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Prostate cancer (PCa) is the second most common cancer among men worldwide (1-3). The latest estimated data from the International Agency for Research on Cancer as of April 2025 (from the GLOBOCAN 2022 database) clearly predicts that the number of cases will double by 2040(1). Early-stage PCa typically presents no obvious clinical symptoms, leading numerous patients to seek medical attention only when the disease has progressed to a middle or advanced stage. Thus, early detection of PCa is key in effective treatment and improved patient prognosis. Clinical screening for PCa primarily involves digital rectal examination, prostate-specific antigen (PSA) testing and imaging studies. Prostate biopsy remains the most established method for diagnosing PCa. Current guidelines from The European Association of Urology, The National Comprehensive Cancer Network and The American Urological Association (4-7) all designate prostate biopsy as the ‘gold standard’ for diagnosing this cancer subtype. When conducted under standardized procedures, prostate biopsy is considered a safe diagnostic approach. Prior to biopsy, multi-modal imaging assessment is recommended (8).
The prostate imaging reporting and data system (PI-RADS) (9) serves as a standardized scoring system for evaluating prostate MRI results. The decision to proceed with a biopsy should be based on the PI-RADS score in conjunction with the individual circumstances of the patient and other examination findings, such as the tumor marker PSA test result (10). The PI-RADS score ranges from 1-5, with higher scores indicating a greater likelihood of PCa. A score of 3 typically indicates moderate suspicion and does not definitively rule out malignant lesions. The necessity for a biopsy should be determined based on a comprehensive assessment of the clinical symptoms of the patient (such as frequent urination and difficulty urinating), serum PSA levels, age, family history and other factors. If PSA levels are elevated or symptoms are severe, a biopsy may be recommended for pathological diagnosis. In cases where the initial biopsy result is benign but there are signs of disease progression, a repeat biopsy may be warranted. Conversely, if the patient is in poor health, close observation and regular follow-up may be preferred. When the PI-RADS score is ≥4, the risk of PCa markedly increases, making biopsy strongly advisable for a definitive diagnosis. The combined biopsy strategy-utilizing both systematic and targeted biopsy-has become a mainstream approach (11).
Studies have indicated that this combined method can notably enhance the detection rate of clinically significant PCa (csPCa), achieving rates as high as 68%, while also reducing the likelihood of missed diagnoses (10,12-14). As a result, improving the accuracy of biopsy equipment to elevate the positive detection rate and facilitate early PCa diagnosis has become a priority in the field. While transrectal ultrasound (TRUS)-guided prostate biopsy remains a traditional method, new imaging technologies have emerged, though they often face challenges such as insufficient detection accuracy and low positive biopsy rates. Recently, the introduction of prostate biopsy robots has further advanced the field. By integrating imaging, image fusion and artificial intelligence, these technologies simplify the biopsy process, enhance feasibility and improve the accuracy of outcomes. Previously published literature (15-17) has discussed a number of possible ultrasound technologies for prostate biopsy. The present review aimed to summarize the latest advancements in new ultrasound technologies for targeted prostate biopsy and to compare new technologies, whilst including contradictory findings and cost-benefit analyses.
MUS is a novel technology that provides high resolution images, notably improving the visualization of tissue details. Operating at a frequency of 29 MHz, MUS achieves a spatial resolution of 70 µm, which is comparable to the size of prostate ducts. This represents a 300% increase in spatial resolution compared with the traditional ultrasound (18). The high resolution of the MUS system allows for detailed visualization of the catheter anatomy and cellular density, thereby enhancing the understanding of prostate anatomy. Preliminary research has demonstrated that MUS exhibits higher sensitivity in detecting PCa, establishing itself as a promising diagnostic imaging technique for the disease. For example, a study was conducted involving 67 patients who underwent prostate biopsy with the ExactVu™ 29 MHz MUS system, revealing detection rates of 56.7% for real-time MUS-guided biopsy compared with 44.8% for traditional biopsy (19). A meta-analysis by Dariane et al (20) further determined that MUS-guided biopsy outperformed systematic biopsy in detecting csPCa while identifying a number of non-csPCA cases. Therefore, MUS represents a viable biopsy method. Future prospects for the novel 29-MHz high-resolution MUS include the development of a scoring system, known as prostate risk identification-MUS, which aims to enhance precision and accuracy in a PCa setting (19,21). This scoring system assesses the severity based on the observed structural damage, echo characteristics and boundary morphology of the glands under high-frequency (29 MHz) MUS, ranging from 1 point (very low risk) to 5 points (very high risk); it is a standardized 5-point Likert scale specifically designed for MUS. This system could assist urologists in achieving accurate and reproducible results for PCa detection, comparable to those obtained using MRI-based PI-RADS scoring.
