Version May 2024
INTRODUCTION — Worldwide, prostate cancer is the second most common cancer diagnosed in males according to data from the GLOBOCAN database. In the United States, it is estimated that prostate cancer will be diagnosed in approximately 268,490 males in the United States in 2022 and account for approximately 34,500 deaths [1].
Although widespread use of serum prostate-specific antigen (PSA) screening of healthy males has resulted in decreases in cancer-related mortality, this benefit has been accompanied by increased detection and treatment of many cancers bearing low metastatic potential (ie, clinically insignificant lesions) [2]. (See "Screening for prostate cancer", section on 'PSA testing'.)
A priority in the management of males with prostate cancer is the ability to accurately assess the presence of clinically significant lesions, to accurately assess the extent of disease at diagnosis, and to characterize the risk of future progression, thereby avoiding unnecessary overtreatment in males at low risk for progression, and undertreatment that may contribute to treatment failures, especially for those males opting for active surveillance. (See "Active surveillance for males with clinically localized prostate cancer", section on 'Indications'.)
Magnetic resonance imaging (MRI) offers increasingly reliable visualization of potentially significant prostate cancers and thus has shown advantages as a means by which to better select patients for biopsy and facilitate direct targeting of lesions during biopsy. MRI also provides information for staging tumor extent and monitoring treatment response.
The technology of prostate MRI, the new prostate imaging reporting and data system (PI-RADS), and MRI's current and potential clinical applications are reviewed in this topic. The clinical presentation and diagnosis of prostate cancer, the initial staging evaluation, and transrectal ultrasound (TRUS)-guided prostate biopsy are discussed in detail separately. (See "Clinical presentation and diagnosis of prostate cancer" and "Initial staging and evaluation of males with newly diagnosed prostate cancer" and "Prostate biopsy".)
TECHNOLOGY — Key advances that have contributed to the increased clinical utility of magnetic resonance imaging (MRI) of the prostate include the use of magnets with high field strength, the use of an endorectal coil, and the development of a novel set of imaging sequences that can be used in combination (so-called multiparametric MRI) to improve both lesion identification and characterization.
Magnet strength — MRI of the prostate was introduced in 1982 using a 0.08 Tesla (T) magnet [3]. Since then, MRI hardware and software have advanced considerably with the introduction and widespread adoption of higher strength magnets (1.5 to 3.0 T). Increased field strength improves both imaging resolution (due to an increased signal-to-noise ratio) and the speed of imaging.
Most radiologists consider a field strength ≥1.5 T essential for prostate imaging, and most major academic and high-volume centers use and recommend 3 T as the optimal platform. The typical examination time, including patient preparation and placement of an intravenous line for contrast administration, is 40 to 50 minutes.
Endorectal coil — The endorectal coil was introduced for prostate MRI in 1989 [4,5]. Although initial studies suggested that this technique offers improved spatial resolution and reduces local motion of the prostate during imaging, the frequency of its use has diminished with advances in MRI hardware and software technology.
Whether an endorectal coil is always useful is not certain, and there is an increasing trend away from its use. Satisfactory results have been obtained with both 1.5 and 3 T magnets without the use of an endorectal coil [6]. Taking these factors into consideration as well as the variability of MRI equipment available in clinical use, the prostate imaging reporting and data system (PI-RADS) Steering Committee recommends that supervising radiologists strive to optimize imaging protocols in order to obtain the best and most consistent image quality possible with the MRI scanner used [7]. Cost, availability, patient preference, and other considerations need to be considered.
Multiparametric imaging — There are three individual imaging sequences that should be obtained during a prostate MRI examination. These include diffusion-weighted imaging (DWI) with an apparent diffusion coefficient (ADC), T2-weighted (T2W) imaging, and dynamic intravenous contrast-enhanced (DCE) imaging [8].
In brief, each sequence allows for noninvasive assessment of three forms of tissue:
●Diffusion-weighted imaging – DWI measures the mobility of water molecules due to Brownian motion. The ADC is a quantitative measure reflecting this motion. In general, prostate cancer has increased cell density, which is imaged as an area with focally restricted free-water diffusion. This is best detected by using high-b-value DWI with resulting ADC maps. The restricted area can be detected as a focal high signal (white) on DWI combined with a focal low-signal (black) lesion on the corresponding ADC image.
The "b-value" is a reflection of the strength and timing of the gradients used to obtain the images. The operator, when prescribing the sequence parameters, selects this. For optimal prostate DWI MRI, the MRI systems must be capable of obtaining high-b-value diffusion sequences to allow stronger diffusion, and rapid scan times to allow DCE sequence acquisition. Most magnets in clinical practice have this capability.
The radiologist can then measure the ADC value for a particular region of interest. The discovery and verification of the relationship between the ADC value and the Gleason pattern have been a major advance in the development of multiparametric prostate MRI. The ADC value is inversely related to the Gleason grade of the tumor; thus, the lower the ADC, the higher the Gleason grade [9]. If a focal lesion is found in the gland to have restricted diffusion with an ADC value at 800 or less, it is very likely that this lesion is clinically significant, which is defined here as containing a component of Gleason pattern 4 disease. DWI images are the primary ones for assessment of the peripheral zone and are, of course, also used in the transition zone along with T2W.
●T2-weighted imaging – Prostate T2W imaging, which reflects local tissue water, can delineate the normal prostate zonal anatomy, clearly showing the transition and peripheral zones. The peripheral zone is depicted as a region of high signal (white) on T2W images, and the transition zone is depicted as a mix of both high- and low-signal areas reflecting the typical patterns of benign prostate hyperplasia. T2W imaging detects cancer as focal regions of moderately low signal intensity. T2W images are the primary ones for assessment of the transition zone.
