Do I need a NOMOGRAM to make a good decision ?    <br /> Hein Van Poppel, MD,PhD<br />   Steven Joniau, MD<br />Leuven, Be...
In 2008 about 33.000 man died of PCa in N.Am., and 90.000 in Europe<br />Howcan we do better?<br />
Do I need a NOMOGRAM to make a good decision ?    <br />“The answer is no”            Hein Van Poppel<br />“The answer is ...
Situation in the past<br />For decades, staging and  prognosticationinvolvedwell-knownprognostic  factors:<br />cTNM<br />...
Whydecision aids?<br />Physicianjudgement is the basis for risk estimation, patient counseling, and decisionmaking<br />Th...
Nomograms<br />Currently the most accurate tool to predictoutcomes in PCapatients<br />Basedonknowntreatmentoutcomesfor a ...
Whatcan we usenomogramsfor?<br />1. Pre-biopsyprostate cancer risk calculation<br />2. LocalPCastagingpost-biopsy<br />Est...
Whatcan we usenomogramsfor?<br />4. Post-treatmentestimation of outcome<br />Biochemicalrelapse<br />Clinicalrelapse<br />...
Predictiveaccuracy of existingnomograms<br />    Chun F et al. World J Urol 2007;25:131-42<br />
Limitations of nomograms<br />Bias due to development cohort<br />Oftenbasedonsingle-centre series  and/or data fromtertia...
Limitations of nomograms<br />Imply a concept of stability:<br />No change, noevolution in surgerytechniques and methods,…...
Limitations of nomograms<br />Surrogateendpoints in most nomograms<br />Pathologic stage prediction<br />Biochemicalrecurr...
Summary: limitations of nomograms<br />Bias due to development cohort<br />High volume, tertiary care centers<br />Retrosp...
Howmany more nomograms do we need?<br /><ul><li>Confusingvariety of available tools</li></ul>How do we decidewhich (ifany)...
Thismay all beveryinteresting, BUT…<br />Do these predictionsreallychangeyourclinicaljudgement?<br />Will theyinfluenceyou...
Questions to Michael Kattan<br />about a givenpatient<br />Should weomit a biopsy…?<br />Should weadvocate Active Surveill...
No proofonadvantage of use of nomograms<br />Use of nomograms has notyet been implementedsufficientlyinto routine urologic...
How to improve PA<br />PredictiveAccuracy (PA) is suboptimal<br />           -  Novelbiomarkersassociatedwithbiologicbehav...
Whatis the future?<br />Ultimately, improvedimagingstudies and high-throughputgenomicswillreplace the use of nomograms, as...
Do patientsneed<br />nomograms ?<br />    No, ifthey are whatthey are today, onlyprovidingestimations of a chance, whilefo...
 The experts canorcannotusenomograms to this end</li></li></ul><li>I do notneed the actually<br />availablenomograms …<br ...
BACK - UP<br />26<br />
29<br />Prostate cancer: Decision aids<br />Univariate and multivariableanalysis<br />Risk groupings<br />Probability tabl...
30<br />Prostate cancer: Evaluatingpredictive tools<br />Predictiveaccuracy of the model<br />Internal and externalvalidat...
Definition of nomogram<br />Statisticaldefinition<br />Graphicalrepresentation of a mathematicalformulaoralgorithm<br />In...
