American Urological Association - MRI of the Prostate, Standard Operating Procedure (SOP)

advertisement

Home Guidelines Policy Statements MRI of the Prostate SOP

MRI of the Prostate, Standard Operating Procedure (SOP)

Authors

Marc A. Bjurlin, DO, MSc, Peter R. Carroll, MD, Scott Eggener, MD, Pat F. Fulgham, MD, Peter A. Pinto, MD, Jonathan N. Rubenstein, MD, Daniel B. Rukstalis, MD, Samir Taneja, MD, Ismail Baris Turkbey, MD

AUA Staff

Jody Donaldson

Consultant

Kirsten Hahn Aquino

Introduction

Multi-parametric MRI (mpMRI) has proven a valuable diagnostic tool in the management of prostate cancer.  The excellent resolution and high signal-to-noise ratio provided by MRI, combined with the functional measurements of water diffusion and contrast enhancement give an improved insight into the underlying histopathology of the prostate.  Enthusiasm in the urologic community for the use of prostate MRI is evident in the dramatic increase in utilization.

While mpMRI offers a positive predictive value (PPV) of 85% for prostate cancer for index lesions where the Prostate Imaging Reporting and Data System (PI-RADSTM v2) is > 3, there remains a significant problem with subjective and inconsistent interpretation of lesions and with false positives, particularly in the transition zone.1,2   mpMRI is being extensively promoted for the purpose of directing prostate biopsy either exclusively or as a fused technology in conjunction with transrectal ultrasound(TRUS).

The purpose of this paper is to evaluate the available evidence and make practical recommendations about how MRI can best be deployed by clinicians across the spectrum of prostate cancer care and management, including initial diagnosis, pre-treatment risk assessment and staging, and active surveillance. The Multi-parametric Prostate MRI Consensus Panel has performed a thorough literature review and examined the potential applications of this imaging modality in the diagnosis, staging and management of men with clinically localized prostate cancer.  Information on this subject is evolving so rapidly that in some cases there is not enough evidence available to make definitive recommendations based on data alone.  Therefore, these recommendations are based in part on a critical review of the literature and in part on collective expert opinion.

Technique of Prostate MRI

Prostate MRI has recently been increasingly used to guide prostate cancer clinical management. This growing interest in MRI has led to a significant variation and heterogeneity in image acquisition, interpretation and pre-biopsy image processing, which can easily hinder patient care. To address these issues the American College of Radiology (ACR) and the European Society of Urogenital Radiology (ESUR) published the basic guidelines for MRI acquisition and interpretation in early 2015.3 This document strongly stated that the technical details of prostate MRI, which ultimately affects the imaging protocol, should be tailored to the patient`s needs and the clinical questions raised by the referring physician. In this section we will cover technical points such as equipment, basic parameters, image interpretation and communication of these findings with urologists.

Equipment Specifications

Prostate MRI can be obtained with a 1.5Tesla (T) or 3.0T magnet with or without using an endorectal coil (ERC). Although there are some papers comparing these different techniques, there is as yet no prospective and randomized study addressing which equipment is superior in cancer detection and staging.4,5 We will group technical specifications as minimum and ideal standards:

Minimum Standards

3.0T magnet systems provide twice the signal-to-noise ratio (SNR) compared to 1.5T systems resulting in increased spatial and temporal resolution, which ultimately results in an improvement in image quality. Despite this difference, prostate MRI obtained at a 1.5T can still yield diagnostic images for lesion detection.3 However, use of an ERC should be considered especially if older 1.5T systems are used or local staging is planned with newer 1.5T magnets. For 3.0T systems, per minimum standards, the consensus of experts in the field states that an ERC is not necessary for lesion detection. However, an ERC`s necessity for local staging is still under debate. It should be noted that for non-ERC prostate MRIs, either at 1.5T or 3.0T, susceptibility to artifacts secondary to the presence of rectal gas can easily diminish image quality especially during diffusion-weighted MRI. Per minimum standards, patients should be asked to empty their bowel prior to prostate MRIs.3

Use of 1.5T magnets (instead of 3.0T) magnets can be recommended in particular situations in which 3.0T incompatible implanted medical devices or conditionally  compatible 3.0T devices may result in significant susceptibility artifacts (secondary to local magnetic field inhomogeneity).  Distortion related to these devices can easily degrade the quality of prostate MRI.3 A minimum standard prostate MRI, if protocoled carefully, can be used to detect lesions and be helpful for staging within its limitations.

Preferred/Ideal Standards:

Prostate MRI obtained at 3.0T with combined use of endorectal and surface coils currently stands as the most ideal technique for tumor detection and staging. ERC provides 5 times more SNR compared to surface coil and this certainly results in improved spatial resolution and image quality.6 Currently, the necessity of ERC at 3.0T remains uncertain; however, it is documented that the improvement in SNR can also improve the spatial resolution sufficiently so that capsular invasion can be detected.7

Use of an ERC itself during image acquisition may not necessarily be enough to obtain an ideal prostate MRI. The current consensus is to use liquid barium or perfluorocarbon instead of air, since air can easily induce susceptibility artifacts on diffusion weighted imaging (DWI).3 It should be noted that ERC can result in patient discomfort and placement of an ERC requires an on-site physician. Although the ideal MRI can provide more optimum lesion detection and staging, it can cost more due to the use of ERC.

MRI Parameters

Prostate MRI is usually termed as “multi-parametric MRI” since it incorporates the combined use of anatomic and functional pulse sequences. Anatomic pulse sequences include T1 and T2 weighted (W) MRI. T1W MRI is not used for lesion detection, however the purpose of its acquisition is to document biopsy related residual hemorrhage, which can mimic prostate cancer at mpMRI. T1W MRI should be acquired in the axial plane using spin echo or gradient echo sequences. T2W MRI is the work-horse of mpMRI since the anatomic details can be best delineated on T2W MRI, mainly in the axial plane. T2W MRI should be acquired in three planes (sagittal, axial, and coronal) using spin echo sequences.  

Basic parameters are as follows:

  1. Slice thickness: 3mm without gap
  2. Field of view (FOV): 12-20cm covering entire prostate and seminal vesicles
  3. In plane dimension: ≤0.7mm (phase) x ≤0.4mm (frequency).3

Functional pulse sequences include diffusion weighted MRI (DW MRI) and dynamic contrast enhanced MRI (DCE MRI). It should be noted that magnetic resonance spectroscopy is no longer recommended to use for clinical purposes, however its use is encouraged for research purposes only. DW MRI evaluates the Brownian motion of water molecules within tissue and this motion is restricted in cancer harboring tissues. DW MRI has two key components, apparent diffusion coefficient (ADC) maps and high b value DW MRI.  “b-value” is a factor related to field strength and gradient timing which can influence the diffusion-weighted images. Two or more b values are needed to calculate ADC maps from DW MRI utilizing a mono-exponential decay model. ADC values extracted from maps are quantitative, however the “intra-” and “inter-“ patient variability can be significant for ADC values, and therefore ADC maps are mostly used for qualitative interpretation. For ADC maps, if only two b‐values can be acquired due to time or scanner constraints, it is preferred that the lowest b‐value should be set at 50‐100sec/mm2 and the highest should be 800‐1000sec/mm2. Additional b‐values between 100 and 1000 may provide more accurate ADC calculations. High b DW MRI can either be acquired or calculated. The current recommendation is using a b value of ≥1400sec/mm2.  A high b value DW MRI is also utilized qualitatively in conjunction with ADC maps.

Technical specifications of image acquisition for DW MRI are as follows:

  1. Echo-time (TE) : ≤90 msec; Repetition time (TR): ≥3 000 msec,
  2. Slice thickness: ≤4mm without gap
  3. FOV: 16-22cm covering entire prostate and seminal vesicles
  4. In plane dimension: ≤2.5mm (phase and frequency).3

DCE MRI evaluates the vascularity of the prostate in order to identify permeability changes related to tumor angiogenesis. DCE MRI consists of T1W gradient echo images obtained before, during and after injection of gadolinium-based contrast agents (GBCA).

