Expert Insights on MRI-US Fusion-Guided Biopsy

Introduction

In 2023, prostate cancer was detected in approximately 288,300 men in the United States, positioning it as the most diagnosed non–skin cancer among men.¹ Advanced diagnostic tools that include multiparametric MRI increasingly have become available for use in clinical practice and have supported early and accurate diagnosis.¹

Urology Times® recently hosted a Viewpoints panel discussion regarding the role of MRI in diagnosing and managing prostate cancer. The discussion was led by David I. Lee, MD, FACS, professor of Clinical Urology and director of the Comprehensive Prostate Cancer Program at University of California, Irvine Health. Panelists were Firas F. Abdollah, MD, a senior urologist, the vice chair of academics and research in the Department of Urology and the director of the Vattikuti Urology Institute Center for Outcomes Research Analytics and Evaluation at Henry Ford Medical Center–Lakeside in Sterling Heights, Michigan; Evan Kovac, MD, CM, FRCSC, associate professor of Surgery and director of Urologic Oncology at Rutgers Health New Jersey Medical School in
Newark, New Jersey; and Ruben Olivares, MD, associate professor of Urology at Glickman Urological Institute at the Cleveland Clinic in Cleveland, Ohio. Topics of conversation included use of MRI technologies before and during prostate biopsy, the value of MRI-ultrasound (MRI-US) fusion-guided biopsy, and recommendations for integrating these tools into clinical practice.

Following is a summary of key points and takeaways from the discussion.

Use of MRI in Workup Before Biopsy

Patients often come to Dr Abdollah’s clinic after testing by their primary care physician identifies an elevated prostate specific antigen (PSA) level. Biopsy is the diagnostic standard for prostate cancer.² Before recommending biopsy, Dr Abdollah identifies any patient who does not need a biopsy. He confirms PSA elevation by excluding any reasons that could contribute to a false positive and running a second PSA test if only 1 had been conducted. For patients with a confirmed PSA elevation, he then recommends an MRI. Dr Abdollah said, “A lot of research [results show] that a good quality MRI does actually help you to avoid unnecessary biopsy in many patients who don’t really need it.” Most patients educated on the value of MRI choose to receive the procedure. In addition to MRI, Drs Oliveras and Lee noted that genomic evaluation via urine or blood and other tools may be used to determine whether a biopsy is necessary.

MRI-Targeted Biopsy

When MRI results show that a biopsy is warranted, MRI can also support a biopsy that offers more accuracy and improved information regarding exact disease grade. This can help clinicians differentiate between clinically significant prostate cancer that needs treatment and clinically insignificant prostate cancer that does not need treatment. “MRI imaging has come a long way in helping us to meet the goal of not overdiagnosing prostate cancer,” shared Dr Abdollah. The MRI offers a better understanding of what is happening inside of the prostate, Dr Olivares commented, so that biopsies can target a specific area of concern in the prostate. “We can guide our biopsy to reach only that area, which increases the performance and precision of the test,” he said. Ultrasound, by contrast, is helpful to determine the location of the prostate [cancer], but “a great majority of prostate cancer is invisible to the US.”

Dr Abdollah noted the differing results between the conventional blind biopsy and MRI-targeted biopsy. “For almost 30% of patients who undergo conventional biopsy, the biopsy does miss their clinically significant cancer,” he said. By comparison, “[clinically significant cancer] has been detected more and more with an MRI-targeted technique.” In addition, the grade determined by MRI-targeted biopsy is very similar to the grade confirmed by final pathology. The additional information on stage and location of the cancer offered by MRI enables a tailored treatment approach that is specific to the patient and his disease characteristics.

Transrectal versus transperineal biopsy

MRI can be used with both transrectal (TR) biopsy and transperineal (TP) biopsy. TR biopsy guided by US has been used as the main approach for diagnosing prostate cancer, although over the past decade there has been a gradual shift toward TP biopsy.² Dr Kovac described benefits and challenges associated with each approach. TR biopsy is quicker, he shared, and “you still get a very accurate diagnosis.” However, TR biopsy is associated with increased risk of infection, with approximately 3% to 5% of patients being readmitted for infection despite the use of prophylactic antibiotics.2 Dr Kovac noted that with the increasing rates of antibiotic resistance, clinicians must use antibiotics judiciously, which is one of the reasons that he switched from using TR biopsy to employing TP biopsy. TP biopsy also offers a higher rate of diagnosis for anterior cancers.² “Early evidence supports that the diagnosis [with TP biopsy] may be more accurate,” Dr Kovac said. “So for a number of reasons that are both evidence-based and patient-driven, I’ve transformed my practice into TP-only.” He conducts TP biopsy in the ambulatory setting with sedation. Once he developed proficiency, he found that patients had a positive experience in this environment.

