Smith Blog

Watch Dr. Lee Richstone give a presentation on Multiparametic 3T MRI of the Prostate.

Will MR imaging provide the answers for prostate cancer dilemmas?

Lee Richstone, MD* and Eran Ben-Levi, MD**
The Smith Institute for Urology*
Diagnostic Imaging Center at the Center for Advanced Medicine**
The North Shore-Long Island Jewish Health System

Urologists and patients are faced with dilemmas at nearly every phase of prostate cancer management.  From prostate cancer detection, staging to treatment, many fundamental questions remain.  It is in this context that advances in prostate imaging could have a major impact in clinical practice with the potential to revolutionize the way we localize and stage prostate cancer, individualize treatment, and manage patients after treatment failure.  Multiparametric magnetic resonance imaging (MP-MRI), which integrates MR spectroscopic imaging (MRSI), diffusion weighted imaging (DWI), and/or dynamic contrast enhanced MRI (DCE) with traditional T2 weighted MRI, may be such an imaging breakthrough.

T2 MRI Scanning: Endorectal vs. Pelvic Phased Array, and 1.5 vs 3.0T Scanning
Standard T2-weighted MRI with 1.5 Tesla (T) scanners has been employed to detect and localize prostate cancer, which is characterized by decreased signal intensity compared to the normal peripheral zone.  The use of an endorectal coil in addition to external coils (pelvic phased array) allows for superior imaging.1,2  The use of 3.0T scanners offers increased spatial resolution, speed, and improved localization and staging.3  Clinically, endorectal MRI can incrementally improve upon preoperative nomograms in predicting seminal vesicle invasion (SVI) and extracapsular extension (ECE).4,5  Endorectal MRI has demonstrated clinical utility, altering the pre-surgical plan for neurovascular bundle preservation vs. resection in 39% of patients and 78% of high risk patients.6  Prostatic venous anatomy and membranous urethral length as evaluated with endorectal MRI have been correlated with estimated blood loss and postoperative continence, respectively, and some argue that MR based surgical planning has improved patient selection and pathological outcomes.7 However, significant limitations of T2 endorectal MRI exist, including limited sensitivity and specificity for detection of low stage, low grade disease, limitations in detecting prostate cancer in regions other than the peripheral zone, difficulty distinguishing prostate cancer from post-biopsy hemorrhage or prostatitis, and lack of inter-observer reliability.1,8-11   As a result, the value of T2 endorectal MRI as a single modality has been debated.11,12

Functional MRI Techniques: MRSI, DWI, and DCE
MRSI differentiates normal from cancerous prostate tissue by detecting differences in the concentration of various metabolites within the cytoplasm and extracellular space.10  Compared with normal tissue, prostate cancer is characterized by reduced or absent citrate and polyamines and elevated choline and creatine.13,14 Enthusiasm accompanied the early use of MRSI, which can be used to assess tumor location, volume, stage and may correlate with Gleason grade.2,15  Although some data has suggested that MRSI may be superior to T2 MRI alone, a multi-institutional study failed to demonstrate such advantages.14,16,17 Diffusion weighted imaging of prostate cancer is predicated on differences in the motion of water within normal vs. malignant tissue. Prostate cancer demonstrates reduced average water diffusivity compared with benign tissue, perhaps due to increased cell density within cancerous tissue.18 DWI detects prostate cancer with high spatial resolution and may be superior to T2 MRI alone in sensitivity and specificity of cancer detection and prediction of tumor aggressiveness.11,19  Dynamic contrast enhanced MRI takes advantage of tumor angiogenesis and increased microvascularity of malignant vs. benign tissue.  Malignant tissue differs from benign tissue with respect to microvessel density, blood flow, vascular morphology and permeability, and flow dynamics.12 Following gadolinium-DTPA contrast administration, prostate cancer typically demonstrates not only a greater peak enhancement, but also differs with respect to time to peak and washout.20 Interpretation of DCE can involve qualitative, semi-quantitative, or quantitative analysis.12 A growing body of literature suggests that DCE may significantly improve cancer detection, localization, and staging.11,16,21,22 Continuing research is aimed at determining the ideal DCE protocol and data analysis methodology in order to standardize the technique and allow for wider application.

