MEDICAL POLICY

POLICY
RELATED POLICIES
POLICY GUIDELINES
DESCRIPTION
SCOPE
BENEFIT APPLICATION
RATIONALE
REFERENCES
CODING
APPENDIX
HISTORY

Intensity Modulated Radiotherapy of the Prostate

Number 8.01.526

Effective Date June 9, 2014

Revision Date(s) 06/09/14; 06/10/13

Replaces 8.01.47

Policy

Intensity-modulated radiotherapy (IMRT) of the prostate may be considered medically necessary for the following:

  • Treatment of primary localized (non-metastatic) prostate cancer of an intact prostate when an escalation radiation dose greater than 75 Gy (grays) is planned.

OR

  • Treatment of prostate cancer after prostatectomy surgery when:
  • The prostate specific antigen (PSA) remains detectable at least 6 months after surgery; or
  • The PSA is detectable and increases on two or more lab determinations; or
  • The post-operative pathology report states the tumor is stage T3b to T4; or
  • The post-operative pathology report documents positive surgical margins

IMRT of the prostate is considered investigational when used in combination with radioactive implant treatment (brachytherapy).

IMRT of the prostate is considered investigational for other indications not listed as medically necessary.

Intra-fraction image guidance systems* (i.e., real-time within fraction image guidance) used with IMRT are considered not medically necessary. (See Related Policies).

*Examples of the imaging devices include: Calypso® 4D Localization System, AlignRT® radiotherapy positioning system, RayPilot® 4D intra-fraction image guidance system.

Related Policies

2.03.10

Real-Time Intra-Fraction Motion Management During Radiation Therapy

6.01.10

Stereotactic Radiosurgery and Stereotactic Body Radiation Therapy

8.01.10

Charged-Particle (Proton or Helium Ion) Radiation Therapy

8.01.48

Intensity-Modulated Radiation Therapy (IMRT): Cancer of the Head and Neck or Thyroid

8.01.49

Intensity-Modulated Radiation Therapy (IMRT): Abdomen and Pelvis

8.01.59

Intensity Modulated Radiation Therapy (IMRT): Central Nervous System Tumors

Policy Guidelines

Localized prostate cancer is defined as cancer confined to the prostate, or locally advanced cancer that is confined to adjacent structures and/or local lymph nodes. For localized prostate cancer, IMRT may offer advantages in both local tumor control and reducing toxicity to adjacent normal tissues.

Non-localized prostate cancer is defined as cancer that can be easily identified in organs and tissues well away from the prostate and the immediately surrounding tissues For non-localized prostate cancer; it is uncertain whether IMRT may offer advantages in both local tumor control and reducing toxicity to adjacent normal tissues. Radiation to the prostate is not usually given as part of treatment for non-localized prostate cancer.

The following table outlines radiation doses that are generally considered tolerance thresholds for these normal structures in the pelvis.

Radiation Tolerance Doses (TD) for Normal Tissues of the Pelvis

TD 5/5 (Gy)a

TD 50/5 (Gy)b

Portion of organ involved

Portion of organ involved

Site

1/3

2/3

3/3

1/3

2/3

3/3

Complication End Point

Spinal cord

50

50

47

70

70

NP

Myelitis/necrosis

Small intestine

50

NP

40

60

NP

55

Obstruction/perforation

Colon

55

NP

45

65

NP

55

Obstruction/perforation/ ulceration/fistula

Rectum

NP

NP

60

NP

NP

80

Severe proctitis/necrosis/

stenosis/fistula

Bladder

NP

80

65

NP

85

80

Symptomatic bladder contracture and volume loss

Femoral head

NP

NP

52

NP

NP

65

Necrosis

a TD 5/5, the average dose that results in a 5% complication risk within 5 years

b TD 50/5, the average dose that results in a 50% complication risk within 5 years

NP – not provided

TD – tolerance dose

1 centigray [cGy] = 0.01 gray [Gy]

The tolerance doses in the table are a compilation from the following 2 sources:

  • Morgan MA (2011). Radiation oncology. In DeVita, Lawrence, and Rosenberg, Cancer (p.308). Philadelphia: Lippincott Williams and Wilkins.
  • Kehwar TS, Sharma SC. Use of normal tissue tolerance doses into linear quadratic equation to estimate normal tissue complication probability. Source URL: http://www.rooj.com/Radiation%20Tissue%20Tolerance.htm. Last accessed May, 2014.

Definition of Terms

Excerpt from the TNM staging system for prostate cancer from the American Joint Committee on Cancer (AJCC) retrieved from: http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-staging. Last accessed May, 2014.

