Prostate Biopsy in 2017

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Prostate Biopsy in 2017 Bob Djavan, MD, PhD Professor and Chairman, Department of Urology, Rudolfinerhaus Foundation Hospital,Vienna, Austria Director Vienna Urology foundation Board member Scientific Committee of the EAU and executive Board ESOU

Prostate Cancer 2017 Over 1 million TRUS biopsies! Most unnecessary PSA Screening: 20% reduction mortality Most men do not benefit from aggressive treatment Identify the high risk (treat) & avoid detection of low grade Push MR Imaging EAU and AUA

Optimal prostate biopsy 2017 Adequate Detection of clinically significant prostate cancers (sensitivity) and if Index Cancers Accuracy of negative sampling (negative predictive value) Limited Detection of clinically insignificant cancers and, Good Concordance with whole gland surgical pathology results to allow accurate risk stratification and Aiding 3D Disease localization for (focal) treatment selection Djavan & Rocco, BMJ, 344:8201, 2011

FDA currently approved biomarkers for screening PSA PCA3 p2psa PHI score (Derived from a combination of tpsa, fpsa, p2psa) Khauli 2015

1. More is better!

2. Go Lateral!

De La Taille Study 303 men with different indications for biopsy 6 cores 22,7% + 6 lateral cores 28.3% + 6 TZ cores 30.7% + 3 mid-line cores 31.3% +12% De la Taille et al. Urology, 61: 1181-86, 2003

Jones Study Saturation Technique (24 cores) Does Not Improve Cancer Detection as an Initial Prostate Biopsy Strategy Men with PSA 2.5 to 9.9 ng/dl: cancer in 53 of 122 (43.4%) saturation biopsies and 26 of 58 (44.8%) 10-core biopsies Jones et al., J Urol,February 2006

and!... Chan et al, J Urol, 2181-84, 2001

PCA DETECTED ON FIRST BIOPSY ventral dorsal DJAVAN, J.UROL.66:1679, 2001 SCHLEMMER, CA IMAG, 2011

DETECTED ON REPEAT BIOPSY

WHERE DOES TRUS BIOPSY STAND IN 2017?

TRANSRECTAL 16 SECTOR BIOPSY

TEMPLATE TRANSPERINEAL BIOPSY Mabjeesh et al, BJU Int, 2012 Hu Y et al, BJU Int, 2012 1. Standard 12 cores 10mm RLE 2. Standard 12 cores 15mm RLE 3. 14 (12 PZ + 2TZ) cores 5mm RLE 4. 18 (12 PZ + 6 Ant) cores 10mmRLE 14

Accuracy of TRUS biopsy for PCa >/=0.5cc Lecornet et al. BAUS ONC 2010 Mabjeesh et al., BJU Int, 2012 16

bibliographic search using PubMed covering the period up to July 2012 yielded approximately 550 articles! - 10/12 core schemes better than traditional sextant - If cores > 12, then the increase in diagnostic yield is only marginal - Only limited evidence supports the use of more than 12 cores or saturation on initial Bx - Apical and laterally directed sampling increases cancer detection rate

1986-2010 Find ANY Cancer!

2010-2016 Find SIGNIFICANT Cancer

2017? Find SIGNIFICANT Cancer & Provide a cancer Grade Map

Finding HG Cancer is not enough!

How reliable are Standard TRUS prostate biopsies?

How reliable are prostate biopsies? Changes in prostate cancer grade on serial biopsy in men with Low Risk PCa Porten SP et al., J Clin Oncol 2011

How reliable are prostate biopsies? Changes in prostate cancer volume on serial biopsy in men undergoing active surveillance Volume increase in 25% Porten SP et al., J Urol 2011

Conventional TRUS Biopsy unable to predict unilateral disease! Tareen, et al, BJU Int, 2009

What is the Core Problem? n=3453 Bx The Operator was a significant multivariate Predictor of Biopsy outcome OR 0.67 to 0.89, p=0.003

Multiparametric MRI mpmri: T2 + at least two functional (DWI / DCE / MRSI) Barentsz JO, Richenberg J, Clements R, Choyke P, Verma S, Villeirs G, et al. ESUR prostate MR guidelines 2012. Eur Radiol 2012; 22(4):746 757