CEUS involves the injection of microbubbles of contrast agent into the peripheral veins of patients to observe the filling of the prostate with the contrast agent, which reflects the perfusion of prostate microvessels. Targeted biopsy of the prostate guided by CEUS can enhance the detection rate of PCa (22). A commonly used ultrasound contrast agent in clinical practice is SonoVue (Bracco), also known as Sonofo Micro-Sulfur Hexafluoride Bubbles. With a diameter of ~2.5 µm, it is similar in size to red blood cells in the blood. After being injected through the median vein in the elbow, it can freely pass through the blood and reach the target organ or tissue. SonoVue is currently the most widely used ultrasound contrast microbubble system and is a pure blood pool contrast agent that does not penetrate the extravascular space. This characteristic allows it to more accurately reflect the morphological features and blood perfusion of tumors. Qi et al (23) found that contrast-enhanced TRUS was markedly more accurate compared with traditional grayscale imaging in measuring the size of prostate tumors, with a mean underestimation of ~3.9 mm for grayscale imaging compared with 0.6 mm for contrast-enhanced transrectal ultrasonography. In addition, Wang et al (24) discovered that molecular imaging of in situ PCa using nano-bubble ultrasound contrast agents targeting membrane PSA demonstrated notable advantages in diagnosing PCa, such as reduced radiation, lower costs and reduced patient waiting time. Additional studies have indicated that CEUS not only increases the detection rate of PCa but also aids in the grading and staging of the disease (25-28). However, the accuracy of the examination can vary based on the experience of the physician, the obesity level of the patient and the shape of the prostate.
Ultrasound elastography is an innovative ultrasonic diagnostic technology that measures changes in the amplitude of echo signals before and after tissue compression, allowing for the assessment of tissue hardness. This technique effectively differentiates between diseased and normal tissue based on the varying elastic coefficients of different tissues (29). A notable advantage of ultrasound elastography is its ability to detect lesions through changes in tissue hardness, thereby improving the detection rate of lesions compared with traditional 2D gray-scale ultrasound imaging-guided puncture biopsy. Its application in the medical field has been gradually integrated (30). PCa tumor cells proliferate rapidly and are invasive, resulting in a higher number of cancer cells and a harder texture in the lesion area compared with the surrounding normal tissue. Notably, changes in tissue hardness occur earlier compared with alterations in anatomical structure (31) and ultrasound elastography can identify the hardness of internal prostate tissues, thereby revealing lesions. In a prospective study conducted by Brock et al (32), 231 patients with suspected PCa were randomly assigned to either a transrectal real-time elastography-guided biopsy group or a transrectal gray-scale ultrasound-guided biopsy group. The findings indicated a significantly higher cancer detection rate (P=0.007) in patients undergoing biopsy with real-time elastography (40.5%) compared with the gray-scale group (23.8%). Sensitivity and specificity for detecting PCa across 1,386 prostate sectors were 53.5 and 70.5% for real-time elastography, compared with 11.7 and 93.7% for gray-scale ultrasound, respectively. This demonstrated a significant improvement in the accuracy of PCa detection under the guidance of real-time elastography compared with traditional gray-scale ultrasound.
Currently, the main applications of prostate ultrasound elastography include strain elastography (SE) and shear wave elastography (SWE), both of which can guide targeted prostate biopsies. SE involves manually applying pressure to the tissue with a probe. Due to differences in hardness, the tissue undergoes varying deformations, which are visualized in different colors on the imaging, with harder tissue appearing blue and softer tissue appearing red (33). Although SE results cannot be quantitatively analyzed, semi-quantitative information can be obtained by measuring the strain rate between the region of interest and the surrounding normal tissue. SE can perform real-time imaging in any area within the penetration range and targeted biopsies guided by SE, when combined with systematic biopsies, can markedly enhance the detection rate of PCa. Salomon et al (34) found detection rates of 39.1 and 29.0% for systematic and SE-targeted biopsies, respectively, with a combined detection rate of 46.2%. Furthermore, a study by Boehm et al (35) demonstrated that real-time elastography-targeted biopsy achieved a higher overall Gleason assignment accuracy (68.3 vs. 56.7%; P=0.008) compared with systematic biopsy alone. However, the main drawbacks of SE include the need for manual pressurization, poor repeatability and a high dependence on the skill and experience of the operator (36).
