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Prostate Cancer

Prostate Cancer. Julian Mander RPH Urology. Histological Incidence at Autopsy. Histological cancer in autopsy studies 27% Third decade

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Prostate Cancer

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  1. Prostate Cancer Julian Mander RPH Urology

  2. Histological Incidence at Autopsy Histological cancer in autopsy studies 27% Third decade 20% Fourth decade 32% Fifth decade 55% Sixth decade 64% Seventh decade Sakr et al: In Vivo 8:439,1994

  3. Histological Incidence at Autopsy Incidental Prostate Cancer Found at Autopsy (Detroit, MI) W.A. Sakr, et al. Eur.Urol. 30: 138, 1996. Removed the prostate glands from 525 consecutive male trauma victims dying in Detroit during the early 1990s.

  4. Causes of Death in Australia 2011 2.1 LEADING CAUSES OF DEATH , Australia - Selected years - 2002, 2006, 2011 Cause of death 2002 No. Rank 2006 No. Rank 2011 No. Rank Ischaemic heart diseases 26 063 1 23 132 1 21 513 1 Cerebrovascular diseases 12 533 2 11 479 2 11 251 2 Dementia and Alzheimer disease 4 364 6 6 550 4 9 864 3 Trachea, bronchus and lung cancer 7 303 3 7 353 3 8 114 4 Chronic lower respiratory diseases 6 256 4 5 463 5 6 570 5 Diabetes 3 329 9 3 669 8 4 209 6 Colon, sigmoid, rectum and anus cancer 4 649 5 3 857 6 4 087 7 Blood and lymph cancer (including leukaemia) 3 791 7 3 700 7 3 978 8 Heart failure 3 367 8 2 902 11 3 488 9 Diseases of the urinary system 2 887 11 3 197 9 3 386 10 Prostate cancer 2 852 12 2 951 10 3 294 11 Breast cancer 2 716 13 2 643 13 2 937 12 Influenza and pneumonia 3 084 10 2 711 12 2 492 13 Pancreatic cancer 1 834 15 2 077 15 2 416 14 Intentional self-harm 2 320 14 2 118 14 2 272 15 Skin cancers 1 462 17 1 648 17 2 087 16 Accidental falls 629 38 1 288 20 1 845 17 Hypertensive diseases 1 353 20 1 500 18 1 802 18 Cardiac arrhythmias 1 226 21 1 280 21 1 612 19 Cirrhosis and other diseases of liver 1 354 19 1 416 19 1 589 20 Prostate cancer deaths per 100,000 male population 35.5 ~29 29.7 Australian Bureau of Statistics 2013 http://www.abs.gov.au/ausstats/abs@.nsf/Lookup/3303.0Chapter42011

  5. Australian Mortality Data 1985 - 2002 Australian Bureau of Statistics Yearbook Australia 1301.0 - 2005 Health - Article - Cancer Trends

  6. Prostate Cancer & Death in Australia • 2011 Australia 3,294 deaths from prostate cancer 4,959 male deaths from lung cancer 62% of prostate cancer deaths >75 years 41% ‘’ ‘’ ‘’ >80 years Australian Cancer Incidence and Mortality Books (ACIM) http://www.aihw.gov.au/cancer/data/acim_books/index.cfm • ~3% Male deaths are from prostate cancer

  7. Prostate Cancer Deaths in Australia 2011 • Australian figures 2011 Prostate cancer deaths: 3,294 Deaths (Male) from MVA: 921 Australian Govt Dept Transport and Infrastructure http://statistics.infrastructure.gov.au/atsb/login.do?guest=guest&tableId=user/atsbguest/Road%20Deaths%20by%20State%20and%20Territory.txd Suicide (Male) deaths: 1,726 ABS Yearbook 2013 http://www.abs.gov.au/ausstats/abs@.nsf/Lookup/F25E446E1BE6C931CA257B2E000D729C?opendocument • Western Australian Figures 2011 Mortality to incidence ratios (M/I): Males Females Prostate cancer 0.12 Breast cancer 0.17 Lung cancer 0.78 Overall cancer (2005) 0.36 0.30 • Western Australia Figures 2011 Prostate cancer – number diagnosed: 2,086 vs number of deaths: 253 vs road toll: 126 (Male) Breast cancer (female) 1,423 238 Lung cancer (male) 595 462 Colorectal cancer (male) 774 224 Western Australian Cancer Registry http://www.health.wa.gov.au/wacr/statistics/stats_full.cfm

