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## Complete Summary

#### GUIDELINE TITLE

External beam radiation therapy treatment planning for clinically
localized prostate cancer.

#### BIBLIOGRAPHIC SOURCE(S)

Michalski JM, Roach M III, Merrick G, Anscher MS, Beyer DC, Lawton CA,
Lee WR, Pollack A, Rosenthal SA, Vijayakumar S, Carroll PR, Expert Panel
on Radiation Oncology-Prostate. External beam radiation therapy
treatment planning for clinically localized prostate cancer. \[online
publication\]. Reston (VA): American College of Radiology (ACR); 2006.
12 p. \[111 references\]

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previous version: Roach M, Blasko JC, Perez CA,
Beyer DC, Forman JD, Hussey DH, Lee WR, Paryani SB, Pollack A, Potters
L, Scardino P, Schellhammer P, Leibel S. Treatment planning for
clinically localized prostate cancer. American College of Radiology. ACR
Appropriateness Criteria. Radiology 2000 Jun;215(Suppl):1441-8.

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

### COMPLETE SUMMARY CONTENT

 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 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\
Urology

#### INTENDED USERS

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

#### GUIDELINE OBJECTIVE(S)

To evaluate the appropriateness of external beam radiation therapy for
prostate cancer patients

#### TARGET POPULATION

Patients with clinically localized prostate cancer

#### INTERVENTIONS AND PRACTICES CONSIDERED

1.  Patient immobilization and positioning

2.  Prostate localization using retrograde urethrography, computed
    tomography (CT), magnetic resonance imaging (MRI), or ultrasound
    (US)

3.  Radiation treatment planning

4.  Radiation therapy

#### MAJOR OUTCOMES CONSIDERED

-   Utility of radiologic imaging procedures in prostate localization

-   5-year biochemical disease free survival

-   Toxicity and complications associated with radiation therapy

### 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: External Beam Radiation Therapy Treatment Planning
for Clinically Localized Prostate Cancer**

  ---------------------------------------------------------------------------
  **Treatment**        **Appropriateness   **Comments**
                       Rating**            
  -------------------- ------------------- ----------------------------------
  **Simulation Imaging                     
  Tools**                                  

  CT                   9                    

  Immobilization       7                    
  devices (external)                       

  Retrograde           6                    
  urethrogram (RUG)                        

  MRI (using           5                    
  endorectal coil)                         

  MRI (using body      5                    
  coil)                                    

  Immobilization       4                    
  devices (internal,                       
  rectal balloon)                          

  Bony anatomy 2D      3                   To verify isocenter only.
  X-ray simulations                        

  **Treatment                              
  Planning**                               

  IMRT                 8                   Most appropriate for patients
                                           treated with dose escalation.

  3D-CT-based plan     7                    

  Proton beam RT       7                    

  2D-CT-based plan     2                    

  Non CT-based         2                    
  computerized plan                        

  **Field Shaping**                        

  IMRT                 8                    

  3D BEV-designed      7                    
  blocks                                   

  Manually designed    3                    
  blocks from x-ray                        
  simulation films or                      
  diagnostic CT scans                      

  No blocks            2                    

  **Treatment                              
  Localization**                           

  Daily localization   8                    
  with implanted                           
  fiducial markers                         
  (stereoscopic)                           

  Daily transabdominal 7                    
  ultrasound                               

  In room CT-based     7                    
  localization                             

  Daily port film or   6                    
  electronic image                         
  localization: bony                       
  landmarks                                

  Weekly port films or 6                   Will require larger PTV margins
  electronic images                        than daily localization.

