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Prostate cancer what do we see and how do we see it? Caroline Moore MD FRCS(Urol) Consultant Urologist, University College Hospital Senior Clinical Researcher, Division of Surgical & Interventional Science, UCL 1 Overview The


  1. Prostate cancer – what do we see and how do we see it? Caroline Moore MD FRCS(Urol) Consultant Urologist, University College Hospital Senior Clinical Researcher, Division of Surgical & Interventional Science, UCL 1

  2. Overview The prostate • Assessing the prostate for cancer • Digital rectal examination • Prostate specific antigen • Sampling the prostate • Imaging the prostate • Image guided sampling • Image guided management of the prostate • Active surveillance • Focal therapy • 2

  3. 3 The prostate

  4. The prostate

  5. Assessing the prostate: Digital rectal examination 5

  6. 6 Digital rectal examination

  7. 7 Clinical staging of prostate cancer

  8. 8 Prostate cancer in the UK

  9. Prostate cancer in the UK � 6% of men in the UK have a PSA test 1 � 10% of these are raised & prompt a referral for further investigation 2 � 60-90 000 prostate biopsies done in the UK each year 2 � Around 25% of these are positive for cancer 3 � 34 000 men diagnosed with prostate cancer each year 1 Williams N, Hughes LJ, Turner EL, Donovan JL, Hamdy FC, Neal DE, et al. Prostate-specific antigen testing rates remain low in UK general practice: a cross-sectional study in six English cities. BJU Int 2011;108;1402–8. 2 Prostate cancer: diagnosis and treatment. An assessment of need. A report to the National Collaborating Centre for Cancer. T. Cross, S. McPhail. South West Public Health Observatory 3 Roddam AW, Duffy MJ, Hamdy FC, Ward AM, Patnick J, Price CP, et al. Use of prostate specific antigen (PSA) isoforms for the detection of prostate cancer in men with a PSA level of 2–10 ng/ml: systematic review and meta-analysis. Eur Urol 398;48:386–99.

  10. Men with a diagnosis of prostate cancer � Disease contained within the prostate (localised) in 86% 2 � 45% diagnosed with localised prostate cancer are <70 yrs 3 � 14 000 men in the UK could opt for radical treatments each year 4 � Many of these choose active surveillance 1 Cancer statistics registration. Registration of cancer diagnosis in 2006, England. [document on the Internet]. London: Office for National Statistics; 2008 [accessed March 2009]. http://www.statistics.gov.uk/downloads/theme_health/MB1-37/MB1_37_2006.pdf. 2 Albertsen PC, Nease RF, Jr., Potosky AL. Assessment of patient preferences among men with prostate cancer. J Urol 1998;159:158-63. 3 Wei JT, Dunn RL, Sandler HM, McLaughlin PW, Montie JE, Litwin MS, et al. Comprehensive comparison of health-related quality of life after contemporary therapies for localized prostate cancer. J Clin Oncol 2002;20:557-6 4 Systematic review and economic modelling of the relative clinical benefit and cost-effectiveness of laparoscopic surgery and robotic surgery for removal of the prostate in men with localised prostate cancer. Health Technol Assess 16:41, 1-313. Nov 2012

  11. Risk stratification – NICE Risk stratification criteria for men with localised prostate cancer PSA Gleason Clinical (ng/ml) score stage ≤ 6 T1 − T2a Low risk < 10 and and 10 − 20 T2b − T2c Intermediate or 7 or risk 8 − 10 T3 − T4 High risk > 20 or or

  12. Stage migration in UK McVey et al Initial management of low-risk localized prostate cancer in the UK: analysis of the British Association of Urological Surgeons Cancer Registry BJUI 2010: 106, 1161-1164 | doi:10.1111/j.1464-410X.2010.09288.x

  13. NICE guidance (CG 58): Localised prostate cancer: treatment options

  14. Assessing the prostate: Prostate specific antigen 15

  15. Prostate specific antigen (PSA) � Protein measured in the blood � Raised in men with � A large prostate � Prostate cancer � Urinary tract infection � Can measure over 1000 ng/dl in men with metastatic prostate cancer � In the low ranges (below 15) it is more likely to be due to a large prostate than prostate cancer � PSA can fluctuate so repeat readings are needed in monitoring cancer 16

  16. 17 Assessing the prostate: Sampling the prostate

  17. 18 Prostate biopsy

  18. Gleason score � Pathological grading system for samples seen under the microscope � Dr Jameson to discuss further 19

  19. How representative is a core? 15 x 1 x 1mm vs 50 x 40 x 50 mm 1 core =.018 /65cc = 0.02% of prostate volume With thanks to Dr Pedro Olivier, Lisbon

