Reducing the burden of prostate cancer

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  • In men aged <65 years, death rate after 10 years Watchful waiting ~20% Radical Prostatectomy ~10%NNT=10Absolute risk reduction 0.59 (CI 0.41 to 0.84, P=0.004)…Over 65 years, no difference in death rates…1989 to 1999: Recruitment periodRandomised 695 men (Scandinavia)Mean age 65 yearsNon-screen detectedIntermediate Risk Group regarding PC: Palpable tumours: ie clinical stage T2 (75%), PSA 9 (median)Gleason score 6 (median, biopsy) Excluded high grade prostate cancerLymph node positive 10%Mean follow up 8 yearsCause of death evaluated blind Holmberg, Bill-Axelson, NEJM 2002, 2005; JNCI 2008
  • If we look at the US, where PCa diagnosis and treatment is more aggressive, there has been a signifcantly faster fall in the rate of diagnosis of prostate cancer.Age-specific and age-adjusted prostate-cancer mortality peaked in the early 1990s at almost identical rates in both countries, but age-adjusted mortality in the USA subsequently declined after 1994 by –4·17% (95% CI –4·34 to –3·99) each year, four-times the rate of decline in the UK after 1992 (–1·14% [–1·44 to –0·84]). The mortality decline in the USA was greatest and most sustained in patients aged 75 years or older (–5·32% [–8·23 to –2·32]), whereas death rates had plateaued in this age group in the UK by 2000. The mean ratio of USA to UK age-adjusted prostate-cancer incidence rates in 1975–2003 was 2·5, with a pronounced peak around the time that PSA testing was introduced in the USA. Numbers needed to treat to prevent one death from prostate cancer were 33 000 in the 55–64-year age group.Interpretation The striking decline in prostate-cancer mortality in the USA compared with the UK in 1994–2004 coincided with much higher uptake of PSA screening in the USA. Explanations for the diff erent trends in mortality include the possibility of an early effect of initial screening rounds on men with more aggressive asymptomaticdisease in the USA, diff erent approaches to treatment in the two countries, and bias related to the misattribution of cause of death. Speculation over the role of screening will continue until evidence from randomised controlled trials is published.Age Adjust PC Mortality rates: USA v UKAge-specific and age-adjusted prostate-cancer mortality peaked 1990s identical rates in UK & USAAge-adjusted mortality declined after 1992-1994By –4% each year US By -1% each year UKCollin 2008 Lancet Oncology
  • Using PSA alone, 1410 men need to be screened to save one life at 9 yearsCompares Favorably With Other Cancer ScreeningAt 14 years of follow-up, the number who needed to be invited to screening (NNS) to prevent 1 prostate cancer death was 293, whereas the number needed to be diagnosed (corresponding to number needed to treat, NNT) was 12, the Swedish researchers report.These outcomes compare favourably with the well-established screening programs for breast and colorectal cancer."These outcomes compare favourably with the well-established screening programs for breast and colorectal cancer," Dr. Neal comments in the editorial.In their article, the Swedish researchers cite several papers for comparable figures.Mammography for breast cancer screening has reported a NNS of 377 and an RR of 0.68 for women aged 60 to 69 years, and an NNS of 1339 and RR of 0.86 for women aged 50 to 59 years at 11 to 20 years of follow-up. A separate review reported an NNT for mammography of 10 over 10 years.Colorectal cancer screening by fecal occult blood test has reported an RR of 0.84 in 2 separate reviews (after 11.7 - 18.4 years and 7.8 - 13 years, respectively), and an NNS of 1173 after 10 years.Colorectal cancer screening by flexible sigmoidoscopy has reported an RR of 0.69 and an NNS of 489 at median follow-up of 11.2 years. However, as sigmoidoscopy removes any polyps that are found, it is associated with a reduced colorectal cancer incidence, and so an NNT cannot be calculated.
  • reater number of biopsy cores increased the risk of cancer (odds ratio for >6- versus 6-core biopsy, 1.35; 95% confidence interval, 1.18-1.54; P < 0.0005); recent screening led to a smaller increase in risk per unit change in PSA (P = 0.001 for interaction term) and U.S. cohorts had higher risk than the European cohorts (2.14; 95% confidence interval, 1.99-2.30; P < 0.0005).CONCLUSIONS: Our results suggest that the relationship between PSA and risk of a positive prostate biopsy varies, both in terms of the probability of prostate cancer at a given PSA value and the shape of the risk curvClin Cancer Res. 2010 Sep 1;16(17):4374-81. Epub 2010 Aug 24.The relationship between prostate-specific antigen and prostate cancer risk: the Prostate Biopsy Collaborative Group.Vickers AJ, Cronin AM, Roobol MJ, Hugosson J, Jones JS, Kattan MW, Klein E, Hamdy F, Neal D, Donovan J, Parekh DJ, Ankerst D, Bartsch G, Klocker H, Horninger W, Benchikh A, Salama G, Villers A, Freedland SJ, Moreira DM, SchröderFH,Lilja H.
  • The PCPT riskcalculator seems to be more suitable forpatients in whom previous DRE and PSAresults are available, and the ERSPC riskcalculator seems to be more suitable for newpatients in whom no information has beencollected before use, except for not havingprostate cancer.Refer urgently patients:l with a hard, irregular prostate typical of a prostate carcinoma. Prostate-specific antigen(PSA) should be measured and the result should accompany the referral. (An urgentreferral is not needed if the prostate is simply enlarged and the PSA is in the age-specificreference range6.) lCl with a normal prostate, but rising/raised age-specific PSA, with or without lower urinarytract symptoms. (In patients compromised by other comorbidities, a discussion with thepatient or carers and/or a specialist may be more appropriate.) lCl with symptoms and high PSA levelsThe age-specific cut-off PSA measurements recommended by the Prostate Cancer Risk Management Programme are asfollows: aged 50–59 >–3.0 ng/ml; aged 60–69 >–4.0 ng/ml; aged 70 and over >–5.0 ng/ml. (Note that there are no age-specificreference ranges for men over 80 years. Nearly all men of this age have at least a focus of cancer in the prostate. Prostatecancer only needs to be diagnosed in this age group if it is likely to need palliative treatment.)
  • ON conventional T1 and T2 MRI20-40% of significant tumours are missedmany false positives (with inflammation, hemorrhage and scarring mimicking tumour)post-biopsy hemorrhage can last for up to 3 monthsAdding contrast and diffusion sequences takes the sensitivity of MRI to over 90% for significant tumour, including in the transition zone, and without the need for an endorectal coil4Contrast and diffusion also enable us to reliably exclude disease in a third to a half of patients who do not have a significant tumourAhmed Nature Reviews Clinical Oncology
  • Reducing the burden of prostate cancer