The technical specifications of image acquisition for DCE MRI are as follows:

  1. TR/TE: <100msec/<5mseC
  2. Slice thickness: 3mm without gap
  3. FOV: 12-20cm covering entire prostate and seminal vesicles
  4. In plane dimension: ≤2mm (phase and frequency)
  5. Temporal resolution: ≤10sec (<7sec is preferred)
  6. Total scanning time: ≥2 minutes
  7. GBCA dose: 0.1mmol/kg, injection rate: 2-3cc/sec.3

DCE MRI is the most invasive component of prostate mpMRI since it employs GBCA injection. Patients should be carefully checked for their kidney functions (blood creatinine, eGFR (glomerular filtration rate), etc.) to avoid risk of nephrogenic systemic fibrosis.8

Reporting of Findings

Reporting and PI-RADSTM v2

Current guidelines strongly encourage radiologists to use the PI-RADSTM v2 to report prostate mpMRI findings.3 This system is designed to evaluate treatment naïve patients and aims to standardize the mpMRI interpretation. PI-RADSTM v2 defines criteria for scoring for each zone of the prostate on each pulse sequence. For T2W MRI and DW MRI the score range is between 1 and 5, whereas for DCE MRI it is binary (positive or negative). For the peripheral zone, the dominant sequence is DW MRI for scoring, where it is T2W MRI for the transition zone. Role of DCE MRI for scoring is limited to indeterminate lesions with a score of 3 within the peripheral zone. Once scoring for each lesion is completed for each pulse sequence, a final overall PI-RADSTM v2 score should be given for each lesion. This overall score is between 1 to 5, which aims to predict likelihood of including clinically significant disease within the scored lesion: PIRADS=1 (Very Low) suggests clinically significant cancer highly unlikely to be present, PIRADS=2 (Low) suggests clinically significant cancer is unlikely to be present, PIRADS=3 (Intermediate) suggests the presence of clinically significant cancer is equivocal, PIRADS=4 (High) suggests clinically significant cancer is likely to be present, and PIRADS=5 (Very High) suggests clinically significant cancer is highly likely to be present). This overall scoring is based on experts` observations and is therefore semi quantitative; however, research related to this is still ongoing in several academic centers.

Accurate interpretation of prostate MRI requires experience; however, its standards have not yet been clearly defined. One interesting point to note is that use of PI-RADSTM v2 can result in moderate agreement with reasonable sensitivity and tumor detection rates in early studies. Early studies evaluated the multi-reader agreement of PI-RADSTM v2 and accuracy. One study evaluated PI-RADSTM v2 by presenting pre-defined lesions in 94 patients with TRUS/MRI fusion-guided biopsy confirmed prostate cancer with five readers. In the 162 lesions, a positive correlation was found with PI-RADSTM v2 scores between T2W, DWI, DCE, and overall PI-RADSTM v2 scores and Gleason scores (Kendall τ 0.51, 0.42, 0.23, and 0.42, respectively, all p<0.05). Inter-observer agreement (κ score) was 0.46 for overall PI-RADSTM v2 score, with agreement on T2W, DWI, and DCE at 0.47, 0.40, and 0.46, respectively. The agreement was considered “moderate” among all readers.9 A second paper included 6 highly experienced uroradiologists from 6 different institutions to evaluate pre-determined lesions and score features of each lesion and assign a PI-RADSTM v2 score to test inter-observer agreement. PI-RADSTM v2 demonstrated modest reproducibility among 6 readers (κ=0.552). This study included a training session between reading sessions, which did not improve reproducibility. PI-RADSTM v2 seems to perform better in the TZ than previous versions with a κ=0.509 for the TZ and 0.593 for a PI-RADSTM v2 score ≥4. Additionally, agreement on DCE scores was low at κ=0.426.  These findings indicate PI-RADSTM v2 does not suffer from lack of educational exposure, at least among experienced readers, and PI-RADSTM v2 represents a trend toward improved agreement for the TZ.10 Collectively, these early studies indicate PI-RADSTM v2 represents a major step forward in standardizing the acquisition and interpretation of mpMRI, but questions remain and improvements are likely necessary. The varying level of agreement and performance between readers of different experience suggests standardization between experience levels still needs to be addressed.

Marking and processing of mpMRI for Reporting and Biopsy Purposes

It is clear that prostate mpMRI is more commonly used for guiding biopsies rather than local staging. Accurate lesion mapping and dimension measurement are key steps in communication of the results to the referring physicians. PI-RADSTM v2 guidelines provide a sector map which divides the prostate into 12 sectors at apical, mid and base levels of the prostate. Detected lesions can be mapped on this sector map along with their estimated size. PI-RADSTM v2 recommends mapping of the most suspicious 4 lesions on this sector map and such an approach can enhance communication of the prostate mpMRI findings to referring physicians efficiently.3   Documentation of specific imaging series number and image number (e.g. Series 4, Image 15) of index lesions with those lesions clearly marked on the image is crucial to the physician performing subsequent biopsies.

MRI guided biopsies can be performed using cognitive, TRUS/MRI fusion or in-bore MRI guided approaches. Image processing is mandatory mainly for TRUS/MRI fusion-guided approaches. This processing includes two important steps: 1) Segmentation of the prostate within axial T2W MRI, and 2) Labeling the target lesion within the prostate on axial T2W MRI. For segmentation of the prostate, manual, semi-automated or fully automated approaches can be used by radiologists or trained technologists under the supervision of radiologists.11 For labeling the index lesion, a radiologist should manually delineate intra-prostatic target lesion(s) on axial T2W MRI using information from all pulse sequences.  The application of the correct standards in image acquisition, interpretation and processing are critical to the successful use of MRI in this setting However, the collaboration and coordination between radiologists and urologists is also a key component. The radiologists should get continuous feedback regarding image quality and histopathology results of the provided target lesions mapped on mpMRI. In the meantime, the urologist should receive feedback about the quality of the targeted biopsy procedure including results related with possible image fusion/registration and targeting errors. Such an approach will further establish use of mpMRI in prostate cancer clinical care.

Key Points

  1. Optimal scanning technique should utilize 3.0T surface coil plus or minus endorectal coil.
  2. For 1.5T use of an endorectal coil should be considered with older scanners, whereas use of surface coil can be sufficient when using newer 1.5T systems.
  1. The radiographic report should identify all suspicious lesions, up to a total of 4 lesions, with each individual lesion identified using PIRADS™ v2 criteria.

Role of MRI in Screening for Prostate Cancer

The concept of finding a malignancy in the earliest stages of development which could then allow a treatment to eradicate the cancer is inherently attractive to both patients and their physicians. The largest prospective clinical trial to evaluate the effect of population-based screening for prostate cancer, the European Randomized Study of Screening for Prostate Cancer (ERSPC), found a statistically significant reduction in cancer-related mortality in the men treated on the screening arm further supporting the concept of early detection.12 However, this large study found the overall positive effect of screening with prostate-specific antigen (PSA) and digital rectal examination (DRE) to be small and without any change in overall mortality.13 Therefore, the current recommendations of both the American Urologic Association and the American Cancer Society are for each man to review the risks and benefits of screening with their physician and to reach an individual shared decision. 

There has been one recent publication, which has evaluated the role of mpMRI as the initial test for the early detection of prostate cancer. Nam and co-workers recruited 47 men from the general population and performed an MRI as the primary screening test.14  The authors calculated that the MRI had a 66.7% positive predictive value and an 85.7% negative predictive value for the subsequent diagnosis of prostate cancer on biopsy, which may be an improvement over PSA-based early detection, but does not address whether it would improve overall mortality.  MRI may also be considered as a biomarker for high grade prostate cancer which would be the form of this malignancy for which early detection could be most valuable.15 The presence of an MRI suspicious lesion also appears to be an independent predictor for Gleason > 7 adenocarcinoma in biopsy naïve men. This preliminary trial demonstrates the feasibility of mpMRI in the screening setting, but does little to support or refute its effectiveness as a screening tool.

The significance of abnormal MRI findings varies by biopsy indication, largely due to the underlying prevalence of disease within studied cohorts.  For instance, the likelihood of cancer on biopsy of an equivocal mpMRI abnormality is greater in men on surveillance (100% disease prevalence) than in men with one or more previous negative biopsies (low disease prevalence).  In a screening cohort, not risk stratified by PSA, the prevalence of disease would be quite low, potentially making it difficult to establish thresholds for abnormality on mpMRI.   While provocative, mpMRI as a screening application should be considered purely investigational.

Key Point:

  1. There is no current evidence that mpMRI should be routinely used in population-based screening for prostate cancer.

Initial Evaluation of Biopsy-Naïve Patients Suspected of having Prostate Cancer

Initial Evaluation of Biopsy-Naïve Patients Suspected of having Prostate Cancer – Pre-Biopsy Risk Stratification

In general, the problems of overdiagnosis and overtreatment of prostate cancer are not associated with imaging modalities.  These are problems of patient selection.  Using standard transrectal ultrasound-directed biopsies and appropriate selection criteria, positive biopsy rates may be as high as 60% with only 20-25% of patients diagnosed by that modality having low stage, low grade disease. More restrictive selection criteria for biopsy will result in the increased diagnosis of clinically significant cancers and result in a decrease in the diagnosis of low volume low stage disease, independent of the imaging modality used.

As an increasingly useful tool for prostate cancer, detection and risk stratification, mpMRI allows noninvasive assessment of the prostate gland from both an anatomic and a functional perspective. A recent meta-analysis demonstrated sensitivity ranging from 44% to 87% for the detection of clinically significant prostate cancer and negative predictive value (NPV) ranging from 63% to 98% for exclusion of clinically significant prostate cancer.16 The use of mpMRI in clinical practice is critically dependent upon the availability of high quality mpMRI interpreted by radiologists experienced in the technique.

