Micro-ultrasound in the diagnostic pathway of prostate cancer: Emerging roles in initial detection and active surveillance

Abstract

Background:

Multiparametric magnetic resonance imaging has reshaped prostate cancer diagnostics but is limited by cost, accessibility, and workflow complexity. High-resolution micro-ultrasound offers real-time lesion visualization and targeted biopsy capability as a potential complementary imaging modality.

Methods:

A narrative review of the literature was conducted using PubMed and Embase from inception to March 2026. Search terms included “micro-ultrasound,” “MicroUS,” “29 MHz ultrasound,” “PRI-MUS,” “prostate cancer,” “clinically significant prostate cancer,” “biopsy,” and “active surveillance.” Priority was given to randomized trials, prospective comparative studies, systematic reviews, and meta-analyses.

Results:

Micro-ultrasound demonstrates high sensitivity for clinically significant prostate cancer, with randomized evidence from the OPTIMUM trial supporting noninferiority to magnetic resonance imaging–based diagnostic pathways. Prospective studies suggest that micro-ultrasound enables real-time lesion targeting and may detect clinically significant prostate cancer not identified by multiparametric magnetic resonance imaging, supporting a complementary role in combined diagnostic strategies. However, specificity and biopsy-avoidance capacity remain lower than those of multiparametric magnetic resonance imaging. In active surveillance, micro-ultrasound serves as an adjunct for targeted biopsy but does not replace MRI-based protocols.

Conclusions:

Micro-ultrasound is a promising complementary imaging modality that enhances real-time targeting and workflow efficiency. Its primary role lies in integration within multimodal diagnostic pathways rather than replacement of multiparametric magnetic resonance imaging. Further multicentre validation and standardization are required to define its role in clinical practice.

Level of evidence:

Not applicable.

Keywords

micro-ultrasound prostate cancer multiparametric magnetic resonance imaging targeted biopsy clinically significant prostate cancer active surveillance Prostate Risk Identification using Micro-Ultrasound prostate biopsy

Introduction

Prostate cancer remains one of the most frequently diagnosed malignancies among men worldwide, and accurate detection of clinically significant prostate cancer (csPCa) continues to challenge contemporary urologic practice.^1,2 Conventional transrectal ultrasound (TRUS) has historically served as a guidance tool for systematic biopsy, but its limited spatial resolution restricts lesion visualization and contributes to both under-detection of csPCa and overdiagnosis of indolent disease.^1,3

The introduction of multiparametric magnetic resonance imaging (mpMRI) has significantly improved diagnostic pathways by enabling lesion localization, risk stratification, and targeted biopsy. Large prospective trials such as PRECISION and PROMIS have demonstrated that mpMRI-based diagnostic pathways improve the detection of csPCa while reducing unnecessary biopsies.^4,5 Despite these advantages, mpMRI is limited by cost, accessibility, and variability in interpretation, prompting interest in complementary imaging modalities.

High-resolution micro-ultrasound (MicroUS), operating at 29 MHz, provides improved spatial resolution compared with conventional TRUS and enables real-time visualization of prostate tissue microarchitecture.⁶ Furthermore, the development of the Prostate Risk Identification using Micro-Ultrasound (PRI-MUS) scoring system offers a structured framework for lesion characterization analogous to Prostate Imaging Reporting and Data System (PI-RADS) for mpMRI.⁶

This narrative review critically evaluates current evidence on MicroUS in prostate cancer diagnosis and surveillance, compares its performance with mpMRI, and defines its role within contemporary diagnostic pathways. Key RCTs, meta-analyses and prospective studies evaluating MicroUS in clinical settings are summarized in Tables 1 and 2.

Table 1.

Key prospective studies, RCTs, and meta-analyses evaluating MicroUS.

Study	Design	Population	Comparator	Main findings (csPCa)	Key interpretation
Kinnaird et al. (OPTIMUM)⁷	Multicenter RCT	802 men with clinical suspicion of PCa	MicroUS vs mpMRI-fusion ± combination	Detection: 47.1% (MicroUS) vs 42.6% (MRI); noninferior	Strongest evidence; MicroUS comparable to mpMRI pathways
Ghai et al.⁸	Prospective single-center	94 biopsy-naïve men	MicroUS vs mpMRI	Detection: 35% vs 39% (NS); biopsy avoidance: 10% vs 34%; combined: 40%	Comparable detection; MRI better for biopsy avoidance
Garcia-Becerra et al.⁹	Meta-analysis (prospective studies)	Multiple cohorts	MicroUS vs mpMRI	Sensitivity: 0.87 vs 0.88; specificity lower for MicroUS	Confirms similar sensitivity; MRI superior specificity
Abdel Gawad et al.¹⁰	Systematic review & meta-analysis	Prospective studies	MicroUS (standalone)	Sensitivity: ~0.84; specificity: ~0.41; NLR: 0.37	High sensitivity; limited rule-in performance
Avolio et al.¹¹	Prospective single-center	Diagnostic cohort	MicroUS-enhanced pathway	High detection rates of csPCa with MicroUS-targeted biopsy; additional cases identified beyond MRI-targeted biopsy	Supports added value in workflow integration
Pensa et al.¹²	Pathology correlation study	Prostatectomy cohort	MicroUS vs MRI vs histology	Good spatial concordance with pathology	Supports anatomical accuracy of MicroUS

csPCa: clinically significant prostate cancer; GG: Gleason grade group; mpMRI, multiparametric magnetic resonance imaging; mpUS, multiparametric ultrasound; RCT, randomized controlled trial.