  • T=primary tumor
  • N=regional lymph nodes
  • M=distant metastasis
  • T1 – tumor is found incidentally in the prostate and is less than 5% of tissue removed by needle biopsy
  • T2 – tumor is more advanced than T1 but remains confined to the prostate
  • T3 – tumor extends beyond the prostatic capsule
  • T3a – extracapsular invasion unilateral or bilateral
  • T3b – invasion of the seminal vesicle(s)
  • T4 – tumor invades tissue next to the prostate (other than the seminal vesicles) such as urethral sphincter, rectum, bladder and/or pelvic wall
  • N0 – without lymphatic invasion
  • M0 – without metastasis

Coding

The following CPT codes specifically describe IMRT:

CPT

77301

Intensity modulated radiotherapy plan, including dose-volume histograms for target and critical structure partial tolerance specification

77338

Multi-leaf collimator (MLC) device(s) for intensity modulated radiation therapy (IMRT), design and construction per IMRT plan

77385

Intensity modulated radiation treatment delivery (IMRT), includes guidance and tracking, when performed; simple (new code effective 1/1/15)

77386

Intensity modulated radiation treatment delivery (IMRT), includes guidance and tracking, when performed; complex (new code effective 1/1/15)

HCPCS

G6015

Intensity modulated radiotherapy plan, including dose-volume histograms for target and critical structure partial tolerance specification

Description

Radiotherapy (RT) is an integral component in the treatment of prostate cancer. Intensity-modulated radiation therapy (IMRT) has been proposed as a method of radiation therapy that allows adequate radiation therapy to the tumor while minimizing the radiation dose to surrounding normal tissues and structures.

Background

For prostate cancer, RT is one accepted option for treatment. Other treatment options include surgery, hormonal treatment and watchful waiting.

Radiation Techniques

Conventional external-beam radiation therapy (EBRT)

Over the past several decades, methods to plan and deliver radiation therapy have evolved in ways that permit more precise targeting of tumors with complex geometries. Most early trials used 2-dimensional treatment planning based on flat images, and radiation beams with cross-sections of uniform intensity that were sequentially aimed at the tumor along 2 or 3 intersecting axes. Collectively, these methods are termed “conventional external beam radiation therapy” (EBRT).

Three-Dimensional conformal radiation therapy (3D-CRT)

Treatment planning evolved by using 3-dimensional images, usually from computed tomography (CT) scans, to delineate the boundaries of the tumor and discriminate tumor tissue from adjacent normal tissue and nearby organs at risk for radiation damage. Computer algorithms were developed to estimate cumulative radiation dose delivered to each volume of interest by summing the contribution from each shaped beam. Methods also were developed to position the patient and the radiation portal reproducibly for each fraction, and immobilize the patient, thus maintaining consistent beam axes across treatment sessions. Collectively, these methods are termed 3-dimensional conformal radiation therapy (3D-CRT).

Intensity-modulated radiotherapy (IMRT)

IMRT uses computer software and CT and magnetic resonance imaging (MRI) images, offers better conformality than 3D-CRT, as it is able to modulate the intensity of the overlapping radiation beams projected on the target and to use multiple shaped treatment fields. It uses a device (a multi-leaf collimator, [MLC]) which, coupled to a computer algorithm, allows for “inverse” treatment planning. The radiation oncologist delineates the target on each slice of a CT scan and specifies the target’s prescribed radiation dose, acceptable limits of dose heterogeneity within the target volume, adjacent normal tissue volumes to avoid, and acceptable dose limits within the normal tissues. Based on these parameters and a digitally reconstructed radiographic image of the tumor and surrounding tissues and organs at risk, computer software optimizes the location, shape and intensities of the beam ports, to achieve the treatment plan’s goals.

Increased conformality may permit escalated tumor doses without increasing normal tissue toxicity (e.g., proctitis), and thus may improve local tumor control, with decreased exposure to surrounding normal tissues, potentially reducing acute and late radiation toxicities. Better dose homogeneity within the target may also improve local tumor control by avoiding underdosing within the tumor and may decrease toxicity by avoiding overdosing.

Because most tumors move as patients breathe, dosimetry with stationary targets may not accurately reflect doses delivered within target volumes and adjacent tissues in patients. Furthermore, treatment planning and delivery are more complex, time-consuming, and labor-intensive for IMRT than for 3D-CRT. Thus, clinical studies must test whether IMRT improves tumor control or reduces acute and late toxicities, when compared with 3D-CRT.

Methodologic Issues in IMRT research

Multiple-dose planning studies have generated 3D-CRT and IMRT treatment plans from the same scans, then compared predicted dose distributions within the target and in adjacent organs at risk. Results of such planning studies show that IMRT improves on 3D-CRT with respect to conformality to, and dose homogeneity within, the target. Dosimetry using stationary targets generally confirms these predictions. Thus, radiation oncologists hypothesized that IMRT may improve treatment outcomes compared with those of 3D-CRT. However, these types of studies offer indirect evidence on treatment benefit from IMRT, and it is difficult to relate results of dosing studies to actual effects on health outcomes.

Comparative studies of radiation-induced side effects from IMRT versus alternative radiation delivery are probably the most important type of evidence in establishing the benefit of IMRT. Such studies would answer the question of whether the theoretical benefit of IMRT in sparing normal tissue translates into real health outcomes. Single-arm series of IMRT can give some insights into the potential for benefit, particularly if an adverse effect that is expected to occur at high rates is shown to decrease by a large amount. Studies of treatment benefit are also important to establish that IMRT is at least as good as other types of delivery, but in the absence of such comparative trials, it is likely that benefit from IMRT is at least as good as with other types of delivery.

