Download 8.01.61 Focal Treatments for Prostate Cancer

MEDICAL POLICY
POLICY
RELATED POLICIES
POLICY GUIDELINES
CODING
DESCRIPTION
SCOPE
BENEFIT APPLICATION
RATIONALE
REFERENCES
APPENDIX
HISTORY
Focal Treatments for Prostate Cancer
Number
Effective Date
Revision Date(s)
Replaces
8.01.61
November 1, 2016
10/11/16; 11/10/15
N/A
Policy
[TOP]
Use of any focal therapy modality to treat patients with localized prostate cancer is investigational.
Related Policies
[TOP]
7.01.109
Magnetic Resonance–Guided Focused Ultrasound
Policy Guidelines
[TOP]
There is no specific CPT code for these treatments.
Coding
CPT
53899
55899
Unlisted procedure, urinary system
Unlisted procedure, male genital system
Description
[TOP]
Prostate cancer is the second most common cancer diagnosed among men in the United States. Given the
frequent uncertainty in predicting behavior of individual localized prostate cancers, and the substantial adverse
effects associated with whole-gland treatments, investigators have sought to minimize morbidity associated with
radical treatment while reducing tumor burden to an extent that reduces the chances for rapid progression to
incurability. This approach is termed focal treatment. Focal treatment seeks to ablate either an “index” lesion
(defined as the largest cancerous lesion with the highest grade tumor thought to be the lesion that will drive the
natural history of this typically multifocal disease), or, alternatively, to ablate additional non‒index lesions or all
other areas of known cancer. Several ablative methods that have been used to remove cancerous lesions in
localized prostate cancer are addressed in this evidence review.
For individuals who have primary localized prostate cancer who receive focal therapy using laser ablation, highintensity focused ultrasound, cryoablation, radiofrequency ablation, or photodynamic therapy, the evidence
includes 1 high-quality systematic review, studies from 1 registry cohort, and numerous observational studies.
Relevant outcomes are overall survival, disease-specific survival, symptoms, change in disease status, functional
outcomes, quality of life, and treatment-related morbidity. The evidence is highly heterogeneous and
inconsistently reports clinical outcomes. No prospective, comparative evidence was found for focal ablation
techniques versus current standard treatment of localized prostate cancer, including radical prostatectomy,
external-beam radiotherapy (EBRT), or active surveillance. Methods have not been standardized to determine
which and how many identified cancerous lesions should be treated for best outcomes. No evidence supports
which, if any, of the focal techniques leads to better functional outcomes. Although high disease-specific survival
rates have been reported, the short follow-up periods and small sample sizes preclude conclusions on the effect
of any of these techniques on overall survival rates. The adverse effect rates associated with focal therapies
appear to be superior to those associated with radical treatments (e.g., radical prostatectomy, EBRT), however,
evidence is limited in its quality, reporting, and scope. The evidence is insufficient to determine the effects of the
technology on health outcomes.
Background
Localized Prostate Cancer and Current Management
Prostate cancer is the second most common cancer diagnosed among men in the United States. According to the
National Cancer Institute (NCI), nearly 240,000 new cases were expected to be diagnosed in the United States in
2013 and would be associated with around 30,000 deaths. Autopsy studies in the pre prostate-specific antigen
(PSA) screening era have identified incidental cancerous foci in 30% of men 50 years of age, with incidence
reaching 75% at age 80 years.(1) However, NCI Surveillance Epidemiology and End Results data show ageadjusted cancer-specific mortality rates for men with prostate cancer have declined from 40 per 100,000 in 1992
to 22 per 100,000 in 2010. This decline has been attributed to a combination of earlier detection via PSA
screening and improved therapies.
Localized prostate cancers may appear very similar clinically at diagnosis.(2) However, they often exhibit diverse
risk of progression that may not be captured by accepted clinical risk categories (e.g., D’Amico criteria) or
prognostic tools based on clinical findings (e.g., PSA titers, Gleason grade, or tumor stage).(3-7) In studies of
conservative management, the risk of localized disease progression based on prostate cancer‒specific survival
rates at 10 years may range from 15%(8,9) to 20%(10) to perhaps 27% at 20-year follow-up.(11) Among elderly
men (≥70 years) with this type of low-risk disease, comorbidities typically supervene as a cause of death; these
men will die with prostate cancer present rather than from the cancer. Other very similar-appearing low-risk
tumors may progress unexpectedly rapidly, quickly disseminating and becoming incurable.
The divergent behavior of localized prostate cancers creates uncertainty whether to treat immediately.(12,13) A
patient may choose definitive treatment upfront.(14) Surgery (radical prostatectomy) or external beam
radiotherapy (EBRT) are most commonly used to treat patients with localized prostate cancer.(13,15)
Complications most commonly reported with radical prostatectomy or EBRT and with the greatest variability are
incontinence (0%-73%) and other genitourinary toxicities (irritative and obstructive symptoms); hematuria
(typically ≤5%); gastrointestinal and bowel toxicity, including nausea and loose stools (25%-50%); proctopathy,
including rectal pain and bleeding (10%-39%); and erectile dysfunction, including impotence (50%-90%).(15)
American Urological Association guidelines suggest patients with low- and intermediate-risk disease have the
option of entering an “active surveillance” protocol, which takes into account patient age, patient preferences, and
health conditions related to urinary, sexual, and bowel function.(15) With this approach, the patient will forgo
immediate therapy, but continue regular monitoring until signs or symptoms of disease progression are evident, at
which point curative treatment is instituted.(16,17)
Focal Treatment of Localized Prostate Cancer
Given significant uncertainty in predicting behavior of individual localized prostate cancers, and the substantial
adverse effects associated with definitive treatments, investigators have sought a therapeutic “middle ground.”
The latter seeks to minimize morbidity associated with radical treatment in those who may not actually require it
while reducing tumor burden to an extent that reduces the chances for rapid progression to incurability. This
approach is termed focal treatment, in that it seeks to remove-using any of several ablative methods described
next-cancerous lesions at high risk of progression, leaving behind uninvolved glandular parenchyma. The overall
goal of focal treatment is to minimize the risk of early tumor progression and preserve erectile, urinary and rectal
functions by reducing damage to the neurovascular bundles, external sphincter, bladder neck, and rectum.(18-22)
Although focal treatment is offered as an alternative middle approach to management of localized prostate
cancer, several key issues must be considered in choosing it. They include patient selection, lesion selection,
therapy monitoring, and the modality used to ablate lesions.
Patient Selection
A proportion of men with localized prostate cancer have been reported to have, or develop, serious misgivings
and psychosocial problems in accepting active surveillance, sometimes leading to inappropriately discontinuing
it.(23) Thus, appropriate patient selection is imperative for physicians who must decide whether to recommend
active surveillance or focal treatment for patients who refuse radical therapy or for whom it is not recommended
due to the a risk-benefit balance.(24)
Lesion Selection
Proper lesion selection is a second key consideration in choosing focal treatment of localized prostate cancer.
Although prostate cancer has always been regarded as a multifocal disease, clinical evidence shows that
between 10% and 40% of men who undergo radical prostatectomy for presumed multifocal disease actually have
a unilaterally confined discrete lesion, which, when removed, would “cure” the patient.(25-27) This view
presumably has driven the use of region-targeted focal treatment variants, such as hemiablation of the half of the
gland containing tumor, or subtotal prostate ablation via the “hockey stick” method.(28) While these approaches
can be curative, the more extensive the treatment, the more likely the functional adverse outcomes would
approach those of radical treatments.
The concept that clinically indolent lesions comprise most of the tumor burden in a patient with organ-confined
prostate cancer led to development of a lesion-targeted strategy, which is referred to as “focal therapy” in this
evidence review.(29) This involves treating only the largest and highest grade cancerous focus (referred to as the
“index lesion”), which has been shown in pathologic studies to determine clinical progression of disease.(30,31)
This concept is supported by molecular genetics evidence that suggests a single index tumor focus is usually
responsible for disease progression and metastasis.(32,33) The index lesion approach leaves in place small foci
3
less than 0.5 cm in volume, with Gleason score less than 7, that are considered unlikely to progress over a 10- to
20-year period.(34-36) This also leaves available subsequent definitive therapies as needed should disease
progress.