Table 2.

Prospective and workflow-oriented studies evaluating MicroUS in clinical practice.

Study	Design	Population	Strategy	Main findings	Main implication
Avolio et al.¹¹	Prospective single-center	1423 suspected PCa	MicroUS + MRI-targeted + systematic biopsy	Sensitivity: 85%; NPV: 79%; 25 MicroUS-detected additional csPCa cases not identified by MRI	Strong real-world evidence of complementary value; systematic biopsy still relevant
Beatrici et al.¹³	Prospective single-center	425 suspected PCa	MicroUS triage pathway	Negative MicroUS: 52.7%; biopsy avoided: 85.7%; MRI avoided: 92.4%; lower csPCa risk (aHR 0.09)	Suggests rule-out/triage role; not sufficient to replace MRI
Ghai et al.⁸	Prospective biopsy-naïve	94 men	MRI + MicroUS + systematic biopsy	Detection: 39% (MRI) vs 35% (MicroUS); combined: 40%; MRI avoided more biopsies	Strong evidence for complementarity; MRI better for biopsy avoidance
Maffei et al.¹⁴	Prospective AS cohort	100 patients	MRI-guided confirmatory biopsy + MicroUS	Upgrading: 34%; sensitivity: 94.1% (MicroUS) vs 100% (MRI); missed upgrades with MicroUS-only	Useful adjunct in AS; not safe as standalone
Fasulo et al.¹⁵	Prospective single-center	140 surgical patients	Preoperative MicroUS	Sensitivity: 72.1%; specificity: 88.0%; AUC: 0.80 → 0.88 with clinical variables	Promising for EPE prediction; needs validation

aHR: adjusted hazard ratio; AS: active surveillance; AUC: area under the curve; csPCa: clinically significant prostate cancer; EPE: extraprostatic extension; MRI: magnetic resonance imaging; NPV: negative predictive value; PCa: prostate cancer.

Technical principles of MicroUS and PRI-MUS

All clinical evidence reviewed in this manuscript pertains to the ExactVu MicroUS system (Exact Imaging, Markham, Ontario, Canada), which operates at 29 MHz and is the only commercially available MicroUS platform at the time of writing. The generalizability of these findings to future alternative platforms cannot be assumed. MicroUS is a high-frequency ultrasound technology developed to improve the real-time visualization of prostate tissue architecture during diagnostic evaluation and biopsy. Unlike conventional transrectal ultrasound, which typically operates at frequencies between 6 and 12 MHz, MicroUS utilizes a 29-MHz transducer, resulting in substantially increased spatial resolution at the expense of reduced depth of penetration.^1,6 This higher resolution enables visualization of finer glandular structures and tissue heterogeneity that are not appreciable with standard ultrasound techniques.

From a clinical perspective, MicroUS is designed to function as a real-time imaging modality integrated directly into the biopsy workflow. It allows the operator to identify suspicious areas during the procedure itself, enabling targeted sampling without the need for pre-acquired imaging or image fusion systems. This represents a fundamental distinction from mpMRI-based pathways, which rely on prior imaging, lesion segmentation, and cognitive or software-assisted targeting.^2,16

To standardize lesion characterization, the Prostate Risk Identification using MicroUS protocol was developed as a risk stratification system analogous in concept to the Prostate Imaging Reporting and Data System used in mpMRI.⁶ PRI-MUS scores range from 1 to 5, reflecting increasing suspicion for csPCa based on specific imaging features. Suspicious findings include hypoechoic lesions, irregular glandular architecture, echogenic rims, and ductal distortion. These features are assessed dynamically during real-time scanning, allowing immediate targeting of areas with higher PRI-MUS scores.

An important practical advantage of MicroUS is its ability to combine systematic and targeted biopsy within a single session using the same imaging modality. This simplifies workflow logistics and may reduce procedural complexity compared with mpMRI-guided or mpMRI-fusion approaches. In addition, MicroUS can be performed in an outpatient setting without the need for specialized radiologic infrastructure, potentially improving accessibility and reducing delays in diagnosis.^1,2

However, interpretation of MicroUS images is inherently operator-dependent and requires dedicated training. Although the PRI-MUS scoring system provides a structured framework, interobserver variability and the learning curve associated with image interpretation remain important considerations.¹⁶ In addition, the reduced depth of penetration associated with high-frequency ultrasound may limit visualization of larger prostates or anterior lesions in some patients, representing a potential technical constraint. At present, MicroUS technology is primarily available through a single commercial platform, which may limit generalizability and broader implementation across different clinical settings.

Overall, MicroUS represents an evolution of ultrasound-based prostate imaging, shifting its role from a purely guidance tool to a modality capable of lesion detection and real-time risk stratification. Its integration into clinical practice depends not only on diagnostic performance but also on operator expertise, standardization of interpretation, and its positioning relative to established imaging pathways such as mpMRI. Representative imaging features across PRI-MUS categories are shown in Figure 1. The PRI-MUS scoring system and its clinical interpretation are summarized in Table 3.

Figure 1.

Representative MicroUS imaging features across PRI-MUS scores 1–5. Increasing PRI-MUS score reflects progressively higher suspicion for clinically significant prostate cancer based on echogenic patterns and architectural distortion.

Table 3.

PRI-MUS scoring system and its clinical interpretation.

