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Brachytherapy for low-risk or favorable intermediate-risk, clinically localized prostate cancer

Brachytherapy for low-risk or favorable intermediate-risk, clinically localized prostate cancer
Literature review current through: Jan 2024.
This topic last updated: Aug 11, 2022.

INTRODUCTION — Standard options for the initial treatment of men with clinically localized prostate cancer (ie, without distant metastases) include radiation therapy (RT; brachytherapy and/or external beam), radical prostatectomy, or in carefully selected patients, active surveillance. The choice of treatment is determined by a variety of factors, including patient preference, clinician judgment, and resource availability. (See "Localized prostate cancer: Risk stratification and choice of initial treatment".)

Brachytherapy involves the permanent or temporary placement of radioactive sources that are implanted directly into the prostate gland to administer a high dose of radiation directly to the prostate while minimizing radiation to normal tissues. Observational data indicate that as monotherapy, brachytherapy has similar efficacy compared with other forms of radiation and is comparable with other modalities (eg, surgery) in the treatment of low-risk prostate cancer, and it has an important role in combination with external beam RT in the management of some patients with intermediate- and high-risk disease.

The techniques and complications of brachytherapy, along with relevant aspects of patient selection, are reviewed here. The stratification of men with newly diagnosed prostate cancer based on their risk of local recurrence or dissemination, and the application of these techniques to men with low-, intermediate-, and high-risk prostate cancer are discussed separately:

(See "Localized prostate cancer: Risk stratification and choice of initial treatment", section on 'Risk stratification'.)

(See "Initial approach to low- and very low-risk clinically localized prostate cancer".)

(See "Initial management of regionally localized intermediate-, high-, and very high-risk prostate cancer and those with clinical lymph node involvement".)

RISK STRATIFICATION AND THE SELECTION OF THE INITIAL TREATMENT APPROACH — The initial evaluation of men with suspected prostate cancer should include clinical staging based on a digital rectal examination by an experienced clinician to assess the extent of disease, a pretreatment serum prostate-specific antigen (PSA), the Gleason score/grade group in the initial biopsy, and the number and extent of cancer involvement in the biopsy cores. This information allows the stratification of men into clinical risk categories according to the primary tumor, as defined by the National Comprehensive Cancer Network (NCCN) (table 1). This risk stratification system has been utilized in guidelines for treatment of clinically localized prostate cancer from the American Urological Association (AUA)/American Society for Radiation Oncology (ASTRO), which have been largely endorsed by the American Society of Clinical Oncology (ASCO) [1,2].

Imaging studies (radionuclide bone scan, computed tomography [CT] of the abdomen and pelvis, multiparametric magnetic resonance imaging [MRI]) are used selectively to assess for extraprostatic extension, regional adenopathy, or distant metastases, depending on the initial clinical stage and estimate of risk. Imaging for distant disease is not routinely recommended for very low- and low-risk prostate cancer according to the clinical staging system described above, while skeletal scintigraphy and cross-sectional imaging (of the pelvis with or without abdominal imaging) are recommended for those with intermediate- and high-risk disease [1,2]. MRI of the prostate is often obtained in men with low- and very low-risk disease to ensure that high-grade disease has not been overlooked.

The tumor, node, metastasis (TNM) staging system of the American Joint Committee on Cancer (AJCC) uses the clinical stage of disease (or pathologic stage in those who have undergone prostatectomy), the baseline serum PSA, the histologic grade group (based on the Gleason score), and the extent of prostate involvement to divide patients into prognostic stage groups (table 2 and table 3). Among patients without distant metastases, these groups can also be used for selection of initial treatment according to risk, although we prefer to use the clinical risk categories as defined by the NCCN. It should be noted that detailed evaluation of histology, and the impact of tumor size (rather than just the number of positive cores) and gene expression profiling are not fully captured by these risk groups.

Guidelines from expert groups — In general, active surveillance is preferred for men with very low- or low-risk prostate cancer and a reasonable life expectancy, although definitive therapy could be offered to select patients with low-risk disease who have a high probability of progression on active surveillance [1-3]. For men with higher risk disease and a reasonable life expectancy, definitive treatment using external beam radiation therapy (EBRT), brachytherapy, or radical prostatectomy is an appropriate option [4].

