Sperling Prostate Center Clinical Research on MRI-Guided Prostate Therapies

In addition to out growing database of case studies, Sperling Prostate Center is qualified to participate in other clinical research studies designed to help continually improve the outcomes and quality of life for their patients.We collect comprehensive data on MRI-Guided Prostate Laser Ablation procedures. This proprietary data base assembles critical information about the outcomes, follow up and experience of patients treated by Dr. Sperling. Tracking statistics contributes to the Sperling Prostate Center’s standard of excellence in medicine by allowing the team to research, develop and refine their unique clinical protocol while keeping abreast of reported results by other researchers around the world.

Below you will find abstracts, or summaries, of published research articles. Most abstracts contain a brief statement of the Purpose of the study, followed by Materials and Methods, Results, and then the Authors’ Conclusions. We suggest that you begin your reading with the Purpose and the Conclusion segments. If you are interested in further information and statistical analysis, please read the Materials and Methods and Results sections.

At The Sperling Prostate Center, we feel it is important to provide a sample of the science behind what we do. Please read the about that science below.

SECTION ONE

MRI IN DETECTING & IDENTIFYING PROSTATE DISEASE

1. Reports MRI accuracy in detecting tumors by comparing MRI findings with the same prostates after they were surgically removed and examined under a microscope.

TITLE: Correlation of magnetic resonance imaging tumor volume with histopathology.

Turkbey B, Mani H, Aras O, Rastinehad AR, Shah V, Bernardo M, Pohida T, Daar D, Benjamin C, McKinney YL, Linehan WM, Wood BJ, Merino MJ, Choyke PL,Pinto PA. J Urol. 2012 Oct;188(4):1157-63.
Molecular Imaging Program, National Cancer Institute, Bethesda, Maryland 20892-1210, USA.

PURPOSE: The biology of prostate cancer may be influenced by the index lesion. The definition of index lesion volume is important for appropriate decision making, especially for image guided focal treatment. We determined the accuracy of magnetic resonance imaging for determining index tumor volume compared with volumes derived from histopathology.

MATERIALS AND METHODS: We evaluated 135 patients (mean age 59.3 years) with a mean prostate specific antigen of 6.74 ng/dl who underwent multiparametric 3T endorectal coil magnetic resonance imaging of the prostate and subsequent radical prostatectomy. Index tumor volume was determined prospectively and independently by magnetic resonance imaging and histopathology. The ellipsoid formula was applied to determine histopathology tumor volume, whereas manual tumor segmentation was used to determine magnetic resonance tumor volume. Histopathology tumor volume was correlated with age and prostate specific antigen whereas magnetic resonance tumor volume involved Pearson correlation and linear regression methods. In addition, the predictive power of magnetic resonance tumor volume, prostate specific antigen and age for estimating histopathology tumor volume (greater than 0.5 cm(3)) was assessed by ROC analysis. The same analysis was also conducted for the 1.15 shrinkage factor corrected histopathology data set.

RESULTS: There was a positive correlation between histopathology tumor volume and magnetic resonance tumor volume (Pearson coefficient 0.633, p <0.0001), but a weak correlation between prostate specific antigen and histopathology tumor volume (Pearson coefficient 0.237, p = 0.003). On linear regression analysis histopathology tumor volume and magnetic resonance tumor volume were correlated (r(2) = 0.401, p <0.00001). On ROC analysis AUC values for magnetic resonance tumor volume, prostate specific antigen and age in estimating tumors larger than 0.5 cm(3) at histopathology were 0.949 (p <0.0000001), 0.685 (p = 0.001) and 0.627 (p = 0.02), respectively. Similar results were found in the analysis with shrinkage factor corrected tumor volumes at histopathology. CONCLUSIONS: Magnetic resonance imaging can accurately estimate index tumor volume as determined by histology. Magnetic resonance imaging has better accuracy in predicting histopathology tumor volume in tumors larger than 0.5 cm(3) than prostate specific antigen and age. Index tumor volume as determined by magnetic resonance imaging may be helpful in planning treatment, specifically in identifying tumor margins for image guided focal therapy and possibly selecting better active surveillance candidates.

2. Discusses the role of MRI through a review of current and previously published peer-reviewed literature.

TITLE: Prostate cancer – the role of magnetic resonance imaging.

Mocikova I, Babela J, Balaz V. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2012 Jun;156(2):103-7
Radiology Department, FD Roosevelt Faculty Hospital, nam. gen. Svobodu 1, 97517 Banska Bystrica, Slovak Republic.

