Download Brachytherapy for Localized Prostate Cancer

Clinical Policy Title: Brachytherapy for Localized Prostate Cancer
Clinical Policy Number: 05.02.02
Effective Date:
Initial Review Date:
Most Recent Review Date:
Next Review Date:
October 1, 2014
June 18, 2014
July 15, 2015
July 2016
Related policies:
None.
Policy contains:
• Localized prostate cancer.
• Prostate specific antigen (PSA) screening.
• Treatment options — Watchful waiting;
radical prostatectomy; external beam
radiation; brachytherapy.
ABOUT THIS POLICY: Select Health of South Carolina has developed clinical policies to assist with making coverage determinations. Select Health
of South Carolina’s clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services
(CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peer-reviewed professional
literature. These clinical policies along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including
any state- or plan-specific definition of “medically necessary,” and the specific facts of the particular situation are considered by Select Health of
South Carolina when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal
laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. Select Health of
South Carolina’s clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other
health care providers are solely responsible for the treatment decisions for their patients. Select Health of South Carolina’s clinical policies are
reflective of evidence-based medicine at the time of review. As medical science evolves, Select Health of South Carolina will update its clinical policies
as necessary. Select Health of South Carolina’s clinical policies are not guarantees of payment.
Coverage policy
Select Health of South Carolina considers the use of brachytherapy to be clinically proven and, therefore,
medically necessary when the following criteria are met:
• Men with prostate cancer whose tumor is confined to the prostate gland.
• Stage 1 or 2 (defined below).
Tumor (T) staging for prostate cancer:
Stage
T1
T2
T3
T4
Definition
Clinically inapparent: neither palpable nor visible:
• Incidental finding on tissues resected during TURP.
• Identified on needle biopsy initiated by elevated PSA.
Confined within the prostate: one or both lobes.
Tumor spreads through capsule or present at resection margin:
• Uni- or bilateral extra-capsular extension.
• Seminal vesicles involved.
Fixed to or invades adjacent structures.
Limitations:
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No other indications for brachytherapy are covered.
Alternative covered services:
Watchful waiting, radical prostatectomy or external beam radiation.
Background
Brachytherapy (or interstitial radiation) is a form of radiation therapy in which encapsulated sources of
radiation (“seeds”)are implanted directly into or adjacent to tumor tissues, such as prostate cancer. It is
based on the principle that radiation doses decrease as a function of the squared distance from the source,
thus delivering intensive exposure to cancerous tissue while minimizing exposure and adverse effects to
surrounding healthy tissue. Current standard prostate brachytherapy technique achieves a homogeneous
dose distribution according to a customized template based on CT and ultrasound assessment of the tumor
and computer-optimized dosimetry.
Brachytherapy for prostate cancer is well-tolerated, although most patients experience urinary frequency
and urgency that can persist for several months. Only 2 percent to 4 percent of patients are incontinent.
Patients who have undergone a previous transurethral resection of the prostate (TURP) have higher
complication rates.
Prostate cancer is the most common noncutaneous malignancy and the second-leading cause of death in
men. Ninety percent of men with prostate cancer are over age 60, diagnosed with the prostate specific
antigen (PSA) blood test, and have disease believed to be localized to the prostate gland (clinically
localized). Common treatments for clinically localized prostate cancer include watchful waiting, surgery to
remove the prostate gland (radical prostatectomy), external beam radiation therapy and interstitial
radiation therapy (brachytherapy).
Prostate cancer is a clinically heterogeneous disease. A substantial proportion of prostate cancer cases
detected with current screening methods will never cause symptoms during the patients’ lifetimes.
