AUC Prostate Cancer Kuching August 2013 Case Scenario 1: Issue of PSA and biopsy strategy, re-biopsy Cyril Natarajan Case Scenario • 62 y/o retired teacher has mild LUTs, a normal DRE but PSA is 5.1 ng/ml – A. He is worried about Pca. How would you counsel him? – B. He agrees to undergo a TRUS/Bx. Describe the procedure – C. Day 1 post-procedure he is admitted with fever & chills. How would you manage him? – D. HPE shows focal HGPIN in 1 core, but no Pca. What is PIN? What will you do next? – E. Next 2 consecutive PSA readings 6/12 apart are 6.2 & 6.4 respectively. What is the PSA velocity? What is the trigger for a rpt biopsy? – F. Rpt biopsy is performed. How would you do it differently from the 1st biopsy? A. He is worried about PCa. How would you counsel him? • Full urological history • • • • • • • LUTS Age Racial origin Family history History of UTI’s Drug history If advanced disease » Bone pain/leg swelling/LOA/LOW/coagulopathy/recent peripheral neurology Examination • General urological examination – Abdominal examination • • • • Ballotable kidneys Other abdominal mases Hernial orifices External genitalia; external meatus • DRE • Size, consistency, rectal mucosa, palpable nodules, tenderness Counseling PSA counseling • What is PSA? • Significance of a raised PSA? TRUS/Biopsy counseling • Information about the procedure • Efficacy of a TRUS/Bx with respect to PCa • What next if the Bx is positive for PCa? • Explanation about complications PSA • 34 kD serine protease (aka human kallikriene 3); coded by a Chr 19 gene • Secreted uniquely by prostatic ductal epithelium • Biological effect is to liquefy semen • 3 forms in serum • Free • Bound to ACT (α-1 antichymotrypsin) • Bound to AMG (α-2 macrogloblulin) • T ½ : 2 – 3/7 Conditions other than PCa with raised PSA Inflammation Infection BPH Iatrogenic • DRE • Instrumentation Ejaculation Daily variation • 20% (same as DRE and ejaculation) Significance of a raised PSA • Age- and race-specific PSA • Osterling et al, JAMA 1993 • Race ranges added by Morgan et al Predicting PCa from a PSA value • No ‘normal’ PSA value • PCa prevalence with PSA < 4ng/ml PSA Risk of PCa (prevalence) Risk of GL > 7 0 – 0.5 6.6% 0.8% 0.6 - 1 10.1% 1.0% 1.1 - 2 17% 2.0% 2.1 - 3 23.9% 4.6% 3.1 - 4 26.9% 6.7% – Thompson et al, NEJM 2004 (PCPT) For PSA > 4ng/ml Sensitivity 20% Specificity 60 – 70% Predicting PCa with PSA ranges PSA % of PCa (patients > 50yrs) 0-4 Not biopsied 4 - 10 26% > 10 53% Catalona et al, J Urol 1994 PSA range (ng/ml) PPV 20 - 29 74% 30 - 39 90% 50 - 99 100% > 20 87% Gerstenbluth et al, J Urol 2002 Counseling for a TRUS/Bx The procedure • Explanation that core biopsies would be taken using a rectal U/S probe with LA Efficacy • 1st, 2nd, 3rd and 4th biopsies relating to Pca positivity of 22%, 10%, 5% and 4% respectively • Djavan et al, J Urol 2001 • Explanation that biopsies may need to be repeated if initially –ve Further action if biopsies are +ve • Active monitoring • Radical treatment Radiotherapy or Surgery Complications •Haematospermia 37.4% •Haematuria > 1/7 14.5% •Rectal bleeding <2/7 2.2% •Prostatitis 1.0% •Fever > 38.5C 0.8% •Epididymitis 0.7% •Rectal bleeding > 2/7 0.7% •Urnary retention 0.2% •Other complications req. hospitalisation 0.3% Post-procedure counseling • To go to a nearest hospital if • High fever +/- chills and rigors – Telephone contact No. given to patient if he needs advice • Severe bleeding – Haematuria – PR bleeding • Increase fluid intake • Avoid constipation He agrees to undergo a TRUS/Bx. Describe the procedure – Need for prostate biopsies • PSA level • Suspicious DRE • Other factors » Biological age » Potential co-morbidities (ASA Index & Charlson Comorbidity