  Port film or image   2                    
  with initial                             
  treatment only                           

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

**Abbreviations**

-   BEV, beams-eye-view

-   CT, computed tomography

-   D, dimensional

-   IMRT, intensity modulated radiation therapy

-   MRI, magnetic resonance imaging

-   PTV, planning target volume

-   RT, radiation therapy

**Summary of Literature Review**

External beam radiation therapy for localized prostate cancer has
evolved over the past two decades with the introduction of image-based
treatment planning. External beam radiation therapy is a competitive
alternative to radical prostatectomy and brachytherapy. When controlled
for various case selection factors and quality of treatment delivery,
outcome between the various modalities appears to be equivalent. Newer
conformal radiation therapy methods, such as 3D conformal radiation
therapy (3D CRT), intensity modulated radiation therapy (IMRT), and
proton beam radiation therapy, have allowed radiation oncologists to
improve the therapeutic ratio by lowering the dose to surrounding
critical structures while simultaneously safely escalating the dose to
the disease target. This review will detail the practical elements of
radiation dose delivery, including patient set up and immobilization,
target volume definition, treatment planning, treatment delivery
methods, and tools to verify target localization during a course of
external beam radiation therapy.

**Patient Immobilization**

The use of immobilization devices should allow the use of \"tighter
margins,\" reducing the dose received by surrounding normal tissues.
Although some studies suggest that large day-to-day set up errors are
significantly reduced with the use of patient immobilization devices,
this conclusion is not universal. Some of the differences in conclusions
reached by different studies may be explained by differences in the
endpoints and methods of assessment. For example, in the one prospective
series reporting no advantage to using immobilization, the percentage of
large errors (\>5 mm) was not selectively evaluated. Furthermore, based
on the findings of this study it is clear that immobilization devices
that obscure the patient\'s normal anatomy can interfere with an
accurate patient set up.

Another prospective series failed to support patient immobilization. In
this study, patients treated in the supine position without
immobilization actually had significantly less movement in the
craniocaudal direction than patients treated in the prone position with
immobilization (errors \>5 mm: 24% compared to 11%. It is unclear
whether differences in the patients\' positions could explain this
finding. In a prospective randomized study, it was demonstrated that the
average simulation-to-treatment deviation of the isocenter position was
8.5 mm in a control group and 6.2 mm in an immobilized group. The use of
immobilization devices reduced isocenter deviations exceeding 10 mm from
30.9% to 10.6% in the immobilized arm. The average deviations in the
anteroposterior, right-left, and superior-inferior directions were
reduced to 2.9 mm, 2.1 mm, and 3.9 mm for the immobilized group. In
composite, the studies suggest that the haphazard use of immobilization
devices may be worse than none at all. A well thought out and simple
device that allows a comfortable and reproducible set up can reduce
large errors. The commonly used immobilization devices are constructed
of a melted plastic mold material, a solidified foam mold, or a reusable
inflatable mold device.

**Patient Positioning**

Patients may be simulated and treated supine or prone. While some
studies suggested that the prone position may result in less organ
movement others have not confirmed this observation. In the prone
position there may be greater rectal sparing, particularly in patients
with large seminal vesicles. However, a larger percentage of the bladder
may be included and associated with a slightly higher complication
probability. There may also be more patient set up movement errors
because some patients find the prone position less comfortable.
Simulating and treating patients in a standardized set of conditions
(e.g., bladder full) may reduce the variation in prostate position
during the course of treatment. A prone position appears to be
associated with greater prostate motion from normal breathing. The
increased intra-abdominal pressure associated with breathing in a prone
position results in significant movement of the prostate and seminal
vesicles. One study evaluated the impact of breathing on the position of
the prostate gland in four patients treated in four different positions
in whom radiopaque markers were implanted in the periphery of the
prostate using transrectal ultrasound (US) guidance prior to simulation.
Fluoroscopy was performed in four different positions: prone in foam
cast cradle, prone in thermoplastic mold, supine on a flat table, and
supine with a false table under the buttocks. During normal breathing
maximum movement of prostate markers seen in the prone position
(cranial-caudal) ranged from 0.9 to 5.1 mm and anterior-posterior
movement ranged up to 3.5 mm. In the supine position prostate movements
during normal breathing was less than 1 mm in all directions. Deep
breathing resulted in movements of 3.8 to 10.5 mm in the cranial-caudal
direction in the prone position (with and without thermoplastic mold).
This range was reduced to 2.7 mm in the supine position and to 0.5 to
2.1 mm with the use of a false tabletop. Deep breathing resulted in
anterior-posterior skeletal movements of 2.7 to 13.1 mm in the prone
position, whereas in the supine position these variations were
negligible.