MRI-US Fusion-Guided Biopsy

MRI-targeted biopsy supports clear visualization of the lesions and the biopsy process, but it is a complex approach that can be challenging to execute on a large scale. Despite its imaging shortcomings, US enables continuous real-time monitoring of the biopsy process and path.³ MRI-US fusion-targeted biopsy combines these imaging approaches, which can increase biopsy efficacy.³

Cognitive- and software-based fusion

In MRI-US fusion-guided biopsy, MRI and US images are superimposed either by the operator or by software. With the former approach, known as cognitive-based fusion-guided biopsy, the operator cognitively samples the prostate through US with assistance from a visual map from MRI imaging. With the latter approach, known as software-based fusion-guided biopsy, software captures MRI images, matches them with real-time US images, and shows the location of the potential lesion.⁴ Each approach is associated with inherent challenges; cognitive-based fusion depends on the operator’s experience and skill set, and the programs used in software-based fusion are costly and not widely available.⁴

According to Dr Olivares, cognitive-based fusion can be suitable for a large lesion with either posterior access when using TR biopsy or an apical location when using TP biopsy. Software-based fusion can provide an advantage in targeting a small, difficult-to-reach lesion. Overall, “when you’re using [software] to guide your biopsy, you tend to have more consistent results,” he said. Regardless of experience level, “you can rely on software to help you put the needle in the right location.” Dr Abdollah emphasized that MRI information obtained through cognitive-based fusion is still beneficial when software is not available. “Many reports show that the cognitive-based fusion in many cases is probably just as good as the software-based fusion.” He encouraged clinicians not to give up when the software is not available.

Dr Kovac uses a platform that combines both cognitive- and software-based fusion, noting, “Overall, performing fusion biopsy familiarizes you with the anatomy, and using a combined fusion approach like the one I’m using…makes you a better doctor and helps you to understand the organ a lot better.”

Elastic and rigid image registration

Fusion-guided biopsy platforms use either rigid or elastic registration to fuse MRI results with US. The rigid method involves manual rotation and translation of the MRI and US images to globally align the images. By comparison, the elastic method uses semiautomated software to stretch the segmented MRI margin to better fit the real-time US margin. The rigid method preserves true patient anatomy but does not accommodate deformities of the prostate, whereas the elastic method may generate a more precise final image of the lesion but may not depict true anatomy.⁵ Overall, the “software is getting better and better,” according to Dr Kovac. “If the idea is accuracy, then certainly elastic fusion is going to help you to contour the prostate and have a core-registered image that is as accurate as possible.”

Combining MRI-US Fusion-Guided Biopsy and Systemic Biopsy

Most reports suggest that combining targeted and systemic biopsies will offer a better grading of the disease and will detect more clinically significant pathology, according to Dr Abdollah. “You have to get targeted and systemic, because you don’t want to miss anything that is important, especially if you are offering less aggressive treatments or active surveillance,” he said. He noted that while it’s important to know where the cancer is, it is also important to know where the cancer is not. This is especially true for a patient who will receive focal therapy. “We want to make sure we are not missing a clinically significant cancer elsewhere in the gland,” he said. Similarly, for patients receiving precision prostatectomy or who will retain part of their prostate, “we want to be as accurate as possible.”

Dr Oliveras said that taking samples at least 10 mm from the main core can increase the chances of detecting clinically significant prostate cancer. “We always think of the lesion from the MRI as [being] a perfect circle,” said Dr Oliveras. “Unfortunately, prostate cancer does not follow geometrical shapes. Most of the time the lesions are more like a spider or even a star.”