BACKGROUND: This article reviews the potential of magnetic resonance imaging (MRI) in prostate cancer diagnosis.

METHODS: Systematic scan of Pubmed, Ovid, Medline, Elsevier search engines was used, additional information was found through bibliographic review of relevant articles. Results. Substantial progress has been made in the imaging of prostate cancer in MR imaging, as well as in advanced MR spectroscopy.

CONCLUSIONS: MRI is a non-invasive and direct imaging modality useful for cancer staging, therapy response, detection of recurrence and guided biopsy in previous negative biopsies. MRI with 3.0T system, whole-body MRI, dynamic contrast enhanced MRI, diffusion-weighted imaging (DWI) and MR spectroscopy (MRS) have improved tumor staging, assessment of tumor volume, aggressiveness or recurrence. Implementation of endorectal/phased array superficial MRI findings on 1.5 or 3.0T systems into nomograms for prostate pretreatment prediction is warranted. Surface phasedarray coil MRI accurately defines prostate cancer with elevated risk of extraprostatic disease.

3. Explores the merits of pre-prostatectomy MRI as a way to identify extracapsular extention (ECE) or early spread outside the prostate capsule.

TITLE: Preoperative 3-Tesla multiparametric endorectal magnetic resonance imaging findings and the odds of upgrading and upstaging at radical prostatectomy in men with clinically localized prostate cancer.

Hegde JV, Chen MH, Mulkern RV, Fennessy FM, D’Amico AV, Tempany CM. Int J Radiat Oncol Biol Phys. 2013 Feb 1;85(2):e101-7
Harvard Medical School, and Department of Radiology, Brigham and Women’s Hospital, Boston, Massachusetts.

PURPOSE: To investigate whether 3-T esla (3T) multiparametric endorectal MRI (erMRI) can add information to established predictors regarding occult extraprostatic or high-grade prostate cancer (PC) in men with clinically localized PC.

METHODS AND MATERIALS: At a single academic medical center, this retrospective study’s cohort included 118 men with clinically localized PC who underwent 3T multiparametric erMRI followed by radical prostatectomy, from 2008 to 2011. Multivariable logistic regression analyses in all men and in 100 with favorable-risk PC addressed whether erMRI evidence of T3 disease was associated with prostatectomy T3 or Gleason score (GS) 8-10 (in patients with biopsy GS ?7) PC, adjusting for age, prostate-specific antigen level, clinical T category, biopsy GS, and percent positive biopsies.

RESULTS: The accuracy of erMRI prediction of extracapsular extension and seminal vesicle invasion was 75% and 95%, respectively. For all men, erMRI evidence of a T3 lesion versus T2 was associated with an increased odds of having pT3 disease (adjusted odds ratio [AOR] 4.81, 95% confidence interval [CI] 1.36-16.98, P=.015) and pGS 8-10 (AOR 5.56, 95% CI 1.10-28.18, P=.038). In the favorable-risk population, these results were AOR 4.14 (95% CI 1.03-16.56), P=.045 and AOR 7.71 (95% CI 1.36-43.62), P=.021, respectively.

CONCLUSIONS: Three-Tesla multiparametric erMRI in men with favorable-risk PC provides information beyond that contained in known preoperative predictors about the presence of occult extraprostatic and/or high-grade PC. If validated in additional studies, this information can be used to counsel men planning to undergo radical prostatectomy or radiation therapy about the possible need for adjuvant radiation therapy or the utility of adding hormone therapy, respectively.


SECTION TWO

MRI IN PROSTATE DIAGNOSIS: TARGETED BIOPSY

1. Shows the efficacy of MRI-guided biopsy after previous negative TRUS biopsy.

TITLE: MRI-guided prostate biopsy detects clinically significant cancer: analysis of a cohort of 100 patients after previous negative TRUS biopsy.

Roethke M, Anastasiadis AG, Lichy M, Werner M, Wagner P, Kruck S, Claussen CD, Stenzl A, Schlemmer HP, Schilling D. World J Urol. 2012 Apr;30(2):213-8.
Department of Radiology, Comprehensive Cancer Center Tübingen, Eberhard-Karls-Universität, Tübingen, Germany.

PURPOSE: To investigate the positive biopsy rate of MRI-guided biopsy (MR-GB) in a routine clinical setting, identify factors predictive for positive biopsy findings and to report about the clinical significance of the diagnosed tumors.

