Medical Policy

 

Subject: Multiparametric Magnetic Resonance Fusion Imaging Targeted Prostate Biopsy
Document #: RAD.00066 Publish Date:    06/06/2018
Status: Reviewed Last Review Date:    05/03/2018

Description/Scope

This document addresses the use of a “fusion biopsy system” in which a multi-parametric prostate magnetic resonance image (mpMRI) is fused with real-time high definition prostate ultrasound images through the use of specialized equipment and software to target and biopsy areas suspicious for prostate cancer.

Note: Please see the following related documents for additional information:

Position Statement

Medically Necessary:

The use of multiparametric magnetic resonance imaging fusion with rectal ultrasound for targeted biopsy of the prostate is considered medically necessary for individuals with:

Investigational and Not Medically Necessary:

The use of multiparametric magnetic resonance imaging fusion with rectal ultrasound for targeted biopsy of the prostate is considered investigational and not medically necessary for all other indications.

Rationale

Ultrasound-guided biopsy via the transrectal approach has been the standard approach for the detection of prostate cancer in men. The mpMRI, combined with ultrasound imaging can be used to create a three-dimensional view of the prostate. This allows for targeted biopsies which have been proposed to improve prostate biopsy precision.

In a 2014 study by Siddiqui and colleagues, the authors sought to determine if a standard biopsy was necessary if the targeted-MRI approach was also done. All participants in this study (n=1215) underwent mpMRI and subsequently mpMRI/ultrasound fusion biopsy and standard biopsy. A total of 181 participants did not have lesions, leaving 1034 to proceed with biopsy. After additional exclusions, 1003 participants were included in the study. The targeted mpMRI/ultrasound fusion-directed biopsies diagnosed 461 cases of prostate cancer and the standard, systematic approach to biopsy diagnosed 469 cases of prostate cancer with exact agreement between approaches for 690 men (69%). When the standard biopsy cores were combined with the targeted mpMRI approach, an additional 103 cases of prostate cancer were diagnosed (of which 83% were considered low risk, 12% were intermediate risk, and 5% were high risk). The predictive ability of targeted biopsy for differentiating low-risk from intermediate- and high-risk disease in 170 men with whole-gland pathology after prostatectomy was greater than that of standard biopsy or the two approaches combined (area under the curve, 0.73, 0.59, and 0.67, respectively; p< 0.05 for all comparisons). The authors noted that mpMRI/ultrasound fusion was associated with increased detection of high-risk prostate cancer and decreased detection of low-risk prostate cancer, but that additional study would be needed to determine clinical impact, such as recurrence of disease and prostate cancer-specific mortality.

A 2015 study by Kim and colleagues compared targeted mpMRI prostate biopsies to conventional transrectal ultrasound guided biopsies. A total of 34 men received targeted mpMRI biopsy and were individually matched to 34 men who received conventional biopsy. Findings were correlated to Gleason Scores to determine clinical significance. As compared with the conventional ultrasound, mpMRI imaging suspicious biopsies had a significantly higher overall prostate cancer detection (54% vs. 24%, p<0.01) and Gleason score ≥ 7 detection (25% vs. 8%, p<0.01). When compared with conventional ultrasound, mpMRI had similar detection rates for benign prostate tissue (76% vs. 79%, p=0.64), and Gleason score ≤ 6 (16% vs. 14%, p=0.49), and Gleason score ≥ 7 detection (8% vs. 7%, p=1.0).

DaRosa (2015) compared mpMRI-targeted fusion biopsy to transrectal ultrasound-guided biopsy in 72 men with prostate cancer in active surveillance with rising prostate specific antigen (PSA) or an appropriate rebiopsy interval. A total of 19 participants were found to have clinically significant prostate cancer (Gleason score greater than 7): 7 with mpMRI-targeted fusion biopsy alone, 2 by transrectal biopsy and 10 cases by both (p=0.182). The authors concluded that the mpMRI-targeted fusion biopsy resulted in detection of 7 additional cancers (37% of 19 cases). The proportion of cores positive for Gleason score 7 was 6.3 times higher with mpMRI-targeted fusion biopsy compared with transrectal ultrasound-guided (25% of 141 targeted cores versus 4% of 874 systematic cores, p<0.001). Using the Gleason > 6 threshold, 31/72 participants had clinically significant cancer, 10 identified by mpMRI-targeted fusion biopsy alone, 5 by transrectal ultrasound-guided biopsy alone, and 16 by both methods (p=0.302). The proportion of cores positive for clinically significant cancer was 6.2 times higher with mpMRI-targeted fusion biopsy compared with transrectal ultrasound-guided (37% of 141 targeted cores versus 6% of 874 systematic cores, p<0.001). The authors calculated a positive predictive value at clinically significant as 49% and clinically significant at 78%; negative predictive value was 44%. The authors note that “there is a trend toward” detecting more clinically significant cancers.