By contrast, SWE measures the propagation speed of shear waves within tissues to calculate the Young's modulus value, providing a real-time quantitative graph of the elastic properties of soft tissues. In SWE imaging, harder tissues appear red, while softer tissues appear blue. SWE offers a number of advantages, as it does not require manual pressurization, allows for quantitative measurements, provides objective values, has high repeatability and is less dependent on the experience of the operator (37). A meta-analysis by Anbarasan et al (38) indicated that SWE exhibited high sensitivity (77%) and specificity (84%) in detecting csPCa. Fu et al (39) conducted SWE on three sections of the prostate, namely the level of the base, mid-gland and apex of the prostate peripheral zone, along with suspected lesions identified by 2D ultrasound in a study exploring peripheral PCa. The results revealed that with a critical threshold of 42 kPa, SWE demonstrated high sensitivity, specificity, positive predictive value, negative predictive value and accuracy in differentiating between benign and malignant lesions. Furthermore, as the Gleason score and prognosis grade increased, there was a trend toward a higher Young's modulus values in PCa lesions. Therefore, in addition to identifying PCa lesions, SWE holds marked potential for reducing unnecessary biopsies and guiding the acquisition of more valuable tissue during puncture, as well as predicting the pathological score and prognosis of cancer foci.
MRI-TRUS cognitive fusion image-guided biopsy involves integrating a number of MRI scans prior to the procedure with real-time TRUS examination images captured during the biopsy. The target lesion is identified using the MRI images and the biopsy is performed under the guidance of TRUS images (40). This technique requires the physician performing the biopsy to possess strong film interpretation skills. Its advantages include real-time visibility of the lesion during the procedure, accurate targeting for the biopsy and elimination of the need to scan numerous MRI sequences (Fig. 1). Additionally, random systematic biopsies of the prostate can be conducted simultaneously under the guidance of TRUS (41). A study by Drăgoescu et al (42) regarding MRI cognitive fusion-targeted perineal prostate biopsy indicated that this approach outperformed systematic biopsy in detecting overall PCa in larger patient populations and was particularly effective in identifying csPCa. This improvement helped one-fifth of patients avoid missing necessary treatment for PCa. Kuliš et al (43) compared cognitive fusion-targeted biopsy and systematic prostate biopsy in patients with repeated negative systematic biopsies but ongoing clinical suspicion of PCa. The findings revealed that cognitive targeted prostate biopsy based on numerous MRI scans was superior in diagnosing patients, particularly those with persistently elevated PSA levels.
However, this technique relies heavily on the experience of the puncture operator, which introduces a degree of subjectivity. The biopsy results may exhibit marked uncertainty when performed by less experienced practitioners (44). It is also important to consider the potential drawbacks associated with MRI, including costs and the occurrence of artifacts (42-44). MRI equipment is expensive and the examination cost is high, and its accessibility is limited in some areas. Besides, MRI scans take a long time and have complex sequences, requiring high patient cooperation. Gas in the rectum and metal implants (such as hip joint prostheses) can cause uneven local magnetic fields, resulting in artifacts, severe image distortion or signal loss.
Multiple MRI-TRUS software integration-guided targeted prostate biopsy involves storing prostate MRI image data in specialized equipment that is fused with intraoperative real-time ultrasound images. This fusion is achieved automatically and intelligently by the machines, clearly identifying the target area, tracking the TRUS probe and determining the optimal puncture biopsy path (45). This approach reduces the reliance on the ability of the puncture physician to interpret films. The combination of precise positioning from prostate MRI with real-time ultrasound imaging technology meets the requirements for accurately locating and tracking prostate lesion sites. This technology notably enhances the ability to identify prostate lesions during procedures and improves the accuracy of PCa punctures (46).