In a prospective randomized trial of the supine vs. prone position in
patients undergoing conformal radiation therapy, 28 patients were
randomized to commence radiation therapy in the prone or supine position
and then change to the alternate position midway through their treatment
course. After placement of fiducial markers in the prostate for daily
prostate localization, the patients underwent computed tomography (CT)
simulation and treatment planning in both positions. Observed prostate
motion was significantly less in the supine position than the prone
position. Pretreatment positioning corrections were required more often
for patients in the prone position. A dose volume histogram analysis
revealed more bladder wall, rectal wall, and small bowel in the high
dose volumes when patients were in the prone position than in the supine
position. Finally, patients were more comfortable in the supine position
than the prone position. Seven patients that started in the supine
position refused to be treated in the prone position due to discomfort.
Other investigators have confirmed that prostate movement with
respiration is significantly less with patients in a supine position.
Regardless of the type of immobilization device used or the treatment
position chosen, there is no replacement for a careful set up and clear
instructions to patients to get into the same position every day.

**Prostate Target Definition**

The standard terms recommended in International Commission on Radiation
Units and Measurements (ICRU) 50 for specifying dose prescription are
summarized in the Table below.

**Table. Definitions for Treatment Planning**

  -----------------------------------------------------------------------
  **Volume**   **General Definitions and Comments**
  ------------ ----------------------------------------------------------
  GTV (gross   Tumor only, no margin. The entire prostate gland as
  tumor        determined by a CT scan commonly defines the GTV. Gross
  volume)      extension beyond the gland in a patient with a clinical
               stage T3, 4 cancers should be included as the GTV.

  CTV          Includes margin around the GTV for regions of microscopic
  (clinical    risk. This can include adjacent regions at risk of having
  target       subclinical disease such as the seminal vesicles or pelvic
  volume)      lymph nodes.

  PTV          Includes margin around the CTV to allow for patient
  (planning    movement, set up error, and organ movement.
  target       
  volume)      
  -----------------------------------------------------------------------

**Retrograde Urethrography**

Variable recommendations for using retrograde urethrograms (RUGs) during
treatment planning are found in the literature. RUG is primarily used
for identifying the inferior border of the prostate. In the past the
inferior border of the ischial tuberosities has been used as a landmark
for defining the inferior field margin on conventional simulation
radiograph films. Using the ischial tuberosities to define the lower
border of the field will result in an inferior margin that is excessive
in some patients and inadequate in others. RUG appears to more
accurately define the inferior border of the prostate than conventional
simulation plain films alone, because it takes into account large
variations found in individuals who have either a high or low pelvic
floor. However, because of variations in the functional length of the
external sphincter, RUG is probably best used to supplement computed
tomography (CT) (see discussion below). The prostatic apex is 3 to 13 mm
above the most proximal aspect of the urogenital diaphragm as defined by
the urethrogram. Care should be taken not to over inflate the urethra
with iodinated contrast as this may distend or move the prostate from
its relaxed position. A carefully administered RUG does not
significantly alter the position of the prostate gland.

**CT-Based Prostate Localization**

CT is the imaging approach of choice for treatment planning for external
beam irradiation. CT simulators are readily available in most radiation
oncology departments. Because of the rounded shape of the apical portion
of the prostate, the most inferior portion of the gland often cannot be
easily defined. Typically the location of the apex can be resolved to
two or three CT slices obtained at 3 to 5 mm intervals. Because of
difficulty visualizing the prostate on CT, a RUG can be used as a
supplement to CT in this area. When RUG is obtained at the time of
simulation it provides a landmark for comparing port films with
simulation films to ensure that the apical portion of the gland is
adequately covered. In the hands of a very experienced radiologist or
radiation oncologist the use of CT may be adequate. The radiation
oncologist should use multiplanar reconstructions to facilitate prostate
definition on a treatment planning CT. Both sagittal and coronal views
through the gland can help avoid contouring tissue beyond the limits of
the gland both at the apex and the base.