Scope

Medical policies are systematically developed guidelines that serve as a resource for Company staff when determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to the limits and conditions of the member benefit plan. Members and their providers should consult the member benefit booklet or contact a customer service representative to determine whether there are any benefit limitations applicable to this service or supply. This medical policy does not apply to Medicare Advantage.

Benefit Application

N/A

Rationale

This plan specific policy was originally created in 2012 and is updated regularly with searches of the MEDLINE database. The most recent literature search was performed through April, 2014. The following is a summary of the key findings to date.

Intensity-modulated radiation therapy (IMRT) detects the areas of radiation and adjusts the dose weighting and delivery to process the radiation plan. In contrast to 3-dimensional conformal radiotherapy (3D-CRT) that is accurate to within 7 to 10 mm, IMRT restricts the dose and provides accuracy within 1 to 3 mm. The policy focuses on systematic reviews that evaluate outcomes of IMRT treatments in patients with prostate cancer. Also included are summaries of data from the systematic reviews and representative primary studies on adverse effects of treatment. A reduction in adverse effects is likely to be the greatest potential benefit of IMRT. In this regard, the most relevant studies are comparative trials of IMRT vs. 3D-CRT that report on rates of adverse events following treatment.

Systematic Reviews

In 2012, Bauman and colleagues published a systematic review that examined the evidence for IMRT in the treatment of prostate cancer in order to quantify its potential benefits and to make recommendations for radiation treatment programs considering adopting this technique within the province of Ontario, Canada. (1) Based on a review of 11 published reports through March 2009 (nine retrospective cohort studies and two randomized clinical trials [RCTs]) including 4,559 patients, the authors put forth the recommendation for IMRT over 3D-CRT for aggressive treatment of localized prostate cancer where an escalated radiation (>70 Gy) dose is required. There were insufficient data to recommend IMRT over 3D-CRT in the postoperative setting. (1)

Nine of 11 studies reviewed by Bauman and colleagues reported on adverse effects. Six of 9 studies reported on acute gastrointestinal (GI) effects. (1) Four studies (3 retrospective cohort studies and 1 RCT) reported differences in adverse effects between IMRT and 3D-CRT. The RCT included a total of 78 patients, and reported that acute GI toxicity was significantly less frequent in the IMRT group compared to 3D-CRT. This was true for grade 2 or higher toxicities (20% vs. 61%, p=0.001), grade 3 or higher toxicity (0 vs. 13%, p=0.001) and for acute proctitis (15% vs. 38%, p=0.03). In contrast, the second RCT included in this systematic review reported that there were no differences in toxicity between IMRT and 3D-CRT. (1)

Six of 9 studies reported on acute genitourinary (GU) effects. One study, which was a retrospective cohort study including 1,571 patients, reported a difference in overall acute GU effects in favor of 3D-CRT (37% IMRT vs. 22% 3D-CRT, p=0.001). For late GI toxicity, 4 of 9 studies, all retrospective cohort studies with a total of 3,333 patients, reported differences between IMRT and 3D-CRT. One RCT reported on late GI toxicity and did not find any differences between IMRT and 3D-CRT. Five of 9 studies reported on late GU effects, and only one reported a difference in late GU effects in favor of 3D-CRT (20% vs. 12%, p=0.01). Two retrospective cohort studies reported mixed findings on quality of life outcomes. (1) A subsequent economic analysis (based on this systematic review data) demonstrated that for radical radiation treatment (>70 Gy) of prostate cancer, IMRT seems to be cost-effective when compared with an equivalent dose of 3D-CRT from the perspective of the Canadian health care system for 2009. (2)

In 2008, the Agency for Healthcare Research and Quality (AHRQ) published a systematic review comparing the relative effectiveness and safety of various treatments for clinically localized prostate cancer. (3) Studies on IMRT were included in the assessment under the category of EBRT. Based on review of randomized control trials (RCTs) and nonrandomized studies published from 2000 to September 2007, there was no direct evidence (i.e. from RCTs) that IMRT results in better survival or disease-free survival (DFS) than other therapies for localized prostate cancer. Based on case-series data, the absolute risks of clinical and biochemical outcomes (including tumor recurrence), toxicity, and quality of life after IMRT were comparable with conformal radiation. For IMRT, the percent of patients with Grade 1 and 2 acute gastrointestinal (GI) toxicity was 22% and 4%, respectively, the percent of patients with rectal bleeding was 1.6%–10% and the percent of patients with Grade 2 genitourinary (GU) toxicity was 28%-31%. This review concluded that there was low-level evidence that IMRT provides at least as good a radiation dose to the prostate with less radiation to the surrounding tissues (that is undesirable) compared with conformal radiation therapy.(3)

In 2010, an update of the 2008 AHRQ systematic review was undertaken by the AHRQ Technology Assessment Program. (4) As with the 2008 review, this review concluded that the available data were insufficient to compare the effectiveness of the various forms of radiation treatments. Studies on IMRT were included in the assessment under the category of external-beam radiation therapy (EBRT) and thus reported data were not specific to IMRT. While higher EBRT dosages may result in longer-term biochemical control than lower EBRT dosages, overall and disease-specific survival data were inconclusive. Additionally, GU and GI toxicities experienced with EBRT did not seem to differ when standard fractionation was compared to moderate hypofractionization. The authors noted the need for further studies to evaluate outcomes of IMRT for the treatment of prostate cancer. (4) In addition, a subsequent report undertaken by the AHRQ Comparative Effectiveness Review Surveillance Program using the search strategy employed for the 2008 systematic review found no new data on IMRT following a limited literature search of the MEDLINE database through March 2012. (5)

