Prostate cancer modernising the diagnostic pathway 2013-06-11 by Marc Laniado

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  • Br J Cancer. 2011 November 22; 105(11): 1795–1803.Published online 2011 October 27. doi: 10.1038/bjc.2011.430PMCID: PMC3242594Cancer incidence in the United Kingdom: projections to the year 2030M Mistry,1 D M Parkin,1 A S Ahmad,1 and P Sasieni*,1Author information ► Article notes ► Copyright and License information ►This article has been cited by other articles in PMC.Go to:ABSTRACTBackground:Projections of cancer incidence are important for planning health services and to provide a baseline for assessing the impact of public health interventions. Methods:Rates estimated from smooth function age–period–cohort modelling of cancer incidence data from Great Britain 1975 to 2007 are extrapolated to 2030 and applied to UK population projections. Prostate and breast cancer projections take into account the effect of screening. Results:Overall rates of cancer are projected to be stable over the next 20 years, but this masks individual changes. In both sexes, age-standardised rates of cancers of the stomach, larynx, bladder and leukaemia are projected to fall by 1% per year, whereas cancers of the lip, mouth and pharynx (ICD-10 C00-C14) and melanoma are projected to increase by 1% per year. The growing and aging populations will have a substantial impact: numbers of cancers in men and women are projected to increase by 55% (from 149169 to 231026) and 35% (from 148716 to 200929), respectively, between 2007 and 2030. The model used yields similar results to those of Nordpred, but is more flexible. Conclusion:Without new initiatives for smoking and obesity reduction, the number of cancers in the United Kingdom will increase substantially reflecting the growing and aging populations.
  • Age-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 UKIf 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
  • six screeningtrials: Stockholm, Norrkoping, Quebec, ERSPC, Goteborg and PLCO PLCO trial for men age 55 to 74 years1 The ERSPC focuses on men age 55 to 69 years he bulk of evidence is for men age 55 to 69 years included in the ERSPC, Goteborg and PLCO trials. Goteborg trial for men age 50 to 55 years The contamination was 20-25% in the ERSPC trial, and 77% with a PSA screen after five years in the PLCO trial20 with a high exposure to PSA screening and DRE also at inclusion into the trial (prescreening). This likely contributed to the lower-than-expected number of deaths on both arms in the trial.
  • In the not screened group 60 of 1000 (ages of 55 to 69) years develop clinical evidence of prostate cancer within 10 to 14 years Screened: 96 of 1000 men dxPcaprostate cancer Of the 1,000 men who choose NOT to have screening, five will die of their disease within 10 to 14 years. Of the 1000 men who choose screening, four will die of their disease within 10 to 14 years. This amounts to one life saved by screening for every 1000 men screenedEstimates for 25 years are much lessIn the Goteborg centre 14 y of f/u: 293 to be invited for screening and 12 to be diagnosedIn the ERSPC 1035 to be invited and 37 to be diagnosed at 11 yearsUsing PSA alone, 1410 men need to be screened to save one life at 9 yearsOverdiagnosisbetween 23% and 42% in ERSPC and is defined in this document as the detection of a prostate cancer that would have remained undetected during life in the absence of screening Compares 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.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.Numbers needed to screen and to diagnose. Numbers needed to invite to screen and additional number needed to diagnose to avoid one prostate cancer death in the ERSPC (11 years of follow-up) and the Goteborg (14 years of follow-up) studies are as follows: 1,055 to invite and 37 to diagnose, 293 to invite and 12 to diagnose, respectively. However, these estimates are extremely sensitive to follow-up duration and are likely to be much lower over the long term; for example, it has been estimated that the additional number to diagnose is less than 10 over the long term.22,23 NNI 936 after 11 years re death rate
  • BACKGROUNDThe effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen (PSA) testing is not known.Full Text of Background...METHODSFrom November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer (mean age, 67 years; median PSA value, 7.8 ng per milliliter) to radical prostatectomy or observation and followed them through January 2010. The primary outcome was all-cause mortality; the secondary outcome was prostate-cancer mortality.Full Text of Methods...RESULTSDuring the median follow-up of 10.0 years, 171 of 364 men (47.0%) assigned to radical prostatectomy died, as compared with 183 of 367 (49.9%) assigned to observation (hazard ratio, 0.88; 95% confidence interval [CI], 0.71 to 1.08; P=0.22; absolute risk reduction, 2.9 percentage points). Among men assigned to radical prostatectomy, 21 (5.8%) died from prostate cancer or treatment, as compared with 31 men (8.4%) assigned to observation (hazard ratio, 0.63; 95% CI, 0.36 to 1.09; P=0.09; absolute risk reduction, 2.6 percentage points). The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age, race, coexisting conditions, self-reported performance status, or histologic features of the tumor. Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter (P=0.04 for interaction) and possibly among those with intermediate-risk or high-risk tumors (P=0.07 for interaction). Adverse events within 30 days after surgery occurred in 21.4% of men, including one death.Full Text of Results...CONCLUSIONSAmong men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up. Absolute differences were less than 3 percentage points. (Funded by the Department of Veterans Affairs Cooperative Studies Program and others; PIVOT ClinicalTrials.gov number, NCT00007644.)
