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## Complete Summary

#### GUIDELINE TITLE

Permanent source brachytherapy for prostate cancer.

#### BIBLIOGRAPHIC SOURCE(S)

Merrick G, Roach M III, Anscher MS, Beyer DC, Lawton CA, Lee WR,
Michalski JM, Pollack A, Vijayakumar S, Carroll PR, Higano CS, Mauch PM,
Expert Panel on Radiation Oncology-Prostate Work Group. Permanent source
brachytherapy for prostate cancer. \[online publication\]. Reston (VA):
American College of Radiology (ACR); 2006. 16 p. \[91 references\]

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previous version: Potters L, Perez CA, Beyer
DC, Blasko JC, Forman JD, Hussey DH, Lee WR, Paryani SB, Pollack A,
Roach M, Scardino P, Schellhammer P, Leibel S. Permanent source
brachytherapy for prostate cancer. American College of Radiology. ACR
Appropriateness Criteria. Radiology 2000 Jun;215(Suppl):1383-400.

The appropriateness criteria are reviewed annually and updated by the
panels as needed, depending on introduction of new and highly
significant scientific evidence.

### \*\* REGULATORY ALERT \*\*

#### FDA WARNING/REGULATORY ALERT

**Note from the National Guideline Clearinghouse**: This guideline
references a drug(s) for which important revised regulatory and/or
warning information has been released.

-   [October 18, 2007, PDE5 inhibitors, Viagra (sildenafil citrate),
    Levitra (vardenafil HCL), Cialis
    (tadalafil)](http://www.fda.gov/medwatch/safety/2007/safety07.htm#PDE5):
    The PRECAUTION and updated Adverse Reactions Sections of the
    approved product labeling for Viagra, Levitra, and Cialis were
    revised in response to reports of sudden decreases or loss of
    hearing.

### COMPLETE SUMMARY CONTENT

 \*\* REGULATORY ALERT \*\*\
 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 CONTRAINDICATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Prostate cancer

#### GUIDELINE CATEGORY

Treatment

#### CLINICAL SPECIALTY

Internal Medicine\
Oncology\
Radiation Oncology\
Radiology\
Surgery

#### INTENDED USERS

Health Plans\
Hospitals\
Managed Care Organizations\
Physicians\
Utilization Management

#### GUIDELINE OBJECTIVE(S)

To summarize biochemical and quality of life (QOL) outcomes following
permanent prostate brachytherapy, address areas of controversy, and
provide guidelines for clinical management

#### TARGET POPULATION

Patients with prostate cancer undergoing permanent source brachytherapy

#### INTERVENTIONS AND PRACTICES CONSIDERED

1.  Brachytherapy

    -   Iodine (I)-125 monotherapy

    -   Palladium (Pd)-103 monotherapy

    -   Iridium (Ir)-192 boost with external beam

    -   I-125 boost with external beam

    -   Pd-103 boost with external beam

2.  Alternative treatments

    -   External beam prostate/seminal vesicle (SV) only

    -   Observation only

    -   Radical prostatectomy

    -   External beam pelvis and prostate

    -   Androgen ablation only

    -   Temporary hormonal and external beam

    -   Transurethral resection only

    -   Permanent hormonal and external beam

3.  Androgen ablation plus brachytherapy

    -   Temporary

    -   Orchiectomy/permanent

#### MAJOR OUTCOMES CONSIDERED

-   Quality of life

-   Biochemical progression-free survival rates

-   Adverse effects of permanent source brachytherapy

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

The guideline developer performed literature searches of peer-reviewed
medical journals and the major applicable articles were identified and
collected.

#### NUMBER OF SOURCE DOCUMENTS

The total number of source documents identified as the result of the
literature search is not known.

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Not Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

Not stated

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review with Evidence Tables

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

One or two topic leaders within a panel assume the responsibility of
developing an evidence table for each clinical condition, based on
analysis of the current literature. These tables serve as a basis for
developing a narrative specific to each clinical condition.

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus (Delphi)

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

Since data available from existing scientific studies are usually
insufficient for meta-analysis, broad-based consensus techniques are
needed for reaching agreement in the formulation of the appropriateness
criteria. The American College of Radiology (ACR) Appropriateness
Criteria panels use a modified Delphi technique to arrive at consensus.
Serial surveys are conducted by distributing questionnaires to
consolidate expert opinions within each panel. These questionnaires are
distributed to the participants along with the evidence table and
narrative as developed by the topic leader(s). Questionnaires are
completed by participants in their own professional setting without
influence of the other members. Voting is conducted using a scoring
system from 1-9, indicating the least to the most appropriate imaging
examination or therapeutic procedure. The survey results are collected,
tabulated in anonymous fashion, and redistributed after each round. A
maximum of three rounds is conducted and opinions are unified to the
highest degree possible. Eighty percent agreement is considered a
consensus. This modified Delphi technique enables individual, unbiased
expression, is economical, easy to understand, and relatively simple to
conduct.