Because the selection criteria for mpMRI and biopsy vary widely within the published literature, stratification by mpMRI suspicion score allows better determination of the reproducibility of mpMRI targeted biopsy in cancer detection.  The MRI score has been shown to be the single most important determinant of prostate cancer risk. In a recent prospective study of 1,042 men who underwent mpMRI followed by MRI or ultrasound fusion biopsy, lesion suspicion score was the most powerful predictor of clinically significant cancer detection (odd ratio = 6.5, P<0.01).17 The PI-RADSTM v2 scoring system corresponds with the detection of prostate cancer and clinically significant disease as the suspicion score increases. Based on targeted biopsy on a per lesion basis, the overall cancer detection rates of PI-RADSTM v2 2, 3, 4 and 5 scores for all tumors ranges from 0-22%, 10-16%, 30-77% and 78-89%, respectively.18,19 The cancer detection rate of PI-RADSTM v2 2, 3, 4, and 5 scores for Gleason > 7 has been reported to be  5.6%, 0%, 21.3% and 75%, respectively.18

mpMRI has been reported to predict more aggressive disease including a positive correlation of mpMRI findings with D‘Amico risk scores.20 Moreover, individual MRI sequences such as ADC maps derived from DWI and quantitative parameters of DCE have been reported to predict tumor aggressiveness in a noninvasive manner. ADC values derived from DWI images are inversely correlated with the Gleason score of lesions at biopsy or surgery and may further influence risk stratification, however the confidence intervals are widely overlapping, limiting the ability to use ADC as a surrogate of Gleason score.21 ADC measurements have been shown to improve accuracy in discriminating Gleason score 3+4=7 from Gleason score 4+3=7  tumors.22 Decreasing ADC values may represent a strong risk factor of harboring a poorly differentiated prostate cancer, independent of biopsy characteristics.22 Furthermore, ADC may have potential for predicting extracapsular extension (ECE) as well as seminal vesicle invasion (SVI) before surgery in patients with prostate cancer, thus improving preoperative staging.23-25

In an attempt to improve on the current limitations of prostate cancer screening, risk calculators in the form of multivariable mathematical models and nomograms predicting overall cancer detection as well as clinically significant prostate cancer have been developed.26,27 Employing mpMRI may assist in the decision as to whether a man needs a prostate biopsy and has been incorporated into several decision making models.  In a study of 175 men, Salami et al. demonstrated mpMRI outperforms the Prostate Cancer Prevention Trial risk calculator in predicting clinically significant prostate cancer, and its application may help select patients who will benefit from diagnosis and treatment.28  Recently, Bjurlin et al. developed nomograms for the pre-biopsy setting predicting the risk of both overall and Gleason score ≥7 cancer on both MRI-Ultrasound fusion and systematic biopsy with a high degree of accuracy by incorporating the MRI suspicion score, PSA density, and age.29 Employing these nomograms may help determine the necessity for biopsy in a wide variety of clinical scenarios. For example, utilizing the nomograms of Bjurlin et al., a 75-year-old man with a PSA of 6.2, prostate volume of 45 cm3 (PSA density 0.14 ng/ml-cc), and a low MRI suspicion score has a 28% chance of harboring prostate cancer, but less than a 5% chance of Gleason score ≥7 prostate cancer and he may choose to defer a biopsy.29 Conversely, a 55-year-old man with the same PSA level, prostate volume, and MRI finding may choose to undergo a biopsy given the natural history of prostate cancer in a man his age. Predictive models incorporating MRI findings provide important information for physicians and patients in assessing an individual’s risk for prostate cancer. The use of risk assessment tools identifies those men who may benefit most from a biopsy.  The accurate assessment of the risk of harboring clinically significant disease allows for individualized patient counseling.

Key Points:

  1. MRI suspicion score correlates well with the likelihood of clinically significant cancer, potentially allowing pre-biopsy risk stratification for individualized decision-making.
  2. Clinically, MRI-suspicion scores (based on ADC value and diffusion weight imaging) correlate with the risk of adverse pathology on radical prostatectomy, risk of biochemical relapse following surgery, and the likelihood of progression on active surveillance.
  3. The implementation of mpMRI-based risk stratification in clinical practice, particularly in guiding clinical decision-making, is predicated upon the availability of high quality mpMRI and experienced readers.
  4. Data derived from pre-biopsy mpMRI can enhance the predictive ability and overall diagnostic accuracy of currently available clinical prediction tools.

Evaluation of Biopsy Naïve Patients Utilizing mpMRI

In men presenting for a first prostate biopsy, the potential advantages of mpMRI and targeted biopsy are twofold: improving detection of high-grade cancer and avoiding detection of low-grade disease by selectively targeting tumor foci which are more likely to be clinically significant.  The performance characteristics of mpMRI targeted biopsy vary with the clinical indication, in part, due the variable prevalence of disease in the study cohort.  As such, the absolute rates of detection, when not stratified by suspicion score, may vary between series, but trends remain similar. Several studies reporting outcomes of combined MRI-targeted biopsy and systematic biopsy among men with no previous biopsy have suggested the potential to achieve these goals using mpMRI in the primary biopsy setting.30-33 Delongchamps et al. compared outcomes of targeted and systematic biopsy among 391 men presenting for first biopsy. The investigators reported improved detection of high-grade cancer using targeted biopsy, which missed only 2/63 (3%) Gleason ≥7 cancers detected by systematic biopsy while detecting an additional 17 high-grade cancers.31 Additionally, 39 Gleason 6 cancers identified on systematic biopsy were avoided by targeted biopsy. Pokorny et al. similarly observed that MRI-targeted biopsy increased the detection of intermediate/high-risk disease by 18% and decreased the diagnosis of low-risk cancer by 89% in a prospective trial of 223 men.32 Mendhiratta et al. observed a 15% increase in Gleason score ≥7 cancers by MRI-US fusion targeted biopsy as compared to systematic biopsy among 382 consecutive biopsy naive men.33 Additionally, the majority of cancers missed by targeted biopsy were clinically insignificant by Epstein (62%) and University of California at San Francisco Cancer of the Prostate Risk Assessment (UCSF-CAPRA) (82%) criteria, suggesting that systematic biopsy largely contributes to the detection of low-risk disease among biopsy naive men undergoing both targeted and systematic biopsies.33 Despite these observations, most series to date suggest a persistent, low rate of clinically significant cancer detection on systematic biopsy among men with no previous history of prostate biopsy, drawing concerns about routine avoidance of systematic biopsy in this cohort.

Baco et al. reported outcomes of the first randomized trial to compare cancer detection rates between MRI targeted biopsy and systematic biopsy among men with no previous history of biopsy.24  175 biopsy-naive men were randomized to MRI-ultrasound fusion-targeted biopsy and 12-core systematic biopsy (MRI group) or systematic biopsy with visually targeted biopsy for digital rectal exam or TRUS-visualized abnormalities only (control group). Overall cancer detection rates, or clinically significant cancer detection rates, did not differ between the MRI and control groups (59% vs 54%, p = 0.4; 44% vs 49%, p = 0.5, respectively). The authors noted, the study was limited by an inadequate sample size, as the trial was initially powered to identify a 20-25% difference in cancer detection rate.24 The majority of comparative trials have suggested that cancer detection rates, are in fact, relatively similar between MRI-targeted and systematic biopsy in this cohort, but also consistently suggest a greater rate of high grade cancer detection when combined. As such, the routine use of pre-biopsy MRI in men at suspicion of prostate cancer, with no previous history of biopsy, remains controversial, particularly in view of the cost of MRI and MRI-targeting platforms, and the unclear downstream effect on cost.  Further refinements in imaging, and MRI-targeting strategies, may be required before routine use of MRI-targeted sampling in all men presenting for prostate biopsy should be considered.  Ongoing randomized trials, such as the Prostate MR Imaging Study (PROMIS) and Prostate Evaluation for Clinically Important Disease: Sampling Using Image Guidance Or Not (PRECISION) trial, will offer further insight into utilization and adoption.

Key Points:

  1. mpMRI-targeted prostate biopsy in men at suspicion of prostate cancer, with no previous history of prostate cancer, detects more clinically significant prostate cancer when combined with systematic biopsy, and less clinically insignificant prostate cancer, than systematic biopsy alone.
  2. The use of mpMRI targeted biopsy alone, among men at suspicion of prostate cancer with no previous history of biopsy, risks missing a small number of clinically significant cancers identified by systematic biopsy alone. Therefore, use of systematic biopsy in conjunction with MRI-targeted sampling is advisable in this group if MRI-targeting is used.
  3. The clinical impact of mpMRI-targeted biopsy in men with no previous history of prostate biopsy remains controversial, due to an unclear magnitude of clinical impact relative to cost. In considering its use, quality of mpMRI, experience of interpreting radiologist, cost of mpMRI, and availability of alternate biomarkers should be considered.
  4. There may be added value to pre-biopsy MRI in selected biopsy naïve patients where technical challenges prevent good prostate visualization by ultrasound. (e.g. Absent or restricted anal access.  Large prostate or extensive calcification of prostate preventing evaluation of the anterior gland.  Patient at risk for bleeding or infection where a negative MRI might obviate biopsy.  Patient with a nodule when pre-treatment staging/planning is anticipated.)
  5. There is insufficient data to recommend routine MRI in every biopsy naïve patient under consideration for prostate biopsy. Its use may be considered in men for whom clinical indications for biopsy are uncertain (minimal PSA increase, abnormal DRE with normal PSA, or very young or old patients).