●Dynamic intravenous contrast-enhanced imaging – DCE images are those obtained after the rapid intravenous injection of contrast (gadolinium-DTPA [diethylenetriamine penta-acetic acid]) and subsequent rapid imaging. These images depict the local vascular environment and are useful to assess vascularity in specific regions of the prostate. Focal prostate cancer typically has areas of abnormal neovascularity that can be depicted by analysis of changes such as early arterial enhancement, wash in, and wash out.
●Magnetic resonance spectroscopy imaging – Magnetic resonance spectroscopy imaging (MRSI) has been used in prostate imaging and can offer an assessment of the metabolic characteristics of intraprostatic foci. MRSI is not included in PI-RADS version 2 (PI-RADS v2) for focal prostate cancer characterization. It can be used to detect cancer recurrence after treatment [7]. However, MRSI is not used routinely.
Prostate imaging reporting and data system (PI-RADS) — The International Prostate MRI Working Group developed PI-RADS to standardize prostate MRI examination performance and reporting [10,11]. In 2014, PI-RADS v2 was released, and it was published in 2016 [7]. An updated version, PI-RADS v2.1, which was published in 2019, revises the technical parameters for image acquisition and modifies the interpretation criteria for MRI data, among other changes [12].
PI-RADS is a system used to characterize and assess all focal intraglandular prostate nodules seen on MRI. The system includes technical standards for scanning hardware, and protocols for image acquisition and interpretation. It also provides standardized terminology for reporting, and a sector map for all locations within the gland.
For PI-RADS v2 and v2.1, images should be acquired, if possible, with a 3 T magnet, and imaging at <1.5 T is specifically not recommended. Endorectal coil use is not required but is allowed if thought necessary for image quality. DWI with high-b-value (ie, ≥1400 seconds/mm2) DCE imaging should be routinely included. (See 'Technology' above.)
The PI-RADS system categorizes prostate lesions based on the likelihood of cancer according to a five-point scale, defined as the following:
●PI-RADS 1 – Clinically significant cancer is highly unlikely to be present.
●PI-RADS 2 – Clinically significant cancer is unlikely to be present.
●PI-RADS 3 – The presence of clinically significant cancer is equivocal.
●PI-RADS 4 – Clinically significant cancer is likely to be present.
●PI-RADS 5 – Clinically significant cancer is highly likely to be present.
In two separate studies, the probability of finding a clinically significant cancer in males with PI-RADS 3, 4, or 5 lesions was 12 and 23 percent, 60 and 49 percent, and 83 and 77 percent, respectively [13,14].
In general, a clinically significant cancer can be defined as a lesion that is predicted to have a grade group of 2 or higher (table 1) with either a volume ≥0.5 mL or extraprostatic extension. Other criteria to refine risk stratification by incorporating other measures, such as genomic profiling and histologic subtype, have been proposed but have not yet been widely agreed upon. (See "Localized prostate cancer: Risk stratification and choice of initial treatment", section on 'TNM staging and Gleason grade group'.)
A "typical" focal prostate cancer can be depicted as a low area of restricted diffusion, low T2W, and hyperenhancing after intravenous contrast injection [15]. All focal lesions are evaluated on all sequences, and the parameters can be assessed and scored by PI-RADS.
Overall, prostate MRI performed according to PI-RADS v2 demonstrates high sensitivity and moderate specificity for detection of clinically significant prostate cancer. The following data are available:
●A systematic review of the diagnostic performance of PI-RADS v2 for detection of prostate cancer included 21 studies, totaling 3857 patients [16]. The overall pooled sensitivity for any prostate cancer diagnosis was 89 percent, and the specificity was 73 percent. In subgroup analysis, the overall pooled sensitivity for clinically significant prostate cancer was 89 percent, with a specificity of 64 percent. At a cutoff of PI-RADS ≥4 for determining clinically significant prostate cancer, the sensitivity and specificity were 90 and 62 percent, respectively, while for a cutoff of PI-RADS ≥3, sensitivity was 96 percent but specificity dropped to 29 percent.
●In the PRECISION (Prostate Evaluation for Clinically Important Disease: Sampling Using Image Guidance or Not?) trial, the detection rates for clinically significant prostate cancer for PI-RADS 3, 4, and 5 lesions in males with no prior biopsy were 12, 60, and 83 percent, respectively [13]. (See 'Initial presentation with no prior biopsy' below.)
●Notably, when measured on a per-lesion basis, the range of sensitivities reported has been lower (75 to 85 percent), which suggests that MRI-directed biopsy for only those PI-RADS ≥3 lesions might miss a proportion of prostate cancers [17-19].
In fact, in one report in which systematic biopsy was compared with MRI-directed biopsy (which was typically undertaken for PI-RADS ≥3 lesions), there were 29 cases (11 percent) in which clinically significant disease was detected by systematic biopsy only and where targeted biopsy was benign or found only insignificant disease [20]. (See 'Should males with positive MRI scans only undergo targeted biopsy?' below and 'Methods for MRI-targeted prostate biopsy' below.)
Some validation studies including multiple readers have shown a high degree of agreement in assigning PI-RADS scores, including between prostate-dedicated and general body radiologists, while others do not:
●In a study of five radiologists using the PI-RADS v2 system, agreement when scoring index lesions was 93 percent, and it was 74 percent for the detection of all lesions [21].
●On the other hand, another study of 408 males with 503 MRI-detected prostate lesions found substantial variation in PI-RADS distribution and yield of a clinically significant (ie, grade group 2 or higher (table 1)) cancer [22]. Across radiologists, the significant cancer detection rates ranged from 3 to 27 percent for PI-RADS 3 lesions, 23 to 65 percent for PI-RADS 4 lesions, and 40 to 80 percent for PI-RADS 5 lesions.
Management of PI-RADS 3 lesions — Most studies measuring the diagnostic performance of prostate MRI have defined prostate imaging reporting and data system (PI-RADS) ≥3 lesions as positive for a clinically significant cancer [16]. However, the published literature regarding the significance of a PI-RADS 3 lesion is conflicting [20,23-27], and whether or not all PI-RADS 3 lesions require a biopsy is controversial. In several studies, the range of clinically significant prostate cancers in males found to have PI-RADS 3 lesions ranged from 12 to 33 percent [13,26,28-31]. Furthermore, the diagnostic yield of biopsy is variable depending on whether or not there is an abnormality suitable for targeted biopsy.