The guidelines from the AUA/ASTRO and ASCO endorse shared decision making, which explicitly considers cancer severity (risk stratification), patient values and preferences, life expectancy, pretreatment general functional status and genitourinary symptoms, expected posttreatment functional status, and potential for salvage treatment [1,2].

Regarding the specific role of EBRT and brachytherapy, the following recommendations are available from the AUA/ASTRO, which have largely been endorsed by ASCO [1,4]:

Clinicians may offer single-modality EBRT or brachytherapy for patients who elect radiation therapy (RT) for low-risk prostate cancer.

Clinicians may offer EBRT or brachytherapy monotherapy for favorable intermediate-risk prostate cancer.

Clinicians should inform men considering proton beam therapy that it offers no clinical advantage over other forms of definitive treatment.

Clinicians should inform men with localized prostate cancer considering brachytherapy that it has similar effects to EBRT with regard to erectile dysfunction and proctitis but can exacerbate urinary obstructive symptoms. For men with non-cancer-related obstructive lower urinary function, surgical approaches may be preferred. If RT is used for these patients or those with a previous significant transurethral resection of the prostate (TURP), low-dose rate brachytherapy should be avoided.

Risk stratification and treatment options appropriate for each risk category are discussed separately. (See "Initial staging and evaluation of males with newly diagnosed prostate cancer" and "Initial approach to low- and very low-risk clinically localized prostate cancer" and "Initial management of regionally localized intermediate-, high-, and very high-risk prostate cancer and those with clinical lymph node involvement".)

RATIONALE — Brachytherapy allows a higher dose of radiation to be given to the target area while minimizing radiation exposure to the surrounding normal tissues.

Brachytherapy is more convenient than external beam radiation therapy (EBRT). While conventional EBRT requires seven to eight weeks of treatments five times per week (or hypofractionated EBRT consisting of 300 cGy in 20 to 60 Gy fractions), brachytherapy using permanent prostate implantation of either low-dose rate (LDR) or high-dose rate (HDR) seeds can be completed in a single outpatient visit. When combined with EBRT, LDR brachytherapy, or HDR implants, the course of treatment can be shortened compared with a course of dose-escalated EBRT alone.

The greatest deterrent to more widespread use of brachytherapy is the limited number of practitioners who are skilled at performing these procedures. Other potential drawbacks of brachytherapy include the risk for severe toxicity to the bladder, urethra, and rectum because of their anatomic proximity to the prostate and the high dose intensity close to the radiation source when not properly performed. Furthermore, the rapid drop-off in radiation dose can lead to undertreatment if the tumor has spread beyond the planned area of treatment. Usually, brachytherapy is combined with EBRT in patients with or at high risk for extraprostatic spread who are thought to be at increased risk of recurrence.

TECHNIQUE — During brachytherapy, the radiation sources are positioned within the prostate using a transperineal approach under imaging guidance (typically transrectal ultrasound) [5,6]. Prostate brachytherapy is usually performed under light general or spinal anesthesia.

The radiation is delivered either with permanent low-dose rate (LDR) radioactive sources (seeds) or by the placement of temporary high-dose rate (HDR) sources into hollow catheters or needles that have been positioned in the prostate.

Low-dose rate brachytherapy — Depending on the size of the gland, approximately 75 to 125 radioactive seeds (each approximately 5 mm in length) are permanently implanted into the prostate gland according to a computerized treatment plan (image 1). The old retropubic technique relied on freehand placement of the radiation sources. That approach was abandoned 30 years ago in favor of ultrasound-guided procedures that usually rely on a perineal template to ensure more precise placement of sources and better, more homogeneous dose distributions.

The planned radiation therapy (RT) dose is emitted over several months, depending on the specific isotope [7]. Both iodine-125 (I-125) and palladium-103 (Pd-103) are widely used; the available data do not indicate that one isotope is more effective than the other [8-13]. Cesium-131 (CS-131) has also been used and has the shortest half-life [14,15].

High-dose rate brachytherapy — For HDR brachytherapy, transperineal catheters are inserted into the prostate, usually through a template that is fixed to the perineum. The hollow guides are then loaded with an isotope such as iridium-192 (Ir-192). Treatment planning is performed using computed tomography (CT) or ultrasound data sets. The dwell position of the sources within the catheters can be altered over time to optimize the resultant dose distribution. The HDR brachytherapy dose is usually administered in one to four large-dose fractions over a period of time, typically 24 to 40 hours. Patients receiving more than one fraction are usually admitted to the hospital (typically a 23-hour "outpatient stay") for treatment when delivering multiple fractions, and they retain the perineal catheters in place for the entire period.