  • 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
  • T1 imagesEvery 10 to 15 sIn plane similar to T2 and DWIRecurrence linear in front of the apexLook for where uptake is fastestCommon if malignant/benign ratio is 80%, pattern 4 disease,Loose stromaSome
  • Lesion is rated high if one or two sequences are abnormal even if one sequence is normalSignificant tumour is defined as >0.2cc or Gleason 3+4 or higher
  • While there is some lower-quality evidence (quality rating=c) that an absolute reduction in prostate-cancer mortality rate may be associated with population-wide screening of men in their 40’s at average risk, the benefit is relatively small. Howard et al.92 noted that annual PSA screening of men in their 40’s is associated with a 10-year prostate cancer- specific mortality rate of 0.037 deaths/1000 men compared to 0.041 deaths/1000 men if no screening was performed. While the evidence of benefit of screening of men age 40 to 55 years indicates that the effect size is marginal at best, at least in terms of prostate-cancer specific mortality, the weight and quality of the evidence demonstrating the harms of screening remains high. literature in this area is quite dynamic Malmo, Sweden, that a single PSA measurement taken between age 33 to 50 years is highly predictive of subsequent prostate cancer diagnosis and advanced stage at diagnosis. Whether or not this information would lead to a decrease in morbidity or mortality from the disease is uncertain, however, and to this end, the benefit of this risk stratification is uncertain.
  • risk of dying of prostate cancer is about 3% 1977 to 2005 the life time risk of being diagnosed with prostate cancer rose 2.3 fold from 7.3% to 17% life time risk of death from this disease decreased by 20% from 3% to 2.4% ERSPC (using a cutpoint of 3.0ng/mL) suggest that PSA screening will correctly predict the presence of prostate cancer in about one of every four biopsies. 20% of elevated values will return to normal within one year PSA levels also vary with age, race, BMI and prostate volume PSA increase as a result of benign BPH, prostatitis and any prostate manipulation such as prostate massage every 1,000 men tested, approximately 100 to 120 will have an elevated PSA value. TRUS biopsyone third will experience some type of mild to severe symptom including pain, fever, bleeding, infection or problems urinating. 4% will be hospitalized within 30 days after biopsy For every 1,000 men screened: twowill develop serious cardiovascular events, one will develop DVT or PE, 29 will develop erectile dysfunction, 18 will develop incontinence and less than 1% will die from treatment over 10 years60 men of every 1000 between the ages of 55 to 69 years will develop clinical evidence of prostate cancer within 10 to 14 years if they choose NOT to be screened; while approximately 96 of every 1000 men will be diagnosed with prostate cancer if they choose to be screened.88 Of the 1,000 men who choose NOT to have screening, five will die of their disease within 10 to 14 years. Of the 1000 men who choose screening, four will die of their disease within 10 to 14 years. This amounts to one life saved by screening for every 1000 men screened; RSPC document a relative risk reduction of prostate cancer-specific death of 21% at a median follow-up of 11 yearsabsolute reduction in prostate cancer-specific mortality was relatively small (0.10 deaths per 1,000 person-years or 1.07 deaths per 1,000 men randomized), studies have documented that men with less than a 10 to 15 year life expectancy are unlikely to realize a benefit from aggressive treatment for localized prostate cancer96 and as such, it follows that the earlier disease detection associated with screening in these men likely will be less beneficial, if beneficial at all.
