BETH ISRAEL DEACONESS MEDICAL CENTER Prostate MR Neil M. Rofsky, MD Harvard Medical School Current Clinical Practice DIGITAL RECTAL EXAMINATION PSA ( ~ 20% False negative) BIOPSY (18-25% False negative) Each specimen = 1/10,000 of the gland volume Gleason grading (tumor severity ) has variability 2 largest areas of cancer tissue Imaging to Address Clinical Challenges Need reliable staging Treatment Options Gland confined vs. extraglandular (T2 vs. T3) Rising PSA Repeat Negative Biospy S/P Tx Most men will have it, relatively few will die from it How can we identify the bad actors? How do we monitor watchful waiting/active surveillance? MR Imaging Evaluations T2WI Straight forward False + s + DCE s detection Requires software Diffusion Improve detection and specificity MR Spectroscopy Difficult to perform MRI Anatomic Review Seminal Vesicles Transverse/axial sagittal coronal Base Midprostate Apex Peripheral Zone Central Gland ( CZ & TZs) Seminal Vesicles Anterior Fibromuscular Stroma 1
Axial View Dynamic Contrast Enhanced MRI (DCE-MRI) Contrast kinetics (Gd( Gd-DTPA) Surrogate of vascular microenvironment Related to angiogenesis MRI trade-offs: Spatial resolution α 1 temporal resolution ~70% of cancers occur in the peripheral zone Contrast Administration The 3 Time Point- 3TP algorithm wash-out pattern: color hue (3) wash-in rate: color intensity (256) 7 continuous 1:35 measurements - no time gap Measurement 1 2 3 4 5 6 7 Time 0 1:35 3:10 4:45 6:20 7:55 9:30 11:05 PRE POST CM intensity Initial rate ±10% CONTRAST MEDIA: 20mL of Gd @ 4ml/sec t 0 Wash-in t 1 Wash-out t 2 time A model based A model calibration based map calibration relates map color relates hue/intensity color in hue/intensity in each h pixel each to pixel to 1. 1. microvascular microvascular permeability permeability (K) and 2. (K)( ) and extracellular volume fraction (v1). 2. extracellular volume fraction (v1).( Degani et al. Nature Medicine 1997 DCE- Interpretation DCE MRI pre DCE MRI EARLY post Rad-Path Correlation DCE MRI LATE post contrast DCE MRI 3TP-MAP T2c T2c T2a 2
HR T2-W MRI % Staging Accuracy in 32 Patients w/ path correlation: Comparison of T2W, DCE and Combined Data Sets 3T endo-rectal MRI of the Prostate 700µ x 500µ x 1.5 mm Note. All data are percentages. For AUC, numbers in ( )s are 95% CIs. Improvement vs. T2W MR images for reader 2 (P =.042). 3TP 3TP Bloch, et al Radiology. 2007 Oct; 245:176-85. Bloch, et al., Acad Radiol 2004 Higher Resolution for Finer Details MRI Impacting Clinical Practice -Smaller tumors -Better visualization of relevant anatomy Identify a target for bx PSA, no dx PSA, s/p tx Assist in watchful waiting 61 y.o.. man, a husband & father Rising PSA 3 neg bx rounds (~60 neg cores!) Virtual 18 core bx (one slice!!) US images rarely reveal a successful target 3
Efficacy Study: MR prompted bx procedure 76 y.o; ; PSA = 31, 3 prior neg bx rounds 2.5 x 1.6 cm 1) Systematic Bx 2) Bx targeted to unique MR findings MR RESULTS: +; anterior BX RESULTS (2 weeks after MR) Cores: 12 Systematic: all NEG 1/6 MR prompted POS (Gleason 3+4) 18 total CONCORDANCE: + Anterior Value of MR to prompt or guide bx Increased +bx+ yield In patients with prior neg bx Compared to saturation bx Success with a variety of MR approaches Relevant cancers detected 77% with Gleason 4 component Most found anterior and apical Less commonly sampled More difficult areas Correlation of Gleason Score and Tumor Size with High Resolution 3T Magnetic Resonance Image-Detected Prostate ncer Elizabeth M Genega 2, B. Nicolas Bloch 1, Robin Elliott 2, William Dewolf 3, Yineng Fu 2, Martin Sanda 3, John Tomaszewski 4, Andrew Wagner 3, Neil M. Rofsky 1, 1 Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston. 2 Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston. 3 Department of Urology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston. 4 Department of Pathology, University of Pennsylvania Harvard Medical School Purpose To compare prostate cancer detected and missed by MRI with whole mount prepared radical prostatectomy specimens. To assess the histological features associated with each group. ncerous histology indicated by black 4
Results of Detailed MRI/Path Correlation: MR- MRI/Path Correlation: 1of 2 tumors detected (both GS 3+4) Most MR negative PCA foci are: GS 6 (87%) 7mm (97%) Sparse Tumors: : Few tumor glands infiltrating between benign glands Undetected 3.5mm Histo D Detected 8mm Histo B ncer indicated by black Subtraction Early late T2 weighted image 56yo w/ PSA (prior to MRI = 27.7) 3 prior NEG bx session; 63 cores prior to MRI 3 months between 3 rd bx and MRI Rad-Path: Conclusions T2-W DCEMRI color map Gleason 4+3 41mm Histo A High resolution T2W and DCE 3T ecmr may be useful for guiding patient management, including: a) Pre-biopsy detection / guidance of unusually located tumors b) Facilitates F/u i) Locally treated cancers (esp. when the tumor is >7mm) ii) Active surveillance Active Surveillance Low grade, low volume tumor No tx,, No adverse effects Survival rates no different reful f/u is essential!! Intent to treat if aggressive features emerge se 1 49 yo African American Man No urinary symptoms; sexually active, single PSA 4.5, Normal prostate exam Biopsy Gleason 6 in less than 20-30% of 2 cores (12 total biopsy cores) 5
NL se 2 Sagittal Image 54 yo man with no family history of P; otherwise fit No urinary symptoms; no erectile dysfunction PSA 3.5, Normal prostate exam Biopsy Gleason 6 in 10% of 1 core (12 total biopsy cores) MRI: 6/08 Pt with progression on active surveillance T2WI Diffusion MAP F/u Bx: : 4/09; Stable PSA Bx: Left mid medial: Few cancer cells Management: maintain active surveillance ADC = 628 mm 2 /s. From: Van As, et al. European Urol Epub 2008 Active Surveillance: Conclusions Active surveillance is an option in well defined patient populations Best done with a rigorous process Vigilant follow-up is essential Imaging can offer additional information for decisions & will likely increase in its role for active surveillance monitoring Acknowledgements Nicholas Bloch, MD Radiology Glenn Bubley,, MD Oncology Hadassa Degani,, PhD Weitzman William DeWolf,, MD Urology Bob Eyre, MD Urology Mark Garnick,, MD Oncology Sandra Gaston, PhD Surgery Elizabeth Genega,, MD Pathology Irving Kaplan, MD Radiation Oncology Herbert Kressel,, MD Radiology Robert Lenkinski,, PhD Radiology Robert Marquis, BS, RT Radiology Ivan Pedrosa,, MD Radiology Martin Sanda,, MD Urology Drew Wagner, MD Urology NIH R01 CA116465 6