Index) » Therapeutic consequences • Risk stratification • Roobol et al, Eur Urol 2010 • 1st elevated PSA should not prompt immediate Bx » Should be verified after a few weeks » Same assay » Standardized conditions ie no non-PCa factors that can elevate PSA • EAU 2013 TRUS/BX preparation Fully informed and consented patient Antibiotic prophylaxis • Routine • ‘Special’ situations eg prosthetic heart valves, valvular heart disease, implants Rectal preparation Patients on anticoagulants • Anti-platelets - Primary or Secondary prophylaxis ? • Other anticoagulants eg warfarin Antibiotic prophylaxis • Wide variety of regimes • Oral or i/v antibiotics state-of-the-art • Types – Quinolones drug of choice • Ciprofloxacin superior to ofloxacin » (EAU 2013) (LE 1B) • Increased drug resistance to quinolones in recent yrs with rise of severe infections post Bx • bacteremia/sepsis can still occur in 0.1% to 0.5% » (Djavan et al, 2001b ; Raaijmakers et al, 2002) • patients at higher risk of developing endocarditis or infection of prosthetic implants, » iv ampicillin (vancomycin, if penicillin allergic) and gentamicin • This patient: – Oral Ciprofloxacin 500mg bd 2/7 prior and 3/7 post-Bx Anticoagulant therapy • Primary prophylaxis – Stop Drug Days of stoppage Low-dose Asprin 5 Clopidogrel 7 Ticlodipine 14 • Warfarin • If high risk of thrombo-emoblic events – ‘bridging’ therapy with heparin • Stopped in all other patients • Secondary prophylaxis – Continue anti-platelets – Stop 2nd anti-platelet and continue ASA • Prospective studies on TRUS/Bx with continued low-dose ASA – – – Maan Z et al, BJUI 2003 Rodriguez et al, J Urol 1998 Herget et al, Can Assoc Radiol J, 1999 Bowel preparation and positioning • Bowels – Bowel cleansing @ home with simple enema or PEG 1-3 days prior to Bx’s – Bisacodyl suppositories on the the night before Bx’s • Positioning • *Left lateral • Buttocks as close to edge of couch as possible • Knee-elbow • Lithotomy TRUS/Bx procedure • Equipment – 7.5MHz trans-rectal bi-directional probe • Multi-planar views – Spring-driven 18G needle core biopsy gun – 22G 7-inch long spinal needle with 10cc syringe – Lignocaine 2%, 5cc bilaterally • peri-prostatic • TRUS guidance along the biopsy channel of the transducer • area between the seminal vesicles and apex of the prostate Systematic scan • DRE – Rule out rectal pathology – Identification of palpable abnormalities • • • • • • Measure gland volume Scan in both planes , base to apex and side to side Record images Echotexture,nodules calcification,symmetry Evaluate the capsule, SV and ED CDI TRUS – visibility of prostate cancer PSA LEVEL 0–4 4 – 10 10 – 20 > 20 % with Trus lesion 15 30 40 75 TRUS – hypoechoic lesions • • • • • • Prostate cancer BPH Ductal ectasia Infarct Prostatitis PIN Prostate biopsy – local anaesthesia Prostate biopsy painful in up to 96% patients severe pain 20% related to age and number of cores 1. Rectal lignocaine Chang J Urol 2001 2. Periprostatic lignocaine pain reduction Nash et al J Urol 1996 Leibovici et al J Urol 2002 Patel et al BJU Int 2001 Pareek G et al, J Urol 2001 Anatomy Transrectal biopsy - technique • • • • Guide visible on USS display Sagittal plane Choose site of biopsy and keep probe still Insert needle through rectal wall until capsule indents • Fire gun and remove needle immediately • Repeat. • Minimum time in rectal wall, try not to biopsy outside the gland Increased cancer detection by directing more biopsies into the lateral PZ • Laterally directed sextant – reduce false negative rate by 50% • Sextant + 2 lat PZ - increased cancer detection 35% [ Eskew J Urol 1997] 14% [ Chang J Urol 1998] • Sextant + 3 lat PZ – increased cancer