**MRI-Based Prostate Localization**

Magnetic resonance imaging (MRI) may be more accurate in delineating the
prostate and seminal vesicles than CT. CT overestimates the size of the
gland approximately 27% to 32%. Several publications have shown some
discrepancy (0.5 to 1 cm) in defining the location of the apex of the
prostate using CT or MRI scanning. One study evaluated co-registration
of CT and MR images in the radiation treatment planning of six patients
with localized prostate cancer to assist with GTV delineation and
identification of prostate position during radiation therapy. The
overall magnitude of contoured GTV was similar for MR and CT; however,
there were spatial discrepancies in contouring between the two
modalities. The greatest systematic discrepancy was at the posterior
apical prostate border, which was 3.6 mm more posterior on MRI than on
CT-defined contouring. Another study compared CT, MRI, and urethrography
to define the prostate apex. They concluded that MRI is superior to CT
or urethrography for localizing the prostatic apex. They suggested that
MRI be used for all patients undergoing radiotherapy for prostate cancer
to define the apex.

Endorectal MRI may detect extracapsular tumor extension, seminal vesicle
invasion, or neurovascular bundle involvement with greater sensitivity,
specificity and accuracy than clinical findings alone. In a series of 38
patients undergoing preoperative endorectal MRI imaging, the accuracy
rates in detecting capsular penetration, seminal vesicle invasion, and
neurovascular bundle involvement were 84%, 97%, and 97%, respectively.
In a larger series of 344 patients, it was reported that endorectal MRI
scanning improved the prediction of extracapsular extension over a
predictive model that included only clinical variables of PSA, Gleason
score, clinical stage, volume of cancer in the biopsy specimens and
perineural invasion. Endorectal MRI appears particularly helpful in
patients who have intermediate or high-risk clinical features.

Magnetic resonance spectroscopy (MRS) can detect variable concentrations
of citrate, choline and creatine in prostate tissue and improve the
accuracy of detecting and localizing prostate cancer.

MRI may also allow better identification of structures adjacent to the
prostate that are associated with erectile function. One study described
25 patients with localized prostate cancer who underwent both CT and
MRI-based treatment planning. They were able to spare the critical
erectile structures more often with an MR T2 and MRI angiogram based
treatment plan than with a plan using conventional CT-based contouring.
At this time, it is unclear whether sparing of the erectile tissues with
MRI-based radiation treatment planning will lead to better sexual
outcome or quality of life. It also remains to be proven that sparing of
these tissues will not compromise long-term tumor control.

The disadvantages to MRI-based prostate localization are limited
availability, CT-MR fusion uncertainties, treatment planning warping,
and a loss of radiography density information for radiation dose
calculation and digital reconstructed radiograph creation for treatment
verification. Several centers are exploring methods to reduce the
dosimetric and positional uncertainties associated with MR simulation.
At this time it is reasonable to use MRI to facilitate the definition of
target volumes, especially if CT-MR fusion capabilities or an MRI
simulator are available.

**Defining the Gross Tumor and the Clinical Target Volume**

Because prostate cancer is often found to be multifocal at the time of
radical prostatectomy, the entire gland is commonly considered the gross
tumor volume for radiation treatment planning purposes. The CTV may
expand the gross tumor volume to account for direct extension, or the
CTV can be extended to encompass adjacent organs or regions of spread.
In prostate cancer, the CTV may encompass the seminal vesicles and
possibly the regional pelvic lymph nodes.

Additional margin for possible extraprostatic extension (EPE) has been
recommended by several authors. In a study of radical prostatectomy
specimens, it was demonstrated that EPE was present in 28% of 376
patients. When EPE was present, the average radial distance of cancer
from the prostate capsule was 0.8 mm with a range of 0.04 to 4.4 mm. The
decision to add additional CTV margin may be most important in patients
with high-risk features, such as a PSA over 20, Gleason score more than
7, or bulky tumors (T2c or greater).