PRI-MUS score	Typical imaging features (MicroUS)	Relative risk of csPCa	Clinical implication
1	Homogeneous echotexture; normal glandular architecture	Very low	No targeted biopsy; routine systematic sampling if indicated
2	Mild heterogeneity; no discrete lesion	Low	Generally low suspicion; biopsy based on clinical context (PSA, risk factors)
3	Mildly hypoechoic area; subtle architectural distortion	Intermediate	Consider targeted biopsy, particularly if additional risk factors present
4	Clearly hypoechoic lesion; irregular margins; architectural disruption	High	Targeted biopsy recommended
5	Markedly hypoechoic lesion; significant distortion; possible capsular irregularity	Very high	Strong indication for targeted biopsy; consider staging implications

csPCa: clinically significant prostate cancer; PRI-MUS: Prostate Risk Identification using Micro-Ultrasound.

Values of risk percentages of csPCa are derived from approximate cohort-dependent ranges reported in selected studies

MicroUS compared with conventional ultrasound

Conventional transrectal ultrasound (TRUS) has historically played a central role in prostate cancer diagnosis; however, its primary function has been limited to guiding systematic biopsy rather than enabling reliable lesion detection. The relatively low spatial resolution of standard ultrasound restricts its ability to distinguish malignant from benign prostate tissue, resulting in poor lesion conspicuity and a reliance on systematic, non-targeted sampling.^1,3 This approach contributes to both the under-detection of csPCa and the overdiagnosis of indolent disease.

MicroUS was developed to address these intrinsic limitations by providing substantially higher spatial resolution and enabling direct visualization of suspicious prostate lesions in real time. Compared with conventional Transrectal Ultrasound of the Prostate (TRUS), MicroUS allows identification of architectural distortions and echogenic patterns associated with malignancy, facilitating targeted biopsy without reliance on systematic sampling alone.^1,6 This represents a shift in the role of ultrasound from a guidance modality to a diagnostic imaging tool.

From a diagnostic standpoint, emerging evidence suggests that MicroUS improves the detection of csPCa compared with conventional TRUS-guided systematic biopsy alone. Prospective studies have demonstrated that MicroUS-guided targeting can increase the yield of clinically significant disease while maintaining procedural simplicity.^13,14 In addition, the ability to perform both systematic and targeted biopsies using a single imaging modality allows for a more efficient and streamlined diagnostic workflow.

In the context of lesion targeting, MicroUS offers a key advantage over conventional ultrasound by enabling real-time visualization of suspicious areas, thereby reducing reliance on random sampling. While conventional TRUS lacks a standardized lesion characterization system, the introduction of the PRI-MUS scoring system provides a structured framework for identifying and targeting suspicious regions during MicroUS-guided biopsy.⁶ This improves consistency and may enhance reproducibility compared with conventional ultrasound approaches.

Beyond initial diagnosis, MicroUS may also have implications for prostate cancer surveillance. Conventional TRUS plays a limited role in active surveillance protocols due to its inability to reliably identify or monitor focal lesions over time. In contrast, the improved resolution of MicroUS raises the possibility of more targeted re-biopsy and lesion tracking in patients undergoing surveillance, although current evidence in this setting remains limited and continues to evolve.^14,17

Despite these advantages, MicroUS does not entirely eliminate the need for systematic biopsy, and its performance remains dependent on operator expertise and experience. Furthermore, although it represents a clear advancement over conventional ultrasound in terms of lesion visualization and targeting capability, its role must be interpreted within the broader diagnostic pathway, particularly in relation to established modalities such as mpMRI.

Overall, MicroUS represents a meaningful evolution of ultrasound-based prostate imaging. Compared with conventional TRUS, it offers improved lesion detection, facilitates real-time targeted biopsy, and holds promise for applications in surveillance, while maintaining the accessibility and procedural advantages inherent to ultrasound. A comparative overview of conventional TRUS, MicroUS, and mpMRI is summarized in Table 4.

Table 4.

Comparative characteristics of conventional TRUS, MicroUS, and mpMRI in prostate cancer diagnosis and surveillance.

Feature	Conventional TRUS	MicroUS	mpMRI
Imaging principle	Low-frequency ultrasound (6–12 MHz)	High-frequency ultrasound (29 MHz)	Multiparametric MRI (T2, DWI, DCE)
Spatial resolution	Low	High	High
Lesion visualization	Limited	Direct visualization possible	High-quality lesion detection
Risk stratification	None	PRI-MUS	PI-RADS
Targeted biopsy capability	Limited (systematic)	Real-time targeting	MRI-targeted (fusion/cognitive)
Sensitivity (csPCa)	Low	High (comparable to mpMRI in selected settings)	High
Specificity	Low	Moderate	Higher
Biopsy avoidance	None	Limited	Significant
Workflow	Simple, real-time	Real-time, integrated	Multi-step (imaging + fusion)
Operator dependency	Moderate	High	Moderate
Standardization	Low	Moderate (PRI-MUS emerging)	High (PI-RADS)
Accessibility	High	Moderate	Variable
Cost	Low	Moderate	High
Active surveillance role	Limited	Adjunct (targeted biopsy)	Central role
Local staging (EPE)	Poor	Emerging	Established

Values represent generalized trends across studies and are not derived from standardized comparative analyses. TRUS: transrectal ultrasound; MicroUS: micro-ultrasound; mpMRI, multiparametric magnetic resonance imaging; PI-RADS: Prostate Imaging Reporting and Data System; PRI-MUS: Prostate Risk Identification using Micro-Ultrasound; csPCa: clinically significant prostate cancer.

Evidence for MicroUS in prostate cancer diagnosis

An expanding body of high-quality evidence, including randomized controlled trials, prospective comparative studies, and multiple meta-analyses, has evaluated the diagnostic performance of MicroUS in detecting csPCa.