The main advantage of HDR brachytherapy is that the maximal dose rate is approximately 1000-fold higher than that achieved with LDR brachytherapy and approximates that delivered by a linear accelerator. Because the rapid drop-off in radiation dose at the edge of the gland can lead to underdosing of the periprostatic tissues, treatment is frequently combined with external beam radiation therapy (EBRT) in patients with high-risk disease. Although some studies suggest slightly lower genitourinary morbidity with HDR compared with LDR, most studies do not support a clear advantage of one form over the other [16-19].

PATIENT SELECTION — The selection of brachytherapy for a patient with low-risk, localized prostate cancer is based on technical feasibility, the absence of coexistent urinary conditions, the ability of the implant to encompass areas of known disease, and clinician or patient preference. Contraindications to brachytherapy are outlined in the table and discussed in more detail below (table 4).

Brachytherapy is commonly performed under general anesthesia, but it can be performed under spinal anesthesia in men who are unable to undergo anesthesia. However, local anesthesia has been used successfully at a limited number of institutions [20,21].

Low-dose rate brachytherapy — As noted above, the following recommendations are available from the American Urological Association (AUA)/American Society for Radiation Oncology (ASTRO), which have largely been endorsed by the American Society of Clinical Oncology (ASCO) [1,4] (see 'Guidelines from expert groups' above):

Clinicians may offer single-modality external beam radiation therapy (EBRT) or permanent low-dose rate (LDR) brachytherapy or temporary high-dose rate (HDR) implant as equivalent forms of treatment for patients who elect radiation therapy (RT) for low-risk prostate cancer.

Clinicians may offer EBRT or LDR brachytherapy or HDR implant brachytherapy as equivalent forms of treatment for favorable intermediate-risk prostate cancer.

LDR brachytherapy may also be appropriate in other patients with intermediate-risk disease, and in those with high-risk disease when used in combination with EBRT and androgen deprivation therapy (ADT). This subject is discussed in more detail elsewhere. (See "Initial management of regionally localized intermediate-, high-, and very high-risk prostate cancer and those with clinical lymph node involvement", section on 'EBRT with brachytherapy boost'.)

A large prostate gland (>50 to 60 g) and/or a large, poorly healed transurethral resection of the prostate (TURP) defect are relative contraindications to LDR brachytherapy (table 4). For men with localized prostate cancer and non-cancer-related obstructive lower urinary function, guidelines from ASCO suggest that surgical approaches may be preferred over RT [1]. However, if RT is used for these patients or those with a previous significant TURP, LDR brachytherapy should be avoided.

High-dose rate brachytherapy — Guidelines from the American Brachytherapy Society (ABS) and the National Comprehensive Cancer Network (NCCN) [22] recommend that HDR brachytherapy be considered as a way to escalate the dose of radiation in men receiving RT as their primary therapy for prostate cancer [23]. HDR brachytherapy is particularly useful in men with intermediate- or high-risk prostate cancer since it can provide highly conformal dose escalation to the target region. (See "Initial management of regionally localized intermediate-, high-, and very high-risk prostate cancer and those with clinical lymph node involvement", section on 'EBRT with brachytherapy boost'.)

Contraindications — A number of factors need to be considered prior to using either LDR or HDR brachytherapy [13,23,24].

Prostate gland size — A large prostate gland (>50 to 60 g) is a relative contraindication to LDR brachytherapy (table 4). A large prostate gland size is less of a restriction with HDR brachytherapy than with LDR brachytherapy, and many clinicians will treat larger glands (>60 g) with HDR brachytherapy [25].

A higher rate of treatment-related morbidity, particularly acute urinary retention, has been observed in patients with a large prostate [6,11]. In addition, an excessively large prostate gland may prevent proper needle placement due to pubic arch interference or may result in inadequate coverage with the radiation. (See 'Complications' below.)

In general, ADT should not be added along with RT for men with low-risk prostate cancer [1,4]. However, a brief course of neoadjuvant ADT prior to brachytherapy may reduce the volume of the prostate, thereby making brachytherapy feasible [26-28]. Treatment for an average of three months with ADT generally decreases the size of the prostate by approximately 30 percent with an acceptable level of toxicity. This approach is supported in guidelines from ASCO [1], but not the AUA/ASTRO [4]. Notably, although ADT can be used to reduce the volume of the prostate gland, this approach does not appear to decrease the risk of urinary morbidity. (See 'Acute toxicity' below.)