In selected patients it is necessary to include the seminal vesicles in
the CTV, which in most patients are well demonstrated on the cross
section CT scans of the pelvis. Nomograms may be used to determine the
probability of extraprostatic extension, seminal vesicle, or pelvic
lymph node involvement using clinical stage, pretreatment PSA, and
Gleason score. One study published an analysis of 344 radical
prostatectomy specimens in which the length of seminal vesicles, length
of involvement by carcinoma, and percentage of seminal vesicle involved
were measured. They found an excellent correlation between the various
prognostic parameters and the probability of seminal vesicle
involvement. Also, in 81 patients with positive seminal vesicle
involvement, the median length of tumor presence was 1 cm. In the entire
population, 7% of patients had seminal vesicle involvement beyond 1 cm.
They concluded that in selected patients seminal vesicles should be
treated and only 2.5 cm (approximately 60% of the seminal vesicle)
should be included within the CTV, unless there is radiographic evidence
of involvement.

In cases where the disease is confined to the gland (clinical stages
T1-2) but the risk of seminal vesicle invasion exceeds 15%, 2 CTVs can
be defined. The first encompasses the prostate and the seminal vesicles
and the second boost CTV is the prostate alone. In these cases, a
radiation dose that controls subclinical disease is prescribed to the
first target volume, and a higher dose is intended for the prostate
itself. When there is evidence of EPE on physical examination or imaging
modalities such as MRI (clinical stage T3), the seminal vesicles should
be included for the total radiation dose prescription.

**Planning Target Volume definition**

The magnitude of the PTV margin depends on several factors. Treatment
setup errors can vary by the method of patient positioning and
immobilization. Internal organs, including the prostate gland, can shift
because of variable filling of the rectum and bladder. The shifts can be
asymmetric, with most movement occurring in the anterior and posterior
directions. In order to assure that an adequate radiation dose treats
the CTV, an appropriate PTV margin must be added. There is a tradeoff
between assuring nearly 100% coverage during each treatment and the
volume of adjacent organs irradiated unnecessarily.

One study evaluated 17 patients with prostate cancer who underwent CT
scanning for treatment planning and three subsequent CT scans obtained
at approximately 2-week intervals during external beam fractionated
irradiation. The authors observed CTV motion of 0.9 mm (left to right),
3.6 mm (cranial-caudal), and 4.1 mm (anterior-posterior) directions.
From this study, the authors concluded that margins between the CTV and
PTV necessary to enclose 95% of the PTV were 7 mm in the lateral and
cranial-caudal directions and 11 mm in the anterior-posterior (AP)
direction.

Another study evaluated prostate and seminal vesicle motion in 50
patients treated in the prone position using CT scans for initial
treatment planning and three scans obtained throughout the course of
radiation therapy. Before the initial CT scans, patients had an enema
and were given 250 ml of bowel contrast by mouth. Patients had an empty
bladder, and 10 cc of air was inserted into the rectum via rectal
catheter. Prior to all CT scans, patients voided, and no additional
procedures were performed. Relative to the initial planning CT, mean
displacements of the prostate were -1.2 ± 2.9 mm in the AP, -0.5 ± 3.3
mm in the superior/inferior, and -0.6 ± 0.8 mm in the lateral direction.
The seminal vesicle displacements were -1.4 ± 4.9 mm, 1.3 ± 5.5 mm,
and - 0.8 ± 3.1 mm in the AP, superior-inferior (SI), and lateral
directions, respectively (negative values indicated displacements to the
posterior, inferior, and left directions). A combination of rectal
volume larger than 60 cc or a bladder volume larger than 40 cc was found
to be predictive for systematic deviations of the prostate and seminal
vesicles of more than 3 mm. Based on the data and the intent to have the
prescription dose achieve at least 93% coverage of the CTV, the authors
calculated the margins to be added to the CTV for defining the PTV.
Based on these reports, it is apparent that beyond the CTV, additional
margins of 5 to 8 mm are necessary to provide adequate coverage of the
prostate and 6 to 11 mm for adequate coverage of the seminal vesicles
when there is no organ distension that would result in a systematic
error.