If consensus cannot be reached by the Delphi technique, the panel is
convened and group consensus techniques are utilized. The strengths and
weaknesses of each test or procedure are discussed and consensus reached
whenever possible. If \"No consensus\" appears in the rating column,
reasons for this decision are added to the comment sections.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

Not applicable

#### COST ANALYSIS

A formal cost analysis was not performed and published cost analyses
were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

Criteria developed by the Expert Panels are reviewed by the American
College of Radiology (ACR) Committee on Appropriateness Criteria.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

**ACR Appropriateness Criteria®**

**Clinical Condition: Permanent Source Brachytherapy for Prostate
Cancer**

**Variant 1: 75-year-old, healthy, IPSS 4, 35 cm^3^ gland by TRUS. PSA
6.5. DRE negative. Biopsy, grade 3+2=5 adenocarcinoma in 2/6 cores.
Negative work-up.**

  --------------------------------------------------------------------------------
  **Treatment**              **Appropriateness   **Comments**
                             Rating**            
  -------------------------- ------------------- ---------------------------------
  **Brachytherapy**                              

  I-125 monotherapy          8                    

  Pd-103 monotherapy         8                    

  Ir-192 boost with external 3                    
  beam                                           

  I-125 boost with external  2                    
  beam                                           

  Pd-103 boost with external 2                    
  beam                                           

  **Alternative Treatments**                     

  External beam              8                    
  prostate/seminal vesicle                       
  (SV) only                                      

  Observation only           8                    

  Radical prostatectomy      4                   Patient health and comorbidities
                                                 must be taken into account.

  External beam pelvis and   2                    
  prostate                                       

  Androgen ablation only     2                    

  Temporary hormonal and     2                    
  external beam                                  

  Transurethral resection    1                    
  only                                           

  Permanent hormonal and     1                    
  external beam                                  

  **Androgen                                     
  Ablation+Brachytherapy**                       

  Temporary (\<6 months)     2                    

  Temporary (\>6 months)     1                    

  Orchiectomy/permanent      1                    

  ***Appropriateness                             
  Criteria Scale*\                               
  1 2 3 4 5 6 7 8 9\                             
  1 = Least appropriate 9 =                      
  Most appropriate**                             
  --------------------------------------------------------------------------------

Note: Abbreviations used in the tables are listed at the end of the
\"Major Recommendations\" field.

**Variant 2: 65-year-old diabetic, IPSS 10, 50 cm^3^gland by TRUS. PSA
9.5. DRE, 1 cm mid-lobe nodule (T2a). Biopsy, grade 3+3=6 in 2/6 cores.
Negative work-up.**

  --------------------------------------------------------------------------------
  **Treatment**              **Appropriateness   **Comments**
                             Rating**            
  -------------------------- ------------------- ---------------------------------
  **Brachytherapy**                              

  I-125 monotherapy          8                    

  Pd-103 monotherapy         8                    

  Ir-192 boost with external 3                    
  beam                                           

  I-125 boost with external  2                    
  beam                                           

  Pd-103 boost with external 2                    
  beam                                           

  **Alternative Treatments**                     

  External beam prostate/SV  8                    
  only                                           

  Radical prostatectomy      8                    

  Observation only           4                    

  External beam pelvis and   3                    
  prostate                                       

  Androgen ablation only     2                    

  Temporary hormonal and     2                    
  external beam                                  

  Transurethral resection    1                    
  only                                           

  Permanent hormonal and     1                    
  external beam                                  

  **Androgen                                     
  Ablation+Brachytherapy**                       

  Temporary (\<6 months)     7                   To reduce the gland size

  Temporary (\>6 months)     2                    

  Orchiectomy/permanent      1                    

  ***Appropriateness                             
  Criteria Scale*\                               
  1 2 3 4 5 6 7 8 9\                             
  1 = Least appropriate 9 =                      
  Most appropriate**                             
  --------------------------------------------------------------------------------

Note: Abbreviations used in the tables are listed at the end of the
\"Major Recommendations\" field.

**Variant 3: 60-year-old mildly hypertensive, IPSS 3, 40 cm^3^ gland by
TRUS. PSA 11.0. DRE, .5 cm right base nodule (T2b). Biopsy, grade 3+4=7
in 3/6 cores. Negative work-up.**

  --------------------------------------------------------------------------------
  **Treatment**              **Appropriateness   **Comments**
                             Rating**            
  -------------------------- ------------------- ---------------------------------
  **Brachytherapy**                              

  I-125 monotherapy          7                   Randomized control trials
                                                 ongoing---addressing these
                                                 modalities.

  Pd-103 monotherapy         7                   Randomized control trials
                                                 ongoing---addressing these
                                                 modalities.

  I-125 boost with external  7                   Randomized control trials
  beam                                           ongoing---addressing these
                                                 modalities.

  Pd-103 boost with external 7                   Randomized control trials
  beam                                           ongoing---addressing these
                                                 modalities.

  Ir-192 boost with external 7                   Randomized control trials
  beam                                           ongoing---addressing these
                                                 modalities.

  **Alternative Treatments**                     

  Temporary hormonal and     8                    
  external beam                                  

  External beam prostate/SV  7                    
  only                                           

  Radical prostatectomy      7                    

  External beam pelvis and   7                    
  prostate                                       

  Observation only           2                    

  Androgen ablation only     2                    

  Transurethral resection    1                    
  only                                           

  Permanent hormonal and     1                    
  external beam                                  

  **Androgen                                     
  Ablation+Brachytherapy**                       

  Temporary (\<6 months)     5                   Clinical trials ongoing.

  Temporary (\>6 months)     5                   Clinical trials ongoing.

  Orchiectomy/permanent      1                    

  ***Appropriateness                             
  Criteria Scale*\                               
  1 2 3 4 5 6 7 8 9\                             
  1 = Least appropriate 9 =                      
  Most appropriate**                             
  --------------------------------------------------------------------------------

Note: Abbreviations used in the tables are listed at the end of the
\"Major Recommendations\" field.