Modeling studies based on U.S. incidence data suggest over-diagnosis rates ranging from 29 percent to 44
percent of all prostate cancer cases detected by PSA screening. Because patients with “pseudo-disease”
receive no benefit from, and may be harmed by, prostate cancer screening and treatment, prostate cancer
detection in this population constitutes an important burden. The United States Preventive Services Task
Force (USPSTF) in 2002 found insufficient evidence that screening for prostate cancer improved health
outcomes, including mortality. It also found little evidence on the harms of the screening process or the
natural history of prostate cancer cases detected with screening.
Prostate cancer screening is problematic because it attempts to mitigate a disease of which we have a poor
understanding by using a test not well-suited to the job, with rates of over-diagnosis estimated at 20
percent to 50 percent for a disease with a current annual incidence > 186,000 in the United States alone.
Side effects of treatment can be considerable and may include lasting effects on urinary, bowel, sexual and
vitality functions. Unfortunately, even patients with clear evidence of indolent disease who are candidates
for surveillance suffer from cancer diagnosis. Indeed, the most common reason patients stop surveillance
and have active treatment is anxiety, not disease progression.
Five-year PSA relapse-free survival with current brachytherapy techniques according to pre-treatment PSA
levels:
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Pre-brachytherapy PSA (ng/ml)
0‒ 4
4 ‒ 10
> 10
5-year actuarial survival (%)
98
90
89
The Gleason score is a system of grading prostate cancer based on its microscopic appearance. It indicates
the sum of predominant histological pattern (graded 1 to 5) and the next most common pattern. Gleason
scores range from two to 10, indicating likelihood a tumor will spread. The higher the score is, the higher
the likelihood of spread. Needle biopsy specimens (versus those from radical prostatectomy) provide
insufficient tissue for complete Gleason scoring and cannot be scored lower than 6 (3 + 3).
Gleason, PSA levels and tumor staging together comprise risk stratification for prostate cancer referenced
in the reviews tabulated under Summary of clinical evidence:
Risk
Low
Intermediate
High
PSA (ng/ml)
< 10
10 ‒ 20
> 20
Gleason
<6
7
8 ‒ 10
Tumor stage
1‒2
2
3‒4
Searches:
Select Health of South Carolina searched PubMed and the databases of:
• UK National Health Services Centre for Reviews and Dissemination.
• Agency for Healthcare Research and Quality Guideline Clearinghouse and evidence-based
practice centers.
• The Centers for Medicare & Medicaid Services (CMS).
We performed searches in July 2015, using the term “brachytherapy.” We included:
• Systematic reviews, which pool results from multiple studies to achieve larger sample sizes and
greater precision of effect estimation than in smaller primary studies. Systematic reviews use
predetermined transparent methods to minimize bias, effectively treating the review as a
scientific endeavor, and are thus rated highest in evidence-grading hierarchies.
• Guidelines based on systematic reviews.
• Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not simple
cost studies), reporting both costs and outcomes — sometimes referred to as efficiency studies
— which also rank near the top of evidence hierarchies.
Findings
•
•
The only brachytherapy indication documented as consistently effective is localized prostate
cancer.
Management options for localized prostate cancer (radical prostatectomy, external beam
radiation and brachytherapy) appear to be fundamentally equivalent in terms of survival
outcomes. Patients and their physicians thus choose among options based on adverse event
profiles or biochemical outcomes, convenience, and other factors not related exclusively to
survival.
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•
•
The current research evidence base is inadequate to determine definitively the best treatment
option, among them brachytherapy, with the optimal balance of benefits and harms for welldefined groups of patients.
Outstanding research issues for prostate cancer include early identification of those men with
PSA screening-detected tumors who should receive immediate or aggressive therapy because
the tumors actually will impact survival, i.e., those patients who will die from their tumors
rather than with them.
Summary of clinical evidence:
Citation
Andras (Cochrane; 2014)
Content
Key points:
Intravascular brachytherapy for peripheral vascular disease
Hayes (2013)
• Randomized controlled trials (RCTs), – August 2013.
• Eight moderate-quality trials (1,090 subjects); brachytherapy as adjunct to stent or balloon.