METHODS: Patients with at least one negative trans-rectal-ultrasound-guided biopsy (TRUS-GB), persistently elevated or rising serum prostate specific antigen (PSA) and at least one lesion suspicious for PCa on diagnostic 1.5 Tesla endorectal coil MRI (eMR) were included. Biopsies were carried out using a 1.5 Tesla MRI and an 18 G biopsy gun. Clinical information and biopsy results were collected; logistic regression analysis was carried out. Definite pathology reports of patients with diagnosis of PCa and subsequent radical prostatectomy (RP) were analyzed for criteria of clinical significance.

RESULTS: One hundred patients were included, mean number of previous biopsies was 2 (range 1-9), mean PSA at time of biopsy was 11.7 ng/ml (1.0-65.0), and mean prostate volume was 46.7 ccm (range 13-183). In 52/100 (52.0%) patients, PCa was detected. Out of 52 patients, 27 patients with a positive biopsy underwent RP, 20 patients radiation therapy, and 5 patients active surveillance. In total, 80.8% of the patients revealed a clinically significant PCa. In univariate regression analysis, only serum PSA levels were predictive for a positive biopsy result. Number of preceding negative biopsies was not associated with the likelihood of a positive biopsy result.

CONCLUSIONS: MR-GB shows a high detection rate of clinically significant PCa in patients with previous negative TRUS-GB and persisting suspicion for PCa.

2. Demonstrates the superiority of MRI for prostate biopsy.

TITLE: Multiparametric MRI and prostate cancer diagnosis and risk stratification.
Turkbey B, Choyke PL. Curr Opin Urol. 2012 Jul;22(4):310-5
Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD.

PURPOSE OF REVIEW: Prostate cancer is the most common solid organ cancer type among American men. Screening and imaging aim to detect early-stage disease that is biologically aggressive. The focus of this study is to review multiparametric MRI in the detection and risk stratification ofprostate cancer.

RECENT FINDINGS: MP-MRI has been shown to be the most accurate noninvasive technique to localize prostate cancer. Recent studies reported that using MRI for guidance during prostate biopsies increases the yield of prostate biopsies. Moreover, multiparametric and particular MRI sequences such as apparent diffusion coefficient values of diffusion-weighted MRI have been found to correlate negatively with tumor Gleason scores.

SUMMARY: Among the existing imaging modalities, multiplanar magnetic resonance is the best at detecting prostate cancers. Some risk stratification is possible based on size, extent and apparent diffusion coefficient values. However, prostate MRI remains nonspecific and biopsies must be performed to confirm whether an abnormality is benign or malignant and to assign Gleason scores.

3. The advantages of MRI vs. transrectal ultrasound guided biopsy.

TITLE: Imaging-guided prostate biopsy: conventional and emerging techniques.
Yacoub JH, Verma S, Moulton JS, Eggener S, Aytekin O. Radiographics. 2012 May-Jun;32(3):819-37.
Department of Radiology, University of Chicago.

Transrectal ultrasonography (US)-guided biopsy is the standard approach for histopathologic diagnosis of prostate cancer. However, this technique has multiple limitations owing to the operator’s inability in most cases to directly visualize and target prostate lesions. Magnetic resonance (MR) imaging of the prostate overcomes many of these limitations by directly depicting areas of abnormality and allowing targeted biopsies. Accuracy in the detection of prostate cancer is improved by the combined use of standard T2-weighted MR imaging and advanced MR imaging techniques such as diffusion-weighted imaging, dynamic contrast-enhanced imaging, and MR spectroscopy. Suspicious-appearing regions of the prostate seen on MR images can be targeted at real-time transrectal US-guided biopsy to improve the diagnostic yield. MR imaging also can be performed for real-time guidance of transrectal prostate biopsy. Studies among patients who underwent at least one transrectal US-guided biopsy with a negative result before undergoing an MR imaging-guided biopsy showed improved detection rates with MR imaging-guided biopsy in comparison with the detection rates achieved with a repeat transrectal US-guided biopsy; however, MR imaging-guided biopsy is a more time-consuming procedure. A technique known as fused MR imaging- and transrectal US-guided biopsy, which relies on the coregistration of previously acquired MR images with real-time transrectal US images acquired during the procedure, shows promise but is limited by deformation of the prostate; this limitation is the subject of ongoing investigation. Another technique that is currently under investigation, MR imaging-guided prostate biopsy with robotic assistance, may one day help improve the accuracy of biopsy needle placement.