A prospective study conducted by Fiard et al (47) showed that 30 patients with suspected PCa who underwent MRI examinations also received routine 12-needle systematic biopsies, along with two additional targeted biopsies of suspicious areas. When comparing the results of systematic and targeted biopsies, both methods demonstrated a sensitivity of 91% in detecting cancer; however targeted biopsies required fewer needles. In an additional study by Yarlagadda et al (48), which included both prospective and retrospective analyses, patients underwent systematic biopsies guided by TRUS and biopsies guided by the fusion of multiple MRI-TRUS software. The findings indicated that, while maintaining the same cancer detection rate, significantly fewer needle cores were sampled during the MRI-TRUS software-guided biopsy, with a reduction of 63% in cores taken (P<0.001).
Currently, numerous types of multiple MRI-TRUS software integration-guided biopsy navigation systems are available on the market, differing in aspects such as software interface, image fusion methods and biopsy path selection (49). These platforms differ in terms of software interface, volumetric-USG acquisition technique, needle tracking method, image fusion algorithm and biopsy route. However, the high cost of these devices limits their widespread adoption in a short timeframe, restricting their overall application.
Robot-assisted ultrasound-guided biopsies utilize a mechanical arm to accurately position the biopsy needle in 3D, determining the direction of the needle, puncture depth and biopsy location while allowing for the removal of all biopsy tissues from a single incision. This system can automatically set the puncture depth, enhance needle placement accuracy and reduce operation time (50). While ultrasound offers low-cost, dynamic real-time imaging, it exhibits marked limitations, as cancer lesions often remain invisible, requiring urologists to manually adjust the TRUS probe during biopsy procedures to achieve clearer ultrasound images. In addition, manual operation of the TRUS probe and biopsy needle poses safety concerns. Targeted prostate biopsies risk needle deformation due to device imaging errors or variations in physician skill, which may lead to incorrect targeting and excessive needle insertions, resulting in complications, such as septic complications and acute urinary retention (51). These issues highlight the current limitations in puncture methods and accuracy.
With advancements in artificial intelligence, researchers are beginning to integrate engineering, minimally invasive surgery and imaging to develop robot-assisted puncture systems (52-54) aimed at improving puncture accuracy, reducing the number of biopsy cores needed and alleviating patient pain. Compared with manual biopsies, robot-assisted ultrasound-guided prostate biopsies allow for more precise needle placement with minimum reliance on physician experience or imaging examinations (55).
Robot-assisted prostate biopsy can alleviate the workload for urologists. An advantage of this system is that numerous biopsies can be performed at a single puncture site; however, the accuracy of the biopsies still heavily depends on the proficiency of the urologist. Phee et al (56) introduced a prototype robotic system designed for the accurate and consistent insertion of biopsy needles into the prostate. This system employed a TRUS probe to capture a series of 2D images of the prostate, which are then used to create a 3D computer model for the organ. Urologists utilize this model to determine biopsy points within the prostate, after which the robotic system calculates the necessary needle insertion positions, allowing for the actual biopsy to be performed. Ho et al (57) designed an ultrasound-guided perineal double-cone concept six-degree-of-freedom prostate biopsy robot system, which has demonstrated safety and accuracy in achieving precise prostate biopsies without harming the urethra of the patient.
Lim et al (55) proposed a robot-assisted system for TRUS-guided prostate biopsy, notable for its needle aiming accuracy of ~1 mm, establishing it as a feasible and safe option for assisting prostate biopsies. However, one limitation of this system is the lack of a supporting structure to maintain the leg posture of the patient, increasing the uncertainty of patient position changes during the procedure, which may affect needle tip positioning accuracy. Yan et al (58) introduced an eight-degree-of-freedom robot system designed for the operation, positioning and insertion of ultrasound probes, aiding physicians in achieving ultrasound probe scanning, needle position adjustments and needle insertions. This structure boasts high rigidity and compactness, facilitating the required movements of both the probe and needle while minimizing the risk of conflict between the robot and the patient.