The appropriate approach to these patients is debated, with some suggesting that prostate-specific antigen (PSA) density and possibly other PSA-related analyses (such as the four kallikrein [4K] score and the Prostate Health Index [PHI]) might be helpful for decision making [29,32-34]. (See "Measurement of prostate-specific antigen", section on 'Advances in PSA testing' and "Screening for prostate cancer".)
Some clinicians (including some of the authors and editors of this topic review) consider, particularly for an older patient with significant morbidities, that an MRI showing a PI-RADS 3 or lower lesion (particularly in the setting of a low PSA density) may be an argument to forego biopsy and continue PSA monitoring. However, this is not a universally accepted approach.
CLINICAL APPLICATIONS — Prostate magnetic resonance imaging (MRI) was initially applied as a tool for staging males with known prostate cancer prior to radical prostatectomy or radiation therapy. In this setting, prostate MRI provides information on the presence or absence of extracapsular disease or on the involvement of the neurovascular bundles and seminal vesicles, and thus, it helps differentiate stage T1/T2 disease from T3 disease (table 2) [35]. (See 'Staging' below.)
Subsequent investigations have established several new roles for prostate MRI; the role gaining the most attention is that of guiding targeted diagnostic prostate biopsies. (See 'Elevated serum PSA with a prior negative TRUS biopsy' below and 'Initial presentation with no prior biopsy' below.)
MRI may also be useful for the evaluation of males in whom the diagnosis of prostate cancer has already been established. The benefits include optimizing tumor localization for the purpose of staging and risk stratification, selecting appropriate candidates with low-risk disease for active surveillance, monitoring during active surveillance, and detecting local failure after radiation therapy [36]. (See 'Staging' below and 'Males choosing active surveillance' below and 'Suspected local recurrence after prostate radiation therapy' below.)
Elevated serum PSA with a prior negative TRUS biopsy — A negative transrectal ultrasound (TRUS) biopsy for cancer in the face of clinically determined need or indication for a prostate biopsy is the most validated and accepted indication for prostate MRI.
MRI is a valuable tool to detect occult prostate cancers in males with persistently elevated prostate-specific antigen (PSA) levels despite negative systematic prostate biopsy [37,38]. Multiparametric MRI provides biopsy target information and can guide a targeted prostate biopsy [39,40]. In this setting, prostate MRI-directed biopsy will detect a clinically significant cancer in as many as 34 to 41 percent of males with a prior negative biopsy, a majority of which will be high grade (grade group ≥2) on subsequent biopsy. Several meta-analyses show that a targeted biopsy demonstrates higher detection rates of clinically significant prostate cancer compared with systemic biopsy in a repeat biopsy setting [41-45].
MRI has particular value in identifying occult tumors in anatomic regions of the prostate that are not conventionally sampled during systematic sextant biopsy, such as the detection of tumors within the anterior zone, which may be inadequately sampled on systematic biopsies [46,47]. Males who are found on prebiopsy MRI to have an anterior lesion could then be selected for anterior samplings in addition to TRUS 12-core biopsy. (See "Prostate biopsy".)
Initial presentation with no prior biopsy — Prostate MRI with MRI-directed biopsy of suspicious lesions is increasingly regarded as a valuable tool for refining risk status for clinically meaningful prostate cancer. Multiparametric MRI-directed biopsy is more sensitive than systematic TRUS-guided biopsy alone for detecting clinically significant prostate cancers and reducing the number of clinically insignificant cancers diagnosed. At many institutions, including those of most of the authors and editors of this topic, all males who have access to it undergo prostate MRI with MRI-directed biopsy, if appropriate, prior to planned TRUS biopsy.
However, there is no consensus on the role of prostate MRI prior to first TRUS prostate biopsy, and not surprisingly, guidelines from expert groups are variable:
●Updated guidelines for prostate cancer diagnosis and management from the United Kingdom National Institute for Health and Care Excellence (NICE) suggest offering multiparametric MRI as the first-line investigation for all people with suspected clinically localized prostate cancer.
●National Comprehensive Cancer Network (NCCN) guidelines recommend consideration of MRI, but they do not provide any guidelines for selecting appropriate candidates [48].
●American Urological Association (AUA) guidelines state that there are insufficient data to recommend routine MRI in every biopsy-naïve patient under consideration for prostate biopsy. Its use may be considered in males for whom the clinical indications for biopsy are uncertain (minimal PSA increase, abnormal digital rectal examination [DRE] with normal PSA, or very young or old patients).
●Updated year 2019 guidelines from the European Association of Urology (EAU) endorse MRI prior to initial biopsy.
●Guidelines from Cancer Care Ontario (CCO) do not advocate MRI prior to initial TRUS-guided biopsy.
Among individuals suspected of having prostate cancer, minimizing overdiagnosis and detecting clinically significant but not insignificant prostate cancer are joint priorities for biopsy-naïve men, most of whom present with an asymptomatic elevation in serum PSA (less commonly with abnormal DRE). Clinically significant cancer is frequently defined as a lesion that is predicted to have a grade group of 2 or higher (table 1) with either a volume ≥0.5 mL or extraprostatic extension; however, this is not universal. (See "Clinical presentation and diagnosis of prostate cancer" and "Localized prostate cancer: Risk stratification and choice of initial treatment", section on 'TNM staging and Gleason grade group'.)
A prostate biopsy might be considered for a man with an elevated PSA or, less commonly, a suspicious finding on DRE. The decision to proceed to prostate biopsy in the setting of an elevated PSA is not automatic; rather, it represents a shared decision that incorporates the patient's health status, estimated life expectancy, perceived likelihood of harboring significant disease, and personal wishes. This subject is discussed in detail elsewhere. (See "Clinical presentation and diagnosis of prostate cancer", section on 'Decision to biopsy'.)