Identification of prostate cancer lesions-disease localization-particularly the index lesion, is critical to oncologic
success of focal therapy. The ability to guide focal ablation energy to the tumor and assess treatment
effectiveness are additionally important to treatment success. At present, no single modality meets the
requirements for all 3 activities.(24,29) Systematic transrectal ultrasound (TRUS)‒guided biopsy alone has been
investigated, but is considered insufficient for patient selection or disease localization for focal therapy.(37-41) A 5
mm transperineal prostate mapping (TPM) biopsy using a brachytherapy template is the current recommended
standard by the European Association of Urology in its 2012 guidelines.(42) TPM can provide 3-dimensional
coordinates of cancerous lesions, and has about 87% to 95% accuracy rates in detecting and ruling out clinically
significant cancer of all sizes.(43,44) However, TPM is resource intensive, requires general anesthesia, and has
been associated with adverse events including urinary retention (6%), prostatitis (4%), and local events such as
perineal hematoma, bruising, and pain (5%).(45) The risk of complications of general anesthesia and the cost of
processing multiple biopsy specimens have been considered to limit the practicality and widespread applicability
of this approach.(23)
Multiparametric magnetic resonance imaging (mp-MRI), typically including T1-, T2-, diffusion-weighted imaging,
and dynamic contrast-enhanced imaging, has been recognized as a promising modality to risk-stratify prostate
cancer and select patients and lesions for focal therapy.(23,29,37) Evidence shows mp-MRI can detect high grade, large prostate cancer foci with performance similar to TPM. (46)For example, for the primary end point
definition (lesion, ≥4 mm; Gleason score, ≥3+4), with TPM as the reference standard, sensitivity, negative
predictive value, and negative likelihood ratios with mp-MRI were 58% to 73%, 84% to 89%, and 0.3 to 0.5,
respectively. Specificity, positive predictive value, and positive likelihood ratios were 71% to 84%, 49% to 63%,
and 2.0 to 3.44, respectively. The negative predictive value of mp-MRI appears sufficient to rule out clinically
significant prostate cancer and may have clinical use in this setting. However, although mp-MRI technology has
capability to detect and risk-stratify prostate cancer, several issues constrain its widespread use for these
purposes. Thus, it is still necessary to histologically confirm suspicious lesions using TPM; mp-MRI requires
highly specialized MRI-compatible equipment; biopsy within the MRI scanner is challenging; and interpretation of
prostate MRI images requires experienced uroradiologists.(47)
Therapy Monitoring
Some controversy exists as to the proper end points for focal therapy of prostate cancer. The primary end point of
focal ablation of clinically significant disease with negative biopsies evaluated at 12 months post-treatment is
generally accepted according to a European consensus report.(37) The clinical validity of MRI to analyze the
presence of residual or recurrent cancer compared with histologic findings is offered as a secondary end point.
However, MRI findings alone are not considered sufficient in follow-up.(37) Finally, although investigators indicate
PSA levels should be monitored, they are not considered valid end points because the utility of PSA kinetics in
tissue preservation treatments has not been established.(34)
Modalities Used to Ablate Lesions
Five ablative methods for which clinical evidence is available are considered herein: focal laser ablation (FLA);
high-intensity focused ultrasound; cryoablation; radiofrequency ablation (RFA); and photodynamic therapy
(PDT).(18,19,21,22,28,29,32,34,37,48,49) Each method requires placement of a needle probe within a tumor
volume followed by delivery of some type of energy that destroys the tissue in a controlled manner. All methods
except FLA currently rely on ultrasound guidance to the tumor focus of interest; FLA uses MRI to guide the probe.
This evidence review does not cover focal brachytherapy (see Related Policies).
Focal Laser Ablation
FLA refers to the destruction of tissue using a focused beam of electromagnetic radiation emitted from a laser. It
is accomplished through transperineal or transrectal introduction of a laser fiber into the cancer focus, with
emission of energy. Tissue is destroyed through thermal conversion of the focused electromagnetic energy into
heat, causing coagulative necrosis. Other terms for FLA include photothermal therapy, laser interstitial therapy,
and laser interstitial photocoagulation.(50)
High-Intensity Focused Ultrasound
High-intensity focused ultrasound works by focusing high-energy ultrasound waves on a single location, which
increases the local tissue temperature to over 80°C. This causes a discrete locus of coagulative necrosis of
approximately 3x3x10 mm. The surgeon uses a transrectal probe to plan, carry out, and monitor treatment in a
real-time sequence to ablate the entire gland or small discrete lesions.
Cryoablation
Cryoablation induces cell death through direct cellular toxicity from disruption of the cell membrane caused by iceball crystals and vascular compromise from thrombosis and ischemia secondary to freezing below -30°C. It is
performed by transperineal insertion under TRUS guidance of a varying number of cryoprobe needles into the
tumor, using a TPM template.
Radiofrequency Ablation
RFA uses energy produced by a 50-watt generator with a frequency of 460 kHz. The energy is transmitted to the
tumor focus through 15 needle electrodes inserted transperineally under ultrasound guidance into the tissue. It
produces an increase in tissue temperature causing coagulative necrosis.
Photodynamic Therapy
PDT uses an intravenous photosensitizing agent that distributes to prostate tissue, followed by delivery of light via
transperineally inserted needles. The light induces a photochemical reaction that causes production of reactive
oxygen species that are highly toxic and reactive with tissue causing functional and structural damage (i.e., cell
death). A major concern with PDT is that real-time monitoring of tissue effects is not possible, and the variable
optical properties of prostate tissue complicate assessment of necrosis and treatment progress.
Regulatory Status
Focal Laser Ablation
The Visualase® Thermal Therapy System was cleared for marketing by the U.S. Food and Drug Administration
(FDA) through the 510(k) process for use to necrotize or coagulate soft tissue through interstitial irradiation or
thermal therapy under MRI guidance in cardiothoracic surgery, dermatology, otolaryngology, gastroenterology,
general surgery, gynecology, head and neck surgery, neurosurgery, plastic surgery, orthopedics, pulmonology,
radiology, and urology, for wavelengths 800 to 1064 nm. FDA product code: LLZ, GEX, FRN.
High-Intensity Focused Ultrasound
In 2015, the Sonablate® 450 (SonaCare Medical) was approved by FDA through a de novo request and classified
the device as class II under the generic name “high intensity ultrasound system for prostate tissue ablation”. This
device was the first of its kind to be approved in the United States. A similar device, Ablatherm® (EDAP TMS),
was cleared for marketing by FDA through the 510(k) process shortly thereafter.
Cryoablation
Some cryotherapy devices cleared for marketing by FDA through the 510(k) process for cryoablation of the
prostate are: Visual-ICE® (Galil Medical), Ice Rod CX, CryoCare® (Galil Medical), and IceSphere (Galil Medical).
FDA product code: GEH.
Radiofrequency Ablation
RFA devices have been cleared for marketing by FDA through the 510(k) process for general use for soft tissue
cutting and coagulation and ablation by thermal coagulation. Under this general indication, RFA may be used to
ablate tumors. FDA product code: GEI.
Photodynamic Therapy
FDA has granted approval to several photosensitizing drugs and light applicators. Photofrin® (porfimer sodium)
and psoralen are photosensitizers, ultraviolet lamps used in the treatment of cancer, were cleared from marketing
by FDA through the 510(k) process. FDA product code: FTC.
Scope
[TOP]
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
[TOP]
N/A
Rationale
[TOP]
Populations
Individuals:
 With primary
localized
prostate cancer
Interventions
Interventions of interest are:
 Focal therapy using laser
ablation
Comparators
Comparators of interest are:
 Surgery (radical
prostatectomy)
 External-beam radiotherapy
 Active surveillance
Individuals:
 With primary
localized
prostate cancer
Interventions of interest are:
 Focal therapy using highintensity focused
ultrasound
Comparators of interest are:
 Surgery (radical
prostatectomy)
 External-beam radiotherapy
 Active surveillance
Individuals:
 With primary
localized
prostate cancer
Interventions of interest are:
 Focal therapy using
cryoablation
Comparators of interest are:
 Surgery (radical
prostatectomy)
 External-beam radiotherapy
 Active surveillance
Individuals:
 With primary
localized
prostate cancer
Interventions of interest are:
 Focal therapy using
radiofrequency thermal
ablation
Comparators of interest are:
 Surgery (radical
prostatectomy)
 External-beam radiotherapy
 Active surveillance
Individuals:
 With primary
localized
prostate cancer
Interventions of interest are:
 Focal therapy using
photodynamic therapy
Comparators of interest are:
 Surgery (radical
prostatectomy)
 External-beam radiotherapy
 Active surveillance
Outcomes
Relevant outcomes include:
 Overall survival
 Disease-specific survival
 Symptoms
 Change in disease status
 Functional outcomes
 Quality of life
 Treatment-related morbidity
Relevant outcomes include:
 Overall survival
 Disease-specific survival
 Symptoms
 Change in disease status
 Functional outcomes
 Quality of life
 Treatment-related morbidity
Relevant outcomes include:
 Overall survival
 Disease-specific survival
 Symptoms
 Change in disease status
 Functional outcomes
 Quality of life
 Treatment-related morbidity
Relevant outcomes include:
 Overall survival
 Disease-specific survival
 Symptoms
 Change in disease status
 Functional outcomes
 Quality of life
 Treatment-related morbidity
Relevant outcomes include:
 Overall survival
 Disease-specific survival
 Symptoms
 Change in disease status
 Functional outcomes
 Quality of life
 Treatment-related morbidity
This policy was created in April 2015, based on a literature review of the PubMed database from January 2005 to
March 3, 2015. The current evidence review includes a literature search of PubMed through July 26, 2016. No
prospective, comparative studies were identified for any of the ablative technologies. Evidence comprises case
series and other observational studies. This review only includes evidence on primary focal therapy for prostate
cancer; it does not consider the recurrent or salvage setting.