**Localization for Prostate Radiation Therapy**

Megavoltage imaging with position correction can reduce the magnitude of
systematic setup errors in daily external beam radiation therapy. One
study demonstrated in a randomized trial that an integrated megavoltage
imaging system with repositioning during treatment would improve the
accuracy of treatment from 4.3 mm to 2 mm and reduce the frequency of
displacement errors \>5 mm from 69% to 7%. Another study reported a time
trend in patient setup deviations on the order of 4 to 11 mm. They
argued that portal images should be taken during the entire course of
treatment and that verification imaging should not be limited to the
start of therapy.

New strategies to reduce the uncertainty in daily treatment delivery and
the magnitude of the PTV margin have been introduced. These methods
employ daily imaging of the prostate in the treatment room. Radiopaque
implanted fiducial markers can be imaged with electronic portal imaging
or stereoscopic kilo voltage imaging devices. One study evaluated
prostate motion in 55 patients in whom gold seeds were implanted at the
base of the gland. Initial simulation was obtained in a supine position
with a full bladder and repeated after patients received 40 Gy. Prostate
motion was observed in the posterior direction (5.6 mm ± 4.1 mm) and in
the inferior direction (5.9 mm ± 4.5 mm). In 30% of the patients the
base of the prostate was displaced posteriorly and in 11% in the
inferior direction by more than 10 mm. A series of 10 patients reported
that margins could be reduced using daily fiducial marker localization
and pretreatment position correction. After prostate localization and
adjustment, the position errors were reduced to 1.3 to 3.5 mm
left-right, 1.7 to 4.2 mm anterior-posterior, and 1.6 to 4.0 mm
inferior-superior in prone patients, and 1.2 to 1.8 mm left-right, 0.9
to 1.8 mm anterior-posterior, and 0.8 to 1.5 mm inferior-superior in
supine patients. New radiofrequency transponders can localize the
prostate in a manner similar to gold markers but without additional
radiation dose to the patient. These transponders can also be tracked
real-time during a treatment session, allowing for immediate
intervention if the prostate moves outside the radiation field.

**Transabdominal Ultrasound**

Transabdominal ultrasound (US) has been used to localize the prostate
for treatment planning and during daily radiation therapy delivery with
accuracy parallel to that of CT scanning of the pelvis. One study
evaluated 23 patients with CT simulations on whom prostate-only fields
based on CT scans were created with no PTV margin. Ten of the patients
also had prostate localization with a transabdominal ultrasound system.
The absolute magnitude differences in CT and US were small (AP mean 3 mm
± 1.8 mm, lateral mean 2.4 mm ± 1.8 mm, superior/inferior mean 4.6 mm ±
2.8 mm). In a second study, they evaluated 35 patients that had US
localization in the CT simulation room. There was a high correlation
between the CT-defined position of the prostate and the position
determined by US. The authors felt the transabdominal US was simple and
expeditious and improved their ability to localize the position of the
prostate with the patient at the treatment machine for daily
irradiation. Using an US-based system, another study reported that
without US localization, organ motion would have caused the CTV to move
outside the PTV margin in 23.3% to 41.8% of the treatments.

**CT Imaging**

Newer linear accelerators and treatment rooms have introduced
tomographic volumetric imaging capabilities that allow daily capture of
3D image data. Both megavoltage and kilo voltage CT reconstructions can
display the daily position of the prostate and adjacent organs at risk,
thereby allowing treatment position to be adjusted to assure the
entirety of the target is in the daily treatment volume.