• Insufficient evidence.
Key points:
Cost-effectiveness of observation vs. immediate treatment for low-risk prostate cancer
Costs and outcomes data from Medicare and published literature for brachytherapy, intensitymodulated radiation or radical prostatectomy for men ages 65 – 75 with newly diagnosed low-risk
disease.
• Observation (watchful waiting) more effective and less costly than immediate treatment.
• Brachytherapy was the most effective and least expensive immediate treatment.
Key points:
•
Kearns (2013)
Cost-effectiveness of enhancements to angioplasty for infrainguinal arterial disease
Lansbury (2013)
Poor reporting and insufficient evidence.
Key points:
Non-metastatic squamous cell carcinoma of the skin
Liu (2013)
Insufficient evidence.
Key points:
High vs. low dose rate for early stage oral cancer
Bonet (2012)
• RCTs and controlled clinical trials (CCTs), – June 2012.
• Dose rates comparable but current evidence insufficient for routine use.
Key points:
Extrahepatic biliary tract cancers
Reveiz (Cochrane; 2012)
• English-language studies – Dec 2008.
• Surgery plus radiation significantly better than surgery alone for cholangiocarcinoma.
Key points:
Non-small cell lung cancer
•
RCTs: brachytherapy vs. external beam – 2012.
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Citation
Varela (2012): Galicia
(Spain) HTA Agency
Hayes, Inc. (2011)
Content
• Fourteen trials (953 subjects).
• Insufficient evidence.
Key points:
High dose for head and neck cancer
Insufficient evidence.
Key points:
Breast cancer
Moderate evidence: for early-stage breast cancer brachytherapy is safe and as an adjunct to
lumpectomy and whole breast irradiation improves tumor control and survival.
• Combination of three interventions is equivalently effective to mastectomy.
• One well-designed study suggests brachytherapy can also improve outcomes of non-surgical
breast-conserving therapy, but a single study is insufficient for definitive conclusions.
• Pending additional research, current evidence insufficient to replace whole-breast radiation with
brachytherapy.
Key points:
•
Peinemann (Cochrane;
2011)
Low dose rate brachytherapy for localized prostate cancer
RCTs for low dose rate vs. radical prostatectomy, external beam or no treatment – 2010.
One (N = 200) vs. radical prostatectomy trial with high risk of bias and no primary outcomes
reported.
• Insufficient evidence.
Key points:
•
•
Wang (Cochrane; 2010)
Locally advanced cervical cancer
Flynn (2009)
• RCTs, – Nov 2009.
• Four trials (N = 1265).
• NS differences with comparators except for small bowel complications with high dose rate.
Key points:
Localized prostate cancer
Nineteen reviews, including Wilt (2008) and Graham (2009), below.
Treatment options equivalent in terms of survival; selections made for other reasons.
Outstanding research issues: early identification of men whose tumors will impact survival or
quality of life.
Key points:
•
•
•
Graham (2009): UK Institute
for Clinical Excellence
Research recommendations
•
•
•
•
“Further research is required into the identification of prognostic indicators in order to differentiate
effectively between men who may die with prostate cancer and those who might die from
prostate cancer.”
The greatest uncertainties are around the identification of which cancers are of clinical
significance and over the choice of radical treatment, and in which settings they are appropriate.
With the diagnosis of prostate cancer being made more frequently in asymptomatic men, it is of
growing importance to know which of these men are likely to benefit from aggressive treatment.
Research is required into the clinical and cost effectiveness of treatments aimed at the
elimination of disease in men with localized prostate cancer, with locally advanced disease and
with locally recurrent disease.
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Citation
Wilt (AHRQ; 2008)
Content
• This research should include a rigorous examination of procedures, such as brachytherapy
(localized disease only), cryotherapy and high-intensity focused ultrasound, as well as
combinations of surgery and radiotherapy with hormonal therapy and chemotherapy. The
endpoints should include survival, local recurrence, toxicity and quality of life.