  • Prostate cancer modernising the diagnostic pathway 2013-06-11 by Marc Laniado

    1. 1. Prostate Cancer:Modernising The DiagnosticPathwayMarc Laniado MD FEBU FRCS(Urol)Consultant Urological Surgeon@marclaniadowww.windsorurology.co.ukmarclaniado@gmail.commarc.laniado@nhs.net
    2. 2. 70% more prostate cancer cases by 2030>75 y65 to 74 y50 to 64yAgestandardisedrateCruderateOverallnumbersSource: Mistry 2011 BJC
    3. 3. We are here to arm ourselves against this threat
    4. 4. Without change, deaths from prostatecancer increase by 60% in 2030Cancer Site 1990 Cancer Site 2010 Cancer Site 2030Lung 39,176 Lung 34,859 Lung 44,986Bowel* 19,365 Bowel* 16,013 Bowel* 19,032Breast** 15,141 Breast** 11,556 16,304Stomach 9,795 Prostate 10,721 Pancreas 11,449Prostate 8,926 Pancreas 7,901 Breast** 11,133Pancreas 6,935 Oesophagus 7,610 Oesophagus 10,087Oesophagus 5,979 Stomach 4,960 Liver 7,918Bladder 5,468 Bladder 4,907 Bladder 6,272Ovary 4,528 Leukaemia 4,504 Leukaemia 5,500Non-Hodgkin Lymphoma 3,998 Non-Hodgkin Lymphoma 4,452 Kidney 5,097Source: Cancer Research UK 2013
    5. 5. Optimal outcome: reduce death rates!0204060801001201970 1980 1990 2000 2010 2020Noofmenper100,000menYearIncidence and Mortality Rates per 100,000 by Yearincidence ratesmortality ratesWe want to see adecline in mortality
    6. 6. Risk prediction, mpMRI and targeted biopsiesallow safer diagnosis in men with true riskUse risk calculators toidentify men at risk3T multiparametric MRIcan rule out people forfurther investigationTargetedtransperineal biopsiesdiagnoses accurately
    7. 7. Risk calculators beat human risk estimationconsistently
    8. 8. Would you refer this man for investigation?68 years oldAfrican American Man,Positive family of PcaNormal feeling small, prostatePSA 2.6no prior biopsy….
    9. 9. What about this man?55 years oldwhite male,No family historyProstate feels abnormal and largePSA 0.3no prior bx,recommendation? – Biopsy, right?
    10. 10. Search Google for SWOP Risk CalculatorStart with SWOP “Risk calculator 3 + DRE”
    11. 11. Enter findings on rectal exam, DRE volume andPSA, click calculate
    12. 12. Results aregiven forrisk of anycancer andadvancedor highgradecancerRefer ifany risk > 20% orhigh grade risk > 4%
    13. 13. Largeprostates -less likely tocontaincancercomparedto smallprostatesfor thesame PSA
    14. 14. Calculator is more accurate predictorAny prostate cancer = 1%Advanced/high grade PCa=0.18%Any prostate cancer = 22%Advanced/high grade Pca = 5%
    15. 15. Knowing your risk in relevant
    16. 16. Years after diagnosisDead fromprostatecancerDeadfromothercauses4% chance of dying after 10 y for lowrisk disease in PSA era in 65 year oldContains Gleason pattern 3 only1 2 3 4 5
    17. 17. 40% chance of dying at 10 years for highrisk disease in PSA era in a 65 year oldYears after diagnosisDeadfromprostatecancerDeadfromotherreasonsGleason pattern 4 or 51 2 3 4 5
    18. 18. More testing in US associated withfewer deaths and faster fall than UK4 fold faster falland lower in US
    19. 19. Could low assessment rates forprostate cancer in UK be responsible?
    20. 20. Even simple PSA-based screening reducesprostate cancer deaths by 25%
    21. 21. Screening programmes only beneficialif little routine testing20 – 30%reduction indeath ratesNo change indeath rate
    22. 22. 35 men needed to be diagnosed byscreening to save 1 life at 12 years
    23. 23. PIVOT trial showed treatment benefits inhigh risk prostate cancer
    24. 24. Reluctance to test for prostate cancerhas been overdone
    25. 25. Current Tissue Diagnosis Pathway isUnfit for Today
    26. 26. On standard unguided biopsies – evensmall lesions may seem to be importantBiopsy needles passing from rectum into prostateAnteriorPosterior
    27. 27. Unguided or transrectal biopsies misstumours esp. anterior cancersBiopsy needles passing from rectum into prostateAnteriorPosterior
    28. 28. Unguided biopsies may glance animportant cancer, underrepresenting itBiopsy needles passing from rectum into prostateAnteriorPosterior
    29. 29. Multiparametric MRI localises prostate cancerand informs on the severity – Best Current Test
    30. 30. mpMRI (1) shows cancer as black areasHistology shows cancer inred and MRI in black