Increasingly, as supported by NCCN guidelines [48], multiparametric prostate MRI and serum biomarker testing are being used to assist in this initial assessment of an elevated PSA as an alternative to routine initial TRUS-guided biopsy. Prostate serum biomarkers (eg, four kallikrein [4K] assays, percent free PSA, Prostate Health Index [PHI] score) have not been directly compared with MRI in this setting, and the order in which these tests should be applied is not clear [49]. (See "Measurement of prostate-specific antigen", section on 'Serum free and bound PSA' and "Measurement of prostate-specific antigen".)
Previously, the standard prostate cancer diagnostic pathway included TRUS-guided biopsies, with multiple needles and systematic sampling of the prostate gland without knowledge of the likely locations of the tumors. A large proportion of males undergoing TRUS biopsies do not have any cancers detected [28]; these negative biopsies still incur attendant morbidities, and the ability to detect clinically significant disease is limited. Overdiagnosis of clinically unimportant cancers contributes unnecessarily to patient anxiety and leads to overtreatment and overtreatment-related harm. On the flip side, underdiagnosis and undertreatment of clinically important cancers also occur because of tissue sampling and risk stratification errors, and this contributes to treatment failures, particularly for those patients who opt for active surveillance. (See "Prostate biopsy", section on 'Systematic biopsy' and 'Males choosing active surveillance' below.)
Prostate MRI with MRI-directed biopsy is increasingly regarded as a valuable tool for refining risk status for clinically meaningful prostate cancer, although it has not yet replaced TRUS-guided biopsy, and there is no general consensus on which patients should get an MRI and whether or not MRI can replace TRUS-guided biopsy. Multiparametric MRI may be more sensitive than systematic TRUS-guided techniques for detecting clinically significant prostate cancers and for reducing the number of insignificant cancers diagnosed, although the available data suggest that the information obtained is complementary to that obtained using TRUS-guided biopsy, and at most institutions, a systematic TRUS-guided biopsy is still recommended even if the MRI shows a suspicious lesion. (See 'Should males with positive MRI scans only undergo targeted biopsy?' below.)
Comparative data — Prospective studies of prebiopsy MRI in males with elevated PSA or clinical suspicion for prostate cancer have suggested a potential benefit for MRI/ultrasound fusion to increase the detection of clinically significant, higher risk disease while lowering the detection of lower risk, clinically insignificant disease. The following comparative data are available:
●In the multicenter PROMIS study, 576 biopsy-naïve males referred for prostate biopsy because of elevated PSA, abnormal DRE, or a positive family history underwent 1.5 Tesla (T) MRI followed by concurrent standard TRUS biopsy and transperineal template mapping biopsy sampling the entire prostate at 5 mm intervals, which served as a reference standard [28]. MRI was more sensitive than TRUS biopsy for clinically significant cancer, defined as Gleason score ≥4+3 or cancer length ≥6 mm (93 versus 48 percent), but it was also less specific (41 versus 96 percent). The negative predictive value (NPV) of multiparametric MRI for the detection of clinically significant cancer was higher than that for TRUS biopsy (89 versus 74 percent), while the positive predictive value (PPV) was lower (51 versus 90 percent).
A strategy of foregoing biopsy among males with low-suspicion MRIs (scores equivalent to prostate imaging reporting and data system [PI-RADS] 1 and 2 (see 'Prostate imaging reporting and data system (PI-RADS)' above)) might have avoided a biopsy in 27 percent of males and would have missed only 5 percent of the clinically significant cancers. The authors concluded that TRUS biopsy performs poorly as a diagnostic test for clinically significant prostate cancer, that MRI used as a "triage" test before first prostate biopsy could identify one-quarter of males who might safely avoid biopsy, and that it might improve the detection of clinically significant cancer. However, this is not yet a standard approach at most institutions. (See 'Do males with a negative MRI need TRUS biopsy?' below.)
Importantly, due to the era of the study's conception, the MRI studies were performed on a lower field strength magnet than is used in many centers today, and it employed a five-level Likert reporting system rather than the modern PI-RADS version 2 (PI-RADS v2) rubric. (See 'Prostate imaging reporting and data system (PI-RADS)' above.)
●The diagnostic accuracy of prostate MRI only, MRI plus targeted biopsy, any MRI pathway (MRI with [if the MRI was positive] or without [if the MRI was negative] targeted biopsy), and systematic biopsy, as compared with template-guided biopsy as the reference standard, was addressed in a Cochrane review of 18 studies [44]. Among these diagnostic strategies, the MRI pathway had the most favorable diagnostic accuracy for the detection of clinically significant prostate cancer (the primary target condition was defined as International Society of Urological Pathology [ISUP] grade 2 or higher prostate cancer (table 1)) in biopsy-naïve males or those with a prior negative biopsy. Compared with template-guided biopsy, the MRI pathway had a pooled sensitivity of 72 percent (95% CI 0.60-0.82) and a pooled specificity of 96 percent (95% CI 0.94-0.98). Assuming a baseline cancer prevalence of 30 percent, this would result in 216 true positives, 28 false positives, 672 true negatives, and 84 false negatives per 1000 men. In contrast, the pooled sensitivity for systematic biopsy was 62 percent (95% CI 0.19-0.93), and the specificity was 100 percent (95% CI 0.91-1.00). Again, assuming a baseline cancer prevalence of 30 percent, this would result in 189 true positives, 0 false positives, 700 true negatives, and 111 false negatives per 1000 men. The MRI pathway still missed some males with important prostate cancers.