SECTION THREE

MRI-GUIDED PROSTATE TREATMENT

1. The first Phase I study (9 patients) designed and approved prior to recruiting patients reveals the safety and efficacy of MRI-guided focal laser ablation. Additionally, the authors recorded pre-treatment (baseline) urinary and sexual function in order to compare with post-treatment function. No significant differences were noted.

TITLE: MR Imaging-guided focal laser ablation for prostate cancer: Phase I trial
Oto A, Sethi I, Karczmar G, McNichols R, Ivancevic M, Stadler W, Watson S, Eggener S. Radiology. 2013 Feb 25. [Epub ahead of print]

Department of Radiology (A.O., I.S., G.K.), Section of Hematology/Oncology, Department of Medicine (W.M.S.), Department of Health Studies (S.W.), and Section of Urology, Department of Surgery (S.E.), University of Chicago, (Chicago IL); Visualase, Houston, Tex (R.M.); and Philips Healthcare, Cleveland

PURPOSE: To evaluate the feasibility and safety of magnetic resonance (MR) imaging–guided laser-based thermotherapy in men with clinically low-risk prostate cancer and a concordant lesion at biopsy and MR imaging.

MATERIALS AND METHODS: This HIPAA-compliant phase I prospective study was approved by the institutional review board. Informed consent was obtained from all patients. Transperineal MR imaging–guided focal laser ablation for clinically low-risk prostate cancer was performed in patients with a Gleason score of 7 or less in three or fewer cores limited to one sextant obtained with transrectal ultrasonography (US)-guided biopsy and a concordant lesion at MR imaging. Lesions were targeted with a laser ablation system. Periprocedural complications were recorded. The International Prostate Symptom Score (IPSS) and the Sexual Health Inventory for Men (SHIM) score were collected before and after the procedure. MR imaging–guided biopsy of the ablation zone was performed 6 months after treatment. The prostate-specific antigen level, IPSS, and SHIM score before and after ablation were compared by using the Wilcoxon signed rank test.

RESULTS: Treatment was successfully completed in nine patients (procedure duration, 2.5–4 hours; mean laser ablation duration, 4.3 minutes). Immediate contrast-enhanced posttreatment MR imaging showed a hypovascular defect in eight patients. Self-resolving perineal abrasion and focal paresthesia of the glans penis each occurred in one patient. The mean (±standard deviation) IPSS and SHIM score at baseline were 5.8 ± 5.3 and 19.0 ± 8.0, respectively. Average score changes were not significantly different from zero during follow-up (P = .18–.99). MR imaging–guided biopsy of the ablation zone showed no cancer in seven patients (78%) and Gleason grade 6 cancer in two (22%).

CONCLUSION: Transperineal MR imaging–guided focal laser ablation appears to be a feasible and safe focal therapy option for clinically low-risk prostate cancer.

2. Identifies the suitability of MRI to guide focal tumor ablation (destruction).

TITLE: MRI-guided interventions for the treatment of prostate cancer.
Bomers JG, Sedelaar JP, Barentsz JO, Fütterer JJ. AJR Am J Roentgenol. 2012 Oct;199(4):714-20.

Department of Radiology, Radboud University Nijmegen Medical Centre.

OBJECTIVE: The purpose of this article is to evaluate MRI-guided therapies and to investigate their feasibility for focal therapy in prostate cancer patients. Relevant articles were retrieved using the PubMed online search engine. CONCLUSION: Currently, MRI-guided laser ablation and MRI-guided focused ultrasound are the most promising options for focal treatment of the prostate in patients with prostate cancer. Other techniques-that is, cryosurgery, microwave ablation, and radiofrequency ablation-are, for several and different reasons, less suitable for MRI-guided focal therapy of the prostate.

3. A general discussion of the use of image guidance and the promise of focal therapy for qualified patients.

TITLE: Image guidance in the focal treatment of prostate cancer.
Hoang AN, Volkin D, Yerram NK, Vourganti S, Nix J, Linehan WM, Wood B, Pinto PA. Curr Opin Urol. 2012 Jul;22(4):328-35.

Urologic Oncology Branch National Cancer Institute, National Institute of Health, Bethesda, Maryland, USA.

PURPOSE OF REVIEW: The advent of prostate-specific antigen screening has led to a seven-fold increase in the incidence of prostate cancer without a resultant decrease in mortality rate. This has led to the belief that urologists are overdetecting and overtreating clinically insignificant disease. To maintain the delicate balance between high cancer cure rate and overtreatment, which could potentially lead to unnecessary morbidities, focal therapy has emerged as the reasonable middle ground. In this article, we present the conceptual basis and the challenges of focal therapy, while emphasizing the critical role of imaging in focal treatment of prostate cancer.