Otherwise, there is no good evidence that the use of ADT in conjunction with brachytherapy alone improves the oncologic outcome, and some retrospective studies suggest that all-cause mortality may be higher with the use of neoadjuvant ADT in men with a history of severe coronary artery disease (as manifested by heart failure or myocardial infarction) [29]. Despite these data, the available evidence from randomized trials suggests that the vast majority of men with nonmetastatic prostate cancer are not at risk for an excess of ADT-associated cardiovascular problems [30-33]. (See "Side effects of androgen deprivation therapy", section on 'Potential cardiovascular harm'.)

Preexisting urinary symptoms — For men with localized, low-risk prostate cancer and non-cancer-related obstructive lower urinary function, guidelines from ASCO suggest that surgical approaches may be preferred over RT [1]. However, if RT is used for these patients or those with a previous significant TURP associated with a large defect, both HDR and LDR brachytherapy should be avoided. Patients with a small TURP defect and/or urinary symptoms responsive to drug therapy may be suitable for LDR brachytherapy.

Higher levels of urinary morbidity after brachytherapy may be manifested by an increase in prostate-related symptoms or the development of acute urinary retention.

Although there are no definitive criteria for excluding patients from brachytherapy, factors that may be associated with worsening urinary symptoms posttreatment include a high pretreatment urinary symptom score (as assessed by the AUA or International Prostate Symptom Score [IPSS] method (table 5)), a high postvoid residual volume (eg, >100 mL), a large prostate volume, or the need for alpha blockers to control symptoms prior to diagnosis [34-36].

Alpha blockers may be useful to minimize symptoms associated with brachytherapy and decrease the risk of urinary retention. They are generally started a week before the implant and continued for approximately four weeks after implantation.

Other factors — Other factors that may constitute a relative contraindication include a history of prior rectal surgery, pelvic RT, TURP for urinary outlet obstruction (although those with a small defect following TURP may be an exception), or inflammatory bowel disease [23]. Absolute contraindications include a limited life expectancy, unacceptable operative risks, and the presence of technical factors precluding satisfactory treatment.

ONCOLOGIC OUTCOMES — Oncologic outcomes following prostate brachytherapy using both low-dose rate (LDR) and high-dose rate (HDR) techniques have improved significantly over time, which may be attributable to both improvements in implantation technique and better patient selection [37-42]. Some of this apparent improvement may also be due to bias caused by Gleason score reclassification over time, leading to exclusion of patients with a less favorable prognosis. (See "Interpretation of prostate biopsy", section on 'Gleason grading system'.)

Versus other modalities — There are no randomized trials that provide adequate data to compare brachytherapy with other treatment modalities as initial therapy in men with low-risk, localized prostate cancer. The choice of brachytherapy over external beam radiation therapy (EBRT), radical prostatectomy, or active surveillance is generally based on a combination of factors, including treatment-related complications as well as clinician and patient preferences. (See "Initial approach to low- and very low-risk clinically localized prostate cancer", section on 'Outcomes and the choice of therapy'.)

The available data comparing brachytherapy with other local therapies for low-risk and intermediate-risk disease are briefly summarized here, and discussed in more detail elsewhere (see "Localized prostate cancer: Risk stratification and choice of initial treatment" and "Initial approach to low- and very low-risk clinically localized prostate cancer", section on 'Outcomes and the choice of therapy' and "Initial management of regionally localized intermediate-, high-, and very high-risk prostate cancer and those with clinical lymph node involvement", section on 'Radiation therapy versus prostatectomy'):

The Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT) was designed to compare brachytherapy with radical prostatectomy, but it was discontinued because of poor accrual [43]. Health-related quality of life was analyzed after five years in patients who either had been randomized or had undergone screening for the trial. In the 168 men who completed a follow-up survey five years later, brachytherapy was significantly better in terms of urinary and sexual functioning.

In addition, several retrospective analyses have compared outcomes following brachytherapy versus high-dose EBRT, and these results suggest that brachytherapy is at least equivalent for biochemical control and may be more effective at achieving lower prostate-specific antigen (PSA) nadirs [44-47].