Evaluation of Men with Previous Negative Biopsy by mpMRI

Among men with persistent suspicion of prostate cancer despite previous negative biopsy, the rationale for pre-biopsy mpMRI is in the detection of occult cancers missed by previous systematic sampling.  These cancers are often located in the anterior transition zone or fibromuscular stroma, the extreme apex, or base, and would likely be missed by routine systematic sampling.  There is minimal consensus on the indication for repeat biopsy in clinical practice, and, as a result, the cancer detection rates vary widely among reported series.  Nonetheless, series that have incorporated mpMRI targeted sampling in their repeat biopsy scheme have consistently demonstrated increased cancer detection relative to systematic sampling, unique cancer detection among MRI-targeted cores, and consistent cancer detection rate, regardless of number of previous biopsy sessions.

Historically, serial biopsy series have demonstrated a declining rate of cancer detection with each biopsy.  As an example, Roehl et al. noted a cancer detection rate of 29%, 17%, 14%, 11%, 9% and 7% respectively on serial repeat systematic biopsy, while Sonn et al. reported no change in significant cancer detection rate (GS≥7 or CCL≥4 mm) among men with 1, 2, 3, or ≥4 negative biopsies (range, 23%-29%). 34,35

The rate of cancer detection on repeat biopsy when incorporating MRI-targeted cores has varied from 11-54%, while the rate of clinically significant cancer detection has varied from 10-40%, likely due to variation in patient selection, MRI technique, and biopsy technique.  Several series have demonstrated increased high-grade cancer detection by MRI-targeted biopsy (MRI-TB), when compared to systematic biopsy (SB), among men with one or more prior negative systematic biopsies. Sonn et al, for example, observed that targeted biopsy detected more clinically significant cancers and fewer clinically insignificant cancers than systematic biopsy.35 

In addition to increased cancer detection, other authors have noted that systematic biopsy contributes relatively little in the detection of clinically significant cancer in this cohort.  Among 140 men, Salami et al. similarly observed that targeted biopsy detected more clinically significant cancer than systematic biopsy (48% vs 31% of total cohort), and that MRI-targeted biopsy missed only 3.5% of clinically significant cancers found uniquely on systematic biopsy.28  Mendhritta, et al, evaluated 172 men undergoing repeat biopsy by combined MRI-US fusion targeting and systematic sampling.  While systematic biopsy was negative in 14/31 (48%) men with Gleason ≥ 7 cancer noted on MRI-targeted sampling, MRI-targeted biopsy missed no high-grade cancers.33

Additionally, in each of these studies, pre-biopsy suspicion score strongly predicted the likelihood of high grade cancer on biopsy.  In the study of Mendhiratta, et al., a pre-biopsy mpMRI suspicion score of < 4 carried negative predictive values of 95% and 100% for the detection of Gleason 3+4 and Gleason ≥ 4+3 disease, respectively.33

Key Points:

  1. The current primary application of mpMRI is in men with a rising serum PSA level for whom there is a suspicion for prostate cancer despite a previous negative prostate biopsy.
  2. When high-quality prostate MRI is available, it should be strongly considered in any patient with a prior negative biopsy who has persistent clinical suspicion for prostate cancer and who is undergoing a repeat biopsy.
  3. The decision whether to perform MRI in this setting must also take into account results of any other biomarkers, the cost of the examination, as well as availability of high quality prostate MRI interpretation.
  4. Patients receiving a PI-RADSTM v2 assessment category of 3-5 warrant repeat biopsy with image guided targeting.
  5. While TRUS-MRI fusion or in-bore MRI-targeting may be valuable for more reliable targeting, especially for MRI lesions that are small or in difficult locations, in the absence of such targeting technologies, cognitive (visual) targeting remains a reasonable approach in skilled hands.
  6. However, performing solely targeted biopsy should only should be considered once quality assurance efforts have validated the performance of prostate MRI interpretations with results consistent with the published literature.
  7. In patients with a negative or low-suspicion MRI (PI-RADSTM v2 assessment category of 1 or 2, respectively), other ancillary tests (i.e., PSA, prostate-specific antigen density(PSAD), prostate-specific antigen velocity(PSAV), prostate cancer antigen 3(PCA3), Prostate Health Index (PHI)) may be of value to identify patients warranting repeat systematic biopsy, although further data is needed on this topic.
  8. If a repeat biopsy is deferred on the basis of the MRI findings, then continued clinical and laboratory follow-up is advised and consideration should be given to incorporating repeat MRI in this diagnostic surveillance regimen.

Staging and Treatment Planning of Prostate Cancer

Role of mpMRI in staging Prostate Cancer

Even before it was being studied for localizing prostate cancer and guiding prostate biopsies, mpMRI was used for staging prostate cancer.36  mpMRI has utility for assessing the presence/absence of significant cancer, prediction of organ confined disease (OC), prediction of extraprostatic (EPE)/extracapsular extension (ECE) of cancer, and assessment of seminal vesicle invasion.   [Note: although EPE is often considered the preferred terminology for extraprostatic extension of prostate cancer due to the lack of a true capsule on the prostate, others use ECE; due to this, EPE and ECE may be used interchangeably].   Results of the mpMRI can be integrated into currently available clinical staging systems for risk stratification. 

Use in detecting clinically significant disease:

When determining the utility of mpMRI in the diagnosis and staging of cancer, studies comparing MRI images to final surgical pathology at radical prostatectomy are used.  Turkbey studied 45 patients and found a 98% PPV of MRI in identifying cancer on final pathology.37  Sensitivity of detection was higher for lesions >5 mm in size and in patients with Gleason score >7.37 Similarly, in 122 men who underwent mpMRI before radical prostatectomy, Le showed a 72% overall sensitivity for detecting tumors with Gleason score 7 or higher or tumors > 1 cm in size.38 Of the tumors missed on mpMRI, 75% were Gleason 6 while only 4% were Gleason 8 or higher.  Baco et al showed a 95% concordance between the index tumor location on biopsy and final pathology and Delongchamps showed that mpMRI underdetected only 4% of patients with significant cancer and an index tumor was missed in 1 of 125 patients.39,40

Use in predicting organ confined disease:

MpMRI has also been shown to provide improved risk assessment over prior diagnostic tools such as nomograms.  Gupta showed that mpMRI was more accurate in predicting organ confined (OC) disease on pathological analysis than Partin tables in 60 men who underwent radical prostatectomy. The sensitivity, specificity, PPV, and NPV of mpMRI in predicting OC disease were 81.6%, 86.4%, 91.2%, and 73.1%, respectively.41 In a second study of 158 men, Gupta again showed radiologic staging using mpMRI was more accurate in predicting organ confined disease (AUC 0.88) than the Partin tables (AUC 0.70).  In this study, predicting organ confined disease was improved when mpMRI was combined with PSA level (AUC, 0.91).42 It is unclear that this significantly changes clinical decision making.

Use in predicting extracapsular (extraprostatic) extension:

MpMRI has high sensitivity, specificity, PPV, and accuracy in predicting ECE at the time of radical prostatectomy (Table 1), although is less accurate in finding focal ECE.  The clinical utility in changing patient outcomes from this information has yet to be established.

Somford showed an overall accuracy of 73.8% of preoperative mpMRI to detect ECE on final pathology in 183 men undergoing radical prostatectomy. On multivariate analysis, only PSA and stage on mpMRI were associated with ECE, with mpMRI being the strongest predictor.7 Gupta showed mpMRI had a sensitivity, specificity, PPV, and NPV in detecting ECE of 77.8%, 83.4%, 66.7%, and 89.7%.[i]   Raskolnikov similarly showed a sensitivity, specificity, and PPV and NPV for ECE to be 48.7%, 73.9%, 35.9% and 82.8%, respectively, in 169 patients, but showed that mpMRI was not reliably able to identify microfocal ECE.   On multivariate regression analysis, only patient age and MRI/TRUS fusion guided biopsy Gleason score were independent predictors of ECE on final radical prostatectomy pathology. 43 In 87 patients with clinically localized prostate cancer with a pre-operative mpMRI who underwent a radical prostatectomy (of which 31 had ECE), Boesen showed a sensitivity and specificity of up to 81% and 78% for ECE by mpMRI.44 Feng showed that mpMRI could predict ECE in all zones, independent of PSA, Gleason score, and clinical stage but was least sensitive at the apex, and was less accurate for focal ECE. Overall, sensitivity, specificity, PPV and NPV of mpMRI for ECE were 70.7%, 90.6%, 57.1%, and 95.1%, respectively.45

Schieda showed the importance of using a standardized scoring system such as PI-RADSTM when evaluating for ECE.  When using PI-RADSTM compared to non-standardized reporting (in 65 and 80 patients, respectively), PI-RADSTM scoring had a 59.5% sensitivity, 68% specificity, and 62.7% accuracy for ECE, which was more uniform across readers, compared to 24.5% sensitivity, 75% specificity, and 42% accuracy for non PI-RADSTM scoring.46

Table 1: Sensitivity, specificity, PPV, NVP and accuracy in predicting ECE on mpMRI. 