RECENT FINDINGS: Multiple phase I trials have demonstrated the feasibility, short-term efficacy, and safety of focal therapy. Fundamental to the success of these trials and the ultimate acceptance of focal therapy is the integral role of imaging in optimal patient selection. Among the differentimaging modalities, only ultrasound and multiparametric MRI are intimately involved in the detection, diagnosis, staging, and treatment of prostatecancer. Each modality has its own unique advantages and shortcomings. Recent advances in enhanced ultrasound modalities, functional MRIs, and biopsy platforms have taken focal therapy one step closer to becoming the standard of care.

SUMMARY: Although early results of phase I focal therapy trials are encouraging, long-term oncological outcomes remain to be elucidated. Incorporation of these technological advances into large prospective trials is needed to establish focal therapy as an important asset in the urologist’s armamentarium against prostate cancer.

4. One Canadian center’s early experience with MRI-guided focal laser ablation.
TITLE: Real-time magnetic resonance imaging-guided focal laser therapy in patients with low-risk prostate cancer.

Raz O, Haider MA, Davidson SR, Lindner U, Hlasny E, Weersink R, Gertner MR, Kucharczyk W, McCluskey SA, Trachtenberg J. Eur Urol. 2010 Jul;58(1):173-7.

Department of Surgical Oncology (Division of Urology), University Health Network, Princess Margaret Hospital, and the University of Toronto, Toronto, Ontario, Canada.

Two patients with low-risk prostate cancer (PCa) were treated with outpatient in-bore magnetic resonance imaging (MRI)-guided focal laser ablation. The tumor was identified on MRI. A laser fiber was delivered via a catheter inserted through a perineal template and guided to the target with MRI. The tissue temperature was monitored during laser ablation by MRI thermometry. Accumulated thermal damage was calculated in real time. Immediate post-treatment contrast-enhanced MRI confirmed devascularization of the target. No adverse events were noted. MRI-guided focal lasertherapy of low-risk PCa is feasible and may offer a good balance between cancer control and side effects.

5. This presentation abstract reports Dr. Sperling’s results with 59 patients treated by MRI-guided focal laser ablation. Dr. Sperling presented his results at the April 3-7, 2013 annual meeting of the American Society for Laser Medicine and Surgery (Boston MA).

TITLE: Image guided interstitial prostate laser ablation.

R. Bard, D. Sperling, J. Futterer. Presented at the April 3-7, 2013 annual meeting of the American Society for Laser Medicine and Surgery (Boston, MA).

PURPOSE: to follow thermal treatment progress of prostate cancers with 3-D power Doppler sonography (3D-PDS) and 3-T DCE MRI and to compare retrospectively the short term side effects compared with HIFU.

MATERIAL AND METHODS: 59 patients with Gleason grade 3 or 4 focal prostate cancer were prospectively scanned with a GE Voluson E-9 unit employing linear 18 mhz probe with conventional 3d/4d imaging using 3d angio and glass body power Doppler image reconstruction. All patient images were imaged by DCE-MRI with 3.0 T Siemens unit within one week of sonogram. Patients (21) from 1/2/12 to 7/1/12 were treated with 980 wavelength diode laser with endfire heat distribution after local ultrasound guided anesthesia of the neurovascular bundles. Safety thermal zones were outlined to protect rectum, bladder and neurovascular bundles using MRI telethermometry. Five year data from 2005-2010 on 101 patients consecutively followed by HIFU were studied retrospectively for short term and long term effects and compared with the European group.

RESULTS: 3D-PDS and DCE-MRI showed the tumor vascularity absent posttreatment in 21/21 patients. Patients returned to work immediately without catheter. No posttreatment complications were noted at 6 months. 36 HIFU patients had strictures during the first 6 months which were successfully treated. 31 HIFU patients showed recurrent tumors in the treated area between 3-52 months post ablation.

CONCLUSIONS: Vascular imaging combining DCE-MRI and Doppler ultrasound appears useful in preoperative planning, guidance and follow up of laser ablative treatments. While the 6 month follow up showed no short term side effects, the long term disability and recurrence rate are not established. The 6 month HIFU complication rate was 35% and the 5 year recurrence rate in the American cohort group was 30%. The 7 year HIFU recurrence in the European group was 25%.

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