  8. Prostate Cancer Incidence and Mortality Trends USA

  9. Prostate Cancer Incidence and Mortality Trends USA Prostate Cancer Incidence Rates* by Race and Ethnicity, U.S., 1999–2009 Prostate Cancer Death Rates* by Race and Ethnicity, U.S., 1999–2009 * USA Govt Centre for Disease Control and Prevention http://www.cdc.gov/cancer/prostate/statistics/race.htm

  10. Aetiology of Prostate Cancer • Testosterone Promotes prostate cancer development Prostate cancer does not develop in eunuchs Testosterone supplements problematic in men with normal serum testosterone levels • Genetics Mutations in BRCA1 (on chromosome 17) and BRCA2 (on chromosome 13), important risk factors for ovarian cancer and breast cancer in women, have also been implicated in prostate cancer. Other linked genes include the Hereditary Prostate Cancer Gene (HPC1) on chromosome 1, said to be responsible for 3% of prostate cancers. • Dietary Factors Little scientific evidence for dietary factors involved in the development of prostate cancer. Relatively rare in South East Asian populations with diets high in phytoestrogens such as soy.

  11. Pathology Morphology • Adenocarcinoma 99% cell of origin – basal cell most likely, not lumenal cell • Ductal carcinoma 0.141% • Mucinousadenocarcinoma 0.103% • Small cell carcinoma 0.056% (neuroendocrine) • Carcinosaroma 0.07% • Embryonalcarcinosarcoma 0.06% Differentiation = Gleason score Based on morphological appearance (grade 1 – 5) where two most common morphologies are added to give a sum score (2 – 10) Gleason 3 + 4 = 7 where 3 is the most common morphological pattern and 4 is the second most common pattern If three morphological patterns, first number is most common pattern and second number is the pattern with the highest grade Higher score = poorer differentiation = worse prognosis Gleason 3 Gleason 4 Gleason 4 Gleason 5

  12. Gleason Score and Prognosis • Gleason score is an independent prognostic indicator: Gleason 5 - 6 moderate grade cancer Gleason 7 intermediate grade cancer Gleason 8 - 10 high grade cancer The disease-specific mean survival (DSMS) in 305 men in Sweden diagnosed at TURP 1975 – 1990 who had no curative treatment (no staging information used) Gleason score 4-5 20 years 6 16 years 7 10 years 8-10 5 years Gleason score and % cancer were independent predictors of DSMS (P < 0.001). Prognostic Value of Gleason Score in Prostate Cancer Egevad et al BJU Int2002 Apr;89(6):538-42.

  13. Clinical Management • Cancer screening and PSA • Diagnosis – TRUS biopsy and MRI • Prostate cancer prevention – “chemoprevention” • Expectant management “watchful waiting”................. • Curative therapy for Localized Disease (< T3 ) Surgery Perineal prostatectomy Radical retropubic prostatectomy with dorsal vein ligation 1979 and neurovascular preservation 1982 by Patrick Walsh Laparoscopic radical prostatectomy Robotic laparoscopic radical prostatectomy HIFU and Cryotherapy Radiotherapy External External beam DXRT Conformal external beam DXRT IMRT Intensity Modulated Radiotherapy IGRT Image Guided Radiotherapy Internal LDR brachytherapy ( I125 seeds) HDR brachytherapy

  14. P.S.A. - Prostate Specific Antigen • PSA is a Single chain glycoprotein. • 237 amino acids long translated as a 261 AA prepropeptide from chromosome 19 gene designated LKLK 3. • Glycosylated PSA has MW 28,400 daltons. • Functions as a serine protease, recognized as a member of the human kallikrein family. • Functions to liquefy semen coagulum by breaking down gel forming proteins semenoglobulin I, semenoglobulin II and fibronectin, releasing spermatozoa. • Originally identified in Japan in 1966 by Hara, whoinitially reported their findings on γ-seminoprotein in 1966 in Nippon HoigakuZasshi, the Japanese Journal of Legal Medicine, and in 1971 were able to characterize this protein. Although this antigen was later shown to be similar to PSA the original publications were in Japanese and consequently not available to the English - speaking scientific community. This was early work on a forensic science test for rape.

  15. P.S.A. - Prostate Specific Antigen • Synthesized in prostatic ductal epithelium and acini and secreted into prostatic ducts to become a component of semen. • Detected in female and male periurethral glands, apocrine sweat glands, some breast cancers, some salivary gland cancers and breast milk. • Thought to diffuse across cells and basement membrane to enter bloodstream, diffusion increased in inflammation and prostate cancer. • Half life 2.2 - 3.2 days. • Immunoreactive PSA subgroup free PSA 1% - 30% of this group bound PSA bound to alpha 1 antichymotrypsin.