 

Sensitivity

Specificity

PPV

NPV

Accuracy

Notes

Somford7

 

 

 

 

73.8

 

Gupta41

77.8

83.4

66.7

89.7

 

 

Raskolnikov43

48.7

73.9

35.9

82.8

 

Not reliable for micro-focal disease

Boesen44

81

78

 

 

 

 

Feng45

70.7

90.6

57.1

95.1

 

Lowest sensitivity at apex, less accurate for focal ECE

Schneida46

(using PI-RADS)

59.5

68

 

 

62.7

 

Use in predicting seminal vesicle invasion:

Preoperative identification of seminal vesicle invasion of prostate cancer can have important implications in treatment recommendations and surgical planning.  MRI has a high sensitivity and specificity for seminal vesicle invasion.  Soylu showed specificity of 96% to 98% and a PPV of 70% to 79% for mpMRI correctly identified seminal vesicle invasion in 131 men.25 Another study found that targeted biopsy detected cancer in 71% of 28 lesions in the seminal vesicles with moderate to high suspicion for malignancy on MRI. 47

Role on MRI in selecting therapy (local management, surgical choice and technique

Identification of pathologic features of cancer is important to help guide therapy in an individual patient.  Results of the MRI can be integrated into currently available clinical staging systems, and the information can be extrapolated to help risk stratify patients, guide therapy choice, and inform surgical technique.   Therapeutic technique including surgical technique, radiation planning, and antihormonal therapy may be modified based upon the improved accuracy of radiologic staging over clinical staging. 

Radical prostatectomy planning

MRI has been shown to be helpful to surgeons in pre-operative planning, although it has yet to be proven that it leads to improved patient outcomes.  Park studied 353 men who underwent radical prostatectomy with a pre-operative mpMRI where the surgeon determined preoperatively the degree of nerve sparing (bilateral, unilateral, none) they would use first without incorporating the mpMRI findings, and then once again after reviewing the MRI.  The surgical plan was changed in 26% of the patients, to either a more aggressive nerve sparing approach (57%) or a wider margin of resection (43%).  In patients with intermediate and high risk features, a change was made in 83% and 89%, respectively.48   Similarly, McClure showed that the surgeon changed their initial surgical plan in 28 of 104 (27%) patients after reviewing the MRI.[i]  The surgical plan was changed to a nerve-sparing technique in 17 of the 28 patients (61%) and to a non-nerve-sparing technique in 11 (39%). Seven of the 104 patients (6.7%) had positive surgical margins. In patients whose surgical plan was changed to a nerve-sparing technique, there were no positive margins on the side of the prostate with a change in treatment plan.[ii]  There is no direct evidence that changing the surgical plan resulted in a difference in margin status in any patient.

Radiation therapy planning and androgen deprivation therapy (ADT) duration

Accurate radiological staging is important for target volume definition and dose prescription in conformal radiotherapy when treating prostate cancer.  Kamrava showed that 12% (21 of 183) of patients were stratified into a higher risk category using a MRI/TRUS fusion biopsy, and 18% were upgraded to intermediate or high risk from the low risk group.50 Panje studied 122 patients who underwent radiation therapy and found tumor stage shift occurred in 55.7% of patients after mpMRI. Upstaging was most prominent in patients showing high-risk PSA levels (>20 ng/dL) (73%), but was also substantial in patients presenting with low-risk PSA levels (< 10ng/dL) (50%) and low-risk Gleason scores (45.2%). Risk group changes occurred in 28.7% of the patients with consequent treatment adaptations regarding target volume delineation and duration of androgen deprivation therapy.51

Muralidhar et al studied the SEER database and identified 60,165 men who underwent radical prostatectomy and noted their clinical and pathologic features and their 10-year prostate cancer specific mortality (PCSM).  Patients with occult T3a disease on MRI had less than half the risk of PCSM as those with clinical T3 disease, and a subset of those men had similar risk as patients with pathologic T2 disease. Therefore, it is suggested that radiation-managed patients with low-grade/intermediate-grade T3a disease by MRI may only need short-term ADT, but those with T3b or high-grade occult T3a disease (who have similar PCSM as those presenting with cT3 disease) should be treated aggressively, including long-course ADT when managed by radiation.52

Role of MRI in evaluating regional lymphatics

Currently available imaging modalities for the evaluation of lymph nodes in patients with intermediate to high risks prostate cancer have high specificity and accuracy but only low to moderate sensitivity.  MRI appears to be equivalent to computerized tomography (CT) and positron emission tomography (PET) in this regard.

Heck et al prospectively compared CT scan, DWI MRI and [11C]choline PET/CT in 33 intermediate- and high-risk prostate cancer patients who then underwent radical prostatectomy with extended lymph node dissection. Metastases were detected in 14 of 33 (42%) patients and in 92 of 1,012 (9%) lymph nodes.  All three imaging techniques exhibit a low sensitivity with less than two thirds of lymph node metastases being detected. Overall diagnostic efficacy did not differ significantly between imaging techniques.53  Van den Bergh compared PET-CT to DWI MRI in 75 patients at high risk for lymph node metastasis (10-35% risk based upon Partin tables) and showed that MRI does not add value in the evaluation of lymph nodes in patients with a negative[i] PET-CT.   There was low sensitivity of (8.2% and 9.5%) and a positive predictive value (PPV) of 50.0% and 40.0% for both[ii] C-choline PET-CT and DW MRI, respectively.  Even when both imaging modalities were combined, sensitivity values remained too low to be clinically useful.54 Pasoglou et al evaluated 30 consecutive patients with high risk prostate cancer and showed that a combination of mpMRI with concomitant whole body MRI had a higher sensitivity (100% vs. 85%) and higher specificity (100% vs. 88%) for metastasis (bone and lymph nodes combined) when compared to bone scan with X-ray and CT scan.55

Von Below showed that MRI DWI had a 90% specificity, 55% sensitivity, and 72.5% accuracy for lymph node metastasis in 40 patients with intermediate- and high-risk prostate cancer, 20 of whom had histologically proven lymph node positive disease. The true-positive patients had significantly more involved lymph nodes (mean 6.9 versus 2.7), with larger diameter (mean 12.3 versus 5.2 mm) compared with the false-negative group.56 Vallini showed that using 3.0T DWI MRI with a multiple b value SE-EPI sequence may help distinguish benign from malignant pelvic lymph nodes in patients with prostate cancer.57

Key Point:

  1. Staging patients with prostate cancer using MRI to evaluate possible lymph node metastasis can be considered in selected patients (T3/T4 and T1/T2 patients with nomograms predicting the risk of lymph node metastasis >10%.
  2. mpMRI/TRUS may offer valuable staging information when performed prior to definitive local therapy. However, the current staging accuracy has not demonstrated the capability to rule out microscopic capsular extension or positive margins.

Evaluation for Local Recurrence

MpMRI can be of value in men with biochemical failure after radical prostatectomy and radiation therapy, to help evaluate for local recurrence versus systemic recurrence, to help guide biopsies, and to help inform therapy choice.  Suspicion of recurrence in the setting of biochemical failure is a valid reason for clinicians to request a mpMRI.