Randomized controlled trials

The strongest evidence to date is provided by the OPTIMUM trial, a multicenter randomized noninferiority study including 802 men with clinical suspicion of prostate cancer.⁷ Patients were randomized to undergo either MicroUS-guided biopsy or MRI-guided/conventional ultrasound biopsy. MicroUS-guided biopsy detected Grade Group ⩾ 2 prostate cancer in 47.1% of patients compared with 42.6% in the MRI-based group, meeting predefined noninferiority criteria (set to −10%). Importantly, MicroUS enabled real-time lesion targeting without requiring pre-procedural imaging or fusion platforms, highlighting a potential advantage in workflow efficiency.

These findings support the concept that MicroUS can achieve diagnostic performance comparable to mpMRI-based pathways in men with clinical suspicion of prostate cancer, although outcomes remain influenced by operator experience and institutional expertise.

Systematic reviews, meta-analyses, and high-level comparative validation studies

Beyond randomized evidence, the comparative performance of MicroUS has been further clarified by meta-analyses and prospective validation studies. These data consistently suggest that MicroUS achieves high sensitivity for csPCa, although specificity remains more variable and generally lower than that of mpMRI.

A relevant, though not directly equivalent, comparative study is the CADMUS trial, a prospective multicenter paired-cohort study evaluating multiparametric ultrasound (mpUS) against mpMRI in men at risk of prostate cancer. mpUS is a composite modality incorporating greyscale, Doppler, contrast-enhanced ultrasound, and elastography, and is technically distinct from MicroUS, which relies solely on a 29 MHz high-frequency transducer. CADMUS findings are therefore not directly transferable to MicroUS but remain contextually informative insofar as they illustrate the broader diagnostic behavior of advanced ultrasound-based imaging relative to mpMRI.¹⁸ CADMUS showed that multiparametric ultrasound was positive in 89% of patients compared with 78% for mpMRI, indicating a higher biopsy referral rate with ultrasound. For clinically significant cancer, multiparametric ultrasound alone detected 66/257 (26%) cases compared with 77/257 (30%) with mpMRI alone. Importantly, when both tests were considered together, 83/257 (32%) clinically significant cancers were detected; of these, 6 were detected exclusively by ultrasound and 17 exclusively by mpMRI. These findings illustrate a recurring theme in the MicroUS literature: ultrasound-based imaging may detect a substantial proportion of csPCa but tends to do so at the cost of lower specificity and increased biopsy rates, while also identifying a subset of cancers missed by MRI.

Meta-analytic evidence broadly supports this interpretation. In the prospective-only comparative meta-analysis by Garcia-Becerra et al.,⁹ pooled sensitivity was 0.87 for MicroUS and 0.88 for mpMRI, whereas pooled specificity was 0.25 for MicroUS and 0.30 for mpMRI. The summary receiver operating characteristic confidence regions overlapped, and meta-regression found no significant difference in sensitivity but identified a significant difference in specificity favoring mpMRI. Positive predictive values were modest for both modalities, whereas negative predictive values were relatively high across prevalence scenarios. Taken together, these findings suggest that MicroUS performs similarly to mpMRI in ruling out csPCa but remains more prone to false-positive findings.

The prospective-only diagnostic accuracy meta-analysis by Abdel Gawad et al.¹⁰ further strengthens the evidence for high MicroUS sensitivity while reinforcing its specificity limitations. Across five prospective studies, pooled sensitivity for standalone 29 MHz MicroUS was 0.84 and pooled specificity 0.41. Additional metrics, including a negative likelihood ratio of 0.37, suggest a modest rule-out role rather than strong rule-in performance. These findings support the interpretation of MicroUS as a complementary or triage adjunct, particularly when mpMRI is unavailable, contraindicated, or delayed.

Overall, synthesis of these higher-level studies supports three key conclusions. First, MicroUS demonstrates consistently high sensitivity for csPCa detection. Second, mpMRI retains an advantage in specificity and biopsy avoidance, which remains clinically important. Third, the incomplete overlap between ultrasound-based and MRI-based detection suggests that the two modalities are better viewed as complementary rather than strictly interchangeable.

Prospective comparative and workflow-oriented studies

Prospective comparative and workflow-oriented studies provide important insight into how MicroUS performs within real clinical pathways, beyond randomized trials and meta-analyses. These studies suggest that MicroUS can detect csPCa at rates broadly comparable to mpMRI in selected settings, while also offering incremental value through real-time targeting and detection of lesions not identified by MRI.

In a prospective biopsy-naïve cohort, Ghai et al.⁸ reported csPCa detection rates of 39% with MRI-targeted biopsy and 35% with MicroUS-targeted biopsy (p = 0.22), supporting comparable detection performance between the two modalities. The combined MRI plus MicroUS pathway detected csPCa in 40% of men, suggesting complementary diagnostic information. In the same study, 67% of MRI lesions were prospectively visible on MicroUS, enabling real-time targeting, while biopsy avoidance was more frequent with MRI (34%) than with MicroUS (10%), emphasizing that similar detection performance does not necessarily translate into equivalent biopsy avoidance.

A larger prospective single-center series by Avolio et al.¹¹ further illustrates the incremental role of MicroUS within combined diagnostic workflows. In 1423 men with suspected prostate cancer, MicroUS demonstrated 85% sensitivity and 79% negative predictive value for csPCa. Among patients diagnosed on targeted cores alone, 25 csPCa cases were identified exclusively by MicroUS-targeted biopsy compared with only 4 identified exclusively by MRI-targeted biopsy. In addition, MicroUS identified suspicious lesions in mpMRI-negative patients, some of which were confirmed as clinically significant on biopsy.

