Ashutosh Tewari, MD ., Adnan Ali, Robert Leung, Naveen Gumpeni, MD . Center for Prostate Cancer, Weill Cornell Medical College, New York, NY
Corresponding Author: Ashutosh Tewari, Md. Director, Center For Prostate Cancer, Lefrak Center For Robotic Surgery, Professor Of Urology And Public Health, Weill Cornell Medical College, New York Presbyterian Hospital, New York, Ny. Email: firstname.lastname@example.org
Current prostate cancer diagnostic techniques are under scrutiny due to lack of conclusive data from screening trials and concerns about the large number of unnecessary biopsies that are being performed [1, 2]. Indeed, although nearly a million biopsies are performed annually, they only result in the diagnosis of roughly 250,000 prostate cancer cases: This means 75% of biopsies performed do not necessarily have clinical value [3-5]. In addition, there are often instances where biopsies are not diagnosing clinically relevant prostate cancer. The prostate-specific antigen (PSA) test, the most commonly used screening test, targets a highly volatile biomarker; as a result, the test produces a significant number of false positives and false negatives: PSA generally misses 15% of prostate cancer cases when PSA registers in the “normal range” . This diagnostic imprecision leads to numerous unnecessary, blind, and random biopsies; a large number turn out to be negative or of indolent cancers. The test also underestimates the actual cancer stage, missing significant Gleason 7 cancer in up to 30% of screened cases . Thus, PSA as a diagnostic marker and systematic biopsy as a confirmation tool are far from perfect. There is an acute need for developing more representative biomarkers and increasing the accuracy of biopsy techniques. Magnetic Resonance Imaging (MRI), a medical imaging technique employed to image the nuclei of atoms in the body, is typically used in neurological and orthopedic diagnostic efforts. MRI also offers immense promise in the diagnosis of prostate cancer, particularly in providing a more accurate picture of a tumor’s current state and nature (aggressive versus indolent). This essay will offer an introduction to the use of MRI in prostate cancer diagnosis, focusing on its contributions in the use of guided biopsies, the use of the technology in assisting active surveillance, and the benefits and costs of using the technology. Overall, while still in the early stages, MRI will allow for a more accurate diagnosis for clinicians and more confidence in decisions for patients.
ROLE OF MRI IN PROSTATE CANCER IMAGING
The ideal multi-parametric MRI for prostate cancer detection and staging would include T1 (for demonstrating high signal blood products) and T2 (demonstrating the anatomy) weighted imaging and functional imaging that includes diffusion weighted imaging and dynamic contrast enhanced imaging with the use of pelvic phased-array coil along with an endorectal coil on a high field-strength magnet. To obtain sub millimeter resolution T2 weighted images necessary for local staging 3mm thin sections with a 14cm field of few are required . The cancer commonly demonstrates decreased signal intensity relative to the high-signal intensity normal peripheral zone on T2 weighted images . For detection of prostate cancer the sensitivity ranges from 60 to 96%, but has poor specificity . But, for detecting extracapsular extension or seminal vesicle invasion the sensitivity and specificity of MRI is 73% to 80% and 97-100% respectively . Diffusion weighted imaging allows the mapping of diffusion of water molecules within tissue. Apparent diffusion co-efficient is helpful in differentiating between low, intermediate and high risk Gleason scores . DW-MRI along with T2 weighted imaging has 89% sensitivity and 91% specificity 
There are a few notable limitations of MRI: temperature, post-biopsy hemorrhage, different MP-MRI sequence, and magnetic susceptibility in the tissue, could vary the MP-MRI results, affecting values (such as ADC) that may hamper tumor detection, leading to either under or overestimation of tumor presence and extent. With the increase in number of biopsy cores in recent years, a longer delay (typically 6-8 weeks) is recommended between biopsy and MR imaging to avoid post biopsy changes [14-16]. However, MR imaging adds value to both DRE and transrectal US-guided biopsy (P .01 for each) in cancer detection and localization in the prostate .
At our institution multi-parametric MRI findings are used for better surgical management and improving the functional outcomes in each individual patient based on unique disease characteristics. The information from MRI helps in making informed decisions during surgery for achieving oncological goals of cancer extirpation (negative surgical margins) and preservation of periprostatic tissue and nerves to improve functional outcomes (continence and sexual functions).
MRI GUIDED BIOPSIES
Three techniques of fusion have been described: 1) Cognitive fusion’ 2) In-Bore MRI -MRI Fusion and; 3) MRI -TRU S Fusion. Cognitive fusion simply requires the TRUS operator to target areas where previously reviewed MRI demonstrated significant lesions. This technique, although quick and easy, is subject to human error. During “in-bore” MRI-guided biopsy, the radiologist fuses a previous MRI demonstrating a lesion with a concurrent MRI . Using this method reduced the number of cores taken, with exact localization of significant tumors, and there is decreased detection of indolent tumors. However, this technique requires two MRI’s and takes a longer duration of time. The third method MRI-TRUS fusion is done in two steps: first a multiparametric endorectal MRI is done; the studies are then loaded on to software where the radiologist marks the prostate
gland and the regions of interest for biopsy in different slices and views of the MRI, known as segmentation. This information is then loaded on to the device. The second step involves realtime MRI-TRUS fusion to create a three-dimensional real-time reconstruction of the prostate on which the aiming and tracking of biopsy site is done. This technique can be done in an outpatient setting under local anesthesia within a few minutes. Currently,
the FDA has approved five devices for MRI-TRUS fusion biopsy. The Artemis device (Eigen, GrassValley, California, USA) has a mechanical arm with transducer probe and is capable of tracking and recording biopsy locations.