After radical prostatectomy, mpMRI is a useful tool because there is both a functional component and anatomic component to the test, the combination can be used to help differentiate among local recurrence of tumor, normal residual prostate tissue, or scar or fibrosis with granulation tissue.58 MRI should be able to differentiate fibrosis and atrophic remnant seminal vesicles after prostatectomy from local relapse. DCE imaging appears to be the most sensitive sequence to detect local recurrence, but DWI could be substituted as a reasonable alternative without compromising diagnostic accuracy.59 Linder identified 187 men who underwent endorectal coil MRI with dynamic gadolinium-contrast enhancement followed by TRUS- guided prostatic fossa biopsy; local recurrence was identified in 132 patients, with 124 (94%) detected on e-coil MRI. The median PSA was 0.59 ng/mL (range < 0.1-13.1), and median lesion size on MRI was 1 cm.  Sensitivity, specificity, PPV and NPV was 91%, 45%, 85% and 60% respectively.60 Since current evidence suggests that for salvage radiation therapy, lower pre-radiation PSA levels correspond to more durable responses, it is important to note that even in patients with a low PSA (< 0.4 ng/mL) the sensitivity was 86%.61  When a lesion was identified on MRI, the positive biopsy rate was 65%, and positive biopsy rates were 51% if the lesion was < 1 cm, 74% if 1-2 cm, and 88% if > 2 cm. 60

mpMRI can also be used to help targeted biopsies to more accurately diagnose radiation failure and to possibly determine who may benefit more from local and even focal salvage therapy.62 Diagnostic accuracy in the identification of tumors is better with a multi-parametric approach over strictly T2WI or DCE.   Brachytherapy, external beam radiotherapy, and focal therapies tend to diffusely decrease the signal intensity of the peripheral zone on T2-weighted images due to the loss of water content, consequently mimicking tumor and hemorrhage. The combination of T2WI and functional studies like DWI and DCE imaging improves the identification of local relapse. Tumor recurrence tends to restrict on diffusion images and avidly enhances after contrast administration. 59

Muller showed that in 10 patients, all had positive findings suspicious for local recurrence on mpMRI per entrance criterion. MRI-TRUS biopsies were positive in 10/16 lesions (62.5%) and 8/10 (80%) patients.63 Similarly, Roy evaluated 28 patients after surgery and 32 after radiation with a suspicion for recurrence and found that sensitivity with T2WI and spectroscopy sequences after surgery was 57% and 53%, respectively, and was 71% and 78%, respectively, after radiation.  DCE-MRI alone showed a sensitivity of 100% and 96%, respectively, for post-surgery and post-radiation groups. DWI alone had a higher sensitivity for radiation (96%) than for surgery (71%). The combination of T2WI plus DWI plus DCE-MRI provided a sensitivity as high as 100% for detection of recurrence after radiation.64 Wu carry out a meta-analysis to assess the effectiveness of MRI during the follow-up of patients with prostate cancer after undergoing radiation or radical prostatectomy. 14 studies were identified, 7 after surgery and 9 after radiation.  DCE images were more sensitive and specific than T2 weighted images, but sensitivity was highest when DCE was combined with spectroscopy for both post-surgical and post-radiation patients.65 

Key Point:

  1. It is possible that mpMRI may be useful for follow up evaluation of men treated with radical prostatectomy or in situ ablative therapies (cryoablation or high frequency focal ultrasound, and radiation therapy). However, current information has not determined the diagnostic accuracy of this imaging modality in these settings.

Use of MRI for Surveillance of Prostate Cancer

The concept of observation as a therapeutic option for men with clinically localized prostate cancer has been well established and is associated with excellent long term progression free survival in men with favorable malignancy on prostate biopsy. Chodak demonstrated in a large multi-institutional pooled analysis of 828 men that conservative therapy, also known as watchful waiting , resulted in an 87% disease specific survival at 10 years for men with either grade 1 (equivalent Gleason sum 5,6)or grade 2 (likely equivalent Gleason sum 7)cancer. The finding that the metastasis free survival for men with Grade 2 adenocarcinoma was only 58% at 10 years suggested that there was a role for a more active monitoring strategy in some men.66

A contemporary modification of the watchful waiting paradigm is considered active surveillance with some percentage of men transitioning from observation to curative intervention following evidence of disease progression on repeat prostate biopsy. A variety of classification schema have been developed to best identify men with the form of low risk prostate cancer that may be optimally managed with surveillance. The Prostate Cancer Research International Active Surveillance Study (PRIAS) monitored 5302 men in 18 countries for evidence of disease reclassification over time with a total of 52% and 73% of men moving to intervention at 5 and 10 years.67 Since approximately one-third of men treated with delayed intervention using radical prostatectomy still had favorable pathology ( Gleason sum 3+3 , pT2) the authors speculated on opportunities to more accurately identify  progression so that men could continue on the active surveillance pathway.68

Despite the established outcomes of watchful waiting series, overall survival statistics for comparable active surveillance protocols is still lacking with a wide variety of metrics used to predict the optimal candidates for this approach and to define parameters for transitioning care from surveillance to intervention.69 Conti et al reviewed 1097 men treated with radical prostatectomy and discovered that the published criteria for enrollment in active surveillance resulted in a variable risk of disease reclassification on biopsy or with unfavorable pathology at the time of intervention.70 The variability in outcomes relative to the selection criteria applied for enrollment into an active surveillance program was recapitulated by Elamin in 2016.71 Clearly, the optimal implementation of active surveillance for men with low risk prostate cancer is still under development with need for clarity around the type of diagnostic testing and surveillance intensity.

Several diagnostic modalities are currently being evaluated for enhanced performance in the management of men on active surveillance.  A simple change from a transrectal approach for prostate biopsy to transperineal biopsy has been found to more accurately predict clinical risk category but with similar risk of pathologic upgrading.72,73 Similarly, use of MRI–fusion biopsy techniques may better identify those with high-risk disease. Additional clinical information supports the role of molecular markers, such as genomic arrays as well as PHI and PCA3, as well as stratification by extent of Gleason score 4 adenocarcinoma in selecting men for active surveillance protocols.74-77

Importantly, any information extracted from the prostate biopsy is ultimately limited by the accuracy of the biopsy itself. Recent advances in prostate imaging with ultrasound and MRI have been shown to improve the targeting of biopsy to regions in the prostate that are most likely to harbor clinically significant cancer> Therefore, it remains possible that a targeted biopsy under advanced imaging guidance will optimally select men for all therapeutic options including active surveillance. MRI has been demonstrated to improve the detection of clinically significant prostate cancer at the time of initial biopsy which could better identify individuals who would not qualify for active surveillance with as many as 10% of men reclassified as higher risk by the MRI targeted biopsy.78,79 Schoots  et al performed a systematic literature review in 2015 and found that MRI will identify a suspicious lesion in more than 60% of men who would be candidates for active surveillance which increases the likelihood of clinically significant disease.80 Therefore, an MRI guided targeted prostate biopsy represents an advance in the determination of clinically significant prostate cancer prior to enrollment in any treatment pathway including active surveillance. Although the current evidence is inadequate to establish that mpMRI guided biopsy is a required step in the pathway for active surveillance, it has become clear that improved biopsy approaches should be employed before a man can safely choose active surveillance or even watchful waiting.

Once men select active surveillance as a management option for their low risk prostate cancer the specific details of follow up represent important costs and treatment intensity concerns. A negative MRI has been found to be associated with upgrading (> Gleason 6 in 27% of men suggesting that this imaging modality alone cannot be used to monitor men on active surveillance.80 An unchanged MRI has also been associated with an 80% NPV for biopsy upgrading during an active surveillance investigation.81 Again, the variability of treatment intensity and the lack of standardization for MRI findings suggests that this modality may be useful for the initial categorization of men as candidates for active surveillance, but is not sufficient for use as a primary test during the surveillance interval.82 Despite this conclusion, significant opportunities exist for further refinement of active surveillance protocols to better risk stratify men at initial entry into these protocols and to better target the regions of the prostate that could harbor a malignancy that would require a delayed therapeutic intervention. The combination of advanced imaging with MRI, altered biopsy approaches, (e.g. transperineal), and the use of molecular markers may ultimately improve the outcomes of non-curative therapies beyond those established with traditional watchful waiting.

Key Point: 

  1. Multi-parametric prostate MRI has been demonstrated to improve the diagnosis of intermediate risk and high-risk prostate cancer on targeted prostate biopsy which could be beneficial for identifying men as candidates for active surveillance protocols. However, the current information about MRI is not sufficient to support a role for repeat MRI without a prostate biopsy in monitoring men on active surveillance.

Conclusion

The information obtained by mpMRI represents a significant addition to traditional imaging techniques for the management of prostate cancer.  mpMRI has the potential to improve the timely identification of clinically significant prostate cancer.  Enhanced targeting approaches, has the potential to reduce the cost of care through the reduction of unnecessary or inaccurate prostate biopsy procedures.

Current evidence supports the performance of mpMRI in men with a rising PSA following an initial negative standard prostate biopsy procedure. It is likely that a targeted biopsy, using a combination of mpMRI and ultrasound-guided transrectal or transperineal biopsy, will become the preferred method for an initial prostate biopsy in a biopsy naïve man with an abnormal DRE or an elevated PSA value. It is also likely that mpMRI can be beneficial to men with a presumed clinically localized prostatic adenocarcinoma prior to selecting definitive therapy. The information obtained from advanced imaging appears to offer some useful information for surgical planning with both extirpative and ablative treatments.

Current enthusiasm for the potential benefit of advanced imaging with the mpMRI suggests that more evidence will be forthcoming regarding the role of this modality in men managed with active surveillance and possibly in population based screening programs for prostate cancer. These applications should be considered investigational at this time.