Role of MRI in Surveillance

Currently, there is no standard protocol for active surveillance, and the approach is based on understanding of the disease, according to Dr Kovac. “The question of who should and should not go on active surveillance is a hot topic,” he said, “especially in the low-volume, intermediate-risk patient.” MRI plays an important role in surveillance; it can more accurately characterize patients who require surveillance, more accurately risk-stratify patients already on active surveillance, and help tailor surveillance to each patient.

Additionally, MRI may substitute for biopsy on certain occasions among correctly selected patients. Current guidelines for conducting biopsy in active surveillance vary from every year to every 2 to 4 years, said Dr Abdollah. However, biopsy can be an unpleasant experience, and some patients will shift from surveillance to active treatment to avoid biopsy. For a patient on active surveillance who had a negative MRI, Dr Kovac is comfortable delaying the next biopsy, particularly if they had a confirmatory biopsy. This approach “makes it much more palatable for the patient to stay on surveillance and not suffer from surveillance fatigue,” he said.

For those who need biopsy, Dr Abdollah shared, 90% of patients request to be put to sleep when offered the choice between local anesthesia and sedation. This approach is “easier and more acceptable to the patient, especially if he has to come back for more biopsies,” he said, and it can result in better adherence to active surveillance protocols. In addition, if the patient’s gland is already well-sampled, targeted biopsy could “benefit the patient by [involving] a shorter biopsy and perhaps less risk of infection depending on the modality,” said Dr Kovac. Overall, Dr Lee noted the importance of offering several options to the patient who needs biopsy and of being comfortable with those options. “Have a good relationship with your operating room staff and your anesthesiologist, but also be comfortable with local anesthesia,” he said.

The active surveillance landscape is likely to change considerably over the next few years, according to Dr Kovac. “We have a few ongoing, randomized trials that are looking at an aggressive initial biopsy versus standard active surveillance versus an initial aggressive fusion biopsy with a saturation template and then no subsequent biopsy,” he said. “We also cannot forget that we have the option to utilize nitrous oxide.”

Advantages of MRI-US Fusion-Guided Biopsy With Focal Therapy

The aim of focal therapy is to ablate the clinically significant prostate cancer and enable active surveillance of the rest of the prostate, shared Dr Olivares. “[With focal therapy], we have to know exactly what is happening inside of the prostate; in other words, it is an image-based therapy,” he said. “The starting point of any focal therapy program is the quality of your MRI and quality of your fusion.”

Dr Kovac stated that focal therapy involves a team effort across multiple steps. “We want to develop a target, to biopsy and accurately characterize that target, and to [determine] its biology,” he said. “[We want to ablate the target lesion] while preserving sexual and urinary function and allowing [patients] to keep their prostate.” This process requires a robust imaging platform with good technology. Imaging with 3-dimensional modeling compensates for inflammation-based swelling or movement; in addition, it can tailor the shape of the ablation to reduce the risk of producing incontinence when targeting lesions that are difficult to access.

Focal therapy also involves experienced radiologists to aid in developing the target; further, genomics to decipher the biology of the lesion and other tools may be used. Seasoned pathologists also play an important role in accurately characterizing the cancer under the microscope to identify possible candidates for focal therapy.

Integrating MRI-US Fusion-Guided Biopsy Into Practice

Regarding the use of fusion-guided biopsy in practice, Dr Abdollah noted that he did not experience difficulty with performing the biopsy, but was challenged initially with learning and troubleshooting the software. For him, learning the software involved a greater time investment up front. At first, to perform a targeted biopsy under local anesthesia, segmentation took 4.5 minutes for him to complete, and the overall biopsy took him 13 minutes. “I don’t think it’s difficult to learn…” he said, and “doing more biopsies [improves] your time.” Findings from a report from investigators in France showed that for clinicians who started to use targeted MRI, it typically took 40 cases to plateau on time invested for performing a segmentation and 50 cases to plateau on time invested for performing the biopsy overall.⁶ Dr Abdollah added that it would take 25 to 45 cases to reach a good detection rate. “[Currently], with the updates the software got, it’s running really smoothly,” he said.