These findings help explain why MicroUS is increasingly used not as a replacement for mpMRI but as an adjunct within MRI-informed diagnostic pathways. The observed concordance and discordance between modalities suggest that MicroUS and mpMRI detect overlapping but non-identical subsets of clinically significant disease. This has important implications for combined targeting strategies, including MRI–ultrasound fusion and real-time biopsy workflows.

Taken together, prospective workflow-oriented studies support a nuanced interpretation of MicroUS. They reinforce its value as a real-time targeting tool, demonstrate its ability to detect csPCa missed by mpMRI in selected patients, and support the rationale for combined imaging strategies. However, they also confirm that mpMRI may remain superior for biopsy avoidance and that systematic biopsy continues to play a role in contemporary diagnostic pathways.

MicroUS and mpMRI: A complementary relationship with context-dependent exceptions

The comparison between MicroUS and mpMRI cannot be reduced to a binary choice. Current evidence consistently shows that the two modalities differ in diagnostic behavior, comparable in sensitivity, divergent in specificity and biopsy avoidance, and that they identify overlapping but non-identical subsets of clinically significant disease. These characteristics define a complementary rather than substitutive relationship in most clinical settings. Whether MicroUS can function as a primary modality in specific constrained context is a separate, more limited question addressed later in this section.

The strongest direct comparative evidence is provided by the OPTIMUM randomized noninferiority trial.⁷ In biopsy-naïve men, MicroUS-guided biopsy detected Grade Group ⩾ 2 prostate cancer in 47.1% of patients compared with 42.6% for MRI/conventional ultrasound fusion-guided biopsy, meeting the predefined noninferiority threshold. A combined MicroUS/MRI strategy achieved a similar detection rate (46.9%), supporting the conclusion that MicroUS can perform comparably to MRI-based targeting in this setting. These findings validate MicroUS as a high-performing image-guided biopsy modality. Recent updates in clinical guidelines further reflect the evolving role of MicroUS. The current European Association of Urology (EAU) Guidelines on Prostate Cancer acknowledge MicroUS as an emerging imaging modality; however, unlike the National Comprehensive Cancer Network (NCCN), they do not yet designate MicroUS-guided biopsy as a formally recommended alternative to MRI-targeted biopsy at expert centers, reflecting a more cautious interpretation of the available evidence that is relevant to European clinical practice. The NCCN Prostate Cancer Early Detection Guidelines (version 2.2026) acknowledge that MicroUS-guided biopsy performed at experienced centers may represent an alternative to MRI-targeted biopsy, based on randomized evidence demonstrating noninferiority in detecting csPCa, most notably from the OPTIMUM trial.^7,19

However, comparable cancer detection does not imply full clinical interchangeability. In a prospective biopsy-naïve study by Ghai et al.,⁸ csPCa detection was 39% with MRI-targeted biopsy and 35% with MicroUS-targeted biopsy, whereas biopsy avoidance was achieved in 34% of men using the MRI pathway compared with only 10% using MicroUS. This represents a clinically relevant distinction, as mpMRI may retain an advantage when the objective is to reduce unnecessary biopsies. In the same study, a combined MRI-plus-MicroUS pathway detected csPCa in 40% of patients, and 67% of MRI lesions were prospectively visible on MicroUS, supporting the practical value of integrating the two modalities.

This complementary relationship is further contextually supported by the CADMUS trial (noting that CADMUS evaluated mpUS rather than MicroUS specifically) which demonstrated that advanced ultrasound-based imaging and mpMRI identify overlapping but non-identical subsets of clinically significant disease. While the precise figures from CADMUS cannot be attributed to MicroUS, the directional finding of complementary detection is consistent with evidence from MicroUS-specific prospective studies.¹⁸ When both imaging modalities were considered together, more csPCa was detected than with either modality alone; notably, some cancers were detected exclusively by ultrasound and others exclusively by mpMRI. At the same time, ultrasound-based imaging was more frequently positive, resulting in higher biopsy referral rates. This highlights a consistent trade-off: ultrasound-based approaches may capture additional cancers but often at the cost of lower specificity.

Meta-analytic data reinforce this interpretation. In the prospective-only meta-analysis by Garcia-Becerra et al.,⁹ pooled sensitivity was similar for MicroUS and mpMRI (0.87 vs 0.88), whereas specificity favored mpMRI (0.25 vs 0.30). Similarly, the prospective diagnostic accuracy meta-analysis by Abdel Gawad et al.¹⁰ demonstrated high sensitivity but limited specificity for MicroUS, supporting its role as a complementary or triage modality rather than a universally substitutive test.

An important practical dimension of this comparison is how the two modalities are integrated in clinical workflows. In real-world practice, many centers combine mpMRI and MicroUS through sequential targeting, cognitive fusion, or software-assisted fusion approaches. This is rational because mpMRI provides pre-biopsy lesion localization and whole-gland risk stratification, whereas MicroUS enables real-time structural visualization at the time of biopsy. Prospective studies suggest that this combined approach may improve lesion targeting and detect cancers missed by either modality alone.^8,11 In a large prospective series by Avolio et al.,¹¹ MicroUS-targeted biopsy identified 25 csPCa cases exclusively compared with only 4 identified exclusively by MRI-targeted biopsy, and MicroUS also detected clinically significant lesions in some mpMRI-negative patients. These findings support the role of MicroUS as an adjunct that can enhance MRI-informed diagnostic pathways rather than replace them.