A smallexercise…<br />Patient XX<br />PSA 6.4<br />cT2a<br />BiopsyGleason score 6 in 2 cores<br />
What is the risk of…<br />ECE?<br />	20%	40%	60%	80%<br />SVI invasion?<br />5%	10%	15%	20%<br />pN+?<br />2%	4%	6%	8%<br />
What is the risk of…<br />ECE?<br />	20%	40%	60%	80%<br />SVI invasion?<br />5%	10%	15%	20%<br />pN+?<br />2%	4%	6%	8%<br />
What is the risk of…<br />ECE?<br />	20%	40%	60%	80%<br />SVI invasion?<br />	5%	10%	15%	20%<br />pN+?<br />2%	4%	6%	8%<br />
What is the risk of…<br />ECE?<br />	20%	40%	60%	80%<br />SVI invasion?<br />5%	10%	15%	20%<br />pN+?<br />2%	4%	6%	8%<br />
What is the risk of biochemicalrelapseaftersurgery…<br />	25%	50%	75%	100%<br />
What is the risk of biochemicalrelapseaftersurgery…<br />25%	50%	75%	100%<br />
Anothersmallexercise…<br />Patient YY<br />PSA 8.6<br />cT2c<br />BiopsyGleason score 7 on 2 biopsies<br />
What is the risk of…<br />ECE?<br />20%	40%	60%	80%<br />SVI invasion?<br />	5%	10%	15%	20%<br />pN+?<br />2%	4%	6%	8%<br />
What is the risk of…<br />ECE?<br />	20%	40%	60%	80%<br />SVI invasion?<br />5%	10%	15%	20%<br />pN+?<br />	2%	4%	6%	8%<br />
What is the risk of…<br />ECE?<br />	20%	40%	60%	80%<br />SVI invasion?<br />5%	10%	15%	20%<br />pN+?<br />	2%	4%	6%	8%<br />
What is the risk of…<br />ECE?<br />20%	40%	60%	80%<br />SVI invasion?<br />	5%	10%	15%	20%<br />pN+?<br />2%	4%	6%	8%<br />
What is the risk of biochemicalrelapseaftersurgery…<br />25%	50%	75%	100%<br />
What is the risk of biochemicalrelapseaftersurgery…<br />	25%	50%	75%	100%<br />
The American World<br />
The Real World<br />
BRUSSSELS<br />BELGIUM<br />België<br />Belgique<br />Belgien<br />LEUVEN<br />
Nomogramtopredictlowvolumeinsignificantprostatecancer (n=258)<br />58 years<br />30 grams<br />PSA 3,0<br />4mm tumor<br /...
Prediction of biopsyoutcome<br />Karakiewicz PI and Hutterer GC.Nat Clin Pract Urol 2008;5:82–92<br />Karakiewicz PI and H...
Prediction of pathological features clinically localized PCa(before treatment)<br />Karakiewicz PI and Hutterer GC.Nat Cli...
Prediction of pathological features clinically localized PCa(before treatment)<br />Karakiewicz PI and Hutterer GC.Nat Cli...
Prediction of biochemical recurrence with preoperative variables<br />Karakiewicz PI and Hutterer GC.Nat ClinPractUrol 200...
PCa metagram<br />PCa metagram is constructed of <br />16 different treatmentoptions<br />10 outcomesrelated to cancercont...
PCa metagram<br />Data willbeincorporatedinto a software program<br />Physician<br />will enter patient-specific variables...
PCa metagram<br />
What to do to implement the use of nomograms?<br />Update nomograms to contemporarypatientpopulations<br />Novelbiomarkers...
Whymightnomogramsbeimplementedintoclinicalpractice?<br />Appropriatepatient counseling  / decision-making  ?<br />Betterdi...
Limitations of nomograms<br />Suboptimalpredictiveaccuracy<br />Nomogramprediction is not 100% accurate<br />Lack of consi...
EAU PCaguidelines<br />Use of nomograms is onlyincluded 3 times<br />Preoperativestaging(Kattannomogram, Partin tables (= ...
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NY Prostate Cancer Conference - H. Van Poppel - Session 8: Do I need a nomogram to make good decisions (The answer is no)

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NY Prostate Cancer Conference - H. Van Poppel - Session 8: Do I need a nomogram to make good decisions (The answer is no)

  1. 1. Do I need a NOMOGRAM to make a good decision ? <br /> Hein Van Poppel, MD,PhD<br /> Steven Joniau, MD<br />Leuven, Belgium<br />SecondInterdisciplinary Conference<br />MSKCC – ESO New York, 9-4-2011<br />
  2. 2. In 2008 about 33.000 man died of PCa in N.Am., and 90.000 in Europe<br />Howcan we do better?<br />
  3. 3. Do I need a NOMOGRAM to make a good decision ? <br />“The answer is no” Hein Van Poppel<br />“The answer is yes” Michael Kattan<br />
  4. 4.
