How and when to use nomograms for
counseling patients with prostate cancer ?
By the BAU Working Group of Urology
Patient counselling
•
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.
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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
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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.
Tailor based approach
 Bi directional
 Patient preference
 Evidence based data
 Individualised outcome
prediction and prognosis
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Patient counselling
•
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 tables
 Classification and regression tree(CART)
analysis
 Nomograms
 Artificial 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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Partin table
Probability tables
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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
Risk Grouping
Limitations
 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
–
–
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Multivariable logistic regression
Cox proportional hazard analysis
Ex Kattan nomograms for predicting prostate-specific antigen
recurrence after Radical prostatectomy
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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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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 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
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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
– ….
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Ex of contemporary impact
Briganti 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
– ….
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Nomogram predicting the probability of lymph node invasion in patients
undergoing extended pelvic lymphadenectomy
Change in the technique induce a 20% risk increase…
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Briganti et al. Eur Urol 2007
Nomograms for prediction of prostate cancer at needle biopsy
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Karakiewicz PI and Hutterer GC (2008) Predictive models and prostate cancer. Nat Clin Pract Urol 5: 82–92
Prediction of specific pathological features of clinically localized prostate
cancer (before treatment)
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Karakiewicz PI and Hutterer GC (2008) Predictive models and prostate cancer
Prediction of biochemical recurrence with preoperative variables
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Karakiewicz PI and Hutterer GC (2008) Predictive models and prostate cancer
Nat Clin Pract Urol 5: 82–92 doi:10.1038/ncpuro0972
Predictive accuracy of existing nomograms
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Chun F et al. World J Urol 2007
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
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