In our program the real-time fusion of Artemis steps are as follows:
1. Scan – Using an ultrasound connected to the Artemis, a 360O scan of the prostate is performed. The Artemis converts the conventional two-dimensional ultrasound scan into
real-time 3D along with views in different planes- coronal, transverse, and sagittal. Image segmentation computes prostate gland boundaries and volume.
2. Plan – The planning module allows to follow any of the following plans:
a. MR-TRUS Fusion – Segmented data of prostate gland obtained from MRI with marked regions of interest on multiparametric-MRI is loaded on to Artemis before the procedure. During the procedure, nonrigid registration is done with mapping of regions of interests from MRI to TRUS and overlaid in real time. Regions of interest for biopsy are selected.
b. C onventional 6-core, 12-core plans computed and fit to gland shape
c. Custom plans, if defined, can be fit to a candidate prostate shape
d. Revisit plan for a patient with a previous procedure on active surveillance- Maps from previous biopsies are loaded into current prostate shape. Uses gland boundaries from previous and current procedure to incorporate any changes in gland shape and size.
This plan can be used to revisit a positive core from a previous procedure to monitor disease progression in cases of active surveillance.
3. Biopsy– Irrespective of the plan chosen, using real-time biopsy needle tracking capabilities, Artemis allows to achieve accurate needle placement for targeted biopsy of regions and stores the location of biopsy sites. This allows for precise resampling of biopsy sites in active surveillance patients.
4. Report-Generates report with images from biopsy procedure including measurements made during the biopsies, such as linear measurements, prostate volume, etc. The report also includes type of plan and other navigational data. This allows for retrospective case review, with provision to enter PSA and pathology information.
At the initial study, 171 patients who underwent prostate biopsies using the Artemis platform included 106 (active surveillance) patients and 65 (increasing PSA, prior negative conventional biopsy) patients . Prostate cancer was detected in 53% of the male patients. Fusion biopsy-based targeted cores had a higher yield of 21% as compared to 7% for systemic biopsy cores. A higher number of Gleason 7 cores (36% vs. 24%) were also detected.
ROLE OF MRI IN ACTIVE SURVEILLANCE
Although adding MRI to existing diagnostic modalities may confer benefits across a wide range of prostate cancer patients, the technology shows particular promise for those patients with low-risk cancers who choose active surveillance as a treatment strategy. Indeed, although MRI is still not commonly used, they have shown promising results in initial studies. In a recent study conducted with 388 men that had a clinically low-risk of prostate cancer (classified as Gleason score of 6 or less; PSA <10 ng/ml, clinical state T2a), the patients had an endorectal MRI preformed before a confirmatory biopsy. After the biopsy was conducted, urologists reviewed the MRI and judged the image based on a scale of 0 (no tumor) to 5 (definite tumor). Overall, urologists upgraded the Gleason score in 20% (79/388) of patients. MRI scores were helpful in accurately assessing the Gleason score: Scores of 2 or less had a high predictive value for a score upgrade; scores of 5 were also sensitive for upgrading. MRI scores also had a positive impact of upgrading the odds of a confirmatory biopsy. (Vargas et al., 2012).
Although the study was restricted to a limited number of low-risk cancer patients, the results show the potential of using MRI as a more accurate diagnostic tool. MRI may thus play a key role in helping patients to understand whether active surveillance is a viable option. Previously, the inaccuracy of PSA tests made active surveillance for patients with low-risk cancer, without biopsy, somewhat of a gamble. Because active surveillance is
based on the premise that the type and stage of prostate cancer is accurately diagnosed, MRI may now be used to help clinicians in accurately making the diagnosis. At our institution we have an active have an active surveillance protocol that minimizes the role of biopsy and encourages multi-parametric MRI in inclusion and follow-up for this
protocol. Thus our approach has a potential for significantly reducing biopsy in active surveillance patients.
COSTS AND BENEFITS OF MRI
Overall, the use of MRI technology offers numerous benefits in the treatment of prostate cancer. The main benefits of the technology are considered to be:
1) More accurate detection of tumors, decreasing the number of unnecessary and expensive biopsies;
2) Better determination of the location and extension of the tumor, reducing potential side effects;
3) Better prediction of tumor aggression, and thus ability to help patients map out
a treatment course;
4) Non-surgical detection of very small metastases in lymph nodes; 5) For “PSA-recurrent” patients, a whole-body MRI can be conducted (Barentz, 2011).
Although the technology shows great promise, there may also be downsides to its wide-spread use. The first is cost: although multiparametric MRI is accurate, it is also expensive. Thus, it is not economically suitable to be used as a primary screening
test or to completely displace PSA screening (Hoeks, 2009). Indeed, the test should only be used if a PSA result is out of the threshold range. As MRI becomes a more common diagnostic tool in prostate cancer, the ability to skip an expensive biopsy might make a more robust care for the MRI. A second concern is radiation exposure.
With the many known shortfalls of PSA screening as evidence to conduct a biopsy or engage in treatment decisions, MRI provides a number of new options and functionality, in addition to the PSA test, that provides better diagnostic information for the clinician and more informed decisions for the patient. Indeed, multi-parametric MRI is capable of showing the location, extent, and aggressiveness of prostate cancer. The improved diagnostic capability of MRI is expected to end the era of unnecessary blind prostate biopsies and pave the way for future image-guided biopsies. It will help tailor therapies based on each patient’s unique individual requirements and lead to improvements in health care and reduce complications, patient anxiety, and discomfort.
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