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

Patient counselling

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• 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 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.

Doctors’ attitude

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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

“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.

Patient’s expectation

Tailor based approach

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Bi directional Patient preference Evidence based data Individualised outcome

prediction and prognosis

Patient counselling

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• 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.

Example : what is the risk of lymph nodes invasion ?

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What are the different level of EBM supported prediction ?

Risk groupings and probability tablesClassification and regression tree(CART)

analysisNomogramsArtificial neural networks (ANN)

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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

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Probability tables

Partin table

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

Stephenson nomogram

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

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Risk GroupingLimitations

Category summarize cohorts of patients Increment in category may lead to

overestimation of true frequency of endpoint

T1c, Gleason 3+4 Risk of (+) LN

PSA 5,9 ng/dl 8 %

PSA 6,1 ng/dl 12 %

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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

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

Nomogram allows progressive changes of the variables

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Nomogram allows progressive changes of the variables

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Nomogram allows progressive changes of the variables

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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

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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

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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

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Artificial neural networks

Neural networks Layers of nodes

– Input, hidden, output

Dendrites:input– Interconnections by weigthed connection

lines

Axons : output Computational model

High complexity

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Nomograms for predicting prostate-specific antigen recurrence

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Nomograms limitations

Retrospective statistical approachDespite prospective data collection

Modeling criteriaModel 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

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Nomograms limitations

ContemporaneityTool 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– ….

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Ex of contemporary impactBriganti Nomogram

ContemporaneityTool 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– ….

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Nomogram predicting the probability of lymph node invasion in patients undergoing extended pelvic lymphadenectomy

Briganti et al. Eur Urol 2007

Change in the technique induce a 20% risk increase…

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Nomograms for prediction of prostate cancer at needle biopsy

Karakiewicz PI and Hutterer GC (2008) Predictive models and prostate cancer. Nat Clin Pract Urol 5: 82–92

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Prediction of specific pathological features of clinically localized prostate cancer (before treatment)

Karakiewicz PI and Hutterer GC (2008) Predictive models and prostate cancer

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Prediction of biochemical recurrence with preoperative variables

Karakiewicz PI and Hutterer GC (2008) Predictive models and prostate cancerNat Clin Pract Urol 5: 82–92 doi:10.1038/ncpuro0972

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Predictive accuracy of existing nomograms

Chun F et al. World J Urol 2007

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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