  20. Transperineal Template Guided Prostate Biopsies Barzell and Melamed, 2007

  21. NICE Guidance on template guided biopsy (IPG 364) For men with negative results from other biopsy methods (normal governance arrangements) For active surveillance or focal therapy (special arrangements for clinical governance, consent & research) NICE encourages research into template mapping biopsy, particularly the comparison with radical prostatectomy

  22. 24 Assessing the prostate: MR imaging

  23. MRI for anatomical imaging T2 weighted PZ T2 weighted TZ

  24. Addition of 1 functional sequence Dynamic contrast enhancement Tumour vol. 0.2cc 0.5cc Sensitivity 77% 90% Specificity 91% 88% PPV 86% 77% NPV 85% 95% Quantitative DCE Villers et al., 2006; J Urol. 176(6 Pt 1): 2432 ‐ 7

  25. Tumour vol 0.2cc 0.5cc Sensitivity 77% 90% Specificity 91% 88% PPV 86% 77% NPV 85% 95% Villers et al. J Urol December 2006

  26. Diffusion weighted imaging Diffusion weighted • Random movement of water in interstitial space • Cancer restricts movement due to high cell densities and abundance of cell membranes (high signal) • Compare apparent diffusion Apparent diffusion co-efficient coefficients of different acquistion sequences (b values) (low signal) • Short acquisition times • High contrast resolution

  27. 29 Assessing the prostate: Targeted sampling

  28. Assessing the prostate: using MRI to decide who to biopsy and where to biopsy 30

  29. Research Question In men with a clinical suspicion of prostate cancer, does an MRI guided biopsy strategy result in equivalent detection of clinically significant cancer and a lower detection rate of clinically insignificant cancer compared to standard transrectal ultrasound guided biopsies?

  30. 4222 records identified (EMBASE 2106, Pubmed 2052, DARE 4, Cochrane Trials 57, Cochrane Economic evaluations 3) 908 Duplicate records 3314 unique records 3093 not relevant to research question 222 records for full review 70 review articles 60 technical reports 14 relevant abstracts without full reports 10 reports of targeted cores only 18 reports combining standard plus targeted cores 50 reports comparing targeted versus standard cores (16 discrete studies: 3 case reports, 2 RCTs, 1 historical case control)

  31. Identifier Patient population MRI Biopsy Standard cores Targeted cores Mean no. of Navigational Sequence used taken blind to per lesion Total cores Reference No. MRI lesions (range; ER coil system for Analgesia to define target location of (mean per taken max allowed) biopsy lesions patient) 1.5T Phillips Haffner, 2010 555 Gyroscan 1.9 (NR; NR) T2/DCE No US (cognitive) LA No 2 (3.8) NR Intera 3T Phillips T2/DCE/ 10-12 standard + Park, 2011 85 CG1 NR No US (cognitive) NR No 0-3 per patient Achieva DWI up to 3 targeted 3T Phillips US (EM Mean 2.2 (range Sciarra, 2010 101 2.6 (1-7; any) Any 3 positive Yes GA Yes 17.8 (mean) Achieva tracking device) 1-8) (5.8) 1.5T Phillips Labanaris, Spinal 85 Interna 1.15 (1-2; NR) T2 No US (software) No 1-2 (2.3) Total 12 cores 2010 anaesthesia Pulsa ER coil Median 1 (1-3; 2 (median 4, Prando, 2005 71 3T TrioTim T2,DWI, DCE or MRI NR No Targeted only 3) range 2-7) pelvic coil Mean 12.7 in 1.5T group B (range Lee, 2011 180 CG2 Siemens NR DCE or MRS Yes US (cognitive) LA No NR (2.17) 10-16), 10 in Avanto group A Hambrock, 1.5T Signa 42 NR MRS Yes US (software) LA No 2-3 (NR) NR 2010 GE 3.0T Phillips US (MRI images NR (median 9, Singh, 2008 87 Intera NR T2/DWI No also displayed GA No Up to 26 up to 14) Acheiva on US screen) 1.0T Miyagawa, Group A 21; 260 CG3 Siemens 3 All Yes US (cognitive) LA NR 3 (NR) 2010 group B 18 Harmony Max 10 cores: 2 Hadaschik, 3T Phillips NR (NR; max 2 2 per abnormal for tissue bank , 13 T2/DCE Yes MRI Sedation No 2011 Intera sextants) sextant (4) 8 cores for analysis 3T Rastinehad, US (BiopSee 106 Magnetom UK T2 No GA No 2-6 (2-6) Mean 23.2 2010 software) Trio 3T Siemens US (Artemis Natarajan, 47 TrioTim/So 1.4 (NR; NR) NR No software with LA Yes NR NR 2011 matom 3T tracking device) 3T Philiips At least 2 (at Park, 2008 43 Intera 1 (1; 1) DWI No US (cognitive) NR No NR least 2) Achieva

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