Focal Treatments OverviewA high-quality systematic review published by Valerio et al in 2014 compiled the bulk
of the evidence available in the literature on the technologies included herein through 2012.(51) This systematic
review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
52
(PRISMA) guidelines. Only studies that reported actual focal therapy procedures were included. Specific
categories of data to be collected were prespecified. Study selection criteria were prespecified, with dual review
and data extraction, and senior author arbitration as needed. The quality of included studies was assessed using
the Oxford Centre for Evidence-based Medicine level of evidence for therapy. This review and its summarized
statistics serve as the initial evidence source for this evidence review. Additional prospective studies of a
comparative nature are reviewed in subsequent sections below.
A total of 25 series were included that evaluated a number of methods used for focal therapy in the primary
setting. The quality of evidence was low to medium, with no study yielding a level of evidence greater than 2b
(individual cohort study). Twelve series used high-intensity focused ultrasound (N=226); 6 series (N=1400) used
cryoablation (1 study included 1160/1400); 3 used focal laser ablation (N=16); 1 used radiofrequency ablation
(N=14); and 1 used photodynamic therapy (N=6). In 2 series focal treatments were mixed or included
brachytherapy.
Patients in 12 series included in this SR had disease defined as low risk (n=1109 [56%]), intermediate risk (n=704
[36%]), and high risk (n=164 [8%]); risk categories were not available in 13 series. Median age of patients ranged
from 56 years to 73 years. The prostate -specific antigen (PSA) level of patients ranged from 3.8 to 24 ng/mL. An
individual Gleason score was available in 20 series, with 1503 men having a Gleason score of less than 6; 521
with a Gleason score of 7; and 82 with Gleason scores higher than 8. Median follow-up periods for the reported
focal therapy series were 0 to 10.6 years. Disease was localized as follows: transrectal ultrasound (TRUS) biopsy
in 2 series; TRUS biopsy with Doppler ultrasound in 2 series; TRUS biopsy plus magnetic resonance imaging in 6
series; transperineal template-guided mapping biopsy and multiparametric magnetic resonance imaging in 4
series; preoperative assessment was not reported in 11 studies.
In all studies where such data were reported in the Valerio SR, all known areas of cancer were treated; in no
study was it explicitly stated that the index lesion was ablated and that other lesions were left untreated.
Biochemical control based on PSA levels was reported in 5 series using the RTOG-ASTRO Phoenix Consensus
Conference criteria.(53) Other definitions used to define biochemical control were American Society for Radiation
Oncology (ASTRO; 5 series), Stuttgart (1 series), and Phoenix plus PSA velocity greater than 0.75 ng/mL
annually (1 series). Biochemical control rates ranged from 86% at 8-year follow-up (n=318) to 60% at 5-year
(n=56). Because follow-up was too short, progression to metastatic disease was not reported for most studies in
the Valerio review; in those with information available, metastatic progression rates were very low (0%-0.3%).
Although a cancer-specific survival rate of 100% was reported in all series, this must be considered in the context
of the small numbers of patients in individual studies and the short follow-up (only 3 studies had follow-up >5
years).
Across all studies, median hospital length of stay was 1 day; other perioperative outcomes were poorly reported.
Across studies, the most frequent complications associated with treatment of prostate cancer urinary retention,
urinary stricture, and urinary tract infection-occurred in 0% to 17%, 0% to 5%,and 0% to 17%, respectively, of
patients. Only 5 studies reported all 3 complications. Validated questionnaires were used in 9 series to report
urinary functional outcomes; physician-reported rates were used in 5 studies. According to questionnaires, the
pad-free continence rate varied between 95% and 100%, whereas the range of leak-free rates was 80% to 100%.
Validated questionnaire data showed erectile functional rates in 54% to 100%, while physician-reported data
showed erectile functional rates of 58% to 85%. Other adverse outcomes were poorly reported, particularly
quality-of-life data, with only 3 studies reporting the latter.
In 2015, Wolff et al reported results of a systematic review of randomized controlled trials (RCTs) of radiotherapy
(RT) versus other nonpharmacologic treatments, including HIFU and cryoablation for treatment of localized
prostate cancer.(54) The review followed Centre for Reviews and Dissemination and Cochrane guidelines for
conduct and reporting. The selection criteria and outcomes of interest were prespecified. The search included
publications up to February 2014. The reviewers found 2 RCTs of cryotherapy versus RT, but both evaluated
whole-gland instead of focal cryotherapy, and found no RCTs of HIFU versus RT.
Section Summary
Systematic reviews have reported no published prospective, comparative evidence for focal ablation techniques
versus current standard treatment of localized prostate cancer. Evidence consists of case series and
noncomparative observational studies. Studies were generally small with short follow-up. Data on clinical
outcomes such as progression to metastatic disease were not reported for most studies included in the Valerio
review. Perioperative outcomes and other adverse events were also poorly reported.
Laser Ablation
Additional case series and nonrandomized studies have assessed of focal laser ablation(55,56) since the Valerio
review. Studies were small (range, 8-25 men), single arm, lacked long-term follow-up (range, 3-6 months) and did
not report clinical outcomes (e.g., progression-free survival, overall survival).
Cryoablation
The Cryo Online Data (COLD) registry is a database established and supported by a cryotherapy manufacturer.
The data are maintained independently. Physicians submit standardized forms to the database and participation
is voluntary. The registry contains case report forms of pretreatment and posttreatment information for patients
undergoing whole-gland or partial-gland (focal) prostate cryoablation. Patients are stratified into low-,
intermediate-, and high-risk groups. Ward and Jones have described characteristics of the focal cryotherapy
registry patients in 2012.(57) Biochemical success was defined using the ASTRO definitions. The analysis
included 1160 patients treated with focal cryoablation and 5853 treated with whole-gland cryoablation between
1997 and 2007. Report of use of focal cryoablation increased dramatically between 1999 (46 reports) and 2005
(567 reports, p<0.01). The biochemical success at 36 months for focal cryotherapy was 75.7% and was similar to
that of whole gland cryoablation (75.5%); no significant differences between biochemical success for whole-gland
versus focal cryoablation were observed for low-, intermediate-, or high-risk groups (p not given). Urinary
continence was 98.4% in focal versus 96.9% in whole-gland cryoablation.
A matched cohort study published in 2015 included 317 men who underwent focal cryoablation with 317 men who
underwent whole-gland cryoablation.(58) Patients in the study were entered in the Cryo Online Data (COLD)
registry between 2007 and 2013. Median (SD) age at the time of the procedure was 66 (7) years, and median
follow-up time was 58 months. All patients were preoperatively potent men who had low-risk disease according to
the D'Amico risk criteria and were matched according to age at surgery. Outcomes included biochemical
recurrence (BCR) free‒survival, defined according to ASTRO and Phoenix criteria and assessed by Kaplan-Meier
curves. Only patients with PSA nadir data were included in oncologic outcome analysis. Functional outcomes
were assessed at 6, 12, and 24 months after the procedure for erectile function (defined as ability to have
intercourse with or without erectile aids), urinary continence, urinary retention, and rates of fistula formation. After
surgery, 30% (n=95) and 17% (n=55) of the men who underwent whole-gland cryoablation and focal cryoablation,
respectively, underwent biopsy, with positive biopsy rates of 12% and 14%, respectively. BCR-free survival rates
at 60 months according to the Phoenix definition were 80% and 71% in the whole-gland and focal therapy
cohorts, respectively, with a hazard ratio of 0.827 (p>0.1). According to the ASTRO definition, BCR-free survival
was 82% and 73%, respectively (p>0.1). Erectile function data at 24 months were available for 172 whole-gland
and 160 focal therapy‒treated men. Recovery of erectile function was achieved in 47% and 69% of patients in the
whole-gland and focal therapy cohorts, respectively (p=0.001). Urinary function data at 24 months were available
for 307 whole-gland and 313 focal therapy patients. Urinary continence rates were 99% and 100% for the wholegland and focal therapy groups, respectively (p=0.02). Urinary retention at 6, 12, and 24 months was reported in
7%, 2%, and 0.6%, respectively, in the whole-gland treated patients versus 5%, 1%, and 0.9%, respectively, in
the focal therapy cohort. One fistula was reported in each group.
In 2016, Lian et al reported long-term results of a case series of 40 low- to intermediate-risk patients treated with
primary focal cryoablation between 2006 and 2013 by a single urologist in China.(59) Biochemical recurrence was
defined using the Phoenix definition and treatment failure was defined as at least 1 positive biopsy or BCR. Mean
follow-up was 63 months (range, 12-92 months). Two (5%) of 40 patients met the criteria for biochemical failure
and 4 (10%) patients experienced treatment failure. Of the men who were potent before cryotherapy, 20 (77%)
remained potent after treatment. Ninety-eight percent of the men were completely continent during follow-up.