Similar findings were observed in a systematic review of the clinical effectiveness of IMRT for the radical treatment of prostate cancer undertaken by the U.K. Health Technology Assessment Programme in 2010. (6) The authors also performed an economic analysis which demonstrated IMRT to be cost-effective from the perspective of the U.K. National Health Service for 2008/09 if this treatment modality can be used to prolong survival. (7)

An earlier review by the Institute for Clinical and Economic Review (8) reached the following conclusions in 2007:

“The literature on comparative rates of toxicity has serious methodological weaknesses. There are no prospective randomized trials or cohort trials, and the case series that exist are hampered by the lack of contemporaneous cohorts and/or by a failure to describe the selection process by which patients were assigned to IMRT vs. 3D-CRT. Published case series demonstrate consistent findings of a reduced rate of GI toxicity for IMRT at radiation doses from approximately 75–80 Gy [grays]. Data on genitourinary (GU) toxicity have not shown superiority of IMRT over 3D-CRT, nor does the existing data suggest that IMRT provided a lower risk of erectile dysfunction.”

“The literature suggests that the risk of Grade 2 GI toxicity is approximately 14% with 3D-CRT and 4% with IMRT. Thus, the number of patients needed to treat to prevent one case of moderate-severe proctitis is 10, and for every 100 patients treated with IMRT instead of 3D-CRT, 10 cases of GI toxicity would be expected to be prevented.”

Primary studies reporting on outcomes and adverse effects

The use of IMRT for prostate cancer has increased significantly and long-term data on biochemical control rates and toxicity has demonstrated benefits with the use of IMRT in some risk groups. Most studies are case series, with a lack of high-quality, prospective comparative studies where IMRT is compared with standard radiotherapy.

One study reporting comparative data of IMRT compared with 3D-CRT is a publication from the Radiation Therapy Oncology Group 0126 prostate cancer trial. (9) In this trial, the initial protocol was for3D-CRT, but during the trial the protocol was amended to provide IMRT. As a result, 491 patients were treated with 3D-CRT and 257 were treated with IMRT. Radiation exposure for the bladder and rectum were significantly reduced with IMRT. There was a significant decrease in grade 2 or greater late GI toxicity for IMRT on univariate analysis (p=0.039). On multivariate analysis, there was a 26% reduction in grade 2 or higher GI toxicity for the IMRT group, but this difference did not meet statistical significance (p=0.099). There were no differences in early or late GU toxicity between groups. This study offers some comparative data that supports lower toxicity for IMRT, but it is limited by the nonconcurrent use of IMRT and 3D-CRT, and the lack of statistical significance on most outcomes.

Vora and colleagues reported on 9-year tumor control and chronic toxicities observed in 302 patients treated with IMRT for clinically localized prostate cancer at one institution. (10) The median dose delivered was 76 Gy (range 70-77 Gy), and 35% of patients received androgen deprivation therapy. Local and distant recurrence rates were 5% and 8.6%, respectively. At 9 years, biochemical control rates were close to 77% for low-risk, 70% for intermediate-risk, and 53% for high-risk patients (log rank p=0.05). At last follow-up, only 0%/0.7% had persistent grade ≥3 GI/GU toxicity. The high-risk group was associated with a higher distant metastasis rate (p=0.02) and death from prostate cancer (p=0.001). (10)

Alicikus and colleagues reported on 10-year outcomes in 170 patients treated after high-dose IMRT (81 Gy). (11) The 10-year actuarial prostate-specific antigen (PSA) relapse-free survival rates were 81% for the low-risk group, 78% for the intermediate-risk group, and 62% for the high-risk group. The 10-year distant metastases–free rates were 100%, 94%, and 90%, respectively, and cause-specific mortality rates were 0%, 3%, and 14%, respectively. The 10-year likelihood of developing grade 2 and 3 late genitourinary toxicity was 11% and 5%, respectively, and the likelihood of developing grade 2 and 3 late gastrointestinal toxicity was 2% and 1%, respectively. No grade 4 toxicities were observed. These findings indicate that IMRT is associated with good long-term tumor-control and low rates of serious toxicity in patients with localized prostate cancer. (11)