●A slightly different question was addressed in a separate meta-analysis of seven high-quality randomized trials [13,50-55] comparing systematic prostate biopsy versus prebiopsy MRI followed by targeted biopsy with or without systematic biopsy [56]. The following conclusions were drawn:
•Compared with systematic biopsy alone, MRI with or without targeted biopsy was associated with a 57 percent (95% CI 2-141 percent) improvement in the detection of clinically significant prostate cancer and a 77 percent (95% CI 60-93 percent) reduction in the number of cores taken per procedure. The calculated percentage of males who may have potentially avoided a biopsy procedure (based on avoiding a systematic biopsy in males who were found to have multiparametric MRI-negative findings) was 33 percent (95% CI 23-45 percent).
•In most of the trials, it was not possible to assess the risk of complications associated with the targeted biopsy procedure compared with systematic biopsy. One trial showed a decrease in pain and bleeding adverse effects with MRI and targeted biopsy [13].
•In an analysis of five trials, 31 percent of prostate cancer cases (95% CI 15-49 percent) were not visualized on the prebiopsy MRI. Most of these were classified as clinically insignificant, and the risk of a patient having a clinically significant prostate cancer and negative MRI findings ranged between 0 and 23 percent.
•Systematic sampling of the prostate in addition to the acquisition of targeted cores did not significantly improve the detection of clinically significant prostate cancer compared with systematic biopsy alone.
Limitations of this analysis were that two of the trials did not use identical biopsy approaches for all patients in both study groups, variability in the definition of clinically insignificant prostate cancer in all of the trials, and the fact that test properties such as sensitivity and specificity could not be calculated because most patients did not undergo a reference standard procedure (ie, saturation biopsies using a template or prostatectomy).
On the other hand, four other prospective analyses (not included in the meta-analysis) suggest that the information obtained from MRI is complementary to systematic TRUS-guided biopsies, and that the greatest sensitivity for detecting clinically significant disease is achieved by combining the two methods [57-60]. (See 'Should males with positive MRI scans only undergo targeted biopsy?' below.)
Thus, taken together, the available evidence suggests that incorporation of prebiopsy MRI should be recommended for diagnostic pathways for males referred for biopsy because of suspected prostate cancer. However, widespread acceptance of prostate MRI for all males prior to planned biopsy has been limited by significant problems with technical and clinical expertise, leading to one single-institution study reporting subjective and inconsistent interpretation of multiparametric MRI on a per-lesion basis, with false positives (particularly in the transition zone) and false negatives (particularly for smaller non-index lesions) [61]. In addition, several blood markers are now available that can help to predict the risk of high-grade cancer in males with an elevated PSA level, including the free PSA ratio, the PHI, and the 4K score. Since there are no studies comparing any of these tests with prostate MRI, the appropriate sequence of testing prior to prostate biopsy has yet to be determined [62,63].
There have been concerns about the financial cost of MRI, and the economic implications of widespread policies recommending prostate MRI for all males with clinical suspicion for prostate cancer remain unclear. However, multiple studies appear to demonstrate that incorporating prebiopsy MRI into the diagnostic pathway for males referred for biopsy because of clinical suspicion of prostate cancer is cost effective despite the initial expense of MRI because the cost of the MRI is offset by the avoidance of unnecessary biopsies, a decreased detection of clinically insignificant tumors, and a refined estimate of risk, including identifying males with low- and very low-risk disease who might be suitable candidates for active surveillance [64-68]. Notably, these findings are sensitive to test cost, the sensitivity of MRI-targeted biopsy, and the long-term outcomes of males with cancer. (See 'Males choosing active surveillance' below.)
The issue of whether males with a negative MRI can forego systematic biopsy is addressed below. (See 'Do males with a negative MRI need TRUS biopsy?' below.)
Can any test predict who might benefit from prebiopsy MRI? — Some data suggest that higher levels of PSA may identify those males who are most likely to benefit from prostate MRI. In a prospective cohort study of 1003 males undergoing both targeted (MRI/ultrasound fusion) and standard (TRUS) biopsy concurrently because of either an elevated PSA or abnormal DRE, investigators examined the role of PSA in detection of clinically significant prostate cancer [39]. A later analysis of this cohort suggested that the fraction of documented cancer cases that were upgraded to clinically significant disease based on MRI versus TRUS was higher in males with initially higher PSA levels [69]. Among males with PSA values >10 ng/mL, the frequency of upgrading using MRI-targeted versus standard 12-core TRUS biopsy was 24 versus 5 percent; for those with a PSA of 4 to 10 ng/mL, it was 10 versus 3 percent; for a PSA of 2.5 to <4 ng/mL, it was 0 versus 4 percent; and for a PSA <2.5 ng/mL, it was 3 versus 0 percent. The authors concluded that using a threshold PSA level of 5.2 ng/mL captured 90 percent of upgrading by targeted biopsy, corresponding to 64 percent of patients who underwent MRI and a targeted biopsy. Below this value, 12-core TRUS-guided biopsy detected more clinically insignificant cancers. In a smaller subset of 196 males with no prior biopsy, a cutoff of 6.5 ng/mL was advocated to detect 90 percent of clinically significant cancers.
However, in our view, these data are insufficient to conclude that any magnitude of PSA elevation can be used to select males for initial MRI.
Should males with positive MRI scans only undergo targeted biopsy? — Although there is some disagreement on this point internationally [70], at least in the United States, males with a positive MRI scan who undergo MRI-directed biopsy also undergo simultaneous systematic TRUS biopsy as well to optimize cancer detection. This is particularly true when the patient is biopsy naïve.
While it has been suggested that MRI-positive patients undergo only MRI-targeted biopsy, with no accompanying systematic biopsies [13,28,71], this position is countered by the consistent literature finding of higher grade disease not being detected on MRI-directed biopsy cores but on accompanying TRUS biopsy cores (in up to 21 percent of cases), which might have led to undertreatment due to risk misclassification if the TRUS biopsy were eliminated [23,33,39,57,58,60,72-75]. As an example, in one prospective trial, omitting systematic biopsy halved the probability of detecting clinically insignificant prostate cancer, but one in five clinically significant cancers were missed [75].