**Endorectal Balloon**

Use of an endorectal balloon during daily treatment potentially
stabilizes the position of the gland. The balloon also moves the
prostate anteriorly, allowing shielding of the posterior rectal wall. An
endorectal balloon is a controlled intervention that can be reproduced
during the course of radiation therapy. Air in the balloon may decrease
the rectal surface dose by decreasing the electronic buildup and
equilibrium at the air-soft tissue interface. One study reported results
of 100 consecutive patients treated with intensity modulated radiation
therapy (IMRT) and an endorectal balloon. Ten of those patients also
participated in a prostate motion study following gold seed
implantation. Each of these ten patients underwent 10 CT scans during
the course of their radiation therapy. The mean and standard deviation
of superior-inferior target displacements were 0.92 mm and 1.78 mm,
respectively. Of the 100 patients treated with a rectal balloon, 80% had
no rectal complaints and 11% and 6% had grade 1 or 2 acute toxicity,
respectively. They measured the radiation dose at a balloon-tissue
interface using a phantom. The dose at the air-tissue interface is
approximately 15% lower than the dose at the same point without an air
cavity. The dose builds up rapidly so that at 1 and 2 mm away from the
interface, the dose is only approximately 8% and 5% lower, respectively.

**Conventional and Conformal Blocking (2-D, 3-D and IMRT)**

Standard blocking or conventional treatment planning techniques have
traditionally been based on the use of bony landmarks or CT images to
estimate the approximate location of the prostate. Standard blocking
techniques usually involve the use of open square or rectangular blocks
to deliver radiation by bilateral arcs or rectangular fields with
minimal blocking.

3-D conformal radiotherapy (3-DCRT) may allow higher doses to be
delivered than conventional radiation therapy because of greater
flexibility in beam arrangements.

Several prospective trials have demonstrated that 3-DCRT can allow safe
escalation of radiation dose with either equal or lower rates of
morbidity compared to historical or contemporary controls. The RTOG®
prospective dose escalation trial reported the administration of minimum
PTV doses from 64.8 Gy to 79.2 Gy in 1.8 Gy/day fractions and 74 Gy to
78 Gy in 2 Gy/day fractions with lower than expected incidence of grade
3 or worse intestinal or urinary toxicity based upon comparisons to
historical controls. In a British randomized trial at the Royal Marsden
Hospital and NHS Trust, a reduction in grade 1 and 2 late radiation
proctitis was reported in men receiving 3-DCRT compared to men treated
with conventional radiation techniques to doses of 60 to 64 Gy. In a
French cooperative group randomized trial, there was no increase in
acute side effects in patients treated to 70 Gy compared to 80 Gy with
3-DCRT.

IMRT has recently emerged as the \"next generation\" of available
treatment planning technology. IMRT planning begins in nearly an
identical manner to that of forward planned 3-DCRT; however, patient
positioning and reproducibility is far more critical due to the sharp
dose gradients that can be seen with this modality. Daily target
localization method is critical in patients receiving IMRT for prostate
cancer. Suitable methods include transabdominal US, intraprostatic
fiducial markers with daily megavoltage portal or radiographic imaging,
endorectal balloon immobilization, or daily in-room CT imaging. IMRT
treatment planning requires defining dose constraints for the target and
each critical structure. IMRT creates more heterogeneity of dose than
3-DCRT, and the planning prescription needs to define a minimum dose to
cover a predetermined volume of the PTV as well as a maximum dose to a
small volume inside the PTV. Dose limits to organs at risk need to take
into account both upper dose limits as well as the volume of those
organs that are allowed to exceed those limits.

**Dose Prescription for Localized Prostate Cancer**

Several institutions have reported a radiation dose response for
localized prostate cancer based on retrospective reviews. In some
reports, there has not been a benefit for dose escalation above 70 Gy
for low-risk prostate cancer. One study reported no benefit to doses
greater than 77 Gy compared to 67 to 77 Gy for low-risk patients. The
Fox Chase Cancer Center experience did not show a dose response for
doses higher than 72 Gy. This lack of benefit to higher doses may be due
to the small local tumor burden that is readily controlled with
conventional doses. On the other hand, investigators from the Cleveland
Clinic and Memorial Sloan Kettering have shown a biochemical disease
free survival benefit for patients with low risk disease who receive
escalated doses with 3-DCRT or IMRT.