In 2008, Zelefsky et al reported on the incidence and predictors of treatment-related toxicity at 10 years after 3D-CRT and IMRT for localized prostate cancer. (12) Between 1988 and 2000, 1,571 patients with stages T1-T3 prostate cancer were treated with 3D-CRT or IMRT with doses ranging from 66 to 81 Gy. Twenty-two percent were considered to be at low risk, as based on National Comprehensive Cancer Network (NCCN) guidelines. The median follow-up was 10 years. The actuarial likelihood at 10 years for the development of Grade 2 or higher GI toxicities was 9%. The use of IMRT significantly reduced the risk of GI toxicities compared with patients treated with conventional 3D-CRT (13% to 5%; p<0.001). Among patients who experienced acute symptoms, the 10-year incidence of late toxicity was 42%, compared with 9% for those who did not experience acute symptoms. The 10-year incidence of late Grade 2 or higher GU toxicity was 15%. Patients treated with 81 Gy (IMRT) had a 20% incidence of GU symptoms at 10 years, compared with 12% for patients treated with lower doses (p=0.01). Among patients who had developed acute symptoms during treatment, the incidence of late toxicity at 10 years was 35%, compared with 12%. The incidence of Grade 3 GI and GU toxicities was 1% and 3%, respectively. The authors concluded that serious late toxicity was unusual despite the delivery of high radiation dose levels in these patients. They also noted that higher doses were associated with increased GI and GU Grade 2 toxicities, but the risk of proctitis was significantly reduced with IMRT.

Cahlon et al reported on preliminary biochemical outcomes and toxicity with high-dose IMRT to a dose of 86.4 Gy for localized prostate cancer. (13) For this study, 478 patients were treated between August 1997 and March 2004 with 86.4 Gy using a 5- to 7-field IMRT technique. The median follow-up was 53 months. Thirty-seven patients (8%) experienced acute Grade 2 GI toxicity; none had acute Grade 3 or 4 GI toxicity; 105 patients (22%) experienced acute Grade 2 GU toxicity; and 3 patients (0.6%) had Grade 3 GU toxicity. Sixteen patients (3%) developed late Grade 2 GI toxicity; 2 patients (<1%) developed late Grade 3 GI toxicity; 60 patients (13%) had late Grade 2 GU toxicity; and 12 (<3%) experienced late Grade 3 GU toxicity. The 5-year actuarial PSA relapse-free survival, according to the nadir plus 2 ng/mL definition, was 98%, 85%, and 70% for the low-, intermediate-, and high-risk NCCN prognostic groups. The authors concluded that treatment with ultra-high radiation dose levels of 86.4 Gy using IMRT for localized prostate cancer is well tolerated and the early excellent biochemical control rates are encouraging. These results based on a case series should be considered as preliminary.

In 2009, Wong and colleagues reported on a retrospective study of radiation dose escalation in 853 patients with localized (T1c-T3N0M0) prostate cancer. (14) Radiation therapies used included conventional dose (71 Gy) 3D-CRT (n=270), high-dose (75.6 Gy) IMRT (n=314), permanent transperineal brachytherapy (n=225) and external beam radiotherapy (EBRT) plus brachytherapy boost (n=44). All patients were followed for a median of 58 months (range, 3 to 121 months). The authors reported:

“The 5-year overall survival for the entire group was 97%. The 5-year [biochemical control] bNED rates, local control rates, and distant control rates were 74%, 93%, and 96%, respectively, for 3D-CRT; 87%, 99%, and 97%, respectively, for IMRT; 94%, 100%, and 99%, respectively, for BRT alone; and 94%, 100%, and 97%, respectively, for EBRT + BRT. The bNED rates for 3D-CRT were significantly less than those of the other higher dose modalities (P<.0001).”

Intermediate- and high-risk prostate cancer patients in this study had significantly improved 5-year bNED rates with dose escalation. However, in low-risk prostate cancer patients, bNED rates with dose escalation were not improved compared to conventional dose 3D-CRT. The authors also found acute and late grade 2 and 3 GU toxicities were fewer with IMRT than brachytherapy or EBRT plus brachytherapy.

Studies of post-prostatectomy IMRT have demonstrated superior dose distribution to the target volume with the use of IMRT, as compared with 3D conformal radiation delivery, with better sparing of nearby critical healthy tissue structures and less severe toxicity-related morbidity (15).

In 2009, Thompson, et al. reported on the long-term follow-up of a randomized clinical trial of radiotherapy to reduce the risk of metastatic disease in men who had radical prostatectomy surgery. A total of 431 men with pT3N0M0 prostate cancer were randomized to 60 to 64 Gy adjuvant radiotherapy or observation. The primary study end point was metastasis-free survival. Of 425 eligible men 211 were randomized to observation and 214 to adjuvant radiation. In the group of men under observation 70 ultimately received radiotherapy. Metastasis-free survival was reported as significantly greater with radiotherapy (93 of 214 events on the radiotherapy arm vs. 114 of 211 events on observation; HR 0.71; 95% CI 0.54, 0.94; p = 0.016). Survival improved with adjuvant radiation (88 deaths of 214 on the radiotherapy arm vs. 110 deaths of 211 on observation; HR 0.72; 95% CI 0.55, 0.96; p = 0.023). The authors concluded that adjuvant radiotherapy after radical prostatectomy for a man with pT3N0M0 prostate cancer significantly reduces the risk of metastasis and increases survival. (16)

External beam radiation therapy (EBRT) and Brachytherapy

Brachytherapy in combination with EBRT to boost therapeutic effect is one method used by some radiation oncologists for treating high-risk prostate cancer patients. Some authors have suggested that all patients undergoing brachytherapy should receive combined therapy. Sylvester et al. reported the Seattle experience with the 15-year biochemical relapse-free survival (BRFS) for 223 patients. (17) Several published articles supporting the use of external EBRT and brachytherapy are based on the retrospective data from this study. One Phase III clinical trial started in 2003 is focused on Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy with Brachytherapy Alone and may offer guidance about this therapy in the future. Until further strong research is completed, a review of the current literature does not allow any firm conclusions thus this combination treatment strategy is considered investigational.