  16. PSA Levels Affected By : • Prostatitis - levels up to 120 recorded, resolving with antibiotics. • Urine retention - up to 6 fold increase. • Ejaculation - 0.2 ng/ml increase 24 hours later. • Ambulation - decreases PSA up to 20%. • Prostate biopsy - 8 ng/ml increase 4 - 24 hours later. • TURP - 6 ng/ml increase with median return to baseline at 18 days Klein et al, The effects of prostate manipulation on PSA levels. Urologic Clinics of North America May 1998.

  17. PSA as a screening test • PSA is a poor screening test with high sensitivity but very poor specificity • Advocated screening with yearly PSA and DRE for men between 50 and 70 years of age • Earlier commencement of screening advocated for those at risk of hereditary cancer between 40 and 70 years of age • Recommended in some parts of the USA. A policy of the American Urological association. • Prostate cancer screening is not currently recommended by Government health authorities in either Australia or the UK.

  18. PSA as a screening test • Australian Health Technology Advisory Committee (AHTAC) review 1996 - Australian Government Publishing Service 1996. • “As a result of the evaluation of prostate cancer screening against established criteria, AHTAC recommends against the screening of asymptomatic men for prostate cancer.” • “AHTAC recommends: that the use of PSA continue to be supported in the monitoring of men known to have prostate cancer and in patients selected for active treatment for BPH; and that men being offered, or requesting the PSA test must be fully informed of the limitations of the available tests and the possible further diagnostic and treatment choices with which they may be faced should they decide to proceed with the test.”

  19. Total PSA screening studies • PSA > 4ng/ml Overall cancer detection rate PPV 1.5% - 4.1% 33% mean • Incidence of cancer detection on prostate biopsy based on DRE findings and PSA. PSA ng/ml DRE negative DRE positive 0 - 4 4 - 7% 10 - 13% 4 - 10 24 - 25% 41 - 62% >10 31 - 42% 67 - 77% Arcangeli et al Urologic Clinics of N. America, May 1998

  20. PSA Density and Screening • PSA density = Total PSA ng/ml / TRUS determined prostate volume in ml • >0.15 with PSA 4 - 10 reduces number of biopsies 50% misses 50% of cancers Catalona et al : J Urol 153:2031,1994

  21. PSA Velocity and Screening • This is shown to be higher in men with prostate cancer than in BPH • PSA slope cut off 0.75 ng/ml per year with PSA <4 ng/ml sensitivity 79% specificity 66% Smith and Catalona: J Urol 152:1163, 1994 • Difficult because there is a 15% short term variation in PSA levels Stamey et al: J Urol 155: 1977,1996

  22. Age Specific Reference Ranges in PSA • Oesterling et al 471 men in Olmstead County, Minnesota had DRE, PSA and TRUS . Found to have increasing PSA with age at a rate of 0.04 ng/ml per year. Oesterling et al: JAMA 270:860, 1993 • Catalona however found that 30% of organ confined histologically significant cancers in men older than 60 would be missed if age related reference ranges were used. Catalona et al: J Urol 152:2037, 1994 • Age related reference ranges improve specificity at the cost of sensitivity.

  23. Free/Total PSA Ratio in Screening • Note that there are over 50 commercially available PSA assays available and all should have different reference ranges, such is the complexity of the assay. • Measurement of free PSA is difficult and F : T ratios should be validated for each individual test. • Standardisation of these tests is difficult and not yet universal. • %Free PSA falls as prostate cancer develops. • Study PSA range F : T Ratio Sensitivity loss Specificity gain Luderer 4 - 10 <20% 5% 15% Catalona >4 <20% 10% 38%

  24. Free/Total PSA - Netherlands Schroder Study • 9,600 men 54 - 76 years old screened with PSA, DRE and TRUS • 4.3% cancer detection rate • 5.1 biopsy to cancer ratio • 64% of cancers specimen confined at radical prostatectomy • Best sole predictor of prostate biopsy is total PSA • Specificity of PSA in range 4 - 10 is improved with F : T ratio • F : T ratio < 20 in total PSA range 4 - 10 reduces biopsies by 38% misses 12% of cancers Schroder et al: Urologic Clinics of North America, May 1998

  25. Years of Life Saved by Screening • Sensitivity analysis of years of life saved by prostate cancer screening using various estimates of the natural history of prostate cancer. Grade of disease Years of life saved Years of life saved without QOLA with QOLA well differentiated 1.35 1.01 moderately ‘’ 2.58 2.41 poorly ‘’ 2.78 2.68 Chodakmetanalysis: Urologic Clinics of North America May 1998 • The years of life saved using assumptions of the natural history of prostate cancer compare favorably to the years of life saved by other cancer screening programs.