There are specific clinical contexts in which MicroUS may serve as the primary imaging modality in the absence of a viable mpMRI pathway, for instance, when MRI is contraindicated, structurally unavailable, or subject to prohibitive delays. In these scenarios, the randomized evidence from OPTIMUM supports MicroUS as a non-inferior alternative for csPCa detection. However, two important qualifications apply. First, OPTIMUM was conducted at centers with certified MicroUS expertise; its results are not directly transferable to settings without equivalent operator training, irrespective of MRI availability. Second, substituting MicroUS for mpMRI in these contexts accepts a trade-off: the biopsy avoidance benefits that mpMRI provides, which OPTIMUM could not assess by design, is foregone. Clinicians and health systems adopting MicroUS as a primary modality in MRI-limited settings should therefore do so with explicit acknowledgment that detection equivalence does not imply equivalence across all clinically relevant outcomes. Taken together, current evidence supports a complementary and context-dependent role for MicroUS relative to mpMRI. MicroUS can achieve comparable detection of csPCa in selected diagnostic pathways and offers clear workflow advantages through real-time targeting. At the same time, mpMRI remains superior in biopsy avoidance, standardization, and comprehensive anatomical assessment. The most clinically defensible position at present is therefore not “MicroUS versus mpMRI,” but rather how best to integrate both modalities to optimize detection of clinically significant disease while minimizing unnecessary procedures.

Role of MicroUS in active surveillance

Active surveillance (AS) aims to reduce overtreatment while preserving timely identification of grade progression, making accurate repeat assessment essential. In contemporary practice, mpMRI plays a central role in surveillance protocols by enabling lesion localization, targeted confirmatory biopsy, and interval reassessment. However, mpMRI is not a perfect standalone surveillance tool, and repeated MRI-based pathways can be resource-intensive, logistically complex, and variably accessible. In this context, MicroUS has emerged as a potentially useful adjunct for confirmatory and repeat biopsy, particularly because it allows real-time lesion visualization and targeting during the biopsy procedure.

The strongest direct evidence in this setting is provided by the prospective study by Maffei et al.,¹⁴ which evaluated patients undergoing MRI-guided confirmatory biopsy after diagnosis of low-risk prostate cancer. Overall, 34% of patients were upgraded to ISUP grade group ⩾ 2 disease and were excluded from active surveillance. On a per-patient basis, MicroUS demonstrated 94.1% sensitivity and 88.9% negative predictive value, compared with 100% sensitivity and 100% negative predictive value for mpMRI. These findings indicate that MicroUS performs well in identifying patients with upgraded disease but confirm that mpMRI retains superior rule-out performance in this context. Importantly, a hypothetical MicroUS-based pathway would have avoided biopsy in a subset of patients, but at the cost of missing some cases of disease upgrading, representing a clinically meaningful trade-off.

This trade-off is central to interpreting the role of MicroUS in surveillance. The value of MicroUS in AS lies not only in its ability to identify suspicious lesions but also in whether it can safely reduce the intensity of repeated confirmatory procedures. The available evidence suggests that MicroUS can facilitate real-time targeting of suspicious areas and may contribute to event-triggered biopsy strategies, but it does not support replacing mpMRI-based surveillance protocols. Rather, MicroUS appears best positioned as a complementary tool within a multimodal surveillance framework.

A separate prospective study by Beatrici et al.¹³ evaluated MicroUS within an outpatient triage-oriented diagnostic pathway in men with initial suspicion of prostate cancer. In this cohort, negative MicroUS findings were associated with reduced downstream biopsy and imaging burden. However, this study should not be cited as evidence for a surveillance role. Its population consists of biopsy-naïve men under diagnostic evaluation, a fundamentally different clinical scenario from AS, where the relevant question is detection of disease progression in men with established low-risk cancer. The triage metrics reported, including biopsy avoidance and MRI avoidance rates, are not applicable to surveillance protocols, where the mandate is sensitive detection of upgrading rather than reduction of initial diagnostic procedures. Extrapolating these findings to AS would require a dedicated prospective AS cohort with progression as the primary endpoint, which this study does not provide. From a practical perspective, MicroUS offers several advantages in the surveillance setting. It can be performed in an outpatient environment, integrated directly into repeat biopsy sessions, and may facilitate targeted resampling without requiring repeated pre-procedural MRI. This may be particularly valuable in high-volume centers, in patients requiring multiple reassessments, or in healthcare systems with limited MRI availability. In addition, real-time imaging may allow targeting of previously identified lesions while also detecting new suspicious areas during the same procedure.

Nevertheless, important limitations remain. MicroUS does not provide the whole-gland functional assessment available with mpMRI, and current evidence supporting its use in longitudinal lesion monitoring is limited. Available studies are promising but do not yet establish standardized MicroUS-based surveillance protocols or provide long-term oncologic outcome data supporting the reduction of MRI use or omission of protocol biopsies. Furthermore, reliance on MicroUS alone carries a risk of missing a subset of patients with disease progression.

Overall, current evidence supports MicroUS as a clinically useful adjunct in active surveillance, particularly for confirmatory and repeat targeted biopsy. It may help streamline surveillance workflows and reduce procedural burden in selected settings; however, its role remains complementary rather than substitutive relative to mpMRI. Further prospective longitudinal studies are required to determine whether MicroUS can be safely integrated into event-triggered biopsy strategies or used to reduce MRI frequency within standardized surveillance pathways.

