David Gillatt Bristol Urological Institute. David Gillatt Bristol UK

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1 David Gillatt Bristol Urological Institute David Gillatt Bristol UK

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4 Prostate Problems The prostate grows with age - >80% men over 60 have benign enlargement As it grows it can obstruct the flow of urine - >40% over 60 Symptoms poor flow, hesitancy, frequency, up at night Some develop retention acute and chronic

5 Prostate Symptoms Not always caused by the enlarged prostate Bladder instability Nocturnal polyuria body clock! Disease systemic eg diabetes Disease local eg bladder stones. tumours

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8 *Excludes NMSC (non-melanoma skin cancer) Percentages do not add up to 100% due to rounding Source: Cancer Research UK Cancer Incidence in UK Males, (30,142 cases)

9 Cancer Mortality in UK Males (10,614 deaths) Percentages do not add up to 100% due to rounding Source: Cancer Research UK

10 If someone ever invents a method of screening apparently healthy men for prostate cancer, the apparent incidence rates may be expected to rise quite quickly by several hundred percent 1981 Source: Doll R, Peto R. The Causes of Cancer. Oxford: Oxford University Press. 1981

11 PSA Prostate Specific Antigen a simple blood test!!!

12 TURP = Transurethral resection of the prostate Age-standardised TURP rates and crude PSA testing rates Source: Cancer Research UK TURP and PSA testing, Scotland, 81-96

13 Trends in Prostate Cancer Incidence and Mortality in England and Wales, European age-standardised rates Source: ONS (Office for National Statistics) and WCISU (Wales Cancer Intelligence and Surveillance Unit)

14 Age Specific Incidence Rates, 93/03 England and Wales Source: ONS, WCISU

15 Crude Incidence Rates 2002 Source: ONS, WCISU

16 Standardised Registration Ratios English Regions 2002 England Source: ONS

17 Standardised Mortality Ratios in South West PCTs compared to England, Significantly high Significantly low Not significant Source: SWPHO

18 Five Year Relative Survival by Region For people diagnosed and followed up to 31/12/02

19 Incidence / mortality of prostate cancer in 42 PCTs in SW England according to the income domain of IMD Source: SWPHO

20 World Incidence and Mortality, 2002 World Age Standardised Rates Source: Cancer Research UK

21 Can we prevent prostate cancer? Identify risk groups Dietary prevention Chemoprevention

22 Should we shift to a prevention strategy? Role of diet - red meat bad? Lycopenes Selenium Vitamins Green vegetables broccoli, beans Green tea Pomegranate Soy Statins??

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24 REDUCE trial can dutasteride prevent prostate cancer No increased risk of High grade cancer Overall risk cancer reduced by 23% (857 on placebo vs 659 on dutastaeride p=<0.001) Large number treated to prevent death

25 Diagnosing Early Prostate Cancer DA Gillatt

26 Diagnosing Significant Early disease Serum markers - PSA DRE Transrectal Ultrasound

27 The two faces of Janus CaP is the commonest cancer in men in the UK: 27,000 new cases are diagnosed annually The only human cancer that may be curable but may not need to be cured Hardie, Parker et al, BJUI 2005; 95: Cumulative incidence of diagnosis 17% at age 85 yrs Only 2% die from CaP below that age 8.5:1 (US, screened population) Sweden (<10% screened): 6:1 Recent rise in incidence attributable to screening 25% incidence in placebo arm of the PCPT Trial Thompson et al, NEJM 2003; 349: But by no means indolent: >9000 deaths/yr in the UK

28 Natural history & Nomograms Predicting the clinical course is not currently possible 15-yr cancer-specific mortality for a man aged & yrs after conservative treatment: Gleason <7 <10% 12% Gleason 7 72% 40% Gleason >7 90% 55% Albertsen et al JAMA 1998; 280: But Albertsen s data is largely based on TURP histology

29 Screening for Prostate Cancer Incidence and mortality: USA versus England & Wales Oliver et al Lancet

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33 PROSTATE CANCER ADENOCaRCINOMA Multistep progression Normal Grades of Invasive Epithelium Dysplasia Cancer PIN (Prostate Intraepithelial neoplasia) is the most likely precursor of invasive cancer.

34 PREVALENCE The prevalence of prostate cancer is age related. The number of histological (microscopic) disease in a given population seems to exceed that of clinically recognised disease % of men aged over 50 has histological evidence of the disease and by the age of 80, this rises to 60-70%.

35 EXAMINATION Digital Rectal Examination Low sensitivity Only detects tumours in the posterior aspect of the prostate Important 1st line test esp. in detecting palpable tumours that may not be always detectable by PSA or TRUS

36 SERUM PSA Specific to the prostate but NOT to prostate cancer. 97.5% of normal asymptomatic men will have PSA below 4ng/ml. In the UK 25% of men with PSA between 4-10ng/ml, and 65% with PSA >10ng/ml will have prostate cancer.