Section Summary:
Data from the COLD registry comparing focal to whole-gland cryoablation have suggested that BRFS is similar
although perhaps slightly lower in focal cryoablation compared to whole-gland cryoablation while erectile function
preservation was higher. Evidence for other focal therapies continues to consist of small, noncomparative studies.
Results from a phase 3 trial of photodynamic therapy should be available soon.
Photodynamic Therapy
Preliminary results from a trial of TOOKAD, a soluble vascular-targeted photodynamic therapy (VTP), were
presented in 2016 at the 31st Annual European Association of Urology Congress but have not yet been
published. A total of 413 men with low-risk prostate cancer were randomized and followed for 2 years (206 in VTP
plus active surveillance; 207 in active surveillance without VTP).(60) It was reported that 28% of the patients in
the VTP group versus 58% of the control group experienced disease progression (hazard ratio, 0.34; 95%
confidence interval, 0.24 to 0.46; p<0.001) and more patients in the VTP group (49%) versus surveillance group
(14%) had negative biopsies at 2 years. These results cannot be reviewed in full until publication.
Additional nonrandomized studies have assessed of photodynamic therapy since the Valerio review. A
prospective, multicenter phase 2/3 trial by Taneja et al treated 30 men using photodynamic therapy. Follow-up
was limited to 6 months and trialists did not report important clinical outcomes (e.g., progression-free survival,
overall survival).(61)
Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this policy are listed in Table 1.
Table 1. Summary of Key Trials
NCT No.
Ongoing
NCT02303054
NCT02016040
NCT02328807
NCT00877682
Unpublished
NCT01310894
Trial Name
MRI-US Fusion Biopsy-Guided Focal Radio-Frequency Ablation of
the Prostate in Men with Localized Prostate Cancer (FUSAblate
Trial)
Focal Therapy Using High Intensity Focused Ultrasound
(Ablatherm®) for Localized Prostate Cancer
Focal Prostate Radio-Frequency Ablation for the Treatment of
Prostate Cancer
Regional Cryoablation for Localized Adenocarcinoma of the
Prostate
A European Randomized Phase 3 Study to Assess the Efficacy and
Safety of TOOKAD ® Soluble for Localized Prostate Cancer
Compared to Active Surveillance
Planned
Enrollment
Completion
Date
21
Jul 2016
25
Sep 2016
30
Nov 2016
100
Apr 2018
413
Sep 2015
(completed)
NCT: national clinical trial.
Summary of Evidence
For individuals who have primary localized prostate cancer who receive focal therapy using laser ablation, highintensity focused ultrasound, cryoablation, radiofrequency ablation, or photodynamic therapy, the evidence
includes 1 high-quality systematic review, studies from 1 registry cohort, and numerous observational studies.
Relevant outcomes are overall survival, disease-specific survival, symptoms, change in disease status, functional
outcomes, quality of life, and treatment-related morbidity. The evidence is highly heterogeneous and
inconsistently reports clinical outcomes. No prospective, comparative evidence was found for focal ablation
techniques versus current standard treatment of localized prostate cancer, including radical prostatectomy,
external-beam radiotherapy (EBRT), or active surveillance. Methods have not been standardized to determine
which and how many identified cancerous lesions should be treated for best outcomes. No evidence supports
which, if any, of the focal techniques leads to better functional outcomes. Although high disease-specific survival
rates have been reported, the short follow-up periods and small sample sizes preclude conclusions on the effect
of any of these techniques on overall survival rates. The adverse effect rates associated with focal therapies
appear to be superior to those associated with radical treatments (e.g., radical prostatectomy, EBRT), however,
evidence is limited in its quality, reporting, and scope. The evidence is insufficient to determine the effects of the
technology on health outcomes.
Practice Guidelines and Position Statements
National Comprehensive Cancer Network
The National Comprehensive Cancer Network guidelines for prostate cancer (v.3.2016) state that cryosurgery
(cryotherapy or cryoablation) is an “evolving minimally invasive therapy that damages tumor tissue through local
freezing.” It further states that “other emerging therapies such as high intensity focused ultrasound (HIFU) and
vascular-targeted photodynamic (VTP), also warrant further study.”(62)
National Institute for Health and Care Excellence
The National Institute for Health and Care Excellence (NICE) issued guidance on the use cryoablation for
localized prostate cancer in 2012.(48) NICE concluded that current evidence on focal therapy using cryoablation
for localized prostate cancer raises no major safety concerns. However, evidence on efficacy is limited in quantity,
with concern that prostate cancer is commonly multifocal. Therefore this procedure should only be used with
special arrangements for clinical governance, consent, and audit or research.
NICE also issued guidance on the use of focal therapy using high-intensity focused ultrasound (HIFU) for
localized prostate cancer in 2012.(49) It concluded that current evidence on HIFU for localized prostate cancer
raises no major safety concerns. However, evidence on efficacy is limited in quantity, with concern that prostate
cancer is commonly multifocal. Therefore this procedure should only be used with special arrangements for
clinical governance, consent, and audit or research.
In 2014, NICE issued guidance on diagnosis and management of prostate cancer. The recommendations stated
that neither cryotherapy or HIFU should be offered to men with localized prostate cancer or locally advanced
prostate cancer outside of controlled trials comparing their use with established interventions.(63)
American Urological Association
The American Urological Association (AUA) issued guidelines on the management of clinically localized prostate
cancer in 2007, which were reviewed and validity confirmed in 2011.(64) AUA guidelines include the following
recommendation regarding focal treatments:
“In addition to treatment modalities described and evaluated by the panel, a number of additional
treatments as well as combinations of treatments have been used for the management of clinically
localized prostate cancer. These treatments include cryotherapy, high-intensity focused ultrasound, highdose interstitial prostate brachytherapy, and combinations of treatments (e.g., external beam radiotherapy
and interstitial prostate brachytherapy)…. The panel did not include other treatment options … due to a
combination of factors, including limited published experience and short-term follow -up….”
National Cancer Institute
The National Cancer Institute (NCI) updated its information on prostate cancer treatments in 2015.(65) NCI
indicates cryotherapy and HIFU are new treatment options currently being studied in national trials. NCI proffers
no recommendation for or against these treatments.
U.S. Preventive Services Task Force Recommendations
The U.S. Preventive Services Task Force published recommendations for prostate cancer screening. However,
there are no recommendations for focal treatment of prostate cancer.
Medicare National Coverage
There is no national coverage determination (NCD). In the absence of an NCD, coverage decisions are left to the
discretion of local Medicare carriers.
References
[TOP]
1. Dall'Era MA, Cooperberg MR, Chan JM, et al. Active surveillance for early-stage prostate cancer: review
of the current literature. Cancer. Apr 15 2008;112(8):1650-1659. PMID 18306379
2. Bangma CH, Roemeling S, Schroder FH. Overdiagnosis and overtreatment of early detected prostate
cancer. World J Urol. Mar 2007;25(1):3-9. PMID 17364211
3. Johansson JE, Andren O, Andersson SO, et al. Natural history of early, localized prostate cancer. JAMA.
Jun 9 2004;291(22):2713-2719. PMID 15187052
4. Ploussard G, Epstein JI, Montironi R, et al. The contemporary concept of significant versus insignificant
prostate cancer. Eur Urol. Aug 2011;60(2):291-303. PMID 21601982
5. Harnden P, Naylor B, Shelley MD, et al. The clinical management of patients with a small volume of
prostatic cancer on biopsy: what are the risks of progression? A systematic review and meta-analysis.
Cancer. Mar 1 2008;112(5):971-981. PMID 18186496
6. Brimo F, Montironi R, Egevad L, et al. Contemporary grading for prostate cancer: implications for patient
care. Eur Urol. May 2013;63(5):892-901. PMID 23092544
7. Eylert MF, Persad R. Management of prostate cancer. Br J Hosp Med (Lond). Feb 2012;73(2):95-99.
PMID 22504752
8. Eastham JA, Kattan MW, Fearn P, et al. Local progression among men with conservatively treated
localized prostate cancer: results from the Transatlantic Prostate Group. Eur Urol. Feb 2008;53(2):347354. PMID 17544572
9. Bill-Axelson A, Holmberg L, Ruutu M, et al. Radical prostatectomy versus watchful waiting in early
prostate cancer. N Engl J Med. May 12 2005;352(19):1977-1984. PMID 15888698
10. Thompson IM, Jr., Goodman PJ, Tangen CM, et al. Long-term survival of participants in the prostate
cancer prevention trial. N Engl J Med. Aug 15 2013;369(7):603-610. PMID 23944298
11. Albertsen PC, Hanley JA, Fine J. 20-year outcomes following conservative management of clinically
localized prostate cancer. JAMA. May 4 2005;293(17):2095-2101. PMID 15870412
12. Borley N, Feneley MR. Prostate cancer: diagnosis and staging. Asian J Androl. Jan 2009;11(1):74-80.
PMID 19050692
13. Freedland SJ. Screening, risk assessment, and the approach to therapy in patients with prostate cancer.
Cancer. Mar 15 2011;117(6):1123-1135. PMID 20960523
14. Ip S, Dahabreh IJ, Chung M, et al. An evidence review of active surveillance in men with localized
prostate cancer. Evidence Report/Technology Assessment no. 204 (AHRQ Publication No. 12-E003-EF).