**Variant 4: 52-year-old, healthy, IPSS 0, 25 cm^3^ gland. Screening PSA
7.8. DRE negative. Biopsy, grade 3+3=6 in 1/6 cores. Negative work-up.
Concerned about sexual potency.**

  --------------------------------------------------------------------------------
  **Treatment**              **Appropriateness   **Comments**
                             Rating**            
  -------------------------- ------------------- ---------------------------------
  **Brachytherapy**                              

  I-125 monotherapy          8                    

  Pd-103 monotherapy         8                    

  Ir-192 boost with external 3                    
  beam                                           

  I-125 boost with external  2                    
  beam                                           

  Pd-103 boost with external 2                    
  beam                                           

  **Alternative Treatments**                     

  External beam prostate/SV  8                    
  only                                           

  Radical prostatectomy      8                    

  Observation only           2                    

  External beam pelvis and   2                    
  prostate                                       

  Temporary hormonal and     2                    
  external beam                                  

  Androgen ablation only     1                    

  Transurethral resection    1                    
  only                                           

  Permanent hormonal and     1                    
  external beam                                  

  **Androgen                                     
  Ablation+Brachytherapy**                       

  Temporary (\<6 months)     2                    

  Temporary (\>6 months)     1                    

  Orchiectomy/permanent      1                    

  ***Appropriateness                             
  Criteria Scale*\                               
  1 2 3 4 5 6 7 8 9\                             
  1 = Least appropriate 9 =                      
  Most appropriate**                             
  --------------------------------------------------------------------------------

Note: Abbreviations used in the tables are listed at the end of the
\"Major Recommendations\" field.

**Variant 5: 61-year-old, healthy, IPSS 4, 30 cm^3^ gland by TRUS. PSA
10.0. DRE, 1 cm apical nodule (T2a). Sextant biopsy reveals grade 3+3=6
in 2 apical cores. Negative work-up.**

  --------------------------------------------------------------------------------
  **Treatment**              **Appropriateness   **Comments**
                             Rating**            
  -------------------------- ------------------- ---------------------------------
  **Brachytherapy**                              

  I-125 monotherapy          8                    

  Pd-103 monotherapy         8                    

  I-125 boost with external  5                   Clinical trials ongoing.
  beam                                           

  Pd-103 boost with external 5                   Clinical trials ongoing.
  beam                                           

  Ir-192 boost with external 5                   Clinical trials ongoing.
  beam                                           

  **Alternative Treatments**                     

  External beam prostate/SV  8                    
  only                                           

  Radical prostatectomy      8                    

  Observation only           3                    

  External beam pelvis and   3                    
  prostate                                       

  Temporary hormonal and     3                    
  external beam                                  

  Androgen ablation only     2                    

  Permanent hormonal and     2                    
  external beam                                  

  Transurethral resection    1                    
  only                                           

  **Androgen                                     
  Ablation+Brachytherapy**                       

  Temporary (\<6 months)     2                    

  Temporary (\>6 months)     2                    

  Orchiectomy/permanent      1                    

  ***Appropriateness                             
  Criteria Scale*\                               
  1 2 3 4 5 6 7 8 9\                             
  1 = Least appropriate 9 =                      
  Most appropriate**                             
  --------------------------------------------------------------------------------

Note: Abbreviations used in the tables are listed at the end of the
\"Major Recommendations\" field.

**Variant 6: 60-year-old, healthy, IPSS 3, 35 cm^3^ gland by TRUS. PSA
13.5. DRE, 2.0 cm right base nodule (T2b). Biopsy, grade 4+4=8 in 3/6
cores. Negative work-up.**

  --------------------------------------------------------------------------------
  **Treatment**              **Appropriateness   **Comments**
                             Rating**            
  -------------------------- ------------------- ---------------------------------
  **Brachytherapy**                              

  I-125 boost with external  7                    
  beam                                           

  Pd-103 boost with external 7                    
  beam                                           

  Ir-192 boost with external 7                    
  beam                                           

  I-125 monotherapy          2                    

  Pd-103 monotherapy         2                    

  **Alternative Treatments**                     

  Temporary hormonal and     8                    
  external beam                                  

  Radical prostatectomy      7                   With adjuvant radiation or
                                                 hormone therapy as indicated.

  External beam pelvis and   7                   With adjuvant hormone therapy.
  prostate                                       

  Permanent hormonal and     5                   Hormone therapy for
  external beam                                  [\<]{.underline}3 years.

  External beam prostate/SV  2                    
  only                                           

  Androgen ablation only     2                    

  Observation only           1                    

  Transurethral resection    1                    
  only                                           

  **Androgen                                     
  Ablation+Brachytherapy**                       

  Temporary (\<6 months)     5                    

  Temporary (\>6 months)     5                    

  Orchiectomy/permanent      2                    

  ***Appropriateness                             
  Criteria Scale*\                               
  1 2 3 4 5 6 7 8 9\                             
  1 = Least appropriate 9 =                      
  Most appropriate**                             
  --------------------------------------------------------------------------------

Note: Abbreviations used in the tables are listed at the end of the
\"Major Recommendations\" field.

**Variant 7: 68-year-old, hypertensive, IPSS 18, post void residual
(PVR) 20 cc, 92 cm^3^ gland by TRUS, PSA 12.0. DRE, vague induration
entire right lobe. Sextant biopsy reveals grade 3+4=7 in 2 cores on the
right. Negative work-up.**

  --------------------------------------------------------------------------------
  **Treatment**              **Appropriateness   **Comments**
                             Rating**            
  -------------------------- ------------------- ---------------------------------
  **Brachytherapy**                              

  Ir-192 boost with external 5                   Reevaluate after neoadjuvant ADT.
  beam                                           

  I-125 monotherapy          4                   Reevaluate after neoadjuvant ADT.

  Pd-103 monotherapy         4                   Reevaluate after neoadjuvant ADT.