Multiparametric MRI: Comprehensive Imaging with Clinical Applications
Multiparametric MRI integrates T2-weighted imaging with one or more functional technique (MRSI, DWI, and/or DCE) in a single study, with the potential to compensate for the shortcomings of each technique applied individually.  Combining modalities aims to increase the accuracy of MR-based imaging in a convenient single 60-minute study.  Moreover, scanning at 3.0T may improve the performance of individual and combined MRI techniques, and may even obviate the need for an endorectal coil, reducing the invasiveness of the study.11

Clinical applications of MP-MRI begin with prostate cancer diagnosis. For example, the management of patients with negative biopsies, yet persistently abnormal PSA values, is a common clinical dilemma.  Repeat standard biopsy has low yield of cancer detection and saturation biopsies may lead to increased morbidity and the detection of insignificant cancers.23  In a recent prospective, randomized trial of 180 patients with elevated PSA and negative prior biopsies, MP-MRI imaging (DCE/MRSI) led to increased detection of prostate cancer, with 62% being Gleason grade >7.23  A combination of T2, MRSI and DCE imaging had a PPV and NPV of 89% and 93%, respectively.  In this context, MP-MRI may aid urologists in the detection of significant cancers, and avoiding repeated biopsies in patients at lower risk.

Once prostate cancer is diagnosed, it is imperative to improve our ability to distinguish indolent from clinically significant tumors to reduce the extent of overtreatment.  The integration of MRI/MRSI with clinical parameters has been demonstrated to significantly improve the performance of nomograms in predicting insignificant prostate cancer.24  In the future, the further incorporation of DCE, and/or DWI at 3.0T into a single study could further improve our ability to select patients for active surveillance.  Moreover, one could imagine the use of an optimized MP-MRI protocol to avoid biopsy altogether in patients with an elevated PSA but low risk for clinically significant disease.  Such a non-invasive adjunct to screening could revolutionize our approach to prostate cancer detection, limit the diagnosis of indolent disease, and reduce the number of unnecessary biopsies and associated morbidity.

Multiparametric MRI at 3T allows for greater accuracy in detecting prostate cancer.25   With the potential to improve tumor localization, MP-MRI may help in the selection of patients for focal therapy, aid in treatment planning, and demonstrate the efficacy of ablation following minimally invasive or focally-based treatments.26  MP-MRI may be helpful in selecting those intermediate and high-risk patients who are appropriate for surgery and in tailoring the surgical approach.  Similarly, MP-MRI can aid in IMRT and brachytherapy dose-painting for improved treatment planning.7   Post-treatment, MP-MRI  may aid urologists with the common diagnostic challenge of determining whether treatment failure represents local or systemic disease. Various techniques, including DWI, DCE and MRSI have been used to aid in the detection and localization of recurrence after brachytherapy, external radiation treatment, and surgery, which may help in salvage treatment selection, and perhaps allow for focal or focally intensified salvage treatment in the future.7.12,27,28,29

Conclusions:
Multiparametric MRI has significant promise to aid clinicians with common prostate cancer dilemmas.  Currently, MP-MRI can be employed to help detect prostate cancer in the setting of multiple negative biopsies, evaluate cancer stage and guide treatment selection particularly in high risk patients, among other indications.  In the future, MP-MRI may have a major role in selecting patients for active surveillance and/or focal therapies. Future study is necessary to determine the optimal combination of functional techniques, and to develop standardized protocols for data acquisition and analysis.

REFERENCES

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5.    Wang L, Hricak H, Kattan MW, et al. Prediction of Seminal Vesicle Invasion in Prostate Cancer: Incremental Value of Adding Endorectal MR Imaging to the Kattan Nomogram. Radiology 2007; 242:182-188.
6.    Hricak H, Wang L, Wei DC, et al. The Role of Preoperative Endorectal Magnetic Resonance Imaging in the Decision Regarding Whether to Preserve or Resect Neurovascular Bundles during Radical Retropubic Prostatectomy. Cancer 2004;100:2655-63.
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As many of our patients know, Dr. Barbara Shorter, EdD, RD, CDN Associate Professor of Nutrition and  Director of the undergraduate Nutrition Program at Long Island University, has been volunteering her time every other Friday to counsel IC patients.

Well…we are very happy to report that Dr. Shorter has now joined our faculty! She’ll be giving expert advice on the nutritional aspects of many other urological conditions such as kidney disease, kidney stones, interstitial cystitis, prostatitis, and urological cancers.

Barbara Shorter received her Doctorate in Nutrition Education from Teachers College, Columbia University.  She is a registered dietitian with the American Dietetic Association and is a Certified Dietitian/Nutritionist NYS.  Dr. Shorter is an Associate Professor in the Department of Nutrition at the CW Post Campus of Long Island University (LIU) and Director of the Didactic Program in Dietetics.  She recently joined the faculty of the Smith Institute for Urology where she provides nutritional counseling in facets of urology including, pelvic pain, prostate cancer, kidney stone disease, and renal failure.

Prior to Dr. Shorter’s positions in the Academic arena, she was Chief Dietitian for the Catholic Medical Center, and, Senior Nutritionist at the NYU Medical Center Hospital, NYC.

Welcome aboard Barbara!!