IMRT compared to active surveillance

In a 2013 review of data from the Surveillance, Epidemiology, and End Results (SEER) Medicare database, Gandaglia et al evaluated 42,483 patients treated with IMRT or initial observation for prostate cancer between 2001 and 2007. (18) Propensity-score matching of patients in both treatment groups resulted in 19,064 patients for inclusion in the analysis (n= 9,532 in each treatment group). Median follow-up was 50 months. Cancer-specific mortality (CSM) rates at 8 years were 3.4% for IMRT and 4.1% for initial observation (p<0.001). When patients were stratified by risk categories, IMRT was not associated with lower 8-year CSM rates than observation (2.5% vs. 1.7%, respectively, p=0.7) in patients with low- or intermediate-risk disease. The 8-year CSM rates continued to be not statistically significantly different when patients with low- or intermediate-risk disease were stratified by age and Charlson comorbidity index ([CCI] all p≥0.5). In high-risk disease patients, 8-year CSM rates were 5.8% for IMRT versus 10.5% for observation (p<0.001). After stratifying patients according to age (<73, ≥73) and CCI

(≤1, ≥2), in high-risk disease patients, the 8-year CSM rates continued to be statistically significantly better in the IMRT groups than the observation groups (all p<0.002).

Clinical Trials

A search of Clinicaltrials.gov identified several Phase III randomized clinical trials (RCTs) of IMRT for prostate cancer. Some trials were identified comparing IMRT to other radiation modalities for the treatment of prostate cancer.

  • NCT01617161 is a Phase III randomized clinical trial comparing IMRT to proton beam therapy (PBT) to determine which therapy best minimizes the side effects of treatment. This trial has an estimated enrollment of 461 patients and is sponsored by the Massachusetts General Hospital in collaboration with the University of Pennsylvania and the National Cancer Institute. The primary outcome measure is disease-free survival at 5 years. This study is currently recruiting participants with the estimated completion date of January 2016.
  • NCT00326638 is a Canadian randomized Phase III trial, comparing 3D-CRT to helical tomotherapy IMRT in high-risk prostate cancer patients. This trial has an estimated enrollment of 72 patients and is sponsored by the Ottawa Hospital Research Institute. The primary outcome measure is late rectal toxicity from radiotherapy of the prostate. This study is currently recruiting participants with the estimated completion date of May 2014.
  • NCT00331773 a randomized Phase III trial, comparing hypofractionated 3D-CRT or IMRT to conventionally fractionated 3D-CRT or IMRT in favorable-risk prostate cancer. This trial has an estimated enrollment of 1,067 patients and is sponsored by the Radiation Therapy Oncology Group-National Cancer Institute. The primary outcome measure is disease-free survival at 5 years. This study is currently recruiting participants with the estimated completion date of February 2021.
  • NCT00392535 is a randomized ongoing Phase III trial (CHHiP) studied the adverse effects of 3 schedules of IMRT in treating patients with localized prostate cancer versus conventional radiotherapy. The study was undertaken by the U.K. Institute of Cancer Research. This multicenter trial (n=26 centers) had an estimated enrollment of 2,163 patients. The primary outcome measures are acute and late radiation-induced side effects and freedom from prostate cancer recurrence. This study completion date was September 2012, but final results are not published. Preliminary results of this study published in 2008 report that hypofractionated IMRT (57-60 Gy) seems equally well-tolerated as conventionally fractionated treatment (74 Gy) at 2 years of follow-up. (19)
  • NCT00063882 another ongoing Phase III trial is Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy with Brachytherapy Alone for Selected Patients with Intermediate Risk Prostatic Carcinoma. This trial has an estimated enrollment of 600 patients and is sponsored by the Radiation Therapy Oncology Group-National Cancer Institute. This study has an estimated completion date of January 2017.

Summary

In general, when the radiation doses are similar, the available evidence suggests that IMRT provides tumor control rates comparable to existing radiotherapy techniques. In addition, while results are not uniform and are based on retrospective cohort trials, some studies show reductions in GI and GU toxicity. A reduction in clinically significant complications of radiation therapy is likely to lead to an improved quality of life for treated patients. Thus, despite the lack of high-quality comparative studies reporting on clinical outcomes, based on the published literature that provides data on outcomes of treatment; IMRT is another technique that can be used to deliver radiation therapy in the treatment of localized prostate cancer.

Practice Guidelines and Position Statements

The most recent National Comprehensive Cancer Network (NCCN) guidelines (v.1.2014) for prostate cancer indicate, in the principles of radiation therapy, highly conformal radiation therapy should be used in conventional fraction doses of 75.6 to 79.2 GY for patients with low-risk prostate cancer and up to 81 Gy for patients with intermediate and high-risk prostate cancer. Indications are that IMRT is preferred over 3D-CRT to decrease salvage therapy rates the adverse effects of GI toxicity. (19) The NCCN guidelines also indicate 3D-CRT or IMRT may be considered as an initial treatment option in all prostate cancer patients except for patients with a very-low risk of recurrence and less than 20 years’ expected survival.