    31. 31. mpMRI (2) Cancer is stiff and restrictsdiffusion of water moleculesDiffusion WeightedImaging on ‘long B’images showscancer as whiteRestricted diffusionby cancer is whitein this scan
    32. 32. mpMRI (3) early uptake of contrastindicates cancerRosenkrantz 2012
    33. 33. MRI “feels” areas you cannot touch with your finger:anterior tumours – often “no cancer” on TRUS biopsy
    34. 34. mpMRI report shows location andlesion scores
    35. 35. mpMRI lesion is scored from 1 to 5indicating likelihood of significant cancerScore Meaning1 Not suspicious Highly unlikely to contain a clinically significant lesion2 Not very suspicious Unlikely to contain a significant lesion3 Ambiguous Ambiguous!4 Suspicious Likely to contain a clinically significant lesion5 Very suspicious Highly likely to contain a significant lesionSignificant lesion ismore than 0.2cc orGleason pattern 3+4or higher
    36. 36. mpMRI score & report guides likelymanagementScore Meaning Management Plan1 Not suspicious Observe2 Not very suspicious Observe3 Ambiguous Look at other risk factors to determine biopsy e.g.:PCA3 score >35,PSA density > 0.2 ng/ml/cm3 (PSA/prostate vol)4 Suspicious Biopsy5 Very suspicious Biopsy
    37. 37. Indications for mpMRI• Anyone at risk of prostate cancer in whomdiagnosis may be beneficial• PSA > age threshold– 50-50y PSA > 3– 60-69y PSA > 4– 70y + PSA > 5• BEFORE prostate biopsy• After negative biopsy without MRI• Active monitoring
    38. 38. After a Transrectal biopsy, 30 to 70% will have apositive biopsy, After a negative multiparametricMRI only 3% have a positive biopsyMany Advantages of MRI!!
    39. 39. Biopsies of mpMRI targets are morerepresentative of the tumour severityFewer cores need to be taken and the highest grade and cancer length are found
    40. 40. Transperineal guided biopsies enablemore reliable targeting and are saferNo life threatening sepsis orrectal bleeding“Transfaecal” biopsies4% hospitalisation
    41. 41. A grid in front of the perineumpositions the needle accurately
    42. 42. Using USS and MRI fusion, the needleis guided into exactly the correct place
    43. 43. Histology Report Guides Need fortreatmentProstate biopsy map
    44. 44. Optimal Prostate Cancer PathwayPSARisk any Ca >20%Risk high gradePCa>4% or NICE PSAMultiparametric MRIOnly 3% chance of prostate Ca -monitor outside hospitalTransperineal TargetedbiopsiesLow risklocalisedHigh risklocalisedprostatectomyASBrachyFocalTherapyPSA>15 ormpMRI+mpMRI-ve & PSA <15
    45. 45. Prolaris: new test on cell cycle proteinsmay improve prognosis over Gleasonscore
    46. 46. O Gleason <7O Gleason 7O Gleason 8-10
    47. 47. O Gleason <7O Gleason 7O Gleason 8-1015% Gleason 6 > 20% risk
    48. 48. O Gleason <7O Gleason 7O Gleason 8-1015% Gleason 8+ <20% risk
    49. 49. When confident low risk cancer, focalablation to target the lesion is an option
    50. 50. Optimal Prostate Cancer Pathway?PSA< 15Risk any Ca >20%Riskhigh grade PCa>4%or NICE PSAMultiparametric MRIOnly 3% chance of prostate Ca -monitor outside hospitalTransperineal TargetedbiopsiesLow risklocalisedHigh risklocalisedprostatectomyASmpMRI-ve & PSA <15BrachyFocalTherapyPSA>15 ormpMRI+
    51. 51. Multiple guidelines advise on earlydetection
    52. 52. Advise men < 40 years: not to havePSA-based screening• Prevalence– Caucasians 0.1%– African 2%• Autopsy studies: lowvolume and low gradePC
    53. 53. Men aged 40 to 54 years screen if riskfactors• Family History– Prostate Cancer• First degree 130% increase– Father 120% increase– Brother 200% increase• Second degree 100%• More if age < 65 years andrelative < 60 years– Breast cancer• Mother 20% increase in risk(not sister)– BRCA2 gene 7 x increase inrisk if age < 65 years• Race– West Africa SMR 270– Caribbean SMR 200
    54. 54. Aged 55 to 69 : test after shared decisionmaking based on values & preferences• Check baseline mortalityrisk from other comorbidconditions• Individual risk factors• How screening might– influence overall lifeexpectancy– Morbidity from prostatecancer itself– Morbidity from prostatecancer treatment• Decision aids
    55. 55. Do not routinely screen > 70-74 years• If screening, high gradedisease is worthdiagnosing– PSA > 10 ng/ml

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