    1. 1. Reducing the burden of prostate cancer<br />By<br />Marc Laniado MD FEBU FRCS(Urol)<br />7/7/11<br />
    2. 2. Prostate cancer is a big problem for men<br />
    3. 3. Understand how to improve men’s lot with precision<br />
    4. 4.
    5. 5. Diagnose and advise men who may benefit<br />
    6. 6. Follow this 3 point plan to reduce the burden of prostate cancer <br />Integrate available information to calculate risk<br />Use modern diagnostic imaging and biopsy<br />reliable minimally invasive technique<br />
    7. 7. Treatment for early prostate cancer in the right patient reduces mortality<br />
    8. 8. Actively testing for and treating prostate cancer reduces death rate compared to inaction<br />UK<br />USA<br />4 fold faster fall and lower in US<br />
    9. 9. PSA screening reduces death rate by 20 to 30% at 9 years<br />
    10. 10. The problem is that we use PSA in isolation<br />
    11. 11. “Your PSA is normal”...Really??<br />
    12. 12. Even at low PSA levels 2 -4 ng/ml, 20% of prostate cancers are incurable<br />
    13. 13. Integrate prostate cancer risk factors to give a risk of prostate cancer<br />
    14. 14. Google “prostate cancer risk calculator”<br />
    15. 15. Fill in risk factors for individualised risk assessment for prostate cancer<br />
    16. 16. Fill in risk factors for individualised risk assessment for prostate cancer e.g. with BMI<br />
    17. 17. Gives risk of all & high-grade prostate cancer<br />
    18. 18. What are these men’s risk of disease?<br />55 years old<br />white male, <br />No family history<br />Prostate feels abnormal<br />PSA 0.3 <br />no prior bx, <br />recommendation? – Biopsy, right?<br />68 years old <br />African American Man, <br />Positive family of Pca<br />Normal feeling prostate<br />PSA 2.4<br />no prior biopsy<br />Recommendation?- Biopsy, No?<br />
    19. 19. Calculator is more accurate predictor<br />Any prostate cancer=13% <br />High grade cancer=1%<br />Any prostate cancer=31% <br />High grade cancer=11%<br />
    20. 20. How much risk can you take!<br />
    21. 21. NICE Age-specific PSA and corresponding risk of prostate cancer – for individual men, use probability threshold to choose who to refer<br />Pr<br />
    22. 22. 5ARI make PSA & DRE more accurate<br />Cancer<br />prostate<br />Dutasteride/finasteride<br />Cancer same size<br />prostate shrinks<br />
    23. 23. Finasteride halves the PSA in normal men by 6 to 12, but rising PSA suggests high risk prostate cancer<br />High risk PCa<br />Low risk PCa<br />BPH<br />
    24. 24. Prostate cancer risk adjusted for finasteride<br />
    25. 25. Genetic diagnostic tests will become more common<br />Ca <br />Norm <br />BPH <br /> PCA3 RNA <br />
    26. 26. PCA3 is the best single test for prostate cancer<br />Digital Rectal Examination<br />Prostate cancer cells shed in urine<br />Ca <br />Norm <br />BPH <br /> PCA3 RNA <br /> PSA RNA <br />Quantitative Northern Blot for PCA3<br />
    27. 27. PCA3 is not affected by inflammation or prostate size, so can use in big prostates and UTIs<br />
    28. 28. Multiparametric MRI localises prostate cancer more accurately<br />
    29. 29. Multiparametric MRI identifies significant prostate cancer so guiding biopsies<br />Transverse Prostate Sections<br />
    30. 30. Surgery most useful in high grade disease<br />
    31. 31. For higher risk tumours, Da Vinci Prostatectomy has become the 1st choice for surgical treatment<br />
    32. 32. Robotic interface - operating by hand not chop sticks!<br />
    33. 33. Robotic interface allows for more precise surgery than laparoscopy or open surgery<br />
    34. 34. Incision sites are much smaller than open surgery<br />
    35. 35. Robotic interface potentially improves Cancer control, Coitus and Continence<br />Cancer Control<br />“Trifecta”<br />Continence<br />Coitus<br />
    36. 36. 12-fold magnification, robotic precision, scaled motion, tremor filter allows better cancer control<br />
    37. 37. More accurate nerve sparing makes chance of staying potent much greater<br />
    38. 38. Precisely anastomosis makes time to continence much faster<br />
    39. 39. Follow this 3 point plan to reduce the burden of prostate cancer<br />Integrate available information to calculate risk<br />Use modern diagnostic imaging and biopsy<br />reliable minimally invasive technique<br />

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