Lee and colleagues (2016) compared diagnostic outcomes between two different techniques for targeting regions-of-interest on mpMRI; MRI-ultrasound fusion (MR-F) and ultrasound guided visually targeted (VT) biopsy. The primary endpoint was the difference in the detection of high-grade (Gleason ≥ 7) and any-grade cancer between VT and MR-F. Secondary endpoints were the difference in detection rate by biopsy location using a logistic regression model, and difference in median cancer length. The authors identified 396 regions-of-interest in 286 men. The difference in high-grade cancer detection between MR-F biopsy and VT biopsy was -1.4% (95% confidence interval [CI], -6.4% to 3.6%; p=0.6); for any-grade cancer the difference was 3.5% (95% CI, -1.9% to 8.9%; p=0.2). Median cancer length detected by MR-F and VT were 5.5 mm vs. 5.8 mm, respectively (p=0.8). MR-F biopsy detected 15% more cancers in the transition zone (p=0.046), and VT biopsy detected 11% more high-grade cancer at the prostate base (p=0.005). Only 52% of all high-grade cancers were detected by both techniques. The authors concluded that there was insufficient evidence to support a difference in the detection of high-grade or any-grade cancer between VT and MR-F biopsy. However, the performance of each technique varied in specific biopsy locations, and the outcomes of both techniques were complementary. The authors suggest that combining VT biopsy and MR-F biopsy may optimize prostate cancer detection.

A retrospective review by Oberlin and colleagues (2016) reported on 231 men who underwent mpMRI-targeted biopsy; 81 individuals had fusion biopsy and 151 individuals had cognitive biopsy of the prostate. All eligible individuals in the study had an abnormal screening test with an elevated PSA or abnormal digital rectal exam, and active surveillance of prostate cancer. The primary outcome was the overall detection rate of cancer and the secondary outcome was the detection of clinically significant cancer. In the fusion group, 48.1% of the individuals had cancer detected compared to 34.6% in the cognitive group. When the mpMRI fusion group was compared to the conventional transrectal ultrasound biopsy group, the MRI group detected 61.5% of Gleason grade 7-10 cancer compared to 37.5% in the ultrasound group.

In a 2016 retrospective analysis of prospectively generated clinical, imaging and pathologic data, Mariotti and colleagues studied the performance of systematic vs. targeted biopsies in general clinical practice, and reported on 389 men who had mpMRI of the prostate followed by systematic and then MRI-targeted transrectal ultrasound fusion guided biopsy. Targeted biopsies were performed using different fusion systems and a heterogenous group of radiologists and urologists using differing protocols on differing patient populations. Individuals with a previous diagnosis of prostate cancer were excluded. Suspected prostate cancer was diagnosed in 202/389 men using the systematic approach, 182/389 men using the targeted approach, and 235/389 men had prostate cancer diagnosed using the combined targeted and systematic approach. The targeted biopsy diagnosed 11% more intermediate- to high-risk tumors when compared to the systematic biopsy (p<0.0001) and 16% fewer low-risk tumors (p<0.0001). The results were replicated when data from men who were biopsy-naïve and those who had previous negative biopsies were analyzed.

Hansen and colleagues (2016) reported on transperineal biopsy and mpMRI and transrectal ultrasound fusion imaging for 534 individuals with Gleason score ≤ 6: 107 had no previous prostate biopsy, 295 had a prior benign transrectal-guided biopsy, and 159 were on active surveillance for low-risk cancer. A total of 378 participants had Likert 3-5 MRI lesions reported, cancer was detected in 249 participants, and 157 participants had a new Gleason score 7-10 cancer. Gleason 7-10 cancer was detected in 45% of individuals on active surveillance for low-risk cancer, 27% in individuals with a previous benign biopsy, and 39% in individuals with no previous biopsy. The positive predictive value for detecting Gleason 7-10 was: for Likert 3, 0.15; for Likert 4, 0.43 and for Likert 5, 0.63. The negative predictive value of predicting Likert 1-2 findings was 0.60 for excluding any cancer, 0.87 for excluding Gleason 7-10 and 0.97 for excluding Gleason ≥ 4+3. The authors further note that “Not all men with moderately elevated PSA values and an unsuspicious prostate mpMRI read by experienced radiologists need prostate biopsies.”