37 Age Specific PSA ranges In a man of 50 a PSA > 2.5 may be significant > 70 years PSA < 6 may be normal

38 SERUM PSA PSA velocity or change over time is used to monitor disease progression. PSA velocity is significantly greater in men with a clinical diagnosis of prostate cancer

39 What s the fuss? PSA testing is increasing rapidly for the purpose of monitoring as a diagnostic aid Also increasing trend to test asymptomatic men. This will increase the number of men with T1 disease for whom the efficacy of treatment in unknown. Possibility of over-diagnosis of non life threatening disease.

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42 TRUS TRUS is used to Estimate the size of the prostate Diagnose prostate cancer Guide needle biopsies Stage the cancer detected Monitor disease progression prior and after treatment.

43 HOW IT S DONE

44 HISTOLOGICAL GRADE Gleason score 1 - Very well differentiated adenocarcinoma 2 - Well differentiated adenocarcinoma 3 - Moderately differentiated adenocarcinoma 4 - Poorly differentiated adenocarcinoma 5 - Undifferentiated adenocarcinoma

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47 Clinical implementation requires a validated molecular diagnostic technology platform PROGENSA quantitative PCA3 assay Simple, non-invasive urine specimen collected post- DRE Groskopf J et al. Clin Chem 2006;52:

48 Imaging in Uro-Oncology

49 Treating Prostate cancer Early disease Radical Prostatectomy Radiotherapy Brachytherapy Cryotherapy Surveillance

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52 The Da Vinci Robot assisted Prostatectomy

53 Endoscopic Extraperitoneal Radical Prostatectomy (EERPE) Pelvic Lymphadenectomy P O A: External Iliac Artery, V: External IliacVein, M: Psoas Muscle N: Genitofemoral Nerve, O: Obturator Nerve, P: Pubic Arch Jens-Uwe Stolzenburg, University of Leipzig

54 Endoscopic Extraperitoneal Radical Prostatectomy (EERPE) Exposure of the bladder neck, incision of the endopelvic fascia and dissection of the puboprostatic ligaments Ligation of the Santorini plexus Jens-Uwe Stolzenburg, University of Leipzig

55 Nerve- sparing EERPE (neerpe) Anterior Bladder neck dissection Incision of the thin fascia overlaying the anterior-lateral aspect of the prostate. This allows mobilization of the neurovascular bundles before dividing the dorsal Jens-Uwe Stolzenburg, University of Leipzig

56 Nerve- sparing EERPE (neerpe) Dividing the ampullary portions of the vasa deferentia Dissection of the seminal vesicles Jens-Uwe Stolzenburg, University of Leipzig

57 Nerve- sparing EERPE (neerpe) Incision of the posterior Denonvillier s fascia Dissection of the cranial prostatic pedicles (pp) with preservation of the neurovascular bundles (nb) Jens-Uwe Stolzenburg, University of Leipzig

58 Nerve- sparing EERPE (neerpe) Dissection of the caudal prostatic pedicles with preservation of the neurovascular bundles (nb) Preparation of the neuro-vascular bundles close to the apex of the prostate (p) and the urethra (u) Jens-Uwe Stolzenburg, University of Leipzig

59 Nerv- sparing EERPE (neerpe) Apical Dissection (ventral) Apical Dissection (dorsal) Jens-Uwe Stolzenburg, University of Leipzig

60 EERPE - Urethrovesical Anastomosis A: Interrupted sutures The knots are placed extraluminally in the given order) B: Technique of dorsal anastomosis C: Bladder neck reconstruction (in non bladder neck preserving procedure) D: Technique of lateral and ventral anastomosis Jens-Uwe Stolzenburg, University of Leipzig

61 High Intensity Focussed Ultrasound Long term data lacking Tissue characteristics Focal therapy?

62 Present day: Transrectal probe (Sonablate 500)

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65 Modern Cryobiology PROSTATE CRYOTHERAPY 1 st Generation 2 nd Generation 3 rd Generation More even temperature distribution

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67 Advanced Disease Locally Advanced Hormones + radiotherapy Advanced or progressive hormone therapy

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74 Prostate Cancer Is all about risk! Its about knowing the risk the cancer poses and treating accordingly whilst bringing the patient along with you

75 Multi-modality therapy Local therapy Systemic therapy Surgery and/or Radiotherapy Hormone therapy for sensitive cells Chemotherapy for refractory cells

76 Not all pose a threat - some should be monitored PROSTATE CANCER AND RISK