Furthermore, several prospective analyses suggest that the information obtained from MRI is complementary to TRUS-guided biopsies, and that the greatest sensitivity for detecting clinically significant disease is achieved by combining the two methods [57-60,76]. As examples (see "Prostate biopsy", section on 'Targeted biopsy'):
●In the PAIREDCAP (Prospective Assessment of Image Registration in the Diagnosis of Prostate Cancer) trial, 248 biopsy-naïve males with an MRI-visible lesion underwent systematic, cognitive fusion, and software fusion biopsies [60]. Targeted biopsies had higher cancer detection rates per core than systematic biopsy (38 percent software versus 33 percent cognitive versus 15.7 percent systematic), but fewer cores were taken with targeted biopsy (6 versus 12), thus the overall cancer detection rate was similar at 60 percent for systematic and targeted biopsy. The overall cancer detection rate was greatest (70 percent) when systematic and targeted results were combined, as the discordance of tumor locations suggested that the different biopsy methods detect different tumors. Overall, 21 percent had a tumor detected by systematic biopsy that was missed by MRI-targeted biopsy, while 10 percent had a tumor detected by targeted biopsy that was missed by systematic biopsy.
●Similar conclusions were reached in another prospective trial in which 2103 males with elevated serum PSA and MRI-visible prostate lesions underwent both MRI-targeted and systemic biopsy (79 percent had prior biopsy) [76]. Combined biopsy detected more cancers than either method alone (62.4 percent combined, 51.5 percent with MRI, 52.5 percent with systematic biopsy) and was associated with the fewest clinically significant upgrades (defined in this study as grade group 3 or higher (table 1)) in those who underwent subsequent prostatectomy (3.5 percent combined, 8.7 percent with MRI, 16.8 percent with systematic biopsy). The corresponding rates for upgrades to grade group 2 or higher disease were 6.7 percent for combined biopsy versus 18.3 and 30.2 percent for targeted and systematic biopsies, respectively.
Do males with a negative MRI need TRUS biopsy? — There is no consensus on which patients with a negative prostate MRI can forego biopsy, and at most institutions in the United States, males with an elevated PSA and a negative MRI are still referred for TRUS-guided biopsy. This approach is consistent with published guidelines from the AUA, EAU/ESTRO [77], and NCCN [48].
While several studies [13,28,78] have proposed that males with an elevated PSA or abnormal DRE who have negative multiparametric prostate MRI studies (ie, PI-RADS 1 or 2) may forego prostate biopsy (largely based on the high sensitivity and NPV [between 63 and 100 percent] of prostate MRI [28,79-82]), there are few prospective data addressing the validity of this approach, and it is not currently recognized by the AUA or the NCCN [48] clinical guidelines for routine practice.
The following data are available to inform this debate:
●In the PAIREDCAP trial (described above), among a subset of 52 males with negative MRI results who subsequently underwent systematic biopsy, eight (15 percent) were found to have clinically significant cancers [60].
●On the other hand, another trial did not find an increase in clinically significant cancers when standard biopsy was omitted if the MRI was negative. This trial compared MRI-targeted plus standard biopsy if the MRI results suggested prostate cancer versus standard biopsy alone in 1532 males undergoing prostate cancer screening who had a single PSA level ≥3 ng/mL [83]. While fewer clinically insignificant cancers were found in the MRI-targeted biopsy group (12 versus 4 percent), the number of clinically significant cancers was similar (21 versus 18 percent, difference 3 percent, range -1 to 7 percent), and the use of an MRI-based biopsy strategy was deemed noninferior to the standard strategy.
Given that the detection rate in the experimental group was no lower than in the control group, the false negative rate of the experimental group might be comparable with the control group. However, without a gold standard (eg, saturation biopsies, as have been done in other studies), the true numbers of clinically significant cancers that were missed because of the negative MRI is not clear.
Some authors suggest that this approach be limited to those with a lack of high-risk features (eg, clinical suspicion, family history, low PSA density [26,60]), and that low scores on the 4K, PHI, or prostate cancer antigen 3 gene (PCA3) assays [84] might give some confidence that a biopsy is not needed. Use of these assays is discussed in detail elsewhere. (See "Measurement of prostate-specific antigen", section on 'Advances in PSA testing'.)
Staging — Prostate MRI may aid in the staging evaluation by verifying organ-confined status (and thus supporting the decision to perform nerve-sparing radical prostatectomy), evaluating the status of the pelvic lymph nodes, and establishing the location and local extent of the tumor in patients being considered for radiation therapy.
The ability to distinguish between organ-confined tumors (≤T2c) and those that extend beyond the prostate (≥T3a) is an important component of treatment decision making. Multiparametric prostate MRI using a 3 T magnet is useful for predicting extraprostatic extension at surgery [85]. It is often used for surgical planning, specifically to define the relationship of the tumor to the neurovascular bundle and to determine the need or risk of sacrificing the nerves either unilaterally or bilaterally.
There is good evidence that prostate MRI prior to radical prostatectomy can be used to verify organ-confined status and thus support the decision to perform nerve-sparing radical prostatectomy [86]. However, this practice has not been incorporated as a standard of care in major practice guidelines. (See "Initial staging and evaluation of males with newly diagnosed prostate cancer", section on 'Evaluating the extent of local disease'.)
Staging MRI examinations are also used in planning radiation treatments (external beam or brachytherapy); the MRI can provide location information and estimates of tumor volume for dose planning.
The role of MRI for the assessment of pelvic lymph node status has also been evaluated, and it appears to match or outperform computed tomography (CT) [87].