Key points:
Description of included studies (18 RCTs and 473 observational)
•
•
•
•
•
•
No treatment option had consistent results from at least two high-quality RCTs with adequate
follow up and statistical power.
Three RCTs compared major treatment categories (RP vs. RT or WW) and no trials enrolled
men with primarily PSA-detected disease.
Many RCTs were inadequately powered to provide long-term survival outcomes; most reported
biochemical progression or recurrence as main outcomes.
No RCT evaluated cryotherapy, laparoscopic or robotic-assisted RP, primary androgen
deprivation, high-intensity focused ultrasound, proton beam, or intensity-modulated radiation.
Non-randomized studies varied widely in treatment effectiveness and harms, definitions, and
reporting of outcomes.
Many studies included patients with locally advanced disease but did not analyze separately by
stage.
Results from 18 RCTs and one pooled analysis of three trials
• There were 14,595 patients total.
• Fifteen trials evaluated variations of a particular treatment approach (different doses, isotopes or
duration of RT).
• Six trials included men with locally advanced disease (24% of all patients).
• Only some studies reported age, ethnicity, tumor stage or Gleason score.
• Most studies began enrollment before widespread PSA testing.
• Erectile dysfunction occurred frequently after all treatments (RP 58%; RT 43%; androgen
deprivation 86%).
• A higher risk score incorporating histologic grade, PSA level and tumor stage was associated
with increased risk for disease progression or recurrence regardless of treatment.
Conclusions
“Assessment of the comparative effectiveness and harms of localized prostate cancer treatments is
difficult because of limitations in the evidence.”
Glossary
Prostate-specific antigen (PSA) — An enzyme (biochemical catalyst) produced by malignant and
nonmalignant prostate epithelial cells, making it prostate-specific, but not prostate cancer-specific. It also
increases from prostatitis and benign prostatic hyperplasia.
PSA testing for early detection of prostate cancer was approved by the FDA in 1994 and widespread testing
has played a significant role in the proportion of men diagnosed with early-stage cancers; newly diagnosed
cancers are organ-confined or localized in more than 70 percent to 80 percent of men. As noted above, PSA
levels are strongly associated with risk and outcomes of prostate cancer treatment.
Radical prostatectomy — Surgical removal of the prostate.
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Intensity-modulated radiation therapy (IMRT) — Along with conformal therapy, radiation oncology
techniques developed in the 1990s to capitalize on computers’ abilities to plan radiation delivery more
precisely, thus maximizing exposure of tumors while avoiding surrounding tissues.
Watchful waiting or active surveillance — An approach to low-risk, localized prostate cancer involving
regular PSA testing, digital rectal exam and prostate biopsy that avoids the adverse effects associated with
the immediate treatment options (erectile dysfunction, urinary leakage or incontinence) and defers
treatment until mandated by symptoms or objective signs of tumor progression.
References
Professional society guidelines:
American Urological Association Education and Research Inc. Best practice policy statement on cryosurgery
for the treatment of localized prostate cancer. 2008.
Canadian Coordinating Office for Health Technology Assessment, CCOHTA. Pre-assessment: Brachytherapy
for prostate cancer. Ottawa: Canadian Coordinating Office for Health Technology Assessment; 2002.
Ferrer M, Rueda JR, Latorre K, Gutierrez I; Catalan Agency for Health Technology Assessment and Research
(CAHTA), Barcelona. Long term effectiveness of radical prostatectomy, brachytherapy and external 3D
conformational radiotherapy in organ-confined prostate cancer. December 2008.
Flynn K, Adams E, Alligood E, Lawrence V. Systematic reviews for localized prostate cancer. Veterans Health
Administration. Boston, MA: Office of Patient Care Services Technology Assessment Program; 2009.