In an analysis of data performed by the Prostate Cancer Results Study Group (PCRSG), treatment outcomes for both LDR and HDR brachytherapy, both alone and in combination with EBRT, appeared similar to those with other treatment modalities when patients were stratified according to risk [48]. A similar conclusion was reached in a retrospective review of the 10-year outcomes of 1503 men with intermediate-risk prostate cancer who were treated with EBRT, radical prostatectomy, or LDR brachytherapy [47].

COMPLICATIONS — The most frequent complications associated with brachytherapy are toxicity to the urinary tract and rectum, as well as sexual dysfunction. The severity of complications is significantly influenced by pretreatment functional level [49]. The available evidence indicates that the rates of complications have decreased with increasing experience and improvements in techniques [50].

Most of the data for the complications are derived from series using low-dose rate (LDR) brachytherapy.

Urinary — The anatomic proximity of the prostate to the urethra and bladder results in both acute and late urinary tract toxicity from brachytherapy. In addition, transient symptom flares are frequently observed months or years after treatment and may resolve spontaneously.

Acute toxicity — In most patients treated with brachytherapy, there is an acute worsening of urinary symptoms (increased frequency of urination, nocturia, hesitancy, urgency, weak urinary stream) that gradually resolves in most cases [51,52].

This was illustrated by a series of 712 men with localized prostate cancer treated with an iodine-125 (I-125) implant between 1998 and 2003 [51]. External beam radiation therapy (EBRT) was not used in conjunction with brachytherapy.

The median follow-up was 57 months (minimum 34 months). Symptoms were assessed using the International Prostate Symptom Score (IPSS) (table 5).

The mean IPSS prior to brachytherapy for the entire cohort was 6. By six weeks after treatment, most patients experienced an acute exacerbation of urinary symptoms, which was associated with an increase in the IPSS to a mean of approximately 19. After the acute exacerbation, symptoms gradually resolved. The IPSS returned to baseline levels in approximately 85 percent of cases, although this required two or more years in some cases.

On multivariate analysis, factors associated with increased late toxicity included more prostate symptoms at baseline (ie, a higher IPSS), the development of significant acute toxicity, and a larger prostate volume. More recently implanted patients had less acute toxicity, and those given androgen deprivation therapy (ADT) had less late toxicity.

Acute urinary retention is uncommon as a complication following brachytherapy [53,54]. This was illustrated by a series in which 21 of 655 patients (3 percent) required catheterization in the immediate posttreatment period. An increased prostate volume and more severe pretreatment urinary symptoms were associated with an increased risk of acute urinary retention.

Although ADT can be used to reduce the volume of the prostate gland, this approach does not appear to decrease the risk of urinary morbidity. In a retrospective series, 81 patients who had been treated with ADT to reduce the size of their prostate gland were compared with matched controls with similar size prostates who had not required ADT [55]. Those who had received neoadjuvant ADT required prolonged catheterization significantly more frequently following treatment (27 versus 9 percent).

Late toxicity — When brachytherapy is used as monotherapy, clinically significant long-term urinary toxicity following brachytherapy is uncommon. In a series of 1989 men treated with LDR brachytherapy, the rates of severe, late, genitourinary and gastrointestinal toxicities were 7.6 and 0.8 percent, respectively [42], and similar results have been seen in other series [51].

Late urethral strictures are an uncommon complication following brachytherapy [56,57]. In a series of 1030 patients treated with brachytherapy, 94 and 92 percent of patients were free of stricture one year after treatment with brachytherapy alone and brachytherapy plus EBRT, respectively [56]. At four years, 89 and 84 percent remained stricture free.

Urinary symptom flare — A transient worsening of urinary symptoms is frequently observed after resolution of the initial symptoms in men treated with brachytherapy [58-61]. (See 'Acute toxicity' above.)

In a series of 712 men treated with LDR brachytherapy, urinary symptom flare was observed in 52 percent, based on a criterion of an increase in IPSS of ≥5 points compared with the posttreatment nadir (table 5) [51,58]. Symptoms resolved within six months in 65 percent of cases and within one year in 91 percent. The mean interval to the development of a symptom flare was 30 months, and in a few cases, a symptom flare developed more than five years after treatment. In some cases, multiple episodes of increased symptoms occurred.

Factors associated with this increase in symptomatology included more baseline urinary symptoms and more intense symptoms in the immediate posttreatment period.

Radiation proctitis — The incidence of radiation proctitis following brachytherapy for localized prostate cancer is difficult to determine due to differing definitions, length of follow-up, censoring for other events, and reporting methodologies. Most of the available data come from trials using LDR.