  I-125 boost with external  4                   Reevaluate after neoadjuvant ADT.
  beam                                           

  Pd-103 boost with external 4                   Reevaluate after neoadjuvant ADT.
  beam                                           

  **Alternative Treatments**                     

  Radical prostatectomy      8                    

  Temporary hormonal and     8                    
  external beam                                  

  External beam prostate/SV  7                    
  only                                           

  External beam pelvis and   7                    
  prostate                                       

  Observation only           2                    

  Androgen ablation only     2                    

  Transurethral resection    2                    
  only                                           

  Permanent hormonal and     2                    
  external beam                                  

  **Androgen                                     
  Ablation+Brachytherapy**                       

  Temporary (\<6 months)     7                    

  Temporary (\>6 months)     4                    

  Orchiectomy/permanent      1                    

  ***Appropriateness                             
  Criteria Scale*\                               
  1 2 3 4 5 6 7 8 9\                             
  1 = Least appropriate 9 =                      
  Most appropriate**                             
  --------------------------------------------------------------------------------

Note: Abbreviations used in the tables are listed at the end of the
\"Major Recommendations\" field.

**Variant 8: 70-year-old, excellent health, IPSS 18, PVR 125 cc, 80
cm^3^ gland by TRUS. PSA 9.8. DRE, 1 cm left mid lobe nodule (T2a).
Biopsy reveals grade 3+3=6 in 1/6 cores. Negative work-up.**

  --------------------------------------------------------------------------------
  **Treatment**              **Appropriateness   **Comments**
                             Rating**            
  -------------------------- ------------------- ---------------------------------
  **Brachytherapy**                              

  Ir-192 boost with external 3                    
  beam                                           

  I-125 monotherapy          2                    

  Pd-103 monotherapy         2                    

  I-125 boost with external  2                    
  beam                                           

  Pd-103 boost with external 2                    
  beam                                           

  **Alternative Treatments**                     

  External beam prostate/SV  8                    
  only                                           

  Radical prostatectomy      7                    

  Temporary hormonal and     7                    
  external beam                                  

  Observation only           5                   Active surveillance.

  External beam pelvis and   3                    
  prostate                                       

  Androgen ablation only     2                    

  Transurethral resection    2                    
  only                                           

  Permanent hormonal and     2                    
  external beam                                  

  **Androgen                                     
  Ablation+Brachytherapy**                       

  Temporary (\<6 months)     3                    

  Temporary (\>6 months)     2                    

  Orchiectomy/permanent      1                    

  ***Appropriateness                             
  Criteria Scale*\                               
  1 2 3 4 5 6 7 8 9\                             
  1 = Least appropriate 9 =                      
  Most appropriate**                             
  --------------------------------------------------------------------------------

Note: Abbreviations used in the tables are listed at the end of the
\"Major Recommendations\" field.

Permanent prostate brachytherapy has emerged as a highly efficacious
treatment for clinically localized prostate cancer with biochemical
outcomes and morbidity profiles that compare favorably with those of
competing local modalities. The resurgence of interest in prostate
brachytherapy is principally due to the evolution of transrectal
ultrasonography, the development of a closed transperineal approach, and
sophisticated treatment planning software. These imaging and planning
advances dramatically improved the accuracy of seed placement. In
addition, computerized tomography (CT) based postoperative dosimetry
provided the ability to evaluate implant quality and proactively
influence outcome. As brachytherapy outcomes have matured, it has become
increasingly apparent that efficacy and morbidity are dependent on
implant quality. This review summarizes biochemical and quality of life
(QOL) outcomes following permanent prostate brachytherapy, addresses
areas of controversy, and provides guidelines for clinical management.

**Patient Selection**

With the assimilation of brachytherapy into the conventional
uro-oncology armentarium, a rapidly expanding body of literature
regarding patient selection and treatment approach has been published.
Although not all patients are acceptable candidates for brachytherapy, a
reliable set of pretreatment criteria for predicting implant-related
morbidity has not been formulated. While most alleged contraindications
to brachytherapy have been propagated with little supporting data, an
increasing number of evidence-based factors contributing to
brachytherapy-related morbidity have accumulated.

Despite the fact that no clear relationship exists between prostate size
and increased urinary morbidity, large prostate size remains a relative
contraindication to brachytherapy due to technical concerns or the
perception that patients with large prostate glands are at higher risk
for acute and prolonged urinary morbidity. Patients with a prostate
volume \>50 cm^3^ are often counseled not to proceed with brachytherapy
or to first receive neoadjuvant ADT for cytoreduction. But contrary to
popular opinion, patients with large prostate glands can be implanted
with acceptable morbidity. In a study using the patient-administered
Expanded Prostate Cancer Index Composite (EPIC), long-term urinary
function did not correlate with prostate size. On the other extreme,
favorable dosimetry with minimal urinary morbidity has been reported for
patients with prostate glands \<20 cm^3^. In contrast to overall
prostate size, transition zone volume has consistently correlated with
brachytherapy-related urinary morbidity.

Currently, no reliable preimplant criteria can be used to predict
prolonged urinary retention. The role of the IPSS in predicting urinary
morbidity (including urinary retention) has been studied extensively
with conflicting conclusions. Although almost all patients experience
urinary irritation or obstructive symptomatology with 2%-34% developing
acute urinary retention, only 2% -5% require a urinary catheter for more
than one week. The preimplant IPSS does correlate with the duration of
post-implant obstructive symptomatology, but it is not a predictor for
long-term urinary QOL. The prophylactic and prolonged use of alpha
blockers results in a return of IPSS to baseline significantly faster
than in patients not receiving alpha blockers or receiving them after
substantial exacerbation of urinary symptoms.