Graham J, Baker M, Macbeth F, Titshall V. Diagnosis and treatment of prostate cancer: summary of NICE
guidance. Brit Med J. 2008;336(7644): 610 – 612.
Hayes, Inc. Brachytherapy for breast cancer. Directory pocket summary. March 25, 2011.
Varela LL. High dose brachytherapy for head and neck carcinomas. Santiago de Compostela: Galician
Agency for Health Technology Assessment (AVALIA-T). CT2012/03.2012.
Peer-reviewed references:
Alibhai SM, Klotz LH. A systematic review of randomized trials in localized prostate cancer. Can J Urol. 2004;
11(1): 2110 – 17.
Andriole GL, Crawford ED, Grubb RL, et al. Mortality results from a randomized prostate-cancer screening
trial. New Engl J Med. 2009;360(13):1310 – 19.
Andras A, Hansrani M, Stewart M, Stansby G. Intravascular brachytherapy for peripheral vascular disease.
Cochrane Database of Systematic Reviews. 2014;1.
Aus G, Bergdahl S, Lodding P, Lilja H, Hugosson J. Prostate cancer screening decreases the absolute risk of
being diagnosed with advanced prostate cancer--results from a prospective, population-based randomized
controlled trial. Eur Urol. 2007;51(3): 659 – 64.
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Bernstein M, Ohri N, Hodge JW, et al. Prostate-specific antigen bounce predicts for a favorable prognosis
following brachytherapy: a meta-analysis. J Contemp Brachytherapy. 2013;5(4):210 – 14.
Bill-Axelson A, Holmberg L, Filen F, et al. Radical prostatectomy versus watchful waiting in localized prostate
cancer: the Scandinavian prostate cancer group-4 randomized trial. J Natl Cancer Inst. 2008;100(16):1144 –
1154.
Bonet BM, Allal AS, Gich I, Sole JM, Carrio I. Is adjuvant radiotherapy needed after curative resection of
extrahepatic biliary tract cancers? A systematic review with meta-analysis. Cancer Treat Rev.
2012;38(2):111 – 19.
Candy B, Jones L, Williams R, Tookman A, King M. Phosphodiesterase type 5 inhibitors in the management
of erectile dysfunction secondary to treatments for prostate cancer: findings from a Cochrane systematic
review. BJU Int. 2008;102(4):426 – 31.
Canfield SE. Annual screening for prostate cancer did not reduce mortality from prostate cancer:
Commentary. Ann Intern Med. 2009;150(12):JC64 – JC65.
Chen AB, D'Amico AV, Neville BA, Steyerberg EW, Earle CC. Provider case volume and outcomes following
prostate brachytherapy. J Urol. January 2009; 181(1): 113-18.
Chin JL. Post-radical prostatectomy management options for the positive surgical margin: argument for
adjuvant radiotherapy. Urol Oncol. 2009;27(1):87 – 88.
Chun FK, Haese A, Ahyai Sascha A, et al. Critical assessment of tools to predict clinically insignificant
prostate cancer at radical prostatectomy in contemporary men. Cancer. 2008;113(4):701 – 09.
Cooperberg MR, Broering JM, Carroll PR. Risk assessment for prostate cancer metastasis and mortality at
the time of diagnosis. J Natl Cancer Inst. 2009;101(12):878 – 87.
Cosset JM, Flam T, Thiounn N, et al. Selecting patients for exclusive permanent implant prostate
brachytherapy: the experience of the Paris Institut Curie/Cochin Hospital/Necker Hospital group on 809
patients. Int J Radiat Oncol Biol Phys. 2008;71(4):1042 – 48.
Crook J, Lukka H, Klotz L, Bestic N, Johnston M. Systematic overview of the evidence for brachytherapy in
clinically localized prostate cancer. CMAJ. 2001;164(7):975 – 81.