  26. Cost Effectiveness of Prostate CA Screening & Rx • Estimates used because no randomized controlled studies of the effectiveness of prostate cancer screening have been done. • Years of life lost because of prostate cancer age 65 - 74 years Grade Years of life lost Well differentiated 2.2 Moderately ‘’ 4.9 Poorly ‘’ 7.1 • Cost per year of life saved by prostate cancer screening and Rx Age range Saving $US DRE + PSA 50 - 69 2339 - 3005 60 - 69 3905 - 5070 50 - 69 3574 – 4627 Benoit & Naslund: Urologic Clinics of North America, May 1998

  27. Cost per Year of Life Saved By Various Interventions Intervention Cost per year of life saved $US Smoking cessation counseling 5,249 - 15,833 Hypertension control 32,600 CABG 62,900 Renal dialysis 42,000 - 80,300 Liver transplantation 225,000 Screening mammography 20,000 - 50,000 Cervical cancer screening 33,572 Colon cancer screening 28,848 - 113,348 • For prostate cancer, cost per year of life saved through PSA and DRE screening programs compares extremely favorably with that for breast, cervix and colon cancer screening. Benoit & Naslund: Urologic Clinics of North America, May 1998

  28. Conclusion on the socio - economic implications of PSA Screening • Benoit and Naslund, Urologic Clinics of North America, May 1998 “Although men aged 50 - 75 years will potentially benefit the most from PSA screening, this benefit will not be realised until these men are in their seventh and eighth decade of life.” “Society must decide if the years of life saved in these men warrants the use of limited health care resources.” “This decision will be easier when randomised controlled trials are available to quantify the costs and benefits of PSA screening.”

  29. PSA screening – large trial results Mortality Results From a Randomized Prostate-Cancer Screening Trial Andriole et al NEJM 2009 360:13 1310-19 Randomized trial on 76,693 men, annual PSA screening on 38,343 men vs no screening on 38,350 between 1993 – 2001. After 7 years, the incidence of prostate cancer per 10,000 person-years was 116 (2820 cancers) in the screening group and 95 (2322 cancers) in the control group. The incidence of death per 10,000 person-years was 2.0 (50 deaths) in the screening group and 1.7 (44 deaths) in the screening group. Conclusion: After 7 to 10 years of follow up, the death rate from prostate cancer was very low and did not differ significantly between the two study groups.

  30. PSA screening – large trial results Screening and Prostate Cancer Mortality in a Randomized European Study Schroder et al NEJM 2009 360:13 1320-28 182,000 men between ages 50 – 74 years in seven European countries randomized to two groups with one group receiving PSA screening and the other group not having PSA screening, recruited between 1991 and 2003. During a median follow up of 9 years, the cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in the control group. The rate ratio for death from prostate cancer in the screening group as compared with the control group was 0.8. The absolute risk difference was 0.71 deaths per 1,000 men. This means that 1410 would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer. Conclusion: PSA based screening reduced the rate of death from prostate cancer by 20% but was associated with a high risk of overdiagnosis.

  31. End of the PSA Era?

  32. Diagnosis – TRUS Biopsy • Prostate biopsy is required for diagnosis, generally 11 biopsies taken • Transperineal prostate biopsy using trans rectal U/S (TRUS) and 18F “Biopty” guns originally developed by Jim Anderson, interventional radiologist at RPH in 1989 using freehand technique. • All TRUS biopsies done by Jim Anderson using this technique under local anaesthetic up to around 2000 with no antibiotic prophylaxis used. Rare septicaemia if patient had UTI/prostatitis at the time of biopsy (handful of cases over 10 years and around 18,000 TRUS biopsy episodes). • TRUS biopsy largely taken over by urologists around 2000 using trans rectal approach under general anaesthetic. “Lists of TRUS biopsies”. • 3% Gram negative septicaemia rate with transrectal biopsy despite antibiotic prophylaxis. • Now a move nationally by urologists over the last 12 months to move on to transperineal biopsy because of concerns over septicaemia and antibiotic prophylaxis. • Many urologists have this technique from brachytherapy seed placement anyway but this is now being workshopped by urologists in the Eastern States.