  5. 5. Situation in the past<br />For decades, staging and prognosticationinvolvedwell-knownprognostic factors:<br />cTNM<br />Gleason score<br />PSA<br />However, these parameters provide ratherlimitedinformationwhenconsideredseparately<br />
  6. 6. Whydecision aids?<br />Physicianjudgement is the basis for risk estimation, patient counseling, and decisionmaking<br />Thisjudgementmaybebiasedbecause of subjective and objectiveconfounders<br />Development of predictive and prognostic tools<br />Recent explosion in the field of PCadecision aids<br />Shariat SF et al. Cancer 2008;113:3075-99<br />
  7. 7. Nomograms<br />Currently the most accurate tool to predictoutcomes in PCapatients<br />Basedonknowntreatmentoutcomesfor a groupwithsufficientsimilarities to the patient, and having been treated in the samefashion, a number of yearsago<br />
  8. 8. Whatcan we usenomogramsfor?<br />1. Pre-biopsyprostate cancer risk calculation<br />2. LocalPCastagingpost-biopsy<br />Estimation of pTNM<br />3. Pre-treatmentestimation of outcome<br />Biochemicalrelapse<br />Clinicalrelapse<br />Deathfrom prostate cancer<br />
  9. 9. Whatcan we usenomogramsfor?<br />4. Post-treatmentestimation of outcome<br />Biochemicalrelapse<br />Clinicalrelapse<br />Deathfrom prostate cancer<br />5. Predictionof local / systemicfailurewhenbiochemicalrelapse<br />6. Predictionof death in HRPC<br />
  10. 10. Predictiveaccuracy of existingnomograms<br /> Chun F et al. World J Urol 2007;25:131-42<br />
  11. 11. Limitations of nomograms<br />Bias due to development cohort<br />Oftenbasedonsingle-centre series and/or data fromtertiary care centres<br />Retrospectivestatisticalapproach<br />Despiteprospective data collection<br />Specific model selection criteria<br />Model selection criteria excludecertainsubgroups, e.g. patientswho had neoadjuvant HT are excluded in most models <br />Lack of externalvalidation<br />Chun F et al. World J Urol 2007;25:131-42<br />
  12. 12. Limitations of nomograms<br />Imply a concept of stability:<br />No change, noevolution in surgerytechniques and methods,…. impossible to consider recent improvements in technique, knowledge in tumourbiology, and disease characteristics1<br />Lack of periodic updates in contemporarycohorts<br />Development in non-contemporarysituations = inaccurate predictions in contemporary patients2<br />Stage migration/ screen detectedpopulations<br />Change in diagnostic and therapeuticstandards<br />For example: sextant biopsies vs. 10-12 core biopsies<br />Type and dose of Radiotherapy, Surgical techniques<br />Guillonneau B. EurUrol2007 2.Chun F et al. World J Urol2007<br />
  13. 13. Limitations of nomograms<br />Surrogateendpoints in most nomograms<br />Pathologic stage prediction<br />Biochemicalrecurrence<br />Lack of “hard endpoint” nomograms<br />Requiredendpoints:<br />Local and distantrecurrence<br />Disease- specific and overall survival<br />Correct and long-term follow-up and competingcomorbidityanalysis<br />Chun F et al. World J Urol 2007;25:131-42<br />
