1. Predictive Models Are A Better Way To Stratify Patients For Clinical Trials James A. Eastham, MD Memorial Sloan-Kettering Cancer Center

3. When prognostic factors are combined the accuracy of prediction increases

4. Risk-groups

6. Surgery can cure many men with“high risk” cancer

7. Risk groups are often heterogeneous, containing patients who vary widely in prognosis From Mitchell JA et al. J Urol 2005: 173:1126 Low risk Intermediate risk High risk cT1c-T2a, Gl <7, PSA <10 cT2b or Gl 7 or PSA 10-20 cT2c or Gl 8-10 or PSA >20

8. Advantages of nomograms: interpreting discordant results A 59 yo man has a poorly differentiated (Gleason grade 4 + 5 = 9) cancer in 1 biopsy core taken from an impalpable (cT1c) prostate because of a PSA of 6. How likely would surgery control this cancer? 83% 63% 43% 23% 3% A 53 yo man had a PSA 47 when first examined. There was a firm palpable nodule in the prostate (cT2a). Needle biopsy showed Gleason grade 3+3=6 cancer in 3 of 6 cores. Is this a “curable” lesion? What is the 5 yr. freedom from recurrence? 83% 63% 43% 23% 3%

9. Advantages of nomograms: interpreting discordant results A 59 yo man has a poorly differentiated (Gleason grade 4 + 5 = 9) cancer in 1 biopsy core taken from an impalpable (cT1c) prostate because of a PSA of 6. How likely would surgery control this cancer? 83% 58% 43% 23% 3% Answer: 83% (37% confined, 40% ECE, 15% SVI, 8% LN) A 53 yo man had a PSA 47 when first examined. There was a firm palpable nodule in the prostate (cT2a). Needle biopsy showed Gleason grade 3+3=6 cancer in 3 of 6 cores. Is this a “curable” lesion? What is the 5 yr. freedom from recurrence? 83% 58% 43% 23% 3% Answer: 58% (22% confined, 60% ECE, 10% SVI, 8% LN)

10. Includes pretreatment and postoperative predictions. Uses published prostate cancer nomograms. Available at www.mskcc.org/prostate/nomograms

11. Patients used in the preoperative recurrence nomogram validation USA Cleveland Clinic 1168 LSU 583 UCLA 617 USC 1501 Europe Hamburg 1134 Rotterdam 475 Australia Sydney 754 Total6232 Patients Graefen et al., JCO, 2002

12. Predicted vs. Actual Freedom from Recurrence Range of Nomogram Predicted Probabilities Graefen et al., JCO, 2002

13. Continuous Model vs. Staging/Grouping Systems

14. Urologists vs. Preoperative Nomogram 10 case descriptions from 1994 MSKCC patients presented to 17 urologists In addition to PSA, biopsy Gleason grades, and clinical stage, urologists were provided with patient age, systematic biopsy details, previous biopsy results, and PSA history Preoperative nomogram was provided Urologists were asked to make their predictions of 5 year progression-free probabilities with or without use of the preoperative nomogram Concordance indices: Nomogram = 0.67 Urologists = 0.55, p<0.05 Ross P et al., Semin Urol Oncol, 2002

15. Uses of Risk Prediction Models in Clinical Trials Ethically restrict the trial to those at highest risk of failure with standard therapy Reduce sample size requirements by boosting event rates

16. Conclusions Nomogram predictions assist in: Patient counseling Shared decision-making Informed consent Clinical trial design and analysis Free software facilitates computations But…

17. Conclusions Nomograms are not perfect Based on patients treated in the (remote) past Predictive accuracy needs to be improved No information is available on how nomograms impact decision making Do nomograms lead to ‘better’ satisfaction with decisions?