  33. Diagnosis - Prostate “Multiparametric” MRI • New computer software enhancement of contrast MRI is providing more accurate assessment with “Multiparametric” MRI scanning: “Dynamic Contrast Enhanced” imaging DCE “Diffusion weighted imaging” DWI - Difference in Brownian motion of water molecules in cancer vs normal tissue. • Currently at RPH, 1.5 Tesla external MRI with multiparametric processing, DCE and DWI. • 1.5 Tesla vs 3.0 Tesla – possibly not as important as image processing and analysis. • Endorectal coil 3.0 T claimed up to 98% specific and up to 86% PPV with DCE. • MR Spectroscopy up to 93% PPV • Current role seen as a localising test for targeted biopsy after negative biopsy with ongoing PSA rise. • CURRENTLY SHOULD NOT BE USED AS A DIAGNOSTIC TEST WITH AN ABNORMAL PSA TO AVOID BIOPSY.

  34. PATIENT 76 YEAR OLD PSA ELEVATED FOR A NUMBER OF YEARS BIOPSY X4 INFLAMMATORY CHANGES TREATED WITHY CIPROFLOX PIN IDENTIFIED IN BIOPSY SPECIMEN PREVIOUSLY Diffusion Imaging (Brownian motion) T2 Axial Slightly More rostral DWI ADC T2 Axial NAD Axial Ultrasound Lesion visible Hypoechoic Colour map graph Colour map 11 oc ext ant Transperineal systematic cores (11 systematically) additional 2 cores from presumed index lesion at 11 oclock (13 cores in total) 8mm,13mm and 10 mm acinarAdenocarcinoma 11 oclock (Slide courtesy of Jim Anderson)

  35. Prevention • Castrate all adolescent males - prostate cancer unknown in eunuchs in China. • Diets high in phytoestrogen - SE Asian populations and low cancer incidence. • African americans - high testosterone and high incidence of prostate cancer. • “Chemoprevention” – 5 alpha reductase inhibitors finasteride and dutasteride Effective but caution due to relative increase in high grade prostate cancer incidence FDA warns: The results of the PCPT trial showed that men on the finasteride arm had a 24.8% overall lower risk of being diagnosed with prostate cancer when compared to the placebo arm (p<0.0001). The reduction in risk of prostate cancer was limited to Gleason score (GS) 6 or lower prostate cancers. However, there was an increased incidence of GS 8-10 prostate cancers with finasteride versus placebo (1.8% versus 1.1%, respectively).   The results of the REDUCE trial showed that men on dutasteride had a 23% overall lower risk of being diagnosed with biopsy detectable prostate cancer when compared to men on placebo (p<0.0001). This overall risk reduction was limited to a decrease in GS 6 or lower prostate cancers. In contrast, there was an increased incidence of GS 8-10 cancers with dutasteride versus placebo (1% versus 0.5%, respectively).  

  36. Prevention - Finasteride • USA Prostate cancer prevention trial 1993 – 2003 18,882 men with PSA < 3 and normal DRE enrolled. 5 mg of Finasteride per day or placebo. Study closed 15 months before planned closure because overwhelming evidence that the primary end point (prostate cancer prevalence) had been met. 24.8 % reduction in prostate cancer risk. Increased proportion of high grade prostate cancers diagnosed from 1.1% to 1.8%raised (and more likely cause of early closure). Prompted FDA warning. Subsequent analysis suggests finasteride “improved sensitivity of PSA for cancer overall, and especially for high grade cancer”. The Influence of Finasteride on the Development of Prostate Cancer. Thompson et al NEJM 2003; 349: 215

  37. Expectant Management • “Watchful waiting” PSA between 4-10, do repeat PSA at regular intervals, 3 to 6 monthly, act when certain parameters breached. • Pre biopsy - lower chance of cure with higher PSA due to interval progression, significant drop in cure rates once PSA>10. • Post biopsy - little rational basis, chance of successful curative therapy must drop over time (albeit slowly in many cancers). • However, ~50% chance of death from prostate cancer over 10 years without treatment in stage T1c prostate cancer Gleason 7, few +ve biopsies. • Patients should have management options discussed and have a clear course of action in their minds prior to having PSA test. • Ask “what if ?” prior to PSA testing.