In a 2017 study by Hoffman and colleagues, 99 men with elevated PSA, at least one prior negative standard core biopsy and no previous pretreatment of prostate cancer underwent mpMRI followed by ultrasound-fusion-guided perineal biopsy. MpMRI results indicated that 6 participants had presumed benign disease, 21 participants had ambiguous diagnostic findings, and 72 participants displayed PIRADS/PR scores suggestive of malignancy. A total of 33 participants did not show any signs of malignancy upon histopathological exam following fusion guided targeted biopsy while the remaining 66 participants had prostate cancer diagnosed in the suspicious regions. Only two subjects had cancer diagnosed through random biopsy. The overall sensitivity for mpMRI to differentiate between low- and high-grade lesion differentiation (GS less than or equal to 7a vs. greater than or equal to 7b) via PR was 88%, with a negative predictive value of 70% (p=0.74; Fisher’s exact test). While this was a relatively small group of participants at a single center, the mpMRI followed by ultrasound fusion biopsy showed higher detection rates of prostate malignancy than conventional diagnostic procedures.

A 2017 study by Simmons and colleagues reported on the diagnostic accuracy of mpMRI in participants requiring a repeat prostate biopsy at an expert referral center. A total of 249 participants had previous transrectal ultrasound biopsy and were advised to undergo further biopsies. All 249 participants then underwent mpMRI. Radiologists were blinded to the initial biopsies. Using Likert score greater than or equal to 3, a total of 214 participants had a positive prostate mpMRI. When correlated to biopsy findings, this yielded a sensitivity of 97.1% (95% CI: 92-99), specificity of 21.9% (15.5-29.5), NPV 91.4% (76.9-98.1), and PPV 46.7% (35.2-47.8). When a Likert score greater than or equal to 4 was used, a total of 129 participants had a positive mpMRI, yielding a sensitivity of 80.6% (71.6-87.7), specificity of 68.5% (60.3-75.9), negative predictive value (NPV) 83.3% (75.4-89.5), and positive predictive value (PPV) 64.3% (55.4-72.6). The authors cautioned that insignificant cancers can be detected when an mpMRI threshold score of 3 is used to designate suspicious mpMRI, noting as well that among other published studies wide ranges are used in mpMRI protocols, study populations, reference standards, and mpMRI reporting.

In a 2018 study by Kasivisvanathan and colleagues, 500 participants were randomized to either mpMRI targeted biopsy (n=252) or standard biopsy (n=248). Of the participants in the mpMRI targeted group, 71 had MRI results that were not indicative of prostate cancer and did not have biopsy, compared to 235 participants in the standard biopsy group. A total of 95 participants (39%) in the mpMRI group were found to have clinically significant prostate cancer and 23 (9%) with insignificant cancers, compared to 64 participants (27%) in the standard biopsy group with 55 (22%) insignificant cancers. Using MRI-targeted biopsy, 78 (31%) of participants were able to avoid biopsy and fewer men in the MRI-targeted biopsy group than in the standard biopsy group received a diagnosis of clinically significant cancer (adjusted difference, -13 percentage points, 95% CI, -19 to -7, P<0.001). The authors conclude that the use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. The authors also caution that there is room for improvement in attaining consistency in reporting the results of mpMRI and further research is necessary regarding standardization and reproducibility.

In a 2016 joint consensus statement by the American Urological Association and Society of Abdominal Radiology (Rosenkrantz) regarding individuals with prostate MRI and MRI-targeted biopsy, the authors advocate the use of an MRI ultrasound fusion biopsy for repeat biopsy after a prior negative biopsy citing that obtaining concurrent systematic cores can be performed in the same session and it allows collaboration between the radiologist identifying the location of the MRI-defined targets while the urologist performs the biopsy.

The National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for prostate cancer (2018) notes that mpMRI is not recommended for routine use, but it can be considered if prostate specific antigen rises and systematic prostate biopsies are negative.