MUS, CEUS and ultrasound elastography are cheaper and easier to obtain compared with other novel technologies. MRI-TRUS cognitive fusion-guided targeted prostate biopsy is not routinely used due to its high cost, time-consumption and complicated operational procedures. Patients with negative TRUS but positive MRI can undergo MRI-TRUS in suspicious malignant areas. MRI-TRUS image fusion technology allows urologists to progress from blind, systematic biopsy to targeted and tracked biopsy. Multiple MRI-TRUS software integration-guided targeted biopsy requires pre-biopsy multiparametric MRI data, which are obtained and stored in a specific storage hard device. This enables the real-time TRUS imaging and serves a complementary role in systematic biopsy, providing an objective basis for the development of clinical diagnosis and treatment plans. The use of a fusion device makes it costlier compared with systematic biopsy. Multiple MRI-TRUS software integration is convenient, fast and enables real-time imaging and is likely to show high clinical application prospects. With regard to cost-benefit analysis, it has been established that MRI-TRUS cognitive fusion and multiple MRI-TRUS software integration-guided targeted prostate biopsy exhibit improved benefits, with costs decreasing annually and the positive rate of puncture increasing. However, there are still certain problems with MRI-TRUS software benefits. The software sale cost is relatively high and the sales growth rate is not as fast as the cost growth rate, resulting in poor sales benefits. Human error is inevitable in systematic biopsy and the accuracy of diagnosis has not reached the desired effect (59). The application of robot-assisted ultrasound may represent a novel solution to the current dilemma of PCa diagnosis. Robot-assisted ultrasound can not only analyze the imaging information of PCa but also integrate any other diagnosis or treatment information regarding the patient, thus improving the accuracy of prostate-targeted biopsy and effectively monitoring the progress of PCa. However, robot-assisted ultrasound still needs to overcome its limitations, including the lack of extensive multi-center testing, unified industry standards, as well as issues with sharing and privacy, such as data transmission security, protection of sensitive information and legal compliance responsibilities. Yet, overall, the development of robot-assisted ultrasound should bring about promising changes to the diagnosis process (8).
MUS, contrast-enhanced ultrasound, ultrasound elastography and MRI-TRUS fusion imaging serve key roles in targeted prostate biopsy, although each method exhibits limitations and deficiencies (Table I). Robot-assisted targeted biopsy of the prostate not only improves detection accuracy and stability but also reduces operation time and the incidence of surgical complications, thereby decreasing the labor intensity for physicians. However, further research is required regarding robot-assisted prostate biopsy systems. Future investigations should aim to focus on refining and enhancing new ultrasound technologies that guide targeted punctures.
In addition, it is important to improve upon the ability of the robot in accurate imaging fusion of real-time and 3D images, as well as to facilitate intelligent interaction through voice and gesture commands. This would enhance the efficiency of physician operations, enable remote control capabilities and provide patients with convenient access to medical care, even if the patients are far away from the urologists (60). Enhancing the self-decision-making abilities of robots, ensuring they avoid collisions with patients during surgeries and preventing accidental punctures of key Urologists should select the appropriate technology for patients based on their specific conditions. For example, for patients with obesity, MRI navigation or robot-assisted surgery is recommended due to the clear operating field and high flexibility of the instruments. In addition, patients who are allergic to ultrasound contrast agents should opt for non-contrast imaging techniques, such as MUS, ultrasound elastography or MRI navigation and robot-assisted surgery (10,19,22,30). For those with a number of underlying diseases, it is important to consider the opinions of different disciplines and balance the feasibility and safety of the chosen technology (61). For example, for patients with severe cardiovascular diseases and the use of anticoagulant drugs, a cardiologist is required to assess the risks of discontinuing antiplatelet drugs and the urologist needs to evaluate the necessity of biopsy and the risk of bleeding. Urologists should reasonably determine the technical approach based on their experience and the resources available to them.
Overall, to facilitate clinical translation, the following suggestions are proposed: i) Establish a standardized multi-modal imaging acquisition and fusion operation procedure; ii) provide specialized training for urologists in robot-assisted targeted biopsy; and iii) integrate personalized biopsy plans into clinical pathway guidelines for the early diagnosis of PCa. With advancements in medicine and new ultrasound technologies, the application of multi-modal fusion and robot-assisted ultrasound-guided targeted prostate biopsy will become increasingly valuable when paired with personalized plans.
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Funding: No funding was received.
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TJ and LW wrote and edited the present manuscript. SZ revised the manuscript draft. All authors have read and approved the final version of the manuscript. Data authentication is not applicable.
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The authors declare that they have no competing interests.
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