  38. Expectant Management Albertsen et al Competing Risk Analysis for Men Aged 55 to 74 Years at Diagnosis Managed Conservatively for Clinically Localised Prostate Cancer JAMA 280(11), 975 1998

  39. Radical Prostatectomy • Cure 80% PSA 4-10, Gleason < 7, Stage T1c (Positive margin rate average 30% in Perth) • This group of patients have 10 - 20 % mortality from prostate cancer without any treatment over 10 year time frame, depending on age (see previous). • Cure 50% PSA 10-15, generally higher stage. • Morbidity 10% incontinence 80% impotence 0.5% death blood transfusion, rectal injury, lymphocoele • “PSA recurrence” = not cured Rx radiotherapy (? 1/3 cured) hormonal manipulation ? Better local control ? Better survival in this group

  40. Puboprostatic Ligaments and Endopelvic Fascia

  41. Dorsal Vein Ligation

  42. Neurovascular Bundles

  43. Neurovascular Bundle preservation

  44. Radical Prostatectomy • Open radical retropubic prostatectomy Now 4 – 5” midline incision 3 – 4 days hospital stay 2 – 3 weeks indwelling catheter • Laparoscopic radical retropubic prostatectomy 2” incision + port sites 2 – 3 days in hospital 1 – 2 weeks indwelling catheter More rapid return to work • Cancer outcomes the same for open vs laparoscopic radical prostatectomy • Slightly lower impotence rate for laparoscopic radical prostatectomy • Slightly higher complication rate for laparoscopic radical prostatectomy, including rectal injury • Robotic radical prostatectomy

  45. Robotic Radical Prostatectomy • Da Vinci robot developed through the 1990’s and given approval by US FDA in 2000. Installed SJOG Subiaco in 2008. • Purchase cost $3 million in Australia with $300,000 yearly maintenance fees. • Cost $4,000 per case in disposable instruments. • Patient out of pocket costs $7,000 - $8,000 per procedure in Perth. • Four interactive robotic arms controlled from the console. • Endoscopic camera with two lenses gives the surgeon full stereoscopic vision from the console.

  46. Da Vinci Robot

  47. Robotic Radical Prostatectomy • 2012 in USA 367,000 robotic operations performed (all, including prostate). • 1,400 hospitals in USA have at least one Da Vinci robot. • Cancer outcomes no different. • Complication rate the same as manual laparoscopic radical prostatectomy. Incontinence 7% vs 2% open radical prostatectomy Lepor et al Reviews in Urology 2005 Summer; 7(3): 115–127 Impotence 25% vs 30% “ “ “ “ “ Rectorethral fistula 0.53% overall with no good comparison laparoscopic/robotic/open • Hospital stay the same as manual laparoscopic radical prostatectomy, all lapararoscopic prostatectomy 1 – 2 days shorter hospital stay than open radical prostatectomy.

  48. Radiotherapy – External Beam • Results suggest efficacy equal to radical prostatectomy, but staging difficulties and poor data. Comparison of the efficacy of local therapies for localized prostate cancer in the prostate-specific antigen era: a large single-institution experience with radical prostatectomy and external-beam radiotherapy. Kupelian et al Cleveland Clinic J ClinOncol 2002 Aug 15;20(16):3376-85. CONCLUSION: Eight-year biochemical failure rates were identical between radiotherapy and surgery in any subgroup. Outcome is determined mainly by pretreatment PSA levels, bGS, clinical T stage, and, for RT patients, radiation dose. MD Anderson data shows external beam DXRT much better outcomes with higher doses, around 76 Gray, hence newer image guided radiotherapy should be more effective • Six week treatment • Morbidity 2% radiation proctitis 2% radiation cystitis - 50% impotence within first year, increasing thereafter - insignificant incontinence • Pretreatment hormonal manipulation 6 months appears to improve cure rate. • Bladder cancer in 0.58% of 342,937 men treated for CA prostate, twice as likely in DXRT vs radical prostatectomy Secondary Bladder Cancer After Radiotherapy For Localized Prostate Cancer Abern et al Chicago, IL (AUA presentation) J Urology 185, No. 4S, Supplement May 2011

  49. Image Guided Radiotherapy IGRT and IMRT • Image guided linear accelerators used to target the prostate. • IMRT Intensity modulated therapy advanced 3DCRT is now further refined. • Gold seed fiducial markers placed trans perineally using trans rectal U/S. • CT scan imaging data used for planning. • Cone beam flat panel CT used for targeting. • Allowing dose escalation to 78 – 86 Gy (? Use of hydrogel spacer for rectal separation). • Reduced risk of significant complication to 1- 2%. • Long term outcome data not available but early biochemical control (PSA) improved.

  50. IGRT

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