Pubic arch interference (the obstruction of anterior needle placement
insertion by a narrow pubic arch) remains a relative contraindication to
brachytherapy despite limited clinical information supporting such
concerns.

Through the mid-1990s, urinary incontinence developed in approximately
50% of patients with a history of a preimplant transurethral resection
of the prostate gland (TURP). In more contemporary series, however the
risk of incontinence has been reported to be 6% or less due to the
adoption of peripheral source loading and limitation of the radiation
dose to the TURP defect to approximately 110% of the prescription dose.
Using the EPIC instrument, patients with a preimplant TURP were found to
have urinary QOL approaching that of non-TURP brachytherapy patients.

After brachytherapy, approximately 2% of patients develop prolonged
urinary retention, with the vast majority eventually spontaneously
urinating without surgical intervention. Since significant urinary
morbidity has been demonstrated in approximately 50% of patients
undergoing a post-implant transurethral resection of the prostate gland
(TURP), post-implant surgical intervention should be delayed for as long
as possible. To minimize postbrachytherapy TURP-related incontinence,
preservation of the bladder neck at the 5 and 7 o\'clock positions with
minimal cautery has been recommended to maintain sufficient prostatic
urethral blood supply.

Median lobe hyperplasia (the protrusion of hypertrophied prostate tissue
into the bladder) has been reported to be a relative contraindication to
brachytherapy because of concerns for an increased risk of post-implant
urinary morbidity and technical difficulties encountered while
implanting intravesical tissue. In a small contemporary series, 25% of
patients with median lobe hyperplasia developed prolonged post-implant
urinary retention. It is conceivable that preimplant resection of the
intravesical component could reduce the incidence of
brachytherapy-related morbidity.

In addition, other often-quoted contraindications to brachytherapy
including prostatitis, patient age, obesity, diabetes mellitus, and
inflammatory bowel disease have been propagated without clinical or
dosimetric support.

**Brachytherapy Planning**

Favorable brachytherapy results have been obtained with various planning
and intraoperative techniques. It is universally accepted that an
adequate implant should encompass the prostate, but there is no
consensus on what represents the optimal target volume. In addition,
urethral and rectal tolerances are still being defined, while the
significance and degree of dose homogeneity throughout the implant
region remains unclear.

Brachytherapy planning entails preplanning (in which a transrectal
ultrasound volumetric study of the prostate gland is obtained before the
day of implantation) or intraoperative planning. All plans should be
evaluated based on dose volume histograms of the planning target volume,
urethra, and rectum. Generally accepted dosimetric parameters include
V~100/150/200~ (volume of the target area receiving 100%, 150%, and 200%
of the planned dose), D~90~ (dose delivered to 90% of the target
volume), urethral V~125/150~ (the volume of the urethra receiving 125%
and 150% of the prescribed dose), the average urethral dose, and the
R~100~ (volume of the rectum receiving 100% of the prescribed dose).
Plans should attempt to minimize the number of needles and seeds,
provide high-dose coverage to the target, and minimize high dose
volumes.

**Post-Implant Evaluation**

The advent of CT-based postoperative dosimetry provided a unique
opportunity to evaluate quality and proactively predict outcome and
complications. Postoperative CT-based dosimetric analysis provides
detailed information regarding the coverage and uniformity of an
implant, affords the ability to compare various intraoperative
techniques, and provides a sound basis for future improvement. Although
CT determination of prostate volume is widely accepted for external beam
planning, the use of CT for brachytherapy purposes remains
controversial. The accurate delineation of prostate contours on
post-implant CT scans may be difficult because of postoperative edema,
degradation of the image due to implanted metallic seeds, and a tendency
to overestimate prostate volume from CT compared to transrectal
ultrasound. However, if the levator ani muscles are not included in the
CT-determined prostate volume, a close correlation has been demonstrated
for CT and ultrasound-determined prostate volumes. In addition, if
implants are designed and executed with generous periprostatic treatment
margins, the determination of post-implant prostate volume by CT does
not significantly influence dosimetric outcome.

The timing of post-implant CT remains controversial. Some groups
recommend a day 30 CT scan to allow for the resolution of edema, while
others propose day zero dosimetry to provide information about edema at
its maximum extent and for prompt closure of the learning loop. For
intraoperative dosimetric evaluation, knowledge of day 0 threshold
dosimetric parameters is essential to evaluate the advisability of
corrective seed placement.

In 1998, a dose response curve was reported for patients undergoing
monotherapeutic I-125 brachytherapy with superior biochemical results in
patients with a day 30 D~90~ [\>]{.underline} 140 Gy. Subsequently, day
30 D~90~ cut points of 140 Gy and 100 Gy for I-125 and Pd-103,
respectively, were reported. Urethral and rectal dosimetry is predictive
of long-term QOL outcomes and complication rates and should be
determined for each patient. No significant differences in dosimetric
quality have been reported when stratified by isotope.

**Biochemical Outcomes**

In contemporary series, brachytherapy as a monotherapeutic approach for
patients with low-risk features (defined by the American Joint
Commission on Cancer \[AJCC\] in 2002 as PSA [\<]{.underline}10 ng/mL,
Gleason score [\<]{.underline} 6, and clinical stage
[\<]{.underline}T2b) has resulted in high rates of biochemical control
without further improvement following the addition of supplemental
radiation therapy. Biochemical progression-free survival rates of
87%-98% have been reported.