Males choosing active surveillance — MRI of the prostate is often obtained in males with very low- and low-risk disease (table 3) who are considering active surveillance to ensure that high-grade disease has not been missed. There is also the potential for MRI examinations to augment and replace some of the follow-up biopsies, although prospective data to support this strategy are not yet available. Guidelines from expert groups on this point are variable. Guidelines from the AUA/American Society for Radiation Oncology (ASTRO)/Society of Urologic Oncology (SUO) and the American Society of Clinical Oncology (ASCO) state that clinicians could "consider" multiparametric prostate MRI as a component of active surveillance for localized prostate cancer. On the other hand, NCCN guidelines suggest that clinicians "consider" multiparametric MRI only if anterior and/or aggressive cancer is suspected when PSA increases and systematic prostate biopsies are negative [48]. Insurance coverage for prostate MRI is not universal, and this may limit access to patients who are biopsy naïve.
For males with very low- or low-risk prostate cancer (table 3), management with active surveillance has demonstrated favorable long-term treatment-free and oncologic outcomes in appropriately selected patients [88]. (See "Active surveillance for males with clinically localized prostate cancer".)
There is no consensus on the optimal way to select males for active surveillance. The conventional approach to risk stratification in males being considered for active surveillance (PSA, DRE, and histologic examination of systematic prostate biopsy, typically under TRUS guidance) has resulted in the misclassification of risk in as many as one in four patients, based on undergrading (ie, the presence of occult higher grade cancer in males whose initial biopsy shows only Gleason score 3+3 [6] disease) and underassessment of tumor volume. (See "Active surveillance for males with clinically localized prostate cancer", section on 'Indications'.)
In our view, and that of others, MRI of the prostate has become an important component of optimizing patient selection for active surveillance. The strength of MRI in this setting comes from its high NPV (between 68 and 100 percent [79-82]) for clinically significant disease. A negative MRI also provides reassurance to patients that their disease is truly low risk, and thus, it may improve retention in an active surveillance approach. In fact, guidelines from the combined AUA/ASTRO/SUO and ASCO state that males who elect active surveillance should have accurate disease staging that includes systematic image-guided biopsy using ultrasound or MRI guidance [89-92]. A later update of the AUA/ASTRO guidance on localized prostate cancer suggests MRI for all being considered for AS to detect more aggressive disease in other areas of the prostate not sampled in the diagnostic biopsy; however, in light of the possibility of missing clinically significant cancers not visible on MRI, imaging alone should not replace prostate biopsy [93].
The view that prostate MRI may aid in the identification of occult higher grade tumors, even among patients with known clinically low-risk disease, is supported by the following studies:
●In a study of 207 males with previously diagnosed, favorable-risk prostate cancer undergoing first-time MRI/ultrasound fusion biopsy during active surveillance, 14 percent experienced pathologic upgrading in MRI fusion biopsy cores alone that was not detected by systematic sampling [94].
●In another review of 281 males who were initially deemed appropriate for active surveillance based on clinical and biopsy results, 10 percent of the cohort was later reclassified as ineligible for active surveillance following prostate MRI and subsequent biopsy of clinically occult lesions [95].
●In another series of 85 males who qualified for active surveillance on the basis of conventional studies, 25 (29 percent) were later reclassified as not meeting active surveillance criteria based on MRI with MRI/ultrasound fusion-guided confirmatory biopsy [80].
●A systematic review concluded that MRI at the start of surveillance can detect clinically significant disease in one-third to one-half of males [96].
The data are less robust on whether MRI is beneficial as a monitoring tool for males undergoing active surveillance, and it remains uncertain whether the addition of MRI will add value to systematic biopsy and clinical variables in longitudinal follow-up. Nevertheless, guidelines for treatment of clinically localized prostate cancer from the combined AUA/ASTRO and ASCO suggest that clinicians may "consider" multiparametric prostate MRI as a component of active surveillance for localized prostate cancer, but that it should not uniformly replace periodic biopsy [91,93]. This subject is covered in more detail elsewhere. (See "Active surveillance for males with clinically localized prostate cancer", section on 'Monitoring and triggers for intervention with treatment'.)
Another option in this setting to identify males at a higher risk of pathology upgrade at the time of radical prostatectomy is use of one of several validated tissue-based genomic assays (eg, the Oncotype DX Genomic Prostate Score, Prolaris, Decipher). Guidelines from the NCCN and ASCO both support use of these molecular assays to improve risk stratification in males considering active surveillance who have low-risk or favorable intermediate-risk disease if the results of the assay, in conjunction with standard clinical parameters, might change clinical management (eg, males considering active surveillance for low-risk or favorable-risk intermediate-grade disease) [97,98]. Some examples include high-volume Grade Group 1 disease, Grade Group 1 disease with abnormal DRE or high PSA density, or low-volume Grade Group 2 disease (table 1).
The ASCO guideline also addressed the relative value of prostate MRI and tissue biomarkers in this setting, concluding that each of these approaches can provide clinically relevant information regarding the likelihood of upgrading on subsequent biopsy or prostatectomy, there are few studies directly comparing MRI versus genomics in this setting [99,100]. Although there are patients for whom both MRI and biomarker testing can provide independent information, the increased testing intensity would clearly increase cost, and it is not clear which specific patients may benefit from both. (See "Molecular prognostic tests for prostate cancer", section on 'Clinical utility and guidelines from expert groups' and "Active surveillance for males with clinically localized prostate cancer", section on 'Tools to refine the selection of males for AS'.)
Suspected local recurrence after prostate radiation therapy — For males with biochemical failure following radiation therapy for clinically localized prostate cancer who have undergone a negative prostate biopsy, multiparametric MRI may be helpful in differentiating between residual local disease and distant metastatic spread. In addition, for those being considered for salvage prostatectomy, MRI has been used to identify seminal vesicle invasion or extraprostatic extension (features that identify males who are unlikely to achieve long-term disease control). (See "Rising serum PSA following local therapy for prostate cancer: Diagnostic evaluation" and "Rising serum PSA after radiation therapy for localized prostate cancer: Salvage local therapy".)