The American College of Radiology Appropriateness Criteria indicates IMRT is appropriate for field shaping in patients being treated for clinically localized prostate cancer. (20) Additionally, the ACR guidelines indicate IMRT is most appropriate for treatment planning for dose escalation.

The U.S. Preventive Services Task Force (USPSTF) recommendations on screening for prostate cancer include the following statements: “Even if prostate cancer screening is determined to be effective, the length of time required to experience a mortality benefit is greater than 10 years. Because a 75-year-old man has an average life expectancy of about 10 years, very few men age 75 years or older would experience a mortality benefit. Similarly, men younger than age 75 years who have chronic medical problems and a life expectancy of fewer than 10 years are also unlikely to benefit from screening and treatment.” Source URL: http://annals.org/article.aspx?articleid=742052. Last accessed May, 2014.

Medicare National Coverage

There is no national coverage determination.

References

  1. Bauman G, Rumble RB, Chen J et al. Intensity-modulated radiotherapy in the treatment of prostate cancer. Clin Oncol 2012; 24(7):461-73.
  2. Yong JH, Beca J, McGowan T et al. Cost-effectiveness of intensity-modulated radiotherapy in prostate cancer. Clin Oncol 2012; 24(7):521-31.
  3. Wilt TJ, Shamliyan T, Taylor B et al. Comparative effectiveness of therapies for clinically localized prostate cancer: An update of a 2008 Comparative Effectiveness Review Agency for Healthcare Research and Quality. March, 2013. Source URL: http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?productid=1434&pageaction=displayproduct. Last accessed May, 2014.
  4. Ip S DT, Yu W, et al. Radiation Therapy for Localized Prostate Cancer: an Update. Technology Assessment Report. August 13, 2010. Source URL: https://www.cms.gov/coveragegeninfo/downloads/id69ta.pdf. Last accessed May, 2014.
  5. Agency for Healthcare Research and Quality (AHRQ) Comparative Effectiveness Review Surveillance Program. Surveillance Report. CER #13: Comparative Effectiveness of Therapies for Clinically Localized Prostate Cancer. 2012. Source URL: http://effectivehealthcare.ahrq.gov/ehc/products/9/80/TX-for-Localized-Prostate-Cancer_SurveillanceAssesment_20120614.pdf. Last accessed May, 2014.
  6. Hummel S, Simpson EL, Hemingway P et al. Intensity modulated radiotherapy for the treatment of prostate cancer: a systematic review and economic evaluation. Health Technol Assess 2011; 14(47):1-137.
  7. Hummel SR, Stevenson MD, Simpson EL et al. A model of the cost-effectiveness of intensity-modulated radiotherapy in comparison with three-dimensional conformal radiotherapy for the treatment of localised prostate cancer. Clin Oncol 2012; 24(10):e159-67.
  8. Pearson SD, Ladapo, Prosser L. Intensity modulated radiation therapy (IMRT) for localized prostate cancer. Institute for Clinical and Economic Review. 2007. (Combined in a new report titled Management options for low-risk prostate cancer: A report on comparative effectiveness and value. 2010). Source URL: http://www.icer-review.org/wp-content/uploads/2013/04/Management_Options_for_Low-Risk_Prostate_Cancer_Final-2.pdf. Last accessed May, 2014.
  9. Michalski JM, Yan Y, Watkins-Bruner D et al. Preliminary toxicity analysis of 3-dimensional conformal radiation therapy versus intensity modulated radiation therapy on the high-dose arm of the Radiation Therapy Oncology Group 0126 prostate cancer trial. Int J Radiat Oncol Biol Phys 2013; 87(5):932-8.
  10. Vora SA, Wong WW, Schild SE et al. Nine-Year Outcome and Toxicity in Patients treated with IMRT for Localized Prostate Cancer. J Uro 2013.
  11. Alicikus ZA, Yamada Y, Zhang Z et al. Ten-year outcomes of high-dose, intensity-modulated radiotherapy for localized prostate cancer. Cancer 2011; 117(7):1429-37.
  12. Zelefsky JF, Levin EJ, Hunt M et al. Incidence of late rectal and urinary toxicities after three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 2008; 70(4):1124-9.
  13. Cahlon O, Zelefsky JM, Shippy A et al. Ultra-high dose (86.4 Gy) IMRT for localized prostate cancer: toxicity and biochemical outcomes. Int J Radiat Oncol Biol Phys 2008; 71(2):330-7.
  14. Wong WW, Vora SA, Schild SE et al. Radiation dose escalation for localized prostate cancer: intensity-modulated radiotherapy versus permanent transperineal brachytherapy. Cancer 2009; 115(23):5596-606.
  15. Alongi F, Fiorino C, Cozzarini C, Broggi, S, Perna, et al. IMRT significantly reduces acute toxicity of whole-pelvis irradiation in patients treated with post-operative adjuvant or salvage radiotherapy after radical prostatectomy. Radiother Oncol. 2009; 93(2):207-212.
  16. Thompson IM, Tangen CM, Paradelo J, Lucia MS, Miller G, Troyer D, Messing E, Forman J, Chin J, Swanson G, Canby-Hagino E, Crawford ED. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term follow-up of a randomized clinical trial. J Urol. 2009 Mar; 181(3):956-62.
  17. Sylvester JE, Grimm PD, Blasko JC, et al. 15 Year biochemical relapse-free survival in clinical Stage T1-T3 prostate cancer following combined external beam radiotherapy and brachytherapy; Seattle experience. Int J Radiat Oncol biol Phys 67: 57-64, 2007.
  18. Gandaglia G, Karakiewicz PI, Briganti A et al. Intensity-Modulated Radiation Therapy Leads to Survival Benefit Only in Patients with High-Risk Prostate Cancer: a Population-Based Study. Ann Oncol 2014.
  19. Dearnaley D, Syndikus I, Sumo G et al. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: preliminary safety results from the CHHiP randomised controlled trial. Lancet Oncol 2012; 13(1):43-54.
  20. National Comprehensive Cancer Network (NCCN) Practice Guidelines in Oncology: Prostate Cancer. V.2.2014. Accessible online at: http://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf . Last accessed May, 2014.
  21. Michalski JM RMI, Merrick G, et al. Expert Panel on Radiation Oncology-Prostate. American College of Radiology (ACR). External beam radiation therapy treatment planning for clinically localized prostate cancer. 2006.
  22. BlueCross BlueShield Association Medical (BCBSA). Policy Reference Manual. Intensity-Modulated Radiation Therapy (IMRT) of the Prostate. Policy No. 8.01.47, 2014.