MicroUS in local staging and prediction of extraprostatic extension

Accurate preoperative assessment of local tumor extent, particularly the presence of extraprostatic extension (EPE), is essential for surgical planning and risk stratification in prostate cancer. Multiparametric MRI (mpMRI) remains the reference imaging modality for local staging due to its ability to assess capsular integrity, neurovascular bundle involvement, and extracapsular spread. However, mpMRI is not universally available, and its performance may vary depending on radiological expertise and image quality. In this context, MicroUS has been explored as a potential tool for real-time assessment of local tumor characteristics, including features suggestive of EPE.

The most relevant evidence is provided by the prospective study by Fasulo et al.,¹⁵ which evaluated the ability of MicroUS to predict EPE in patients undergoing radical prostatectomy. In this cohort, MicroUS-detected extracapsular extension demonstrated a sensitivity of 72.1%, specificity of 88.0%, positive predictive value of 83.0%, and negative predictive value of 80.5%, with an overall area under the curve (AUC) of 0.80. Importantly, incorporation of MicroUS-derived parameters into clinical models improved predictive performance, increasing the AUC from 0.82 to 0.88. These findings suggest that MicroUS may provide clinically relevant information for local staging and may enhance existing predictive models when integrated with standard clinical variables.

Beyond direct visualization of capsular irregularity or bulging, MicroUS may contribute indirectly to staging through improved identification of index lesions and spatial localization. Studies correlating MicroUS findings with whole-mount pathology have demonstrated encouraging concordance between imaging and histopathological tumor location, supporting the biological plausibility of using high-resolution ultrasound to infer local tumor extent.¹² However, these data remain limited and are largely derived from single-center experiences.

Further developments include the incorporation of MicroUS features into predictive models and nomograms for EPE. These approaches aim to translate imaging findings into quantitative risk stratification tools, although they remain at an early stage of validation and have not yet been integrated into routine clinical practice.

Despite these promising findings, several limitations must be emphasized. The current evidence base for MicroUS in local staging is limited to relatively small, predominantly single-center prospective studies, with a lack of large multicenter validation. In addition, MicroUS provides primarily structural information and does not offer the multiparametric functional assessment available with mpMRI, which remains a key advantage of MRI in staging applications. Operator dependency and the associated learning curve may further influence staging accuracy.

From a clinical perspective, MicroUS should therefore be considered an emerging adjunct in the assessment of local tumor extent rather than a replacement for mpMRI. Its potential advantages include real-time intra-procedural assessment and the possibility of integrating staging information into the biopsy workflow. However, current evidence does not support substituting mpMRI with MicroUS for routine preoperative staging.

Overall, MicroUS demonstrates promising but still preliminary utility in predicting EPE. Further large-scale, multicenter studies and external validation of predictive models are required before it can be incorporated into standardized staging algorithms.

Discussion

MicroUS has emerged as a high-resolution imaging modality with increasing evidence supporting its role in the diagnosis and management of prostate cancer. The present review synthesizes data from randomized trials, prospective comparative studies, and meta-analyses, and suggests that MicroUS represents a clinically meaningful addition to the current diagnostic armamentarium. However, its optimal role is best understood not as a direct replacement for multiparametric MRI (mpMRI), but as a complementary modality that may enhance diagnostic pathways when appropriately integrated.

One of the most consistent findings across the literature is that MicroUS achieves high sensitivity for csPCa. This is supported by both randomized and meta-analytic evidence. The OPTIMUM trial demonstrated noninferiority of MicroUS-guided biopsy compared with MRI-based pathways,⁷ while prospective meta-analyses confirm comparable sensitivity between MicroUS and mpMRI.^9,10 These findings indicate that MicroUS is capable of identifying a substantial proportion of clinically significant disease in selected clinical settings and can function as a reliable targeting modality in biopsy-naïve populations.

At the same time, specificity and biopsy avoidance remain relative limitations of MicroUS compared with mpMRI. Across multiple studies, including CADMUS and prospective comparative cohorts, ultrasound-based approaches tend to result in higher positivity rates and, consequently, more biopsies.^8,18 This reflects a higher rate of false-positive findings, which is a recognized trade-off of highly sensitive imaging modalities. From a clinical perspective, this distinction is critical: while MicroUS may match mpMRI in detecting csPCa, mpMRI may be more effective in reducing unnecessary biopsy, which remains an important goal in prostate cancer diagnostics.

A key insight emerging from recent studies is that MicroUS and mpMRI do not identify identical subsets of disease. Evidence from prospective cohorts demonstrates both concordance and discordance between the two modalities, with each identifying clinically significant cancers missed by the other.^8,11 This observation supports a complementary model in which MicroUS and mpMRI are used together rather than viewed as mutually exclusive alternatives. In particular, MicroUS offers real-time lesion visualization during biopsy, enabling immediate targeting of both MRI-visible and ultrasound-visible lesions and potentially improving sampling accuracy.

This complementary paradigm is especially relevant in the context of integrated diagnostic workflows. Sequential strategies, cognitive fusion, and software-assisted MRI–ultrasound fusion allow mpMRI to provide pre-biopsy lesion localization and risk stratification, while MicroUS enhances intra-procedural targeting. Early evidence suggests that combined pathways may achieve higher detection rates than either modality alone.^8,11 However, even within advanced imaging pathways, systematic biopsy continues to detect a proportion of clinically significant cancers, indicating that complete replacement of systematic sampling cannot yet be recommended.