Studies of MRI following prostate radiation therapy appear to offer benefit in the setting of suspected clinical local recurrence based on rising PSA [101,102]. In the absence of clinical suspicion for disease recurrence, however, MRI is not indicated to assess treatment response. MRI is helpful in males postprostatectomy with biochemical failures, allowing for detection of recurrent or residual disease in the resection bed. This information defines the local tumor recurrence and allows for careful planning and delivery of salvage radiation therapy or focal, image-guided, ablative salvage therapy, such as cryotherapy. Multiparametric MRI may also be helpful in differentiating between residual local disease and distant metastatic spread. (See "Rising serum PSA following local therapy for prostate cancer: Diagnostic evaluation".)
Males considering focal therapy — Ablative technologies that render treatment to a portion of the prostate believed to be a dominant focus of cancer have been limited in their ability to reliably locate and monitor effect. MRI can precisely locate an index lesion to provide guidance in focal image-guided therapy treatments. Data from a prospective study of multiparametric MRI and subsequent saturation biopsy reported an NPV of 84 to 89 percent for the detection of lesions >4 mm and/or Gleason score ≥3+4 [103].
The integration of MRI guidance offers a promising means by which to direct therapies, including high-intensity focused ultrasound, cryotherapy, brachytherapy, or photodynamic therapy, although this application has not yet been evaluated in a prospective manner with longitudinal follow-up. There is consensus that multiparametric MRI will guide these therapies and posttreatment follow-up in combination with PSA [104]. (See "Cryotherapy and other ablative techniques for the initial treatment of prostate cancer".)
METHODS FOR MRI-TARGETED PROSTATE BIOPSY — Directed biopsy targeting prostatic magnetic resonance imaging (MRI) lesions increases the yield and detection rate of clinically significant, high-grade prostate cancer. The location and size of suspicious focal lesions can help in determining the need for transperineal or transrectal approaches to the diagnostic biopsy, along with cognitive, fusion, or gantry image guidance.
Targeted biopsies can be performed using one of several available techniques:
●MRI/ultrasound fusion biopsy (typically transrectal), in which previously obtained MRI images are overlaid with real-time transrectal ultrasound (TRUS) using specific software allowing three-dimensional tracking in space [105-107].
●Cognitive fusion biopsy (typically transrectal), in which the operator reviews the MRI images and then manually correlates them with the real-time TRUS images to biopsy the suspicious area [105,108-110].
●In-bore biopsy (transperineal or transrectal), in which biopsy sites are localized and targeted in real time while a patient is undergoing MRI examination [38,40,111].
All of these approaches have demonstrated comparable tumor detection rates [112,113], but they are all associated with technical challenges, require some training (particularly for urologists, who have less proficiency in MRI interpretation than do interventional radiologists [114]), and may require a greater time commitment during early adoption. Transperineal approaches to MRI-directed biopsies have the advantage of avoiding the rectal wall and of reduced rates of postbiopsy infections [39,115].
SUMMARY AND RECOMMENDATIONS
●Major technical improvements in multiparametric prostate magnetic resonance imaging (MRI) with the standard approach to interpretation using the prostate imaging reporting and data system version 2 (PI-RADS v2) have rapidly expanded the role of MRI in prostate cancer management in many clinical contexts, both prior to and following diagnosis. (See 'Technology' above.)
●Indications for prostate MRI include the following:
•A negative transrectal ultrasound (TRUS) biopsy for cancer in the face of clinically determined need or indication for a prostate biopsy is the most validated and accepted indication for prostate MRI. (See 'Elevated serum PSA with a prior negative TRUS biopsy' above.)
•The available evidence suggests that incorporation of prebiopsy MRI into the diagnostic pathway for a clinically suspected prostate cancer improves the diagnosis of clinically significant disease, reduces adverse effects from biopsy, and can potentially prevent unnecessary biopsies in some individuals. At some institutions, including those of most of the authors and editors of this topic, all males who have access to it undergo prostate MRI prior to planned systematic biopsy. However, there is no consensus on the appropriate selection of males for prebiopsy MRI, and this is an area in evolution. Not surprisingly, guidelines from expert groups are variable. (See 'Initial presentation with no prior biopsy' above.)
Most biopsy-naïve males with a positive MRI scan who undergo MRI-directed biopsy should undergo systematic biopsy as well. (See 'Should males with positive MRI scans only undergo targeted biopsy?' above.)
There is no consensus on which patients with a negative prostate MRI can forego biopsy, and at most institutions, especially those in the United States, males with an elevated prostate-specific antigen (PSA) and a negative MRI are still referred for systematic TRUS-guided biopsy. (See 'Do males with a negative MRI need TRUS biopsy?' above.)
•Prostate MRI may also aid in the staging evaluation by verifying organ-confined status (and thus supporting the decision to perform nerve-sparing radical prostatectomy), evaluating the status of the pelvic lymph nodes, and establishing the location and local extent of the tumor in patients being considered for radiation therapy. (See 'Staging' above.)
•MRI of the prostate is often obtained in males with very low- and low-risk disease (table 3) who are considering active surveillance to ensure that high-grade disease has not been missed. There is also the potential for MRI examinations to augment and replace some of the follow-up biopsies, although prospective data to support this strategy are not yet available. (See 'Males choosing active surveillance' above.)
•For males with biochemical failure following radiation therapy for clinically localized prostate cancer who have undergone a negative prostate biopsy, multiparametric MRI may be helpful in differentiating between residual local disease and distant metastatic spread. In addition, for those being considered for salvage prostatectomy, MRI has been used to identify seminal vesicle invasion or extraprostatic extension (features that identify males who are unlikely to achieve long-term disease control). (See 'Suspected local recurrence after prostate radiation therapy' above.)
ACKNOWLEDGMENT — We are saddened by the death of Nicholas Vogelzang, MD, who passed away in September 2022. UpToDate gratefully acknowledges Dr. Vogelzang's role as Section Editor on this topic, and his dedicated and longstanding involvement with the UpToDate program.
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