Coding

Codes

Number

Description

CPT

0073T

Compensator-based beam modulation treatment delivery of inverse planned treatment using three or more high resolution (milled or cast) compensator convergent beam modulated fields, per treatment session (deleted 12/31/14)

 

77301

Intensity modulated radiotherapy plan, including dose-volume histograms for target and critical structure partial tolerance specification

 

77338

Multi-leaf collimator (MLC) device(s) for intensity modulated radiation therapy (IMRT), design and construction per IMRT plan

 

77385

I ntensity modulated radiation treatment delivery (IMRT), includes guidance and tracking, when performed; simple (new code effective 1/1/15)

 

77386

Intensity modulated radiation treatment delivery (IMRT), includes guidance and tracking, when performed; complex (new code effective 1/1/15)

 

77418

Intensity modulated treatment delivery, single or multiple fields/arcs, via narrow spatially and temporally modulated beams, binary, dynamic MLC, per treatment session (deleted 12/31/14)

ICD-9 Diagnosis

185

Malignant neoplasm of prostate

ICD-10-CM
(effective 10/01/15)

C61

Malignant neoplasm of prostate

HCPCS

G6015

Intensity modulated treatment delivery, single or multiple fields/arcs, via narrow spatially and temporally modulated beams, binary, dynamic MLC, per treatment session (new code effective 1/1/15)

Appendix

N/A

History

Date

Reason

01/10/12

New policy – Add to Therapy section. Recommended for adoption by OAP on November 17, 2011. Approved with 90-day hold for provider notification, effective September 1, 2012.

07/10/12

Related Policies updated: 8.01.59 added and 8.01.525 replaced with 8.01.48, all effective as of September 1, 2012.

08/06/12

Add Related Policy: 2.03.10.

08/21/12

Implementation delayed to January 1, 2013.

12/11/12

Replace policy. Policy is updated and is different than what was published on the public medical policy website before this date. Policy revised with input from clinical vetting. Policy statement now says IMRT is medically necessary for treatment of localized cancer in an intact prostate and for treatment after prostatectomy surgery when criteria are met. Intra-fraction imaging is added as not medically necessary. Description and rationale sections revised based on literature review through October 2012. New references added; others renumbered or removed. Policy statement changed as noted. Policy effective date is January 1, 2013, as was previously noted to allow for provider notification.

06/10/13

Replace policy. Policy statement for post-prostatectomy IMRT changed to read: “the prostate specific antigen (PSA) remains detectable after the first 6 months of surgery”. Added related policies: 6.01.10, 8.01.10. Rationale updated based on a literature review through April 2013. References 1, 2, 5-7, 9, 10, 14 added; others renumbered or removed. Policy statement changed as noted.

06/19/14

Annual Review. Policy updated based on literature review through April, 2014. Minor edits for clarification and readability. Added table of radiation tolerance doses for normal tissue of the pelvis to the Policy Guidelines section. Moved Definition of Terms from Appendix to Policy Guideline section. References 9, 18 added, 3 and 8 updated; others renumbered/removed. Policy statement unchanged.

08/19/14

Update Related Policies. Remove 8.01.527.

1/12/15

Coding update. New CPT codes 77385-77387, effective 1/1/15, added to policy; deleted code 0073T and 77418 noted on policy effective 12/31/14.

02/10/15

Coding update. New code 77387 removed from policy; this is not specific to IMRT.

03/13/15

Coding update. HCPCS code G6015 added to the policy, new code effective 1/1/15.


Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).
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