For patients with intermediate-risk disease as defined by the AJCC (PSA
[\>]{.underline}10 ng/mL or Gleason score [\>]{.underline}7 or clinical
stage [\>]{.underline}T2c), one study reported a 9-year freedom from
biochemical progression rate of 82% with a plateau on the curve for a
Pd-103 monotherapeutic approach. Supplemental radiation therapy (RT) did
not improve the 5-year biochemical outcome for intermediate-risk
patients (84% vs 85%). Another study reported an 8-year biochemical
progression-free survival rate of 95% for hormone-naïve monotherapeutic
intermediate-risk patients with a median post-treatment PSA \<0.1 ng/mL.
In addition, a large, recently published series with 12-year results
failed to demonstrate superior biochemical control rates in patients
receiving supplemental RT. When these data are taken together, no
biochemical advantage has been reported for the addition of supplemental
RT in hormone-naïve intermediate risk brachytherapy patients.
Brachytherapy is relatively resilient to extraprostatic cancer extension
because of its ability to aggressively irradiate the periprostatic
region.

For high-risk patients as defined by the AJCC (2 or 3 of the following
risk factors: PSA [\>]{.underline}10 ng/mL, Gleason score
[\>]{.underline}7, and/or clinical stage [\>]{.underline}T2c), one study
reported a 79% 10-year biochemical progression-free survival (PSA
[\<]{.underline}0.2 ng/mL) for patients receiving supplemental RT
followed by a Pd-103 boost with a plateau on the biochemical
freedom-from-failure curves within 3 years of implantation. For
hormone-naïve high-risk patients undergoing brachytherapy and
supplemental RT, another study reported an approximate 80% 8-year
freedom from biochemical failure rate with a median post-treatment PSA
\<0.1 ng/mL.

Two studies have reported favorable results for high-risk patients
undergoing monotherapeutic brachytherapy. The first reported a 65%
9-year freedom from biochemical progression rate for Pd-103 monotherapy
patients with a pretreatment PSA \>20 ng/mL. The other study stratified
hormone-naïve high-risk patients undergoing brachytherapy without
supplemental RT into day 30 low-dose (D~90~ \<140 Gy for I-125 and \<100
Gy for Pd-103) versus high-dose implants with an 80% 5-year freedom from
biochemical failure in the high dose arm.

Almost all studies of intermediate- and high-risk patients receiving
combined brachytherapy and supplemental RT have reported favorable
biochemical outcomes. However, biochemical progression-free survival in
intermediate- and high-risk patients undergoing monotherapeutic
brachytherapy remains controversial. Three monotherapeutic studies have
reported suboptimal results. None of these studies implanted patients
with generous periprostatic treatment margins or presented post-implant
dosimetric outcomes. Because patients with higher risk features have at
least a 50% chance of extraprostatic cancer extension and the dose
gradient at the periphery of the target volume is as great as 20 Gy/mm,
these patients may not have received adequate doses to sterilize
intraprostatic or extracapsular disease. It is likely that cancer
eradication in intermediate- and high-risk patients treated with a
monotherapeutic approach requires patients with a minimal risk of pelvic
lymph node involvement, limited seminal vesicle extension, and
post-implant dosimetric confirmation of radiation dose to the
intraprostatic and extracapsular regions.

**Adjuvant Androgen Deprivation Therapy**

Despite recent reports detailing favorable biochemical outcomes for
hormone-naïve brachytherapy patients with higher risk features,
intermediate- and high-risk brachytherapy patients often receive ADT as
an extrapolation from the conventional external beam radiation therapy
dose (65-70 Gy) literature. In a matched-pair analysis, no biochemical
benefits for ADT combined with brachytherapy were discerned for any risk
group, Gleason score, pretreatment PSA level, or clinical stage. In
addition, ADT has been implicated in brachytherapy-related morbidity.

Other than its proven role as a cytoreductive therapy, no defined role
for ADT has been demonstrated in brachytherapy patients. Following high
quality brachytherapy, one study reported that ADT did not alter
biochemical outcome for high-risk patients. In contrast, another study
reported a statistically significant improvement in 8-year biochemical
progression-free survival for high-risk (but not low- or
intermediate-risk) patients with the addition of ADT. Although the
results of these two studies appear contradictory, patients in the first
study were treated without supplemental RT while patients in the second
series received pelvic nodal external beam RT. It is possible that the
beneficial effects of ADT are maximized when combined with pelvic nodal
irradiation.

**Supplemental External Beam Radiation Therapy**

The rationale for supplemental external beam RT in conjunction with
permanent prostate brachytherapy includes the enhancement of radiation
dose to the periprostatic region, intraprostatic dose escalation, dose
modification of a technically inadequate implant, and/or irradiation of
the entirety of the seminal vesicles and/or pelvic lymph nodes.
Initially there was agreement that patients with a Gleason score
[\>]{.underline}7, a pretreatment PSA \>10 ng/mL, and/or
[\>]{.underline}T2c prostate cancer should receive supplemental RT.
However, the utility of supplemental RT has been questioned by favorable
results with an implant alone in patients with higher PSA and/or Gleason
scores. Detailed pathology studies indicate that the radial extent of
extraprostatic cancer extension is almost always [\<]{.underline} 5 mm,
which is within the confines of a monotherapeutic brachytherapy dose
distribution. If the prostate gland is implanted with generous
periprostatic treatment margins, supplemental RT is unlikely to improve
the biochemical outcome in low-, intermediate-, and selected high-risk
cases. A prospective randomized trial evaluating 20 Gy of supplemental
RT versus 44 Gy in Pd-103 patients with higher risk features
demonstrated no difference in biochemical control.

**PSA Spikes**

Following brachytherapy, PSA spikes are noted in up to a third of all
hormone-naïve patients. This phenomenon typically occurs 12-30 months
following implantation and most importantly does not adversely impact
long-term biochemical outcome. PSA spikes are least common in patients
with a post-treatment PSA [\<]{.underline} 0.2 ng/mL.