Although some rectal bleeding is relatively common, more serious complications are rare [62-65]. As an example, in a retrospective series of 2752 patients treated with LDR brachytherapy over a 17-year period, the actuarial risk of grade 2 or higher rectal bleeding was 6.4 percent. Predictive factors for bleeding included rectal dose, rectal volume, and coronary artery disease [65]. However, only 27 patients (1 percent) required medical intervention (formalin treatment or cauterization), and fistula or ulceration occurred in only nine cases (0.3 percent).

Screening colonoscopy to rule out concurrent rectal pathology has been recommended for patients who have not had a colonoscopy within the preceding three years because some degree of radiation proctitis is frequent [62]. A negative colonoscopy facilitates conservative management of rectal bleeding during the first two years after brachytherapy if symptoms are consistent with radiation proctitis.

Rectal fistula — Radiation-related rectal fistulas are a serious but rare complication, occurring in fewer than 1 percent of cases [66]. The development of a rectal fistula has not been correlated with clinical or dosimetric factors. Such fistulas may be more frequent when patients have undergone a biopsy or other invasive procedures, and such interventions should be avoided whenever possible.

Sexual dysfunction — The reported incidence of erectile dysfunction varies widely among men who were potent prior to brachytherapy, depending in part on whether data are clinician or patient reported. Rates of erectile dysfunction are similar to that seen with EBRT. In contrast to radical prostatectomy, the onset of erectile dysfunction is gradual following brachytherapy.

The frequency of impotence depends on multiple factors. A validated model has been developed to help predict the probability of erectile function two years after brachytherapy; significant factors include patient age, ethnicity (African-American versus White American or other), body mass index (BMI), and pretreatment sexual health-related quality of life [67].

The impact of LDR brachytherapy on erectile function is illustrated by results from a prospective multicenter analysis of prostate cancer survivors that included 306 patients who were treated with LDR brachytherapy [68]. In this study, poor sexual function was reported in 43 to 48 percent of patients from 2 to 24 months after therapy. Approximately one-third of patients considered sexual dysfunction a moderate or big problem. Similar rates of dysfunction have been reported in other studies [69,70].

The management of erectile dysfunction following radiation therapy (RT) for prostate cancer is discussed separately. (See "External beam radiation therapy for localized prostate cancer", section on 'Sexual dysfunction' and "Treatment of male sexual dysfunction", section on 'Erectile dysfunction'.)

Quality of life — Quality of life and satisfaction with treatment outcome were assessed in a multi-institution prospective series of 1201 prostate cancer survivors [68]. The series included 306 patients who had been treated with brachytherapy, of whom 11 percent also were treated with EBRT.

Factors negatively impacting quality of life following prostate brachytherapy included a significant worsening in urinary symptoms (irritation, incontinence, obstruction) in 18 percent of patients at one year after treatment. Bowel symptoms (urgency, frequency, pain, fecal incontinence, bleeding) were present in 9 percent after one year. Patients reported distress or dysfunction related to overall sexual function in 29 percent of cases at one year.

Second malignancies — Second cancers, particularly of the bladder or rectum, are a theoretical concern in patients who undergo RT for prostate cancer. Although both EBRT and brachytherapy may be associated with a small increase in the incidence of cancer, the risk of dying from a secondary malignancy at 10 to 15 years is very small and appears to be of similar magnitude to the perioperative mortality associated with radical prostatectomy. (See "External beam radiation therapy for localized prostate cancer", section on 'Secondary malignancies'.)

Seed embolization — Migration of the radioactive seeds to the lungs has been described as a complication of LDR brachytherapy [71-74]. Although seed migration may be identified in up to 55 percent of patients who are monitored with routine chest radiographs [73], the clinical implications of this are unclear. There are case reports, however, of seed migration to the heart, lungs, and other organs, occasionally associated with clinical sequelae [74].

The use of stranded seeds appears to decrease the risk of migration [75-77].

Effect of isotope — The available evidence suggests that differences in toxicity between I-125 and palladium-103 (Pd-103) are consistent with the half-lives of the isotopes and that there is no clear preference of one isotope over another:

In a trial that included 352 patients who were randomly assigned to either I-125 (144 Gy) or Pd-103 (125 Gy), those treated with Pd-103 had more intense radiation proctitis during the first month after treatment, but treatment-related symptoms resolved more rapidly than with I-125. These results are consistent with the shorter half-life for Pd-103 (17 versus 60 days with I-125) [12].

