How and when to use nomograms for counseling patients with prostate cancer ?

1. How and when to use nomograms for counseling patients with prostate cancer ? By the BAU Working Group of Urology

2. 62 years old • PSA 8,3 ng/ml • DRE, benign prostatic hypertrophy • Ultrasound (+) • 12 biopsies : • 2 positive on right for a Gleason 7 (3+4) in 25 and 35% of the sample. Patient counselling Patient is concerned and is looking at more information, about which treatment to choose, is think about a radical… He is discussing the need for a extended lymph nodes dissection.

3. Doctors’ attitude Le malade: Je n’ai rien moi, monsieur le docteur. Knock:Qu’est ce que vous en savez. Knock ou le triomphe de la médecine, Jules Romain, Acte 2 scène VI • Unidirectional, paternalistic ‘expert’ physician judgement • Personal physician bias • Historical, no controlled data and attitudes • Overall average outcome prediction

4. Patient’s expectation “Health care is changing fast and patients' experiences and expectations are also changing Patients no longer see themselves as passive recipients of care: increasingly they expect to be involved in all decisions that affect them. ” The European Patient Of The Future (State of Health) by Angela Coulter and Helen Magee, Open University Press, 2003.

5. Tailor based approach • Bi directional • Patient preference • Evidence based data • Individualised outcome prediction and prognosis

6. 62 years old • PSA 8,3 ng/ml • DRE, small nodule (0,7 mm ) in the right prostatic lobe • Ultrasound (+) • 12 biopsies : • 2 positive on right for a Gleason 7 (3+4) in 25 and 35% of the sample. Patient counselling Example : what is the risk of lymph nodes invasion ?

7. What are the different level of EBM supported prediction ? • Risk groupings and probability tables • Classification and regression tree(CART) analysis • Nomograms • Artificial neural networks (ANN)

8. Risk Grouping • Patients are “group” according to several prognostic factors into “risk category” • Univariate or multivariate regression analysis are then performed to estimate the % of occurence of the endpoint. • Ex: Partin table

9. Partin table Probability tables

10. Parker table for risk of death in untreated men with PCa PCa deaths Other cause of death C. Parker et al. British Journal of Cancer (2006) 94, 1361 – 1368

11. Stephenson nomogram Stephenson et al. Clin Oncol 25:2035-2041, 2007

12. Risk GroupingLimitations • Category summarize cohorts of patients • Increment in category may lead to overestimation of true frequency of endpoint

13. Nomograms - definition • Statistical definition • Graphical representation of a mathematical formula or algorithm • Incorporating several predictors modeled as continuous variables • To predict a particular end point • Using traditional statistical methods • Multivariable logistic regression • Cox proportional hazard analysis

14. Ex Kattan nomograms for predicting prostate-specific antigen recurrence after Radical prostatectomy

15. Nomogram allows progressive changes of the variables

16. Nomogram allows progressive changes of the variables

17. Nomogram allows progressive changes of the variables

18. Predictive tool and nomogram criteria • Cohorts • Developmental vs control • Validation • Internal vs external • Predictive accuracy • Discrimination and calibration • Generalizability • Level of complexity • Head-to-head comparison

19. Nomograms and cohorts • Cohort • Developmental cohort • Patient study population • Initial statistical patient sample • Single center of excellence series and/or • Data of high volume surgeons/pathologists from highly specialized tertiary care centers • Control cohort • Control population to test the model and confirm initial predictive accuracy • Internal and/ or external cohort

20. Nomograms and validation • Validation • Internal validation • Specific statistical methods, f.e bootstrapping • External validation • Ideal Gold Standard method of validation • Single or multicenter,same/different level of care • Validation end points • Predictive accuracy • Discrimination and calibration ability

21. Artificial neural networks • Neural networks • Layers of nodes • Input, hidden, output • Dendrites:input • Interconnections by weigthed connection lines • Axons : output • Computational model • High complexity

22. Nomograms for predicting prostate-specific antigen recurrence

25. Nomograms limitations • Retrospective statistical approach • Despite prospective data collection • Modeling criteria • Model selection criteria exclude certain other patient subgroups • Total PSA • Total PSA is an important variable in most nomograms • Lack of specificity • Testing variability ( 30%) • Stage migration

26. Nomograms limitations • Contemporaneity • Tool development in non-contemporary situations • Stage migration/ screen detected populations • Diagnostic and therapeutic standards • E.g. sextant biopsies vs 10 -12 core biopsies • Dose of radiotherapy • Surgical standards • ….

27. Ex of contemporary impactBriganti Nomogram • Contemporaneity • Tool development in non-contemporary situations • Stage migration/ screen detected populations • Diagnostic and therapeutic standards • E.g. sextant biopsies vs 10 -12 core biopsies • Dose of radiotherapy • Surgical standards • ….

28. Nomogram predicting the probability of lymph node invasion in patients undergoing extended pelvic lymphadenectomy Change in the technique induce a 20% risk increase… Briganti et al. Eur Urol 2007

29. Nomograms for prediction of prostate cancer at needle biopsy Karakiewicz PI and Hutterer GC (2008) Predictive models and prostate cancer. Nat Clin Pract Urol5:82–92

30. Prediction of specific pathological features of clinically localized prostate cancer (before treatment) Karakiewicz PI and Hutterer GC (2008) Predictive models and prostate cancer

31. Prediction of biochemical recurrence with preoperative variables Karakiewicz PI and Hutterer GC (2008) Predictive models and prostate cancer Nat Clin Pract Urol5:82–92 doi:10.1038/ncpuro0972

32. Predictive accuracy of existing nomograms Chun F et al. World J Urol 2007

33. What do we need in the future? • Ultimately, improved imaging studies and high-throughput genomics may replace the use of nomograms, as they will provide a real patient-specific staging and prognostication, and allow patient-tailored treatment decisions to be made • In the meantime, nomograms are the best possible alternative and should be actively implemented in EAU prostate cancer guidelines