Dr Kovac noted the varying degrees of investment when initiating a fusion program. “You have to decide what kind of mental load you want to put on yourself when starting this kind of program,” he advised, “because there are many things you can adopt.” A clinician may choose to transition from a standard TR template to a TP template or freehand TP, which can involve a learning curve. In addition to learning the software, clinicians must become familiar with the hardware. “This can raise stress levels during your initial cases,” Dr Kovac shared, from even “just the simple concept of knowing which buttons to push on the machine.” He recommended initially partnering with members of the industry and meeting with representatives from different companies to become familiar with technologies outside of the clinical setting. Industry partners often offer demonstrations and models for clinician practice before a first procedure. In addition, industry partners can attend initial procedures in the operating room to offer guidance as needed. Clinicians can also take advantage of the training resources available on the American Urological Association website that include instruction on effusion and effusion biopsy.

“[Overall], the complexity of [performing] the fusion biopsy is not very high,” said Dr Kovac. “One of the reasons for that is the friendliness of the interface of the equipment…I think that will keep improving with further development of the software and the hardware.”

Clinical Implications and Future Directions

Regarding whether to choose to use MRI-US fusion-guided biopsy, Dr Kovac said, “Why wouldn’t you want to know where the cancer is?” Dr Oliveras shared a similar sentiment. “We have to stop doing blind prostate biopsy. Nowadays, we have the technology, the imaging, and the training available to proceed with fusion prostate biopsy.” Dr Kovac agreed, “We have to be thoughtful about using this [MRI-US fusion] technology….This is an art; it’s not just [about] using this technology blindly.” With the long course of disease, data are immature in regard to identifying the full potential benefit of MRI use in patients with prostate cancer. “It’s important to recognize that [with an MRI-targeted biopsy], we are endeavoring to save somebody’s life,” said Dr Kovac. “I think [that] the data will mature over the next 5 to 10 years, [at which point] we can definitively say that getting an MRI not only helps us to characterize the disease more accurately, but it can also save [patients’ lives].”

In addition to MRI, other technologies for prostate cancer diagnosis and management are emerging. Dr Oliveras predicted that AI would play a more dominant future role in determining prostate cancer location and staging. Dr Kovac believes that the PSMA PET scan will increasingly be used with prostate biopsy over the next few years. “By integrating [PSMA] with MRI, you have a functional scan, a metabolic scan, and then an anatomical scan,” he said. “Combining the 2 into a biopsy modality [will enable you to] even more accurately characterize not just the lesions you see but also functional lesions that may not be seen anatomically.” Although MRI efficiently locates the lesion, PSMA can enhance the ability to stage and determine whether there is extracapsular extension. Eventually, these tools may enable clinicians to see the lesions in real time during surgical procedures. In the meantime, MRI technologies offer clinicians the ability to detect more clinically significant disease, thereby improving diagnostics and decreasing overtreatment.

References

1. Wei JT, Barocas D, Carlsson S, et al. Early detection of prostate cancer: AUA/SUO guideline part I: prostate cancer screening. J Urol. 2023;210(1):46-53. doi:10.1097/JU.0000000000003491
2. Lu M, Luo Y, Wang Y, Yu J, Zheng H, Yang Z. Transrectal versus transperineal prostate biopsy in detection of prostate cancer: a retrospective study based on 452 patients. BMC Urol. 2023;23(1):11. doi:10.1186/s12894-023-01176-y
3. Fang JH, Zhang L, Xie X, Zhao P, Bao L, Kong F. Comparative diagnostic accuracy of multiparametric magnetic resonance imaging-ultrasound fusion-guided biopsy versus systematic biopsy for clinically significant prostate cancer. PeerJ. 2023;11:e16614. doi:10.7717/peerj.16614
4. Pirola GM, Castellani D, Orecchia L, et al. Transperineal US-MRI fusion-guided biopsy for the detection of clinical significant prostate cancer: a systematic review and meta-analysis comparing cognitive and software-assisted technique. Cancers (Basel). 2023;15(13):3443. doi:10.3390/cancers15133443
5. Hale GR, Czarniecki M, Cheng A, et al. Comparison of elastic and rigid registration during magnetic resonance imaging/ultrasound fusion-guided prostate biopsy: a multi-operator phantom study. J Urol. 2018;200(5):1114-1121. doi:10.1016/j.juro.2018.06.028
6. Lenfant L, Beitone C, Troccaz J, et al. Learning curve for fusion magnetic resonance imaging targeted prostate biopsy and three-dimensional transrectal ultrasonography segmentation. BJU Int. 2024;133(6):709-716. doi:10.1111/bju.1628