistant or recurrent prostate cancer and no disseminated disease would provide a clinically meaningful improvement in net health outcome and represents generally accepted medical practice in selected patients. In response to requests, clinical input was received from 8 respondents, include 3 specialty society-level response(s) including physicians with academic medical center affiliation; 3 physician-level responses identified through a specialty society; 2 physician-level responses identified through an academic medical center.

For individuals who have treatment-resistant or recurrent prostate cancer with no disseminated disease, clinical input supports that use of high-dose rate temporary brachytherapy as salvage treatment with or without external-beam radiotherapy is consistent with generally accepted medical practice and that its clinical use is expected to provide a clinically meaningful improvement in net health outcome.

Further details from clinical input are included in the Appendix.

Practice Guidelines and Position Statements

Guidelines or position statements will be considered for inclusion in ‘Supplemental Information' if they were issued by, or jointly by, a US professional society, an international society with US representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

American College of Radiology

American College of Radiology (ACR) Appropriateness Criteria (2014) for the use of HDR brachytherapy to treat prostate cancer were issued.^28, The ACR indicated HDR monotherapy, HDR plus external-beam radiotherapy, and HDR as salvage treatment might be appropriate treatment options. A 2020 practice parameter by the ACR , 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.^29,

American Urological Association et al.

In 2024, the American Urological Association (AUA), together with the American Society for Radiation Oncology (ASTRO) and the Society of Urologic Oncology (SUO), released guidelines on salvage therapy for prostate cancer.^24,According to their recommendations, for patients who experience a recurrence of prostate cancer confirmed by biopsy after initial radiation therapy and are eligible for salvage local treatment, clinicians should consider options such as RP, cryoablation, HIFU, or reirradiation, as part of a shared decision-making approach (Moderate Recommendation; Evidence Level: Grade C). Salvage reirradiation methods include LDR brachytherapy, HDR brachytherapy, or SBRT.

National Comprehensive Cancer Network

The National Comprehensive Cancer Network guidelines (v.4.2026) on the treatment of prostate cancer^30,state that:

• "Brachytherapy alone is an option for patients with favorable intermediate-risk and for carefully selected patients with unfavorable intermediate-risk prostate cancer, depending on life expectancy."

• "LDR or HDR brachytherapy can be added as a boost to EBRT plus ADT in patients with unfavorable intermediate- or high-risk prostate cancer being treated with curative intent and for carefully selected patients with very-high risk disease.”

For patients undergoing salvage therapy, the NCCN indicates that

• “Patients with biopsy-proven recurrence in the prostate after prior RT and without distant metastatic disease can be considered for local therapy...Local therapy options for patients with recurrence in the prostate include reirradiation.” Reirradiation options include LDR brachytherapy, HDR brachytherapy, and SBRT.”

• “Brachytherapy can be considered in patients with biochemical recurrence after EBRT...Decisions regarding the use of brachytherapy in the recurrent-disease setting should consider comorbidities, extent of disease, and potential complications. Brachytherapy in this setting is best performed at high-volume centers."

The NCCN also notes that, while evidence regarding brachytherapy after permanent brachytherapy is limited, “the panel agrees that it can be considered for carefully selected patients”.

National Institute for Health and Care Excellence

In 2006, NICE published guidance on HDR brachytherapy in combination with external-beam radiotherapy for localized prostate therapy.^31, The guidance is as follows:

"Current evidence on the safety and efficacy of high dose rate (HDR) brachytherapy in combination with external-beam radiotherapy for localised prostate cancer appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance."

NICE notes that a multidisciplinary team should be involved in the planning and use of this procedure.

U.S. Preventive Services Task Force Recommendations

Not applicable.

Medicare National Coverage

There is no national coverage determination. In the absence of a national coverage determination, coverage decisions are left to the discretion of local Medicare carriers.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 4.

Table 4. Summary of Key Trials

 NCT: national clinical trial.

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