In a nonrandomized series of 976 consecutive patients, 81 percent of patients were implanted with Pd-103, and 19 percent received I-125 [11]. ADT was given to 43 percent of patients, and brachytherapy was given in conjunction with EBRT in 50 percent. There was no difference between the two isotopes in terms of resolution of urinary symptoms, catheter dependency, or need for surgical intervention following brachytherapy.

Airline travel — Low levels of radiation can be picked up by detection systems at airports or international borders and may trigger alarms after seed implants. Thus, patients who are travelling within three to four months of seed implantation may require documentation specifying the date of treatment, type and dose of radionuclide, treating facility, and contact information for the treating clinician.

SURVEILLANCE AFTER TREATMENT — Surveillance strategies after treatment for localized prostate cancer are discussed separately. (See "Follow-up surveillance after definitive local treatment for prostate cancer".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diagnosis and management of prostate cancer".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Brachytherapy (The Basics)" and "Patient education: Choosing treatment for low-risk localized prostate cancer (The Basics)")

Beyond the Basics topic

SUMMARY AND RECOMMENDATIONS

Risk stratification and treatment selection

The initial evaluation of men with suspected prostate cancer should include clinical staging based on a digital rectal examination by an experienced clinician to assess the extent of disease, the pretreatment serum prostate-specific antigen (PSA), the Gleason score/grade group in the initial biopsy, and the number and extent of cancer involvement in the biopsy cores. This information allows the stratification of men into clinical risk categories according to the primary tumor, as defined by the National Comprehensive Cancer Network (NCCN) (table 1). (See 'Risk stratification and the selection of the initial treatment approach' above.)

Consistent with guidelines from the American Urological Association (AUA)/American Society for Radiation Oncology (ASTRO) and the American Society of Clinical Oncology (ASCO), we endorse shared decision making, which explicitly considers cancer severity (risk stratification), patient values and preferences, life expectancy, pretreatment general functional status and genitourinary symptoms, expected posttreatment functional status, and potential for salvage treatment.

In general, active surveillance is preferred for men with very low- or low-risk prostate cancer and a reasonable life expectancy, although definitive therapy with external beam radiation therapy (EBRT) alone, brachytherapy alone, or radical prostatectomy could be offered to select patients with low-risk disease who have a high probability of progression on active surveillance. For men with higher risk disease and a reasonable life expectancy, definitive treatment using EBRT, with or without brachytherapy, or radical prostatectomy is an appropriate option.

Brachytherapy for low-risk disease – For men with low-risk, clinically localized prostate cancer, low-dose rate (LDR) or high-dose rate (HDR) brachytherapy is an appropriate treatment option, based on the patient's assessment of complications and the potential impact on quality of life. (See "Initial approach to low- and very low-risk clinically localized prostate cancer", section on 'Outcomes and the choice of therapy'.)

Brachytherapy for intermediate-risk disease – HDR or LDR brachytherapy also provides an important option for dose escalation when used in conjunction with EBRT for men with intermediate-risk, localized disease. (See "Localized prostate cancer: Risk stratification and choice of initial treatment", section on 'Risk stratification' and "Initial management of regionally localized intermediate-, high-, and very high-risk prostate cancer and those with clinical lymph node involvement".)

Contraindications – A large prostate gland size (>50 to 60 g) and a high AUA/International Prostate Symptom Score (IPSS) symptom index (≥15 to 20 (table 5)) are relative contraindications to prostate brachytherapy, especially LDR brachytherapy. Although androgen deprivation therapy (ADT) may be useful to downsize the prostate prior to brachytherapy, neoadjuvant hormonal therapy has not been shown to reduce the risk of urinary morbidity for men with pretreatment obstructive uropathy. (See 'Contraindications' above.)

Treatment-related toxicity – The primary toxicities associated with brachytherapy include acute and late urinary complications, radiation proctitis, and sexual dysfunction. (See 'Complications' above.)

ACKNOWLEDGMENT — We are saddened by the death of Nicholas Vogelzang, MD, who passed away in September 2022. UpToDate gratefully acknowledges Dr. Vogelzang's role as Section Editor on this topic, and his dedicated and longstanding involvement with the UpToDate program.

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Topic 6923 Version 47.0

References

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