detection 22% [ Beurton Br J Urol 1997] Sites of Standard and Peripheral Biopsy Peyromaurie et al J Urol 2002 Biopsy strategies No. 6 8 Adv. Disadv Ref. established 30 – 50 % missed Hodge et al 1989 improves diagnosis Presti et al 2000 from 85 – 97% 10 improves diagnosis mainly lateral biopsies Ravery et al 1999 may be no better than 8 12 improves diagnosis more bleeding Brossner et al 2000 compared to 6 but ?8 >12 unproven more complications Babiaan et al 2000 BIOPSY (EUA Guidelines 2013) • On baseline biopsies, the sample sites should be as far posterior and lateral in the peripheral gland as possible • Additional cores should be obtained from suspected areas by DRE/TRUS • DRE-guided Bx’s • Sextant biopsy is no longer considered adequate • Gland volume 30 – 40 mls • At least 8 cores • The British Prostate Testing for Cancer and Treatment Study has recommended 10-core biopsies • Donovan et al, ProtecT Study group, Health Technol Assess 2003 • > 12 cores not significantly more conclusive Targeted biopsy techniques MRI and MR spectroscopy • Reduced citrate and elevated choline levels in cancer. Scheidler et al Radiology 1999 213 47-480 • Improved cancer localisation • Hricak, Radiology 1999 • T2 weighted MRI • Kaji, Radiology 1998 • Accuracy increased 52 – 74% • Specificity increased 26-65% • ? Use in patients with negative biopsy or HGPIN Handling of TRUS/Bx specimens • Storage – Bx’s from different sites in separate vials – Processed in separate cassestes – 18G needle used to lift cores in 10% buffered formalin Day 1 post-procedure he is admitted with fever & chills. How would you manage him? Unstable patient with urosepsis/severe sepsis/septic shock/SIRS • Immediate resuscitation (ABC) • ICU • I/V fluids Hartmans, Colloids • Inotropes, eg Noradrenaline • Antibiotics: Empirical eg Carbapenams, Broad spectrum Cephalosporins, +/aminoglycosides • Full septic work-up • CBD Stable patient • • • • • Admit Change oral antibiotics to I/V B/spectrum Cephalosporins/ Carbapenams Full septic work-up CBD Close monitoring HPE shows focal HGPIN in 1 core, but no Pca. What is PIN? What will you do next? • PIN – Prostate Intraepithelial Neoplasia – Precursor of invasive carcinoma • Precedes cancer by 10 years, • 70% will have PCa by 80 years – Does not secrete PSA HPE shows focal HGPIN in 1 core, but no Pca. What is PIN? What will you do next? • In this patient no indication for re-Bx as only 1 core involved • EAU 2013 (Moore CK et al, J Urol 2005) LE: 2A • only a slightly increased Pca risk (23% to 24%) compared to an initial benign Bx (20%) • F/U needed with serial DRE and PSA • Indications for re-Bx • • • • Suspicious DRE Rising and/or persistently high PSA ASAP Extensive (Multiple Bx sites) HGPIN Next 2 consecutive PSA readings 6/12 apart are 6.2 & 6.4 respectively. What is the PSA velocity? What is the trigger for a rpt biopsy? • PSA velocity – The rise in PSA per year in ng/ml/yr – > 0.75ng/ml/yr assoc. with an increased PCa risk (Carter HB et al, JAMA 1992) – > 0.6 ng/ml/yr (Sun et al, BJUI 2007) – PSAV = 0.5 x (PSA2 – PSA1/T1 + PSA3 – PSA2/T2) • T = Time in yrs • PSAV in this patient – = 0.5 x (6.2 – 5.1/0.5 + 6.4 – 6.2/0.5) – = 1.3 ng/ml/yr • Trigger for rpt Bx: – > 0.75 ng/ml/yr – Abnormal DRE Rpt biopsy is performed. How would you do it differently from the 1st biopsy? • 2nd TRUS/Bx – – – – Transistion zone Bx’s End-firing probe for TZ Bx’s Take 10 to 12 cores if initial cores were not adequate Anterior zone biopsies (transperineal) • Other possible options for re-TRUS/Bx – Saturation Bx’s – – – – 20 cores PCa detection 30 – 43% (depends on no. of previous Bx cores) Can be done transperineally (additional 38% PCa detected 10% AUR Thank You