Rockville, MD: Agency for Research and Quality; 2011.
15. Thompson I, Thrasher JB, Aus G, et al. American Urological Association guideline for management of
clinically localized prostate cancer: 2007 update. 2007;
http://www.auanet.org/common/pdf/education/clinical-guidance/Prostate-Cancer.pdf Accessed October
2016.
16. Whitson JM, Carroll PR. Active surveillance for early-stage prostate cancer: defining the triggers for
intervention. J Clin Oncol. Jun 10 2010;28(17):2807-2809. PMID 20439633
17. Albertsen PC. Treatment of localized prostate cancer: when is active surveillance appropriate? Nat Rev
Clin Oncol. Jul 2010;7(7):394-400. PMID 20440282
18. Jacome-Pita F, Sanchez-Salas R, Barret E, et al. Focal therapy in prostate cancer: the current situation.
Ecancermedicalscience. 2014;8:435. PMID 24944577
19. Nguyen CT, Jones JS. Focal therapy in the management of localized prostate cancer. BJU Int. May
2011;107(9):1362-1368. PMID 21223478
20. Lindner U, Lawrentschuk N, Schatloff O, et al. Evolution from active surveillance to focal therapy in the
management of prostate cancer. Future Oncol. Jun 2011;7(6):775-787. PMID 21675840
21. Iberti CT, Mohamed N, Palese MA. A review of focal therapy techniques in prostate cancer: clinical
results for high-intensity focused ultrasound and focal cryoablation. Rev Urol. 2011;13(4):e196-202.
PMID 22232569
22. Lecornet E, Ahmed HU, Moore CM, et al. Conceptual basis for focal therapy in prostate cancer. J
Endourol. May 2010;24(5):811-818. PMID 20443699
23. Tay KJ, Mendez M, Moul JW, et al. Active surveillance for prostate cancer: can we modernize
contemporary protocols to improve patient selection and outcomes in the focal therapy era? Curr Opin
Urol. Mar 12 2015. PMID 25768694
24. Passoni NM, Polascik TJ. How to select the right patients for focal therapy of prostate cancer? Curr Opin
Urol. May 2014;24(3):203-208. PMID 24625428
25. Scales CD, Jr., Presti JC, Jr., Kane CJ, et al. Predicting unilateral prostate cancer based on biopsy
features: implications for focal ablative therapy--results from the SEARCH database. J Urol. Oct
2007;178(4 Pt 1):1249-1252. PMID 17698131
26. Mouraviev V, Mayes JM, Sun L, et al. Prostate cancer laterality as a rationale of focal ablative therapy for
the treatment of clinically localized prostate cancer. Cancer. Aug 15 2007;110(4):906-910. PMID
17587207
27. Mouraviev V, Mayes JM, Madden JF, et al. Analysis of laterality and percentage of tumor involvement in
1386 prostatectomized specimens for selection of unilateral focal cryotherapy. Technol Cancer Res
Treat. Apr 2007;6(2):91-95. PMID 17375971
28. Muto S, Yoshii T, Saito K, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of
localized prostate cancer. Jpn J Clin Oncol. Mar 2008;38(3):192-199. PMID 18281309
29. Kasivisvanathan V, Emberton M, Ahmed HU. Focal therapy for prostate cancer: rationale and treatment
opportunities. Clin Oncol (R Coll Radiol). Aug 2013;25(8):461-473. PMID 23759249
30. Mouraviev V, Villers A, Bostwick DG, et al. Understanding the pathological features of focality, grade and
tumour volume of early-stage prostate cancer as a foundation for parenchyma-sparing prostate cancer
therapies: active surveillance and focal targeted therapy. BJU Int. Oct 2011;108(7):1074-1085. PMID
21489116
31. Mouraviev V, Mayes JM, Polascik TJ. Pathologic basis of focal therapy for early-stage prostate cancer.
Nat Rev Urol. Apr 2009;6(4):205-215. PMID 19352395
32. Liu W, Laitinen S, Khan S, et al. Copy number analysis indicates monoclonal origin of lethal metastatic
prostate cancer. Nat Med. May 2009;15(5):559-565. PMID 19363497
33. Guo CC, Wang Y, Xiao L, et al. The relationship of TMPRSS2-ERG gene fusion between primary and
metastatic prostate cancers. Hum Pathol. May 2012;43(5):644-649. PMID 21937078
34. Ahmed HU, Emberton M. Active surveillance and radical therapy in prostate cancer: can focal therapy
offer the middle way? World J Urol. Oct 2008;26(5):457-467. PMID 18704441
35. Stamey TA, Freiha FS, McNeal JE, et al. Localized prostate cancer. Relationship of tumor volume to
clinical significance for treatment of prostate cancer. Cancer. Feb 1 1993;71(3 Suppl):933-938. PMID
7679045
36. Nelson BA, Shappell SB, Chang SS, et al. Tumour volume is an independent predictor of prostatespecific antigen recurrence in patients undergoing radical prostatectomy for clinically localized prostate
cancer. BJU Int. Jun 2006;97(6):1169-1172. PMID 16686706
37. van den Bos W, Muller BG, Ahmed H, et al. Focal therapy in prostate cancer: international
multidisciplinary consensus on trial design. Eur Urol. Jun 2014;65(6):1078-1083. PMID 24444476
38. Mayes JM, Mouraviev V, Sun L, et al. Can the conventional sextant prostate biopsy accurately predict
unilateral prostate cancer in low-risk, localized, prostate cancer? Urol Oncol. Mar-Apr 2011;29(2):166170. PMID 19451000
39. Sinnott M, Falzarano SM, Hernandez AV, et al. Discrepancy in prostate cancer localization between
biopsy and prostatectomy specimens in patients with unilateral positive biopsy: implications for focal
therapy. Prostate. Aug 1 2012;72(11):1179-1186. PMID 22161896
40. Gallina A, Maccagnano C, Suardi N, et al. Unilateral positive biopsies in low risk prostate cancer patients
diagnosed with extended transrectal ultrasound-guided biopsy schemes do not predict unilateral prostate
cancer at radical prostatectomy. BJU Int. Jul 2012;110(2 Pt 2):E64-68. PMID 22093108
41. Briganti A, Tutolo M, Suardi N, et al. There is no way to identify patients who will harbor small volume,
unilateral prostate cancer at final pathology. implications for focal therapies. Prostate. Jun 1
2012;72(8):925-930. PMID 21965006
42. Heidenreich A, Bastian PJ, Bellmunt J, et al. European Association of Urology 2012 guidelines on
prostate cancer. 2012; http://uroweb.org/guidelines/ Accessed October 2016.
43. Crawford ED, Rove KO, Barqawi AB, et al. Clinical-pathologic correlation between transperineal mapping
biopsies of the prostate and three-dimensional reconstruction of prostatectomy specimens. Prostate.
May 2013;73(7):778-787. PMID 23169245
44. Hu Y, Ahmed HU, Carter T, et al. A biopsy simulation study to assess the accuracy of several transrectal
ultrasonography (TRUS)-biopsy strategies compared with template prostate mapping biopsies in patients
who have undergone radical prostatectomy. BJU Int. Sep 2012;110(6):812-820. PMID 22394583
45. Tsivian M, Abern MR, Qi P, et al. Short-term functional outcomes and complications associated with
transperineal template prostate mapping biopsy. Urology. Jul 2013;82(1):166-170. PMID 23697794
46. Arumainayagam N, Ahmed HU, Moore CM, et al. Multiparametric MR imaging for detection of clinically
significant prostate cancer: a validation cohort study with transperineal template prostate mapping as the
reference standard. Radiology. Sep 2013;268(3):761-769. PMID 23564713
47. Dickinson L, Ahmed HU, Allen C, et al. Magnetic resonance imaging for the detection, localisation, and
characterisation of prostate cancer: recommendations from a European consensus meeting. Eur Urol.
Apr 2011;59(4):477-494. PMID 21195536
48. National Institute for Health and Care Excellence (NICE). Focal Therapy Using Cryoablation for
Localised Prostate Cancer (IPG423). 2012; https://www.nice.org.uk/guidance/ipg423/chapter/1-guidance
Accessed October 2016.