References

  1. Greer MD, Brown AM, Shih JH et al: Accuracy and agreement of PIRADSv2 for prostate cancer mpMRI: a multireader study. J Magn Reson Imaging 2016; doi: 10.1002/jmri.25372.
  2. Garcia-Reyes K, Passoni NM, Palmeri ML et al: Detection of prostate cancer with multiparametric MRI (mpMRI): effect of dedicated reader education on accuracy and confidence of index and anterior cancer diagnosis. Abdom Imaging 2015; 40:134.
  3. Weinreb JC, Barentsz JO, Choyke PL et al: PI-RADS Prostate Imaging - Reporting and Data System: 2015, Version. Eur Urol 2016, 69: 16.
  4. Heijmink SW, Fütterer JJ, Hambrock T, et al: Prostate cancer: body-array versus endorectal coil MRI imaging at 3 T—comparison of image quality, localization, and staging performance. Radiology 2007; 244: 184.
  5. Turkbey B, Merino MJ, Gallardo EC et al: Comparison of endorectal coil and nonendorectal coil T2W and diffusion-weighted MRI at 3 Tesla for localizing prostate cancer: correlation with whole-mount histopathology. J Magn Reson Imaging 2014; 39: 1443.
  6. Mazaheri Y, Vargas HA, Nyman G et al: Diffusion-weighted MRI of the prostate at 3.0T: comparison of endorectal coil (ERC) MRI and phased-array coil (PAC) MRI-The impact of SNR on ADC measurement. Eur J Radiol. 2013; 82: e515.
  7. Somford DM, Hamoen EH, Fütterer JJ et al: The predictive value of endorectal 3 Tesla multiparametric magnetic resonance imaging for extraprostatic extension in patients with low, intermediate and high risk prostate cancer. J Urol 2013; 190: 1728.
  8. Thomsen HS. Nephrogenic systemic fibrosis: a serious adverse reaction to gadolinium - 1997-2006-2016. Part 1. Acta Radiol 2016; 57: 515.
  9. Muller BG, Shih JH, Sankineni S et al: Prostate Cancer: Interobserver agreement and accuracy with the Revised Prostate Imaging Reporting and Data System at Multiparametric MR Imaging. Radiology 2015; 277: 741.
  10. Rosenkrantz AB, Ginocchio LA, Cornfeld D et al: Interobserver Reproducibility of the PI-RADS Version 2 lexicon: A multicenter study of six experienced prostate radiologists. Radiology 2016; 280: 793.
  11. Garvey B, Türkbey B, Truong H et al: Clinical value of prostate segmentation and volume determination on MRI in benign prostatic hyperplasia. Diagn Interv Radiol 2014: 20: 229.
  12. van Leeuwen PJ, Kranse R, Hakulinen T et al: Impacts of a population-based prostate cancer screening programme on excess total mortality rates in men with prostate cancer: a randomized controlled trial. J Med Screen 2013; 20: 33.
  13. Schröder FH, Hugosson J, Roobol MJ et al: Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 2014; 384: 2027.
  14. Nam RK, Wallis CJ, Stojcic-Bendavid J et al: A pilot study to evaluate the role of magnetic resonance imaging for prostate cancer screening in the general population. J Urol 2016; 196: 361.
  15. Zhang K, Shen Y, Zhang X et al: Predicting prostate biopsy outcomes: A preliminary investigation on screening with ultrahigh b-value diffusion-weighted imaging as an innovative diagnostic biomarker. PLoS One 2016; 11: e0151176.
  16. Futterer JJ, Briganti A, De Visschere, P et al: Can clinically significant prostate cancer be detected with multiparametric magnetic resonance imaging? A systematic review of the literature. Eur Urol2015; 68: 1045.
  17. Filson CP, Natarajan S, Margolis DJ et al: Prostate cancer detection with magnetic resonance-ultrasound fusion biopsy: The role of systematic and targeted biopsies. Cancer 2016; 122: 884.
  18. Mertan FV, Greer MD, Shih JH et al.: Prospective evaluation of the Prostate Imaging Reporting and Data System Version 2 for prostate cancer detection. J Urol 2016; 196: 690.
  19. Osses DF, van Asten JJ, Kieft GJ et al.: Prostate cancer detection rates of magnetic resonance imaging-guided prostate biopsy related to Prostate Imaging Reporting and Data System score. World J Urol 2016; doi 10.1007/s00345-016-1874-7.
  20. Rastinehad AR, Baccala, AA Jr, Chung PH et al: D'Amico risk stratification correlates with degree of suspicion of prostate cancer on multiparametric magnetic resonance imaging. J Urol 2011; 185: 815.
  21. Hambrock, T, Hoeks C, Hulsbergen-van de Kaa C et al: Prospective assessment of prostate cancer aggressiveness using 3-T diffusion-weighted magnetic resonance imaging-guided biopsies versus a systematic 10-core transrectal ultrasound prostate biopsy cohort. Eur Urol 2012; 61: 177.
  22. De Cobelli F, Ravelli S, Esposito A et al: Apparent diffusion coefficient value and ratio as noninvasive potential biomarkers to predict prostate cancer grading: comparison with prostate biopsy and radical prostatectomy specimen. AJR Am J Roentgenol 2015; 204: 550.
  23. Kim CK, Park SY, Park JJ et al: Diffusion-weighted MRI as a predictor of extracapsular extension in prostate cancer. AJR Am J Roentgenol 2014; 202: W270.
  24. Baco E, Rud E, Vlatkovic L et al: Predictive value of magnetic resonance imaging determined tumor contact length for extracapsular extension of prostate cancer. J Urol 2015; 193: 466.
  25. Soylu FN, Peng Y, Jiang Y et al: Seminal vesicle invasion in prostate cancer: evaluation by using multiparametric endorectal MR imaging. Radiology 2013; 267: 797
  26. Williams SB, Salami S, Regan MM et al: Selective detection of histologically aggressive prostate cancer: an Early Detection Research Network Prediction model to reduce unnecessary prostate biopsies with validation in the Prostate Cancer Prevention Trial. Cancer 2012; 118: 2651.
  27. Thompson IM, Ankerst DP, Chi C et al: Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial. J Natl Cancer Inst 2006; 98: 529.
  28. Salami SS, Vira MA, Turkbey B et al: Multiparametric magnetic resonance imaging outperforms the Prostate Cancer Prevention Trial risk calculator in predicting clinically significant prostate cancer. Cancer 2014; 120: 2876.
  29. Bjurlin M, Wysock J, Sakar S et al: MP53-11 a pre-biopsy nomogram for the prediction of the risk of Gleason score ≥ 7 prostate cancer on combined MRI-US fusion targeted and systematic prostate biopsy amoung men with no previous biopsy. J Urol 2016; 195: e701.
  30. Haffner J, Lemaitre L, Puech P et al: Role of magnetic resonance imaging before initial biopsy: comparison of magnetic resonance imaging-targeted and systematic biopsy for significant prostate cancer detection. BJU Int 2011; 108: E171
  31. Delongchamps NB, Peyromaure M, Schull A et al: Prebiopsy magnetic resonance imaging and prostate cancer detection: comparison of random and targeted biopsies. J Urol 2013; 189: 493.
  32. Pokorny MR, de Rooij M, Duncan E et al: Prospective study of diagnostic accuracy comparing prostate cancer detection by transrectal ultrasound-guided biopsy versus magnetic resonance (MR) imaging with subsequent MR-guided biopsy in men without previous prostate biopsies. Eur Urol 2014; 66: 22.
  33. Mendhiratta N, Rosenkrantz AB, Meng X et al: Magnetic resonance imaging-ultrasound fusion targeted prostate biopsy in a consecutive cohort of men with no previous biopsy: reduction of over detection through improved risk stratification. J Urol 2015; 194: 1601.
  34. 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: 390.
  35. Roehl KA, Antenor JA and Catalona WJ: Serial biopsy results in prostate cancer screening study. J Urol 2002; 167: 2435.
  36. Sonn GA, Margolis DJ and Marks LS: Target detection: magnetic resonance imaging-ultrasound fusion-guided prostate biopsy. Urol Oncol 2014; 32: 903.
  37. Turkbey B, Mani H, Shah V et al: Multiparametric 3.0T prostate magnetic resonance imaging to detect cancer: histopathological correlation using prostatectomy specimens processed in customized magnetic resonance imaging based molds. J Urol 2011; 186: 1818.
  38. Le JD, Tan N, Shkolyar E et al: Multifocality and prostate cancer detection by multiparametric magnetic resonance imaging: correlation with whole-mount histopathology. Eur Urol 2015; 67: 569.
  39. Baco E, Ukimura O, Rud E et al: Magnetic resonance imaging transectal ultrasound image-fusion biopsies accurately characterize the index tumor: correlation with step-sectioned radical prostatectomy specimens in 135 patients. Eur Urol 2015; 67: 787.
  40. Delongchamps NB, Lefevre A, Bouazza N et al: Detection of significant prostate cancer with magnetic resonance targeted biopsies— should transrectal ultrasound-magnetic resonance imaging fusion guided biopsies alone be a standard of care? J Urol 2015; 193: 1198.
  41. Gupta RT, Faridi KF, Singh AA et al: Comparing 3-T multiparametric MRI and the Partin tables to predict organ-confined prostate cancer after radical prostatectomy. Urol Oncol 2014; 32: 1292.