  14. 14. Summary: limitations of nomograms<br />Bias due to development cohort<br />High volume, tertiary care centers<br />Retrospectivestatisticalmethodology<br />Specific model selection criteria<br />Lack of externalvalidation<br />Lack of periodic updates in contemporarycohorts<br />Lack of novel more specific markers<br />Surrogate versus clinicallymeaningfulendpoints<br />Predictiveaccuracynot 100%<br />
  15. 15. Howmany more nomograms do we need?<br /><ul><li>Confusingvariety of available tools</li></ul>How do we decidewhich (ifany) nomogram to use in clinicalpractice?<br />PCa metagram (Nuygen and Kattan 2009)<br />frameworkonwhichexistingPCaprediction tools are organised and stratifiedbyaccuracy, quality and usefulness in a clinical setting<br />additionalnomograms are needed …….<br />NguyenCT and Kattan MW. Cancer 2009<br />
  16. 16. Thismay all beveryinteresting, BUT…<br />Do these predictionsreallychangeyourclinicaljudgement?<br />Will theyinfluenceyourdecision-makingprocess?<br />Are these predictionsreallyhelpfulforyourindividualpatient? <br />
  17. 17. Questions to Michael Kattan<br />about a givenpatient<br />Should weomit a biopsy…?<br />Should weadvocate Active Surveillance…?<br />Shall we not go for a RPr…?<br />Can we safelyomit a LND…?<br />Do we give give adjuvant therapy to all…?<br />Will our patient appreciate an estimation of the chance of his time to failure, or to death…? <br />
  18. 18.
  19. 19. No proofonadvantage of use of nomograms<br />Use of nomograms has notyet been implementedsufficientlyinto routine urologicalpractice<br />Studies providingevidence-basedproofon the advantage of usingnomograms over clinicaljudgement are virtually ABSENT<br />No nomogramwill ever take the place of goodclinicaljudgement and information to the patient<br />
  20. 20. How to improve PA<br />PredictiveAccuracy (PA) is suboptimal<br /> - Novelbiomarkersassociatedwithbiologicbehaviour<br />8% increase in PA withinclusion of IL-6 and TGF-β11<br />Plasminogen activator inhibitor type 1, humanglandular kallicrein-2, gene expressionsignatures, plasma endoglin, …<br />- Larger datasets and systematic and clean data collection<br /><ul><li>More sophisticated modeling procedures2</li></ul>Kattan MW et al. J ClinOncol 2003;21:3573-9<br />Shariat SF et al. Cancer 2008; 113:3075-99<br />
  21. 21. Whatis the future?<br />Ultimately, improvedimagingstudies and high-throughputgenomicswillreplace the use of nomograms, as theywill provide a realpatient-specificstaging and prognostication, and allowpatient-tailoredtreatmentdecisions<br />GenomicSignaturesforPersonalisedTherapy<br /> Mammaprint, Coloprint, “Prostaprint “?<br />
  22. 22. Do patientsneed<br />nomograms ?<br /> No, ifthey are whatthey are today, onlyprovidingestimations of a chance, whileforthemit is rather<br /> a black or white scenario<br /><ul><li>Patientsneed to befullyinformed at all decision- </li></ul>making steps<br /><ul><li>Theyneed to find centers where experts are willing to provide thisinformation
  23. 23. The experts canorcannotusenomograms to this end</li></li></ul><li>I do notneed the actually<br />availablenomograms …<br />to make a <br />good<br />decision<br />April 2011<br />
  24. 24.
  25. 25.
  26. 26. BACK - UP<br />26<br />
  27. 27.
  28. 28.