Fang FM, Wang YM, Wang CJ, Huang HY, Chiang PH. Comparison of the outcome and morbidity for localized
or locally advanced prostate cancer treated by high-dose-rate brachytherapy plus external beam
radiotherapy (EBRT) versus EBRT alone. Jpn J Clin Oncol. 2008;38(7):474 – 79.
Gore JL, Kwan L, Lee SP, Reiter RE, Litwin MS. Survivorship beyond convalescence: 48-month quality-of-life
outcomes after treatment for localized prostate cancer. J Natl Cancer Inst. 2009;101(12):888 – 92.
Gosselaar C, Roobol MJ, van den Bergh RCN, Wolters T, Schroder FH. Digital Rectal Examination and the
Diagnosis of Prostate Cancer: a Study Based on 8 Years and Three Screenings within the European
Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam. Eur Urol. 2009;55(1):139 – 47.
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Grubb RL III, Pinsky PF, Greenlee RT, et al. Prostate cancer screening in the Prostate, Lung, Colorectal and
Ovarian cancer screening trial: update on findings from the initial four rounds of screening in a randomized
trial. BJU Int. 2008;102(11):1524 – 30.
Kittel JA, Reddy CA, Smith KL, et al. Long-term efficacy and toxicity of low-dose-rate (125)I prostate
brachytherapy as monotherapy in low-intermediate-, and high-risk prostate cancer. Int J Radiat Oncol Biol
Phys. 2015;92(4):884 – 92.
Peinemann R, Grouven U, Hemkens LG, et al. Low dose rate brachytherapy for men with localized prostate
cancer. Cochrane Database of Systematic Reviews. 2011;7.
Raabe NK, Normann M, Lilleby W. Low-dose-rate brachytherapy for low-grade prostate cancer. Tidsskr Nor
Laegenforen. 2015;135(6):548 – 52.
Wilt TJ, Shamliyan T, Taylor B, et al. Comparative effectiveness of therapies for clinically localized prostate
cancer. Rockville, MD: AHRQ; 2008. 155 pages.
Wilt TJ, Shamliyan TA, Taylor BC., MacDonald R, Kane RL. Association between hospital and surgeon radical
prostatectomy volume and patient outcomes: a systematic review. J Urol. 2008;180(3):820 – 29.
Wilt TJ, Thompson IM. Clinically localised prostate cancer. Brit Med J. 2006;333(7578):1102 – 06.
Wolters T, Roobol Monique J, Bangma Chris H, Schroder Fritz H. Is prostate-specific antigen velocity
selective for clinically significant prostate cancer in screening? European Randomized Study of Screening for
Prostate Cancer (Rotterdam). Eur Urol. 2009;55(2):385 – 92.
Wu AK, Cooperberg MR, Sadetsky N, Carroll PR. Health related quality of life in patients treated with
multimodal therapy for prostate cancer. J Urol. 2008;180(6):2415 – 22.
Zhou EH, Ellis RJ, Cherullo E, et al. Radiotherapy and survival in prostate cancer patients: a populationbased study. Int J Radiat Oncol Biol Phys. 2009;73(1):15 – 23.
Clinical trials:
Reviews in the Summary of clinical evidence (Pages 4–6) cover trials published through 2013.
CMS National Coverage Determinations (NCDs):
None found as of the writing of this policy.
Local Coverage Determinations (LCDs):
Wisconsin Physicians Service. Local coverage determination (LCD): Selective internal radiation therapy
(SIRT) for primary and secondary hepatic malignancy (80Y-microsphere hepatic brachytherapy). L300137.
Effective October 16, 2009; reviewed January 1, 2014.
Commonly submitted codes
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Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is not
an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and bill
accordingly.
ICD-9 Code
185
CPT Code
55875
Description
Comment
Malignant neoplasm of the prostate
Description
Transperineal placement of needles or catheters into prostate for interstitial
radioelement application
77776
Interstitial radiation source application; simple
77777
Interstitial radiation source application; intermediate
77778
Interstitial radiation source application; complex
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