PIRADS 5 Lesion

Role of mpmri in Diagnosis Meta-analysis 0.82 0.82 14 studies 1785 patients Pooled overall sensitivity : 0.78 specificity : 0.79 No previous bx (690 pts ) : 0.71 : 0.77 With previous bx (617 pts) : 0.80 : 0.78 Hamoen EHJ et al. Eur Urol 2015, 69: 1112-1121

Fusion biopsy MR-US fusion allows the information from MRI to be used to direct biopsy needles under TRUS guidance 2 Types: - Cognitive Fusion - Device Fusion Sonn GA, Margolis DJ, Marks LS. Target detection: Magnetic resonance imaging-ultrasound fusion-guided prostate biopsy. Urol Oncol 2013;13:1 9. CM, Kasivisvanathan V, Eggener S, et al. Standards of reporting for MRI-targeted biopsy studies (START) of the prostate: Recommendations from an international working group. Eur Urol 2013; 64:544 52.

Number of devices No. of devices Devices Koelis Trinity 1 Console including US Ascendus 2 Console including US device + magnetic tracker BiopSee 2 Console including US + holding arm including stepper and grid Biojet 3 Console + US device + holding arm including stepper and grid Artemis 2 Console including semi-robotic arm, stepper and grid + US device IS robot (Biobot) 3 Console + US device + robotic unit 31

Siddiqui et al. Eur Urol 2013 582 pts - With lesion MRI (3T ERC) (T2,DWI,DCE,MRSI) - SBx and FBx (Philips software with electromagnetic tracking) - Overall CDR similar for both, but fusion detected more clinically significant PCa using fewer cores. - Targeted biopsy detected 67% more Gleason 4+3 than SBx alone MRI/US Fusion preferentially detects higher grade PCa while missing lower grade tumors

BUT Does mp MRI solves the problem?

How Negative is a Negative mpmri? Retrospective study of 101 RPE spec. with mpmri 68% T1c, mpsa 7.5ng/mL 11% had pt3a & 6%pT3b 2% had pn1 13% had primary GG 4 50% had secondary GG 4 or 5 BUT with Expert Reading: No pt3, less primary GG 4 C: Negative mpmri does NOT exclude significant PCa Need quality assurance Branger, Eur Urol, 2016, A 501

How Negative is a Negative mpmri? Prostate Health Index (PHI) Repeat BX setting, N=168 If mp MRI neg: 47% had cancer and 34% were GS >7 At cut off >35, PHI predicted 86% of cancers if mpmri was negative Sens 86%, Spec 48% and NPV 80% For GS>7: Sens 100%, Spec 48%, NPV 100% Gnanapragasam, Eur Urol, 2016, A384

Where do we still need TRUS Bx? 41 men with unilateral positive biopsy Specimen and MRI blindly rereviewed and mapped for cancer location NPV for uninvolved lobe: TRUS 46.7% MRI 71.4% Both 100 %

Do we need additional SysPBx with Fusion PBx? CDR was 40% for Fus-PBX (75% GS >7) CDR 32% for Sys-PBX (69% GS>7) 15% of GS>7 detected by Sys PBx ALONE! In MVA, max PI-RADs is the strongest predictor of GS>7 in Com-PBx!! To detect High risk PCA, combine Fus-PBX with Sys- PBx Borkowetz et al., Eur Urol, 2016, A503

Do we need additional SysPBx with Fusion PBx? Both Techniques miss apical lesions MR-Bx most often missed cancers in the dorsolateral part (58%) TRUS-Bx missed cancer in the anterior part (79%) We still need both targeted and systemic TRUS Bx Schoutten et al., Eur Urol, 2016

AUA Consensus mp MRI and Biopsy 2017 use mp MRI in combination with sys TRUS biopsy Presentation Title 39

How to get the best out of TRUS biopsy? use 18 G needle with a minimum 17 mm core length improve grey scale TRUS capabilities adequate sampling (16 sector biopsy) correlate number of cores to volume target pararectal, anterior and apical zones separately

Why we still need TRUS Bx mp MRI will increase cancer detection of HG prostete cancer mpmri: Less Biopsies Overall mp MRI Bx Misses GS 6 Prostate cancer Need to combine TRUS + mpmri

Summary Our notion of low risk is going to change The pathway will become dominated by imaging Location and focality (cancer mapping) will become essential

The Rudolfinerhaus Foundation Hospital First orpe by Theodor Billroth In 1867