  29. 29. 29<br />Prostate cancer: Decision aids<br />Univariate and multivariableanalysis<br />Risk groupings<br />Probability tables<br />Artificialneuralnetworks (ANN)<br />Classification and regression tree (CART) analysis<br />Nomograms<br />Shariat SF et al. Cancer 2008;113:3075-99<br />
  30. 30. 30<br />Prostate cancer: Evaluatingpredictive tools<br />Predictiveaccuracy of the model<br />Internal and externalvalidation to ensuregeneralizability<br />Model calibration<br />Level of complexicity<br />Clinicalimplication<br />Head-to-headcomparisons<br />Shariat SF et al. Cancer 2008;113:3075-99<br />Capitanio U et al. The Prostate 2010;70:1371-78<br />
  31. 31. Definition of nomogram<br />Statisticaldefinition<br />Graphicalrepresentation of a mathematicalformulaoralgorithm<br />Incorporatingseveralpredictors modeled as continuous variables <br />To predict a particularendpoint<br />Using traditional statisticalmethods<br /> - Multivariablelogisticregression<br /> - Cox proportional hazard analysis<br />
  32. 32. A smallexercise…<br />Patient XX<br />PSA 6.4<br />cT2a<br />BiopsyGleason score 6 in 2 cores<br />
  33. 33. What is the risk of…<br />ECE?<br /> 20% 40% 60% 80%<br />SVI invasion?<br />5% 10% 15% 20%<br />pN+?<br />2% 4% 6% 8%<br />
  34. 34. What is the risk of…<br />ECE?<br /> 20% 40% 60% 80%<br />SVI invasion?<br />5% 10% 15% 20%<br />pN+?<br />2% 4% 6% 8%<br />
  35. 35. What is the risk of…<br />ECE?<br /> 20% 40% 60% 80%<br />SVI invasion?<br /> 5% 10% 15% 20%<br />pN+?<br />2% 4% 6% 8%<br />
  36. 36. What is the risk of…<br />ECE?<br /> 20% 40% 60% 80%<br />SVI invasion?<br />5% 10% 15% 20%<br />pN+?<br />2% 4% 6% 8%<br />
  37. 37. What is the risk of biochemicalrelapseaftersurgery…<br /> 25% 50% 75% 100%<br />
  38. 38. What is the risk of biochemicalrelapseaftersurgery…<br />25% 50% 75% 100%<br />
  39. 39. Anothersmallexercise…<br />Patient YY<br />PSA 8.6<br />cT2c<br />BiopsyGleason score 7 on 2 biopsies<br />
  40. 40. What is the risk of…<br />ECE?<br />20% 40% 60% 80%<br />SVI invasion?<br /> 5% 10% 15% 20%<br />pN+?<br />2% 4% 6% 8%<br />
  41. 41. What is the risk of…<br />ECE?<br /> 20% 40% 60% 80%<br />SVI invasion?<br />5% 10% 15% 20%<br />pN+?<br /> 2% 4% 6% 8%<br />
  42. 42. What is the risk of…<br />ECE?<br /> 20% 40% 60% 80%<br />SVI invasion?<br />5% 10% 15% 20%<br />pN+?<br /> 2% 4% 6% 8%<br />
  43. 43. What is the risk of…<br />ECE?<br />20% 40% 60% 80%<br />SVI invasion?<br /> 5% 10% 15% 20%<br />pN+?<br />2% 4% 6% 8%<br />
  44. 44. What is the risk of biochemicalrelapseaftersurgery…<br />25% 50% 75% 100%<br />
  45. 45. What is the risk of biochemicalrelapseaftersurgery…<br /> 25% 50% 75% 100%<br />
  46. 46. The American World<br />
  47. 47. The Real World<br />
  48. 48. BRUSSSELS<br />BELGIUM<br />België<br />Belgique<br />Belgien<br />LEUVEN<br />
  49. 49. Nomogramtopredictlowvolumeinsignificantprostatecancer (n=258)<br />58 years<br />30 grams<br />PSA 3,0<br />4mm tumor<br />Low-volume/low-grade cancer was defined as pathologic organ-confined disease and a tumor volume < 0.5 cc with no Gleason grade 4 or 5 cancer. <br />Nakanishi et al., Cancer 2007<br />
  50. 50. Prediction of biopsyoutcome<br />Karakiewicz PI and Hutterer GC.Nat Clin Pract Urol 2008;5:82–92<br />Karakiewicz PI and Hutterer GC.Nat ClinPractUrol 2008;5: 82–92<br />
  51. 51. Prediction of pathological features clinically localized PCa(before treatment)<br />Karakiewicz PI and Hutterer GC.Nat ClinPractUrol 2008;5: 82–92<br />