49. National Institute for Health and Care Excellence (NICE). Focal Therapy Using High-Intensity Focused
Ultrasound for Localized Prostate Cancer (IPG424). 2012; http://www.nice.org.uk/guidance/ipg424
Accessed October 2016.
50. Lee T, Mendhiratta N, Sperling D, et al. Focal laser ablation for localized prostate cancer: principles,
clinical trials, and our initial experience. Rev Urol. 2014;16(2):55-66. PMID 25009445
51. Valerio M, Ahmed HU, Emberton M, et al. The role of focal therapy in the management of localised
prostate cancer: a systematic review. Eur Urol. Oct 2014;66(4):732-751. PMID 23769825
52. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and
meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin
Epidemiol. Oct 2009;62(10):e1-34. PMID 19631507
53. Roach M, 3rd, Hanks G, Thames H, Jr., et al. Defining biochemical failure following radiotherapy with or
without hormonal therapy in men with clinically localized prostate cancer: recommendations of the
RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys. Jul 15 2006;65(4):965974. PMID 16798415
54. Wolff RF, Ryder S, Bossi A, et al. A systematic review of randomised controlled trials of radiotherapy for
localised prostate cancer. Eur J Cancer. Nov 2015;51(16):2345-2367. PMID 26254809
55. Lepor H, Llukani E, Sperling D, et al. Complications, recovery, and early functional outcomes and
oncologic control following in-bore focal laser ablation of prostate cancer. Eur Urol. Dec 2015;68(6):924926. PMID 25979568
56. Natarajan S, Raman S, Priester AM, et al. Focal laser ablation of prostate cancer: phase I clinical trial. J
Urol. Jul 2016;196(1):68-75. PMID 26748164
57. Ward JF, Jones JS. Focal cryotherapy for localized prostate cancer: a report from the national Cryo OnLine Database (COLD) Registry. BJU Int. Jun 2012;109(11):1648-1654. PMID 22035200
58. Mendez MH, Passoni NM, Pow-Sang J, et al. Comparison of outcomes between preoperatively potent
men treated with focal versus whole gland cryotherapy in a matched population. J Endourol. Jul 13 2015.
PMID 26058496
59. Lian H, Zhuang J, Yang R, et al. Focal cryoablation for unilateral low-intermediate-risk prostate cancer:
63-month mean follow-up results of 41 patients. Int Urol Nephrol. Jan 2016;48(1):85-90. PMID 26531063
60. Emberton M. TOOKAD (Padeliporfin) Vascular-Targeted Photodynamic Therapy Versus Active
Surveillance in Men With Low Risk Prostate Cancer. A Randomized Phase 3 Clinical Trial (Abstract
LBA02). Paper presented at: 31st Annual European Association of Urology Congress; 2016, March 13;
Munich, Germany.
61. Taneja SS, Bennett J, Coleman J, et al. Final results of a phase I/II multicenter trial of WST11 vascular
targeted photodynamic therapy for hemi-ablation of the prostate in men with unilateral low risk prostate
cancer performed in the United States. J Urol. Jun 9 2016. PMID 27291652
62. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology:
prostate cancer. Version 3.2016. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf
Accessed October 2016.
63. National Institute for Health and Care Excellence (NICE). Prostate cancer: diagnosis and management
(CG175). 2014; https://www.nice.org.uk/guidance/cg175/resources/prostate-cancer-diagnosis-andmanagement-35109753913285 Accessed October 2016.
64. American Urological Association (AUA). Guideline for the Management of Clinically Localized Prostate
Cancer. 2011; https://www.auanet.org/education/guidelines/prostate-cancer.cfm Accessed October
2016.
65. National Cancer Institute. Prostate Cancer Treatment, Treatment Option Overview. 2015;
http://www.cancer.gov/cancertopics/pdq/treatment/prostate/Patient/page4#_172 Accessed October
2016.
Appendix
[TOP]
N/A
History
[TOP]
Date
07/14/15
11/10/15
10/11/16
Reason
New Policy. Policy created with literature review through March 3, 2015. Use of any focal therapy
modality is considered investigational for treatment of localized prostate cancer.
Annual Review. Policy updated with literature review through July 28, 2015; reference 55 added.
Policy statement unchanged.
Annual Review. Policy updated with literature review through July 26, 2016; references 55-57 and
59-63 were added. Policy statement unchanged.
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).
©2016 Premera All Rights Reserved.
Discrimination is Against the Law
Premera Blue Cross complies with applicable Federal civil rights laws and
does not discriminate on the basis of race, color, national origin, age,
disability, or sex. Premera does not exclude people or treat them differently
because of race, color, national origin, age, disability or sex.
Premera:
• Provides free aids and services to people with disabilities to communicate
effectively with us, such as:
• Qualified sign language interpreters
• Written information in other formats (large print, audio, accessible
electronic formats, other formats)
• Provides free language services to people whose primary language is not
English, such as:
• Qualified interpreters
• Information written in other languages
If you need these services, contact the Civil Rights Coordinator.
If you believe that Premera has failed to provide these services or
discriminated in another way on the basis of race, color, national origin, age,
disability, or sex, you can file a grievance with:
Civil Rights Coordinator - Complaints and Appeals
PO Box 91102, Seattle, WA 98111
Toll free 855-332-4535, Fax 425-918-5592, TTY 800-842-5357
Email [email protected]
You can file a grievance in person or by mail, fax, or email. If you need help
filing a grievance, the Civil Rights Coordinator is available to help you.
You can also file a civil rights complaint with the U.S. Department of Health
and Human Services, Office for Civil Rights, electronically through the
Office for Civil Rights Complaint Portal, available at
https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:
U.S. Department of Health and Human Services
200 Independence Avenue SW, Room 509F, HHH Building
Washington, D.C. 20201, 1-800-368-1019, 800-537-7697 (TDD)
Complaint forms are available at
http://www.hhs.gov/ocr/office/file/index.html.
Getting Help in Other Languages
This Notice has Important Information. This notice may have important
information about your application or coverage through Premera Blue
Cross. There may be key dates in this notice. You may need to take action
by certain deadlines to keep your health coverage or help with costs. You
have the right to get this information and help in your language at no cost.
Call 800-722-1471 (TTY: 800-842-5357).
አማሪኛ (Amharic):
ይህ ማስታወቂያ አስፈላጊ መረጃ ይዟል። ይህ ማስታወቂያ ስለ ማመልከቻዎ ወይም የ Premera Blue
Cross ሽፋን አስፈላጊ መረጃ ሊኖረው ይችላል። በዚህ ማስታወቂያ ውስጥ ቁልፍ ቀኖች ሊኖሩ ይችላሉ።
የጤናን ሽፋንዎን ለመጠበቅና በአከፋፈል እርዳታ ለማግኘት በተውሰኑ የጊዜ ገደቦች እርምጃ መውሰድ
ይገባዎት ይሆናል። ይህን መረጃ እንዲያገኙ እና ያለምንም ክፍያ በቋንቋዎ እርዳታ እንዲያገኙ መብት
አለዎት።በስልክ ቁጥር 800-722-1471 (TTY: 800-842-5357) ይደውሉ።
‫( العربية‬Arabic):
‫ قد يحوي ھذا اإلشعار معلومات مھمة بخصوص طلبك أو‬.‫يحوي ھذا اإلشعار معلومات ھامة‬
‫ قد تكون ھناك تواريخ مھمة‬.Premera Blue Cross ‫التغطية التي تريد الحصول عليھا من خالل‬
‫ وقد تحتاج التخاذ إجراء في تواريخ معينة للحفاظ على تغطيتك الصحية أو للمساعدة‬.‫في ھذا اإلشعار‬
‫ اتصل‬.‫ يحق لك الحصول على ھذه المعلومات والمساعدة بلغتك دون تكبد أية تكلفة‬.‫في دفع التكاليف‬
800-722-1471 (TTY: 800-842-5357)‫بـ‬
中文 (Chinese):
本通知有重要的訊息。本通知可能有關於您透過 Premera Blue Cross 提交的
申請或保險的重要訊息。本通知內可能有重要日期。您可能需要在截止日期
之前採取行動，以保留您的健康保險或者費用補貼。您有權利免費以您的母
語得到本訊息和幫助。請撥電話 800-722-1471 (TTY: 800-842-5357)。
037338 (07-2016)
Oromoo (Cushite):
Beeksisni kun odeeffannoo barbaachisaa qaba. Beeksisti kun sagantaa
yookan karaa Premera Blue Cross tiin tajaajila keessan ilaalchisee
odeeffannoo barbaachisaa qabaachuu danda’a. Guyyaawwan murteessaa
ta’an beeksisa kana keessatti ilaalaa. Tarii kaffaltiidhaan deeggaramuuf
yookan tajaajila fayyaa keessaniif guyyaa dhumaa irratti wanti raawwattan
jiraachuu danda’a. Kaffaltii irraa bilisa haala ta’een afaan keessaniin
odeeffannoo argachuu fi deeggarsa argachuuf mirga ni qabaattu.