Post-treatment prostate biopsies to differentiate viable cancer from a
benign PSA spike can be misleading. A recent publication reported that
despite an increasing PSA and a biopsy positive for recurrent cancer,
patients may experience subsequent normalization of serum PSA without
additional therapeutic intervention.

**Morbidity**

*Urinary Morbidity*

An enlarging body of data demonstrates that brachytherapy-related
urinary morbidity can be lessened with refinements in patient selection,
medical intervention, and intraoperative technique. Following
brachytherapy, almost all patients develop urinary irritation or
obstructive symptomatology, with acute urinary retention in up to 34% of
patients. To ameliorate brachytherapy-related urinary symptoms, alpha
blockers are widely used, and the timing of their initiation may
substantially influence their effect. The initiation of alpha blockers
2-3 weeks prior to implantation with continuation at least until
normalization of the IPSS maximizes the alpha blocker beneficial effect.
Dysuria is common following brachytherapy. Although dysuria is a
relatively common event during the first few years following
brachytherapy, only rarely is it severe in frequency or intensity.

Following brachytherapy, the incidence of urethral strictures ranges
from 1%-12%. Strictures typically involve the bulbomembranous urethra
and are usually easily managed by dilatation. Brachytherapy and
supplemental RT doses to the bulbomembranous urethra represent the
primary risk factors for the development of brachytherapy-related
stricture disease.

Supplemental RT can result in a deleterious effect on long-term urinary
function, including hematuria and incontinence (determined by EPIC).

*Rectal Morbidity*

Rectal complications consist primarily of mild, self-limited proctitis
and have been correlated with rectal dose. The onset of bleeding peaks
at 8 months with an incidence of 4%-12% and usually resolves
spontaneously. Rectal ulceration and fistula formation occasionally have
been reported.

Bowel function assessments by patient-administered questionnaires
illustrate that long-term dysfunction following brachytherapy is
relatively uncommon. Only 12% of patients report bowel function to be
worse after implantation, with the number of preimplant bowel movements,
history of tobacco consumption, median rectal dose, and the use of
supplemental RT predictive for deterioration in bowel habits.

Intraoperatively, careful attention to implant technique and ultrasound
anatomy will reduce the dose to the anterior rectal wall and minimize
bowel dysfunction. Extensive use of both transverse and sagittal
ultrasonography to confirm appropriate needle placement and the use of
multiple ultrasound frequencies helps ensure proper seed placement.

*Erectile Dysfunction*

Although it has been widely asserted that preservation of erectile
function (ED) is more likely after brachytherapy, the incidence of
brachytherapy-induced ED is substantially greater than initially
reported, with rates ranging from 6%-90%. The wide range likely reflects
differences in follow-up, patient selection, implant technique, and mode
of data collection. In general, series with the longest follow-up and
the use of patient-administered questionnaires report lower rates of
potency preservation. Fortunately, most patients with
brachytherapy-induced ED respond to erectogenic agents such as
sildenafil citrate.

Although the etiology of brachytherapy-induced ED is likely
multifactorial, the available data strongly support the proximal penis
as an important site-specific structure. Suboptimal seed placement
(either due to poor planning and/or poor implementation) of periapical
radiation sources results in excessive radiation doses to the bulb of
the penis. As such, refinements in implant technique should result in
lower radiation doses to the proximal penis with increased rates of
potency preservation. To date, no relationship has been established
between brachytherapy-related ED and the dose to the neurovascular
bundles.

From a clinical perspective, potency preservation following
brachytherapy is most closely related to preimplant erectile function.
The presence of preimplant nocturnal erections also predicts for
post-treatment erectile function. Initially, the addition of
supplemental RT was reported to result in a deleterious effect on
erectile function. However, the results of a prospective randomized
trial that limited radiation dose to the proximal penis from both the
supplemental RT and brachytherapy components reported no adverse effect
of RT on potency preservation. The role of neoadjuvant ADT in potency
preservation has also been mixed.

**Conclusions**

The majority of brachytherapy series have demonstrated favorable
morbidity profiles and durable biochemical control rates for patients
with low, intermediate, and high risk features. As brachytherapy
follow-ups have matured, it has become increasingly apparent that
efficacy and morbidity are highly dependent on implant quality.
Continued attempts to refine patient selection, brachytherapy treatment
planning philosophy, intraoperative technique, and post-implant
management should result in further improvements in biochemical outcome
and decreased brachytherapy-related morbidity.

**Abbreviations**

-   ADT, androgen deprivation therapy

-   DRE, digital rectal examination

-   I, iodine

-   IPSS, International Prostate Symptom Score

-   Ir, iridium

-   Pd, palladium

-   PSA, prostate-specific antigen

-   SV, seminal vesicle

-   TRUS, transrectal ultrasound

#### CLINICAL ALGORITHM(S)

Algorithms were not developed from criteria guidelines.

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The recommendations are based on analysis of the current literature and
expert panel consensus.

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

Selection of appropriate radiologic procedures for patients undergoing
permanent source brachytherapy in the management of prostate cancer

#### POTENTIAL HARMS

See the \"Major Recommendations\" field for a complete list of harms
associated with urinary morbidity, rectal morbidity, and erectile
dysfunction.

### CONTRAINDICATIONS

#### CONTRAINDICATIONS

-   Despite the fact that no clear relationship exists between prostate
    size and increased urinary morbidity, large prostate size remains a
    relative contraindication to brachytherapy due to technical concerns
    or the perception that patients with large prostate glands are at
    higher risk for acute and prolonged urinary morbidity.