  52. 52. Prediction of pathological features clinically localized PCa(before treatment)<br />Karakiewicz PI and Hutterer GC.Nat ClinPractUrol 2008;5: 82–92<br />
  53. 53. Prediction of biochemical recurrence with preoperative variables<br />Karakiewicz PI and Hutterer GC.Nat ClinPractUrol 2008;5: 82–92<br />
  54. 54. PCa metagram<br />PCa metagram is constructed of <br />16 different treatmentoptions<br />10 outcomesrelated to cancercontrol, survival and morbidity<br />160 treatment/outcomecombinations<br />Only 31 cells are populatedwithavailable tools<br />Areas of deficiency in the currentcatalog of prediction tools<br />Nguyen CT and Kattan MW. Cancer 2009;115(Suppl 13):3160-2<br />
  55. 55. PCa metagram<br />Data willbeincorporatedinto a software program<br />Physician<br />will enter patient-specific variables<br />willgenerategraphical and tabularpresentation of predictions of treatmentendpoints, with all availablealternativestailored to the individualpatient<br />Limitations of the metagram<br />Not all cells are populated  more tools are needed<br />Lack of prediction tools for LRP, cryoablation and HIFU<br />Survival and morbidityoutcomes are poorlyrepresented<br />Additionalprediction tools assessing risk of metastasis and cancer-specificmortality are needed<br />Nguyen CT and Kattan MW. Cancer 2009;115(Suppl 13):3160-2<br />
  56. 56. PCa metagram<br />
  57. 57. What to do to implement the use of nomograms?<br />Update nomograms to contemporarypatientpopulations<br />Novelbiomarkers to improvepredictions<br />Head-toheadcomparisonsbetweennomograms<br />to select the best-suited model in selectedfields of PCaoutcomes<br />We neednomogramsthat<br />provide accurate predictions of hard clinicalendpoints (clinicalfailure, deathfrom the disease)<br />accuratelypredictdeathfromcomorbiddisease in men withlocalizeddiseaseselectedforradicaltreatment<br />predicttreatment-relatedtoxicity<br />Efforts are needed to improve the accuracy, accessibility and flexibility of nomograms and to provide more evidence to justifytheir routine use in clinical practice1<br />Lughezzani G et al. EurUrol 2010;58:687-700<br />
  58. 58. Whymightnomogramsbeimplementedintoclinicalpractice?<br />Appropriatepatient counseling / decision-making ?<br />Betterdiseaseprognostication ?<br />Follow-up monitoring ?<br />Selection of patientsforclinical trials !<br />
  59. 59. Limitations of nomograms<br />Suboptimalpredictiveaccuracy<br />Nomogramprediction is not 100% accurate<br />Lack of consideration of all predictive risk factors<br />Inability to assemble all knownprognostic factors optimally1<br />To improvepredictiveaccuracy (PA) we need<br />Novelbiomarkersassociatedwith the biologicbehaviour of PCa<br />8% increase in PA withinclusion of IL-6 and TGF-β12<br />Plasminogen activator inhibitor type 1, humanglandular kallicrein-2, gene expressionsignatures, plasma endoglin, …<br />Larger datasets and systematic and clean data collection<br />More sophisticated modeling procedures3<br />Chun F et al. World J Urol 2007;25:131-42<br />Kattan MW et al. J ClinOncol 2003;21:3573-9<br />Shariat SF et al. Cancer 2008; 113:3075-99<br />
  60. 60. EAU PCaguidelines<br />Use of nomograms is onlyincluded 3 times<br />Preoperativestaging(Kattannomogram, Partin tables (= look-up tables)<br />Indication of extendedlymph node dissection(Briganti nomogram)<br />Indication of nerve-sparingsurgery(Partin tables)<br />

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