Background/Overview

Prostate cancer is the most common diagnosed cancer, other than skin cancers, in North American men. Estimated new cases and disease-related deaths from prostate cancer in the United States in 2018 is 164,690 and 29,430 respectively. Prostate cancer is the second leading cause of cancer death in American men, exceeded only by lung cancer. Men in the United States have about 1 chance in 7 of eventually being diagnosed with this malignancy and about 1 man in 41 will eventually die of the disease (ACS, 2018).

The United States Food and Drug Administration (FDA) has cleared several devices which utilize images from a previously performed and interpreted prostate mpMRI and fuse them with real-time high definition prostate ultrasound images through the use of specialized equipment and software.

Definitions

Biopsy: The removal of a sample of tissue for examination under a microscope for diagnostic purposes.

Gleason Grading System: A prostate cancer grading system developed by the 2014 International Society of Urological Pathology (ISUP) Consensus Conference, based on the architectural features of the cancer. Numbers range from 1 to 5. The higher the number, the more undifferentiated the cancer and the more likely the cancer has extended outside of the prostate.

Gleason score: Represents the sum of the two most common Gleason grades observed by the pathologist on a specimen, the first number is the most frequent grade seen.

Magnetic resonance imaging (MRI): A diagnostic technique that uses a cylindrical magnet and radio waves to produce high quality multiplanar images of organs and structures within the body without x-rays or radiation.

Multiparametric magnetic resonance imaging (mpMRI): Combined conventional MRI with diffusion-weighted MRI (DWI), dynamic contrast-enhanced MRI (DCEI), and/or magnetic resonance spectroscopy imaging (MRSI) is known as multiparametric MRI.

Prostate: A walnut-shaped gland in men that extends around the urethra at the neck of the urinary bladder and supplies fluid that goes into semen.

Prostate-specific antigen: A blood test that measures the amount of a specific prostate-related protein in blood, used to screen for prostate cancer and other conditions. A high PSA level in the blood has been linked to an increased chance of having prostate cancer.

Transrectal ultrasound: An ultrasound test in which the sound waves are produced by a probe inserted into the rectum. In men, the structures most commonly examined with this test are the prostate, bladder, seminal vesicles and ejaculatory ducts.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

CPT

 

55899

Unlisted procedure, male genital system [when specified as MRI-targeted biopsy of the prostate]

77021

Magnetic resonance guidance for needle placement (eg, for biopsy, needle aspiration, injection, or placement of localization device) radiological supervision and interpretation [if billed as a component of an MRI-targeted biopsy of the prostate]

 

Note: there is no specific code for MRI-targeted biopsy of the prostate; if CPT codes 77021 plus a prostate biopsy code such as 55700 are used to describe this procedure, the medically necessary criteria will be applied

 

 

ICD-10 Diagnosis

 

C61

Malignant neoplasm of prostate

D07.5

Carcinoma in situ of prostate

D29.1

Benign neoplasm of prostate

D40.0

Neoplasm of uncertain behavior of prostate

R97.2

Elevated prostate specific antigen [PSA]

Z12.5

Encounter for screening for malignant neoplasm of prostate

Z85.46

Personal history of malignant neoplasm of prostate

When services are Investigational and Not Medically Necessary
For the procedure and diagnosis codes listed above when criteria are not met, or when the code describes a procedure indicated in the Position Statement as investigational and not medically necessary.

References

Peer Reviewed Publications:

  1. Ahmed HU, El-Shater Bosaily A, Brown LC, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017; 389(10071):815-822.
  2. Bjurlin MA, Mendhiratta N, Wysock JS, Taneja SS. Multiparametric MRI and targeted prostate biopsy: Improvements in cancer detection, localization, and risk assessment. Cent European J Urol. 2016; 69(1):9-18.
  3. Da Rosa MR, Milot L, Sugar L, et al. A prospective comparison of MRI-US fused targeted biopsy versus systematic ultrasound-guided biopsy for detecting clinically significant prostate cancer in patients on active surveillance. J Magn Reson Imaging. 2015; 41(1):220-225.
  4. Del Monte M, Leonardo C, Salvo V, et al. MRI/US fusion-guided biopsy: performing exclusively targeted biopsies for the early detection of prostate cancer. Radiol Med. 2018; 123(3):227-234.
  5. Hansen N, Patruno G, Wadhwa K, et al. Magnetic resonance and ultrasound image fusion supported transperineal prostate biopsy using the Ginsburg Protocol: Technique, Learning Points, and Biopsy Results. Eur Urol. 2016; 70(2):332-340.
  6. Hoffmann MA, Taymoorian K, Ruf C, et al. Diagnostic performance of multiparametric magnetic resonance imaging and fusion targeted biopsy to detect significant prostate cancer. Anticancer Res. 2017; 37(12):6871-6877.
  7. Kasivisvanathan V, Rannikko AS, Borghi M, et al. MRI-targeted or standard biopsy for prostate-cancer diagnosis. N Engl J Med. 2018 Mar 18.
  8. Kim EH, Vemana G, Johnson MH, et al. Magnetic resonance imaging-targeted vs. conventional transrectal ultrasound-guided prostate biopsy: single-institution, matched cohort comparison. Urol Oncol. 2015; 33(3):109.e1-e6.
  9. Lee DJ, Recabal P, Sjoberg DD, et al. Comparative effectiveness of targeted prostate biopsy using MRIUS fusion software and visual targeting: a prospective study. J Urol. 2016; 196(3):697-702.
  10. Mariotti GC, Costa DN, Pedrosa I, et al. Magnetic resonance/transrectal ultrasound fusion biopsy of the prostate compared to systematic 12-core biopsy for the diagnosis and characterization of prostate cancer: multi-institutional retrospective analysis of 389 patients. Urol Oncol. 2016; 34(9): 416. e9-416. e14.
  11. Oberlin DT, Casalino DD, Miller FH, et al. Diagnostic value of guided biopsies: fusion and cognitive-registration magnetic resonance imaging versus conventional ultrasound biopsy of the prostate. Urology. 2016; 92:75-79.
  12. Rastinehad AR, Abboud SF, George AK, et al. Reproducibility of multiparametric magnetic resonance imaging and fusion guided prostate biopsy: multi-institutional external validation by a propensity score matched cohort. J Urol. 2016; 195(6):1737-1743.
  13. Siddiqui MM, Rais-Bahrami S, Turkbey B, et al. Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. JAMA. 2015; 313(4):390-397.
  14. Simmons LAM, Kanthabalan A, Arya M, et al. The PICTURE study: diagnostic accuracy of multiparametric MRI in men requiring a repeat prostate biopsy. Br J Cancer. 2017; 116(9):1159-1165.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American College of Radiology. ACR Appropriateness Criteria®. Available at: https://acsearch.acr.org/list. Accessed on April 6, 2018.
    • Prostate cancer – pretreatment detection staging and surveillance (2016).
  2. American Urological Association. Guidelines for the Management of Clinically Localized Prostate Cancer: 2017. Available at: http://www.auanet.org/guidelines. Accessed on April 6, 2018.
  3. NCCN Clinical Practice Guidelines in Oncology®. © 2018 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on April 6, 2018.
    • Prostate Cancer (V.2.2018). Revised March 8, 2018.
  4. Rosenkrantz AB, Verma S, Choyke P, et al. Prostate MRI and MRI-targeted biopsy in patients with a prior negative biopsy: a consensus statement of the American Urological Association and the Society of Abdominal Radiology's Prostate Cancer Disease-Focused Panel. J Urol. 2016; 196(6):1613-1618.
Websites for Additional Information
  1. American Cancer Society. Available at: http://www.cancer.org/. Accessed on April 6, 2018.
  2. National Cancer Institute (NCI). Available at: http:// http://www.cancer.gov/. Accessed on April 6, 2018.
Index

Artemis
BioJet
BiopSee®
mpMRI
UroNav
Urostation®
Virtual Navigator

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History

Status

Date

Action

Reviewed

05/03/2018

Medical Policy & Technology Assessment Committee (MPTAC) review.

Reviewed

05/02/2018

Hematology/Oncology Subcommittee review. The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Rationale, Background/Overview, and References sections.

Revised

08/03/2017

MPTAC review.

Revised

07/10/2017

Hematology/Oncology Subcommittee review. Clarification to MN statement.

Reviewed

05/04/2017

MPTAC review.

Reviewed

05/03/2017

Hematology/Oncology Subcommittee review. Updated Rationale, Background/Overview and References sections.

New

07/27/2016

MPTAC review.

New

07/12/2016

Hematology/Oncology Subcommittee review. Initial document development.