Lakkoofsa bilbilaa 800-722-1471 (TTY: 800-842-5357) tii bilbilaa.
Français (French):
Cet avis a d'importantes informations. Cet avis peut avoir d'importantes
informations sur votre demande ou la couverture par l'intermédiaire de
Premera Blue Cross. Le présent avis peut contenir des dates clés. Vous
devrez peut-être prendre des mesures par certains délais pour maintenir
votre couverture de santé ou d'aide avec les coûts. Vous avez le droit
d'obtenir cette information et de l’aide dans votre langue à aucun coût.
Appelez le 800-722-1471 (TTY: 800-842-5357).
Kreyòl ayisyen (Creole):
Avi sila a gen Enfòmasyon Enpòtan ladann. Avi sila a kapab genyen
enfòmasyon enpòtan konsènan aplikasyon w lan oswa konsènan kouvèti
asirans lan atravè Premera Blue Cross. Kapab genyen dat ki enpòtan nan
avi sila a. Ou ka gen pou pran kèk aksyon avan sèten dat limit pou ka
kenbe kouvèti asirans sante w la oswa pou yo ka ede w avèk depans yo.
Se dwa w pou resevwa enfòmasyon sa a ak asistans nan lang ou pale a,
san ou pa gen pou peye pou sa. Rele nan 800-722-1471
(TTY: 800-842-5357).
Deutsche (German):
Diese Benachrichtigung enthält wichtige Informationen. Diese
Benachrichtigung enthält unter Umständen wichtige Informationen
bezüglich Ihres Antrags auf Krankenversicherungsschutz durch Premera
Blue Cross. Suchen Sie nach eventuellen wichtigen Terminen in dieser
Benachrichtigung. Sie könnten bis zu bestimmten Stichtagen handeln
müssen, um Ihren Krankenversicherungsschutz oder Hilfe mit den Kosten
zu behalten. Sie haben das Recht, kostenlose Hilfe und Informationen in
Ihrer Sprache zu erhalten. Rufen Sie an unter 800-722-1471
(TTY: 800-842-5357).
Hmoob (Hmong):
Tsab ntawv tshaj xo no muaj cov ntshiab lus tseem ceeb. Tej zaum
tsab ntawv tshaj xo no muaj cov ntsiab lus tseem ceeb txog koj daim ntawv
thov kev pab los yog koj qhov kev pab cuam los ntawm Premera Blue
Cross. Tej zaum muaj cov hnub tseem ceeb uas sau rau hauv daim ntawv
no. Tej zaum koj kuj yuav tau ua qee yam uas peb kom koj ua tsis pub
dhau cov caij nyoog uas teev tseg rau hauv daim ntawv no mas koj thiaj
yuav tau txais kev pab cuam kho mob los yog kev pab them tej nqi kho mob
ntawd. Koj muaj cai kom lawv muab cov ntshiab lus no uas tau muab sau
ua koj hom lus pub dawb rau koj. Hu rau 800-722-1471
(TTY: 800-842-5357).
Iloko (Ilocano):
Daytoy a Pakdaar ket naglaon iti Napateg nga Impormasion. Daytoy a
pakdaar mabalin nga adda ket naglaon iti napateg nga impormasion
maipanggep iti apliksayonyo wenno coverage babaen iti Premera Blue
Cross. Daytoy ket mabalin dagiti importante a petsa iti daytoy a pakdaar.
Mabalin nga adda rumbeng nga aramidenyo nga addang sakbay dagiti
partikular a naituding nga aldaw tapno mapagtalinaedyo ti coverage ti
salun-atyo wenno tulong kadagiti gastos. Adda karbenganyo a mangala iti
daytoy nga impormasion ken tulong iti bukodyo a pagsasao nga awan ti
bayadanyo. Tumawag iti numero nga 800-722-1471 (TTY: 800-842-5357).
Italiano (Italian):
Questo avviso contiene informazioni importanti. Questo avviso può contenere
informazioni importanti sulla tua domanda o copertura attraverso Premera
Blue Cross. Potrebbero esserci date chiave in questo avviso. Potrebbe
essere necessario un tuo intervento entro una scadenza determinata per
consentirti di mantenere la tua copertura o sovvenzione. Hai il diritto di
ottenere queste informazioni e assistenza nella tua lingua gratuitamente.
Chiama 800-722-1471 (TTY: 800-842-5357).
日本語 (Japanese):
この通知には重要な情報が含まれています。この通知には、Premera Blue
Cross の申請または補償範囲に関する重要な情報が含まれている場合があ
ります。この通知に記載されている可能性がある重要な日付をご確認くだ
さい。健康保険や有料サポートを維持するには、特定の期日までに行動を
取らなければならない場合があります。ご希望の言語による情報とサポー
トが無料で提供されます。800-722-1471 (TTY: 800-842-5357)までお電話
ください。
Română (Romanian):
Prezenta notificare conține informații importante. Această notificare
poate conține informații importante privind cererea sau acoperirea asigurării
dumneavoastre de sănătate prin Premera Blue Cross. Pot exista date cheie
în această notificare. Este posibil să fie nevoie să acționați până la anumite
termene limită pentru a vă menține acoperirea asigurării de sănătate sau
asistența privitoare la costuri. Aveți dreptul de a obține gratuit aceste
informații și ajutor în limba dumneavoastră. Sunați la 800-722-1471
(TTY: 800-842-5357).
한국어 (Korean):
본 통지서에는 중요한 정보가 들어 있습니다. 즉 이 통지서는 귀하의 신청에
관하여 그리고 Premera Blue Cross 를 통한 커버리지에 관한 정보를
포함하고 있을 수 있습니다. 본 통지서에는 핵심이 되는 날짜들이 있을 수
있습니다. 귀하는 귀하의 건강 커버리지를 계속 유지하거나 비용을 절감하기
위해서 일정한 마감일까지 조치를 취해야 할 필요가 있을 수 있습니다.
귀하는 이러한 정보와 도움을 귀하의 언어로 비용 부담없이 얻을 수 있는
권리가 있습니다. 800-722-1471 (TTY: 800-842-5357) 로 전화하십시오.
Pусский (Russian):
Настоящее уведомление содержит важную информацию. Это
уведомление может содержать важную информацию о вашем
заявлении или страховом покрытии через Premera Blue Cross. В
настоящем уведомлении могут быть указаны ключевые даты. Вам,
возможно, потребуется принять меры к определенным предельным
срокам для сохранения страхового покрытия или помощи с расходами.
Вы имеете право на бесплатное получение этой информации и
помощь на вашем языке. Звоните по телефону 800-722-1471
(TTY: 800-842-5357).
ລາວ (Lao):
ແຈ້ ງການນ້ີ ມີຂ້ໍ ມູ ນສໍາຄັ ນ. ແຈ້ ງການນ້ີ ອາດຈະມີຂ້ໍ ມູ ນສໍາຄັ ນກ່ ຽວກັ ບຄໍາຮ້ ອງສະ
ໝັ ກ ຫື ຼ ຄວາມຄຸ້ ມຄອງປະກັ ນໄພຂອງທ່ ານຜ່ ານ Premera Blue Cross. ອາດຈະມີ
ວັ ນທີສໍາຄັ ນໃນແຈ້ ງການນີ້. ທ່ ານອາດຈະຈໍາເປັນຕ້ ອງດໍາເນີນການຕາມກໍານົ ດ
ເວລາສະເພາະເພື່ອຮັ ກສາຄວາມຄຸ້ ມຄອງປະກັ ນສຸ ຂະພາບ ຫື ຼ ຄວາມຊ່ ວຍເຫື ຼ ອເລື່ອງ
ຄ່ າໃຊ້ ຈ່ າຍຂອງທ່ ານໄວ້ . ທ່ ານມີສິດໄດ້ ຮັ ບຂ້ໍ ມູ ນນ້ີ ແລະ ຄວາມຊ່ ວຍເຫື ຼ ອເປັນພາສາ
ຂອງທ່ ານໂດຍບໍ່ເສຍຄ່ າ. ໃຫ້ ໂທຫາ 800-722-1471 (TTY: 800-842-5357).