Intermediate risk disease benefits from escalated radiation doses in
most retrospective analyses. One study reported 5-year biochemical
disease free survival rates of 24%, 65%, and 79% for patients receiving
isocenter doses of \<72 Gy, 72-75.9 Gy, and ≥76 Gy, respectively.
Another study reported 5-year biochemical disease free survival rates of
27%, 51% and 83% for radiation doses of ≤68 Gy, 68-72 Gy, and \>72 Gy,
respectively.

Patients with high-risk disease do not uniformly demonstrate a benefit
to escalated radiation doses. This may be due to the greater burden of
subclinical metastases in patients with high presenting PSA or high
grade disease. A study from the Cleveland Clinic reported improved 5-
year biochemical disease free survival rates for high risk patients of
21%, 29%, and 71% for radiation doses of ≤68 Gy, 68-72 Gy, and \>72 Gy,
respectively. Another study suggested a dose response for biochemical
disease free survival for high risk patients. The authors suggested that
a 5 Gy dose increase beyond 78 Gy may improve PSA control for these
patients. Several randomized trials have been undertaken to demonstrate
whether there is a benefit to high dose 3-DCRT. The first completed and
published study demonstrated a significant biochemical disease free
survival in patients randomized to receive 78 Gy compared to 70 Gy. In
this trial all patients began with radiation to a limited pelvic field
with a standard 4 field arrangement. Patients were then randomized to
receive a conventional field boost to a total isocenter dose of 70 Gy or
a 3-DCRT boost to a total isocenter dose of 78 Gy. The largest gain from
this 8 Gy dose increase was seen in the patients with pretreatment PSA
\>10 ng/mL. In those intermediate risk patients the 5-year biochemical
disease free survival rates were 72% and 44% for 78 G or 70 Gy,
respectively. Another study demonstrated an advantage to high dose
radiation therapy in both low-risk and high-risk patients.

Normal tissue tolerance plays an important role in 3-DCRT and is
critical in IMRT treatment planning. Investigators from MD Anderson
Cancer Center conducted a prospective trial randomizing patients to 70
Gy or 78 Gy using conventional or 3-D conformal approaches. There was no
difference in acute toxicity despite the use of higher doses. However,
with longer follow-up there was a reduction in late complications with
the use of 3-D conformal technique despite the use of higher doses.
Based on their review of rectal toxicity in patients who received
3-DCRT, the Memorial Sloan Kettering dose escalation study recommended
keeping ≤60% of the rectal wall to receive 40 Gy and ≤30% of the rectal
wall should receive ≥75.6 Gy to minimize the risk of grade 2 or greater
rectal toxicity.

Investigators at MD Anderson reported that the organ at risk volumes
receiving high radiation doses are of major importance. The incidence of
grade II/III toxicity at 3 years decreased from 28% to 12% if less than
25% of rectum volume was 70 Gy or more.

#### 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

Appropriate external beam radiation therapy for patients with clinically
localized prostate cancer

#### POTENTIAL HARMS

Radiation therapy is associated with toxicity such as proctitis,
intestinal toxicity, urinary toxicity, severe rectal bleeding.

### 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)

Michalski JM, Roach M III, Merrick G, Anscher MS, Beyer DC, Lawton CA,
Lee WR, Pollack A, Rosenthal SA, Vijayakumar S, Carroll PR, Expert Panel
on Radiation Oncology-Prostate. External beam radiation therapy
treatment planning for clinically localized prostate cancer. \[online
publication\]. Reston (VA): American College of Radiology (ACR); 2006.
12 p. \[111 references\]

#### 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

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

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

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Not stated

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previous version: Roach M, Blasko JC, Perez CA,
Beyer DC, Forman JD, Hussey DH, Lee WR, Paryani SB, Pollack A, Potters
L, Scardino P, Schellhammer P, Leibel S. Treatment planning for
clinically localized prostate cancer. American College of Radiology. ACR
Appropriateness Criteria. Radiology 2000 Jun;215(Suppl):1441-8.

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/ExternalBeamRadiationTherapyTreatmentPlanningforClinicallyLocalizedProstateCancerDoc2.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 Institute on May 17, 2007.

#### 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