In the setting of active surveillance, MicroUS shows promise as an adjunctive tool for confirmatory and repeat biopsy. It enables real-time targeting and may facilitate more efficient surveillance workflows, particularly in outpatient settings. However, current evidence indicates that MicroUS alone cannot safely replace mpMRI-based surveillance protocols, as a small but clinically relevant subset of upgraded cancers may be missed when relying solely on ultrasound findings.¹⁴ Its role in surveillance is therefore best interpreted as complementary, with potential for integration into event-triggered biopsy strategies pending further validation.

Beyond diagnosis, MicroUS may also contribute to local staging and surgical planning, particularly in predicting EPE. Early prospective data suggest that MicroUS can identify features associated with extracapsular disease and may improve predictive models when combined with clinical variables.¹⁵ However, this evidence remains preliminary and is currently insufficient to challenge the role of mpMRI as the reference standard for local staging.

The integration of artificial intelligence (AI) into MicroUS imaging represents a promising avenue to address some of the modality’s current limitations, particularly operator dependency and variability in interpretation. As a real-time imaging technique relying on visual pattern recognition, MicroUS is well-suited to AI-assisted analysis. Early studies suggest that machine learning–based models incorporating MicroUS imaging features may improve the classification of csPCa and enhance diagnostic consistency.²⁰ In addition, AI-driven tools may contribute to the standardization of image interpretation, potentially strengthening the reproducibility of the PRI-MUS scoring system. However, current evidence remains preliminary, with most studies based on retrospective or single-center datasets, and further prospective validation is required before routine clinical implementation.

Despite these encouraging findings, several limitations of the current evidence base should be acknowledged. MicroUS remains operator-dependent, and diagnostic performance is influenced by experience and training, raising concerns regarding reproducibility across centers. While the PRI-MUS scoring system provides a structured framework, it is not yet as standardized or widely validated as PI-RADS for mpMRI.⁶ In addition, although MicroUS demonstrates high sensitivity, its lower specificity may lead to increased biopsy rates and potential overdiagnosis. Technical limitations, including reduced depth of penetration in larger prostates, may also affect lesion detection in certain anatomical regions. Furthermore, heterogeneity across studies and the relative lack of long-term oncologic outcome data limit the strength of current conclusions.

In the United Kingdom, the major transition in prostate diagnostics has been toward local anesthetic transperineal biopsy pathways, primarily driven by reduced infectious complications and wider adoption of MRI-targeted biopsy strategies. Within this evolving landscape, MicroUS platforms such as the ExactVu MicroUS System are emerging as a promising adjunct for transperineal biopsy, offering high-resolution real-time lesion visualization and the potential to improve targeting accuracy. Although currently limited to selected specialist and research-focused centers, MicroUS-guided TP biopsy is gaining interest as a future outpatient “one-stop” diagnostic approach that could complement or, in selected settings, reduce reliance on MRI-based pathways.

Future research should focus on prospective validation of integrated MicroUS–mpMRI diagnostic pathways, particularly in multicenter settings. Standardization of imaging acquisition and interpretation will be essential for wider adoption. In the context of active surveillance, longitudinal studies are needed to determine whether MicroUS can safely support biopsy de-escalation strategies. Advances in artificial intelligence may further enhance diagnostic accuracy and reduce operator dependency, while health-economic analyses will be important to define the cost-effectiveness of MicroUS-based pathways relative to established MRI-driven strategies. Finally, as a narrative rather than a systematic review, this work does not claim exhaustive coverage of the literature and is subject to selection bias inherent to this methodology. Accordingly, conclusions drawn from this review should be interpreted in the context of this design limitation, and the evidence hierarchy presented reflects the authors’ structured appraisal rather than a formal quantitative synthesis.

Conclusion

MicroUS represents a significant advancement in ultrasound-based prostate imaging, offering high spatial resolution and real-time lesion characterization with direct integration into biopsy workflows. Current evidence from randomized trials, prospective studies, and meta-analyses demonstrates that MicroUS can achieve detection of csPCa comparable to that of mpMRI in selected clinical settings.

At present, MicroUS is best considered a complementary modality within the prostate cancer diagnostic pathway. Its principal strengths lie in real-time targeting, workflow efficiency, and accessibility, supporting its use alongside mpMRI or as an alternative in selected scenarios, particularly when MRI is unavailable or contraindicated. In the context of active surveillance, MicroUS shows potential for guiding repeat targeted biopsy, although its role in longitudinal monitoring remains to be clearly defined.

Despite these advantages, important limitations, including operator dependency, lower specificity, limited standardization, and lack of long-term outcome data, currently restrict its role as a standalone imaging modality.

Overall, MicroUS is a promising and evolving technology whose greatest value lies in enhancing multimodal diagnostic strategies rather than replacing established imaging pathways. Further multicenter validation, standardization of interpretation, and long-term outcome studies will be essential to define its role in routine clinical practice.

Footnotes

ORCID iDs

Muhannad Aljoulani

Bhavan Rai

Ethical considerations

Ethical approval was not sought for this article because this is a narrative review of previously published literature and does not involve human participants or patient data.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Author contributions

BS conceived the study and supervised the project. MA performed the literature search, data analysis, and drafted the manuscript. NMB, GL, BR, VH, AOL, EC, and GV contributed to data interpretation and critical revision of the manuscript. All authors reviewed and approved the final version of the manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data availability statement

Not applicable.

Informed consent

Informed consent was not sought for this article because no individual patient data were used.

Guarantor

Bhaskar Somani.

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