  42. Gupta RT, Brown AF, Silverman RK, et al: Can radiologic staging With multiparametric MRI enhance the accuracy of the Partin tables in predicting organ-confined prostate cancer? AJR Am J Roentgenol 2016; 207: 87.
  43. Raskolnikov D, George AK, Rais-Bahrami S, et al: The role of magnetic resonance image guided prostate biopsy in stratifying men for risk of extracapsular extension at radical prostatectomy. J Urol 2015; 194: 105.
  44. Boesen L, Chabanova E, Løgager V et al: Prostate cancer staging with extracapsular extension risk scoring using multiparametric MRI: a correlation with histopathology. Eur Radiol 2015; 25: 1776.
  45. Feng TS, Sharif-Afshar AR, Smith SC et al: Multiparametric magnetic resonance imaging localizes established extracapsular extension of prostate cancer. Urol Oncol 2015; 33: 109.
  46. Schieda N, Quon JS, Lim C, et al: Evaluation of the European Society of Urogenital Radiology (ESUR) PI-RADS scoring system for assessment of extra-prostatic extension in prostatic carcinoma. Eur J Radiol 2015; 84: 1843.
  47. Raskolnikov D, George AK, Rais-Bahrami S et al: Multiparametric magnetic resonance imaging and image-guided biopsy to detect 150 seminal vesicle invasion by prostate cancer. J Endourol 2014; 28: 1283.
  48. Park BH, Jeon HG, Jeong BC et al: Influence of magnetic resonance imaging in the decision to preserve or resect neurovascular bundles at robotic assisted laparoscopic radical prostatectomy. J Urol 2014; 192: 82.
  49. McClure TD, Margolis DJ, Reiter RE et al: Use of MR imaging to determine preservation of the neurovascular bundles at robotic-assisted laparoscopic prostatectomy. Radiology 2012; 262: 874.
  50. Kamrava M, Hegde JV, Abgaryan N et al: Does the addition of targeted prostate biopsies to standard systemic biopsies influence treatment management for radiation oncologists? BJU Int 2016; 117: 584.
  51. Panje C, Panje T, Putora PM et al: Guidance of treatment decisions in risk-adapted primary radiotherapy for prostate cancer using multiparametric magnetic resonance imaging: a single center experience. Radiat Oncol 2015; 10: 47.
  52. Muralidhar V, Dinh KT, Mahal BA et al: Differential post-prostatectomy cancer-specific survival of occult T3 vs. clinical T3 prostate cancer: Implications for managing patients upstaged on prostate magnetic resonance imaging. Urol Oncol 2015; 33: 330.
  53. Heck MM, Souvatzoglou M, Retz M et al: Prospective comparison of computed tomography, diffusion-weighted magnetic resonance imaging and [11C]choline positron emission tomography/computed tomography for preoperative lymph node staging in prostate cancer patients. Eur J Nucl Med Mol Imaging 2014; 41: 694.
  54. Van den Bergh L, Lerut E, Haustermans K et al: Final analysis of a prospective trial on functional imaging for nodal staging in patients with prostate cancer at high risk for lymph node involvement. Urol Oncol 2015; 33: 109.
  55. Pasoglou V, Larbi A, Collette L et al:. One-step TNM staging of high-risk prostate cancer using magnetic resonance imaging (MRI): toward an upfront simplified "all-in-one" imaging approach? Prostate 2014; 74: 469.
  56. von Below C, Daouacher G, Wassberg C et al: Validation of 3 T MRI including diffusion-weighted imaging for nodal staging of newly diagnosed intermediate- and high-risk prostate cancer. Clin Radiol 2016; 71: 328.
  57. Vallini V, Ortori S, Boraschi P et al: Staging of pelvic lymph nodes in patients with prostate cancer: Usefulness of multiple b value SE-EPI diffusion-weighted imaging on a 3.0 T MR system. Eur J Radiol Open 2015; 3: 16.
  58. Vargas HA, Wassberg C, Akin O et al: MR imaging of treated prostate cancer. Radiology 2012; 262: 26.
  59. Panebianco V, Barchetti F, Sciarra A et al: Prostate cancer recurrence after radical prostatectomy: the role of 3-T diffusion imaging in multi-parametric magnetic resonance imaging. Eur Radiol 2013; 23: 1745.
  60. Linder BJ, Kawashima A, Woodrum DA et al: Early localization of recurrent prostate cancer after prostatectomy by endorectal coil magnetic resonance imaging. Can J Urol 2014; 21: 7283.
  61. Siegmann A, Bottke D, Faehndrich J et al: Salvage radiotherapy after prostatectomy—what is the best time to treat? Radiother Oncol 2012; 103: 239.
  62. Ménard C, Iupati D, Publicover J et al: MR-guided prostate biopsy for planning of focal salvage after radiation therapy. Radiology. 2015; 274: 181.
  63. Muller BG, Kaushal A, Sankineni S et al: Multiparametric magnetic resonance imaging-transrectal ultrasound fusion-assisted biopsy for the diagnosis of local recurrence after radical prostatectomy. Urol Oncol 2015; 33: 425.
  64. Roy C, Foudi F, Charton J et al: Comparative sensitivities of functional MRI sequences in detection of local recurrence of prostate carcinoma after radical prostatectomy or external-beam radiotherapy. AJR Am J Roentgenol 2013; 200: W361.
  65. Wu LM, Xu JR, Gu HY et al: Role of magnetic resonance imaging in the detection of local prostate cancer recurrence after external beam radiotherapy and radical prostatectomy. Clin Oncol (R Coll Radiol) 2013; 25: 252.
  66. Chodak, GW: The role of conservative management in localized prostate cancer. Cancer 1994; 74: 2178.
  67. Bokhorst, LP, Valdagni R, Rannikko A et al: A decade of active surveillance in the PRIAS study: An update and evaluation of the criteria used to recommend a switch to active treatment. Eur Urol 2016; doi: 10.1016/j.eururo.2016.06.007.
  68. Newcomb LF, Thompson IM Jr,Boyer HD et al: Outcomes of active surveillance for clinically localized prostate cancer in the prospective, multi-institutional Canary PASS cohort. J Urol 2016; 195: 313.
  69. Bruinsma SM, Bangma CH, Carroll PR et al: Active surveillance for prostate cancer: a narrative review of clinical guidelines. Nat Rev Urol 2016; 13: 151.
  70. Conti SL, Dall’era M, Fradet V et al: Pathological outcomes of candidates for active surveillance of prostate cancer. J Urol 2009; 181: 1628.
  71. Elamin, S, Bhatt NR, Davis NF et al: Validation of selection criteria for active surveillance in prostate cancer. J Clin Diagn Res 2016; 10: PC01.
  72. Scott S, Hemamali S, Chabert, C et al: Is transperineal prostate biopsy more accurate than transrectal biopsy in determining final Gleason score and clinical risk category? A comparative analysis. BJU Int 2015; 116: 26
  73. Bittner N, Merrick GS, Bennett A et al: Diagnostic performance of initial transperineal template-guided mapping biopsy of the prostate gland. Am J Clin Oncol 2015; 38: 300.
  74. Klein EA, Cooperberg MR, Magi-Galluzzi C et al: A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling. Eur Urol 2014; 66: 550.
  75. Nguyen HG, Welty CJ and Cooperberg MR: Diagnostic associations of gene expression signatures in prostate cancer tissue. Curr Opin Urol 2015; 25: 65.
  76. Cole AI, Morgan TM, Spratt DE et al: Prognostic value of percent Gleason grade 4 at prostate biopsy in predicting prostatectomy pathology and recurrence. J Urol 2016; 196: 405.
  77. Cantiello F, Russo GI, Cicione A et al: PHI and PCA3 improve the prognostic performance of PRIAS and Epstein criteria in predicting insignificant prostate cancer in men eligible for active surveillance. World J Urol 2016; 34: 485.
  78. Okoro C, George AK, Siddiqui MM et al: Magnetic resonance imaging/transrectal ultrasonography fusion prostate biopsy significantly outperforms systematic 12-core biopsy for prediction of total magnetic resonance imaging tumor volume in active surveillance patients. J Endourol 2015; 29: 1115.
  79. Ouzzane A, Renard-Penna R, Marliere F et al: Magnetic resonance imaging targeted biopsy improves selection of patients considered for active surveillance for clinically low risk prostate cancer based on systematic biopsies. J Urol 2015; 194: 350.
  80. Schoots IG, Petrides N, Giganti F et al: Magnetic resonance imaging in active surveillance of prostate cancer: a systematic review. Eur Urol 2015; 67: 627.
  81. Henderson DR, de Souza NM, Thomas K et al: Nine-year follow-up for a study of diffusion-weighted magnetic resonance imaging in a prospective prostate cancer active surveillance cohort. Eur Urol 2016; 69: 1028.
  82. Moore CM, Giganti F, Albertsen P et al: Reporting magnetic resonance imaging in men on active surveillance for prostate cancer: The PRECISE recommendations-a report of a European School of Oncology task force. Eur Urol 2016; doi: 10.1016/j.eururo.2016.06.011.

Advertisement

Advertisement