ភាសាែខម រ (Khmer):
េសចកត ីជូនដំណឹងេនះមានព័ត៌មានយា៉ងសំខាន់។ េសចកត ីជូនដំណឹងេនះរបែហល
ជាមានព័ត៌មានយា៉ងសំខាន់អំពីទរមង់ែបបបទ ឬការរា៉ប់រងរបស់អនកតាមរយៈ
Premera Blue Cross ។ របែហលជាមាន កាលបរ ិេចឆ ទសំខាន់េនៅកនុងេសចកត ីជូន
ដំណឹងេនះ។ អន ករបែហលជារតូវការបេញច ញសមតថ ភាព ដល់កំណត់ៃថង ជាក់ចបាស់
នានា េដើមបីនឹងរកសាទុកការធានារា៉ប់រងសុខភាពរបស់អនក ឬរបាក់ជំនួយេចញៃថល ។
អន កមានសិទធិទទួ លព័ត៌មានេនះ និងជំនួយេនៅកនុងភាសារបស់អនកេដាយមិនអស
លុយេឡើយ។ សូ មទូ រស័ពទ 800-722-1471 (TTY: 800-842-5357)។
ਪੰ ਜਾਬੀ (Punjabi):
ਇਸ ਨੋਿਟਸ ਿਵਚ ਖਾਸ ਜਾਣਕਾਰੀ ਹੈ. ਇਸ ਨੋਿਟਸ ਿਵਚ Premera Blue Cross ਵਲ ਤੁਹਾਡੀ
ਕਵਰੇਜ ਅਤੇ ਅਰਜੀ ਬਾਰੇ ਮਹੱ ਤਵਪੂਰਨ ਜਾਣਕਾਰੀ ਹੋ ਸਕਦੀ ਹੈ . ਇਸ ਨੋਿਜਸ ਜਵਚ ਖਾਸ ਤਾਰੀਖਾ
ਹੋ ਸਕਦੀਆਂ ਹਨ. ਜੇਕਰ ਤੁਸੀ ਜਸਹਤ ਕਵਰੇਜ ਿਰੱ ਖਣੀ ਹੋਵੇ ਜਾ ਓਸ ਦੀ ਲਾਗਤ ਜਿਵੱ ਚ ਮਦਦ ਦੇ
ਇਛੁੱ ਕ ਹੋ ਤਾਂ ਤੁਹਾਨੂੰ ਅੰ ਤਮ ਤਾਰੀਖ਼ ਤ ਪਿਹਲਾਂ ਕੁੱ ਝ ਖਾਸ ਕਦਮ ਚੁੱ ਕਣ ਦੀ ਲੋ ੜ ਹੋ ਸਕਦੀ ਹੈ ,ਤੁਹਾਨੂੰ
ਮੁਫ਼ਤ ਿਵੱ ਚ ਤੇ ਆਪਣੀ ਭਾਸ਼ਾ ਿਵੱ ਚ ਜਾਣਕਾਰੀ ਅਤੇ ਮਦਦ ਪ੍ਰਾਪਤ ਕਰਨ ਦਾ ਅਿਧਕਾਰ ਹੈ ,ਕਾਲ
800-722-1471 (TTY: 800-842-5357).
‫( فارسی‬Farsi):
‫اين اعالميه ممکن است حاوی اطالعات مھم درباره فرم‬. ‫اين اعالميه حاوی اطالعات مھم ميباشد‬
‫ به تاريخ ھای مھم در‬.‫ باشد‬Premera Blue Cross ‫تقاضا و يا پوشش بيمه ای شما از طريق‬
‫شما ممکن است برای حقظ پوشش بيمه تان يا کمک در پرداخت ھزينه‬. ‫اين اعالميه توجه نماييد‬
‫شما حق‬. ‫ به تاريخ ھای مشخصی برای انجام کارھای خاصی احتياج داشته باشيد‬،‫ھای درمانی تان‬
‫ برای کسب‬.‫اين را داريد که اين اطالعات و کمک را به زبان خود به طور رايگان دريافت نماييد‬
‫( تماس‬800-842-5357 ‫ تماس باشماره‬TTY ‫ )کاربران‬800-722-1471 ‫اطالعات با شماره‬
.‫برقرار نماييد‬
Polskie (Polish):
To ogłoszenie może zawierać ważne informacje. To ogłoszenie może
zawierać ważne informacje odnośnie Państwa wniosku lub zakresu
świadczeń poprzez Premera Blue Cross. Prosimy zwrócic uwagę na
kluczowe daty, które mogą być zawarte w tym ogłoszeniu aby nie
przekroczyć terminów w przypadku utrzymania polisy ubezpieczeniowej lub
pomocy związanej z kosztami. Macie Państwo prawo do bezpłatnej
informacji we własnym języku. Zadzwońcie pod 800-722-1471
(TTY: 800-842-5357).
Português (Portuguese):
Este aviso contém informações importantes. Este aviso poderá conter
informações importantes a respeito de sua aplicação ou cobertura por meio
do Premera Blue Cross. Poderão existir datas importantes neste aviso.
Talvez seja necessário que você tome providências dentro de
determinados prazos para manter sua cobertura de saúde ou ajuda de
custos. Você tem o direito de obter esta informação e ajuda em seu idioma
e sem custos. Ligue para 800-722-1471 (TTY: 800-842-5357).
Fa’asamoa (Samoan):
Atonu ua iai i lenei fa’asilasilaga ni fa’amatalaga e sili ona taua e tatau
ona e malamalama i ai. O lenei fa’asilasilaga o se fesoasoani e fa’amatala
atili i ai i le tulaga o le polokalame, Premera Blue Cross, ua e tau fia maua
atu i ai. Fa’amolemole, ia e iloilo fa’alelei i aso fa’apitoa olo’o iai i lenei
fa’asilasilaga taua. Masalo o le’a iai ni feau e tatau ona e faia ao le’i aulia le
aso ua ta’ua i lenei fa’asilasilaga ina ia e iai pea ma maua fesoasoani mai ai
i le polokalame a le Malo olo’o e iai i ai. Olo’o iai iate oe le aia tatau e maua
atu i lenei fa’asilasilaga ma lenei fa’matalaga i legagana e te malamalama i
ai aunoa ma se togiga tupe. Vili atu i le telefoni 800-722-1471
(TTY: 800-842-5357).
Español (Spanish):
Este Aviso contiene información importante. Es posible que este aviso
contenga información importante acerca de su solicitud o cobertura a
través de Premera Blue Cross. Es posible que haya fechas clave en este
aviso. Es posible que deba tomar alguna medida antes de determinadas
fechas para mantener su cobertura médica o ayuda con los costos. Usted
tiene derecho a recibir esta información y ayuda en su idioma sin costo
alguno. Llame al 800-722-1471 (TTY: 800-842-5357).
Tagalog (Tagalog):
Ang Paunawa na ito ay naglalaman ng mahalagang impormasyon. Ang
paunawa na ito ay maaaring naglalaman ng mahalagang impormasyon
tungkol sa iyong aplikasyon o pagsakop sa pamamagitan ng Premera Blue
Cross. Maaaring may mga mahalagang petsa dito sa paunawa. Maaring
mangailangan ka na magsagawa ng hakbang sa ilang mga itinakdang
panahon upang mapanatili ang iyong pagsakop sa kalusugan o tulong na
walang gastos. May karapatan ka na makakuha ng ganitong impormasyon
at tulong sa iyong wika ng walang gastos. Tumawag sa 800-722-1471
(TTY: 800-842-5357).
ไทย (Thai):
ประกาศนี ้มีข้อมูลสําคัญ ประกาศนี ้อาจมีข้อมูลที่สําคัญเกี่ยวกับการการสมัครหรื อขอบเขตประกัน
สุขภาพของคุณผ่าน Premera Blue Cross และอาจมีกําหนดการในประกาศนี ้ คุณอาจจะต้ อง
ดําเนินการภายในกําหนดระยะเวลาที่แน่นอนเพื่อจะรักษาการประกันสุขภาพของคุณหรื อการช่วยเหลือที่
มีค่าใช้ จ่าย คุณมีสิทธิที่จะได้ รับข้ อมูลและความช่วยเหลือนี ้ในภาษาของคุณโดยไม่มีค่าใช้ จ่าย โทร
800-722-1471 (TTY: 800-842-5357)
Український (Ukrainian):
Це повідомлення містить важливу інформацію. Це повідомлення
може містити важливу інформацію про Ваше звернення щодо
страхувального покриття через Premera Blue Cross. Зверніть увагу на
ключові дати, які можуть бути вказані у цьому повідомленні. Існує
імовірність того, що Вам треба буде здійснити певні кроки у конкретні
кінцеві строки для того, щоб зберегти Ваше медичне страхування або
отримати фінансову допомогу. У Вас є право на отримання цієї
інформації та допомоги безкоштовно на Вашій рідній мові. Дзвоніть за
номером телефону 800-722-1471 (TTY: 800-842-5357).
Tiếng Việt (Vietnamese):
Thông báo này cung cấp thông tin quan trọng. Thông báo này có thông
tin quan trọng về đơn xin tham gia hoặc hợp đồng bảo hiểm của quý vị qua
chương trình Premera Blue Cross. Xin xem ngày quan trọng trong thông
báo này. Quý vị có thể phải thực hiện theo thông báo đúng trong thời hạn
để duy trì bảo hiểm sức khỏe hoặc được trợ giúp thêm về chi phí. Quý vị có
quyền được biết thông tin này và được trợ giúp bằng ngôn ngữ của mình
miễn phí. Xin gọi số 800-722-1471 (TTY: 800-842-5357).