-   Pubic arch interference (the obstruction of anterior needle
    placement insertion by a narrow pubic arch) remains a relative
    contraindication to brachytherapy despite limited clinical
    information supporting such concerns.

-   Median lobe hyperplasia (the protrusion of hypertrophied prostate
    tissue into the bladder) has been reported to be a relative
    contraindication to brachytherapy because of concerns for an
    increased risk of post-implant urinary morbidity and technical
    difficulties encountered while implanting intravesical tissue.

-   Other often-quoted contraindications to brachytherapy including
    prostatitis, patient age, obesity, diabetes mellitus, and
    inflammatory bowel disease have been propagated without clinical or
    dosimetric support.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

An American College of Radiology (ACR) Committee on Appropriateness
Criteria and its expert panels have developed criteria for determining
appropriate imaging examinations for diagnosis and treatment of
specified medical condition(s). These criteria are intended to guide
radiologists, radiation oncologists, and referring physicians in making
decisions regarding radiologic imaging and treatment. Generally, the
complexity and severity of a patient\'s clinical condition should
dictate the selection of appropriate imaging procedures or treatments.
Only those exams generally used for evaluation of the patient\'s
condition are ranked. Other imaging studies necessary to evaluate other
co-existent diseases or other medical consequences of this condition are
not considered in this document. The availability of equipment or
personnel may influence the selection of appropriate imaging procedures
or treatments. Imaging techniques classified as investigational by the
U.S. Food and Drug Administration (FDA) have not been considered in
developing these criteria; however, study of new equipment and
applications should be encouraged. The ultimate decision regarding the
appropriateness of any specific radiologic examination or treatment must
be made by the referring physician and radiologist in light of all the
circumstances presented in an individual examination.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

#### IMPLEMENTATION TOOLS

Personal Digital Assistant (PDA) Downloads

For information about
[availability](#identifying-information-and-availability), see the
\"Availability of Companion Documents\" and \"Patient Resources\" fields
below.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Getting Better\
Living with Illness

#### IOM DOMAIN

Effectiveness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Merrick G, Roach M III, Anscher MS, Beyer DC, Lawton CA, Lee WR,
Michalski JM, Pollack A, Vijayakumar S, Carroll PR, Higano CS, Mauch PM,
Expert Panel on Radiation Oncology-Prostate Work Group. Permanent source
brachytherapy for prostate cancer. \[online publication\]. Reston (VA):
American College of Radiology (ACR); 2006. 16 p. \[91 references\]

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

1996 (revised 2006)

#### GUIDELINE DEVELOPER(S)

American College of Radiology - Medical Specialty Society

#### SOURCE(S) OF FUNDING

The American College of Radiology (ACR) provided the funding and the
resources for these ACR Appropriateness Criteria®.

#### GUIDELINE COMMITTEE

Committee on Appropriateness Criteria, Expert Panel on Radiation
Oncology--Prostate Work Group

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Panel Members*: Gregory Merrick, MD; Mack Roach III, MD; Mitchell S.
Anscher, MD; David C. Beyer, MD; Colleen A. Lawton, MD; W. Robert Lee,
MD; Jeff M. Michalski, MD, MBA; Alan Pollack, MD, PhD; Srinivasan
Vijayakumar, MD; Peter R. Carroll, MD; Celestia S. Higano, MD; Peter M.
Mauch, MD

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Not stated

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previous version: Potters L, Perez CA, Beyer
DC, Blasko JC, Forman JD, Hussey DH, Lee WR, Paryani SB, Pollack A,
Roach M, Scardino P, Schellhammer P, Leibel S. Permanent source
brachytherapy for prostate cancer. American College of Radiology. ACR
Appropriateness Criteria. Radiology 2000 Jun;215(Suppl):1383-400.

The appropriateness criteria are reviewed annually and updated by the
panels as needed, depending on introduction of new and highly
significant scientific evidence.

#### GUIDELINE AVAILABILITY

Electronic copies: Available in Portable Document Format (PDF) from the
[American College of Radiology (ACR) Web
site](http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria/pdf/ExpertPanelonRadiationOncologyProstateWorkGroup/PermanentSourceBrachytherapyforProstateCancerDoc5.aspx).

ACR Appropriateness Criteria® *Anytime*, *Anywhere*™ (PDA application).
Available from the [ACR Web
site](http://www.acr.org/SecondaryMainMenuCategories/ACRStore/FeaturedCategories/QualityandSafety/ac_pda.aspx).

Print copies: Available from the American College of Radiology, 1891
Preston White Drive, Reston, VA 20191. Telephone: (703) 648-8900.

#### AVAILABILITY OF COMPANION DOCUMENTS

The following is available:

-   ACR Appropriateness Criteria®. Background and development. Reston
    (VA): American College of Radiology; 2 p. Electronic copies:
    Available in Portable Document Format (PDF) from the [American
    College of Radiology (ACR) Web
    site](http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria/pdf/background_dev.aspx).

#### PATIENT RESOURCES

None available

#### NGC STATUS

This NGC summary was completed by ECRI on September 5, 2006. This
summary was updated by ECRI Institute on November 6, 2007, following the
updated U.S. Food and Drug Administration advisory on Viagra, Cialis,
Levitra, and Revatio.

#### COPYRIGHT STATEMENT

Instructions for downloading, use, and reproduction of the American
College of Radiology (ACR) Appropriateness Criteria® may be found on the
[ACR Web
site.](http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria/ACRAppropriatenessCriteriaTermsandConditionsDoc1.aspx)

### DISCLAIMER

#### NGC DISCLAIMER

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Date Modified: 11/3/2008