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Categorical staging vs. prediction models: what is the evidence? Andrew J. Vickers, Ph.D. Assistant Attending Research Methodologist Memorial Sloan-Kettering Cancer Center
How do we normally assess risk in cancer? We don’t do so explicitly We use stage as an approximate surrogate
Clinical decisions based on stage Adjuvant chemotherapy for stage II but not stage I gastric cancer Why is chemotherapy effective if “tumor invades into the muscularis propria layer” but not if it “extends only into the muscularis mucosa”?
Some basic decision theory We want to know a patient’s risk to help determine treatment e.g.: High risk of recurrence: adjuvant therapy Low risk of recurrence: no adjuvant therapy The more accurately we estimate risk, the better our decisions
Statistical model vs. AJCC: Gastric cancer  AJCC IV (32) IIIB (24) IIIA (69) II (117) IB (115) IA (102)
Statistical model vs. AJCC: Melanoma IIC 53% IIB 34% IIA 24% IB 9% IA 2%
As the man on the Clapham ominbus would tell you… More information => better prediction A man with low grade cancer might have positive lymph nodes and high PSA suggesting metastases A man with high grade cancer might have very localized disease curable by prostatectomy
Risk group approach Based on features, we make a crude tree. Most cancer staging systems do this. High grade N Y High PSA & high stage Y HIGH  RISK LOW RISK N
Kattan MW, et al., J Clin. Oncol., 2000.
Theory vs. Practice Risk modeling sounds like a great idea, but what data do we have that it actually helps? Typical study: Obtain a data set with predictors and outcome Compare predictive accuracy of model and AJCC stage or other risk grouping
Comparison of prediction models vs. risk grouping
Recurrence after surgery for upper tract urothelial carcinoma (Ehdaie,submitted) ,[object Object],[object Object]
Conclusion:
“In this single institution study that involved data dependent variable selection, a small change in effect size is unlikely to withstand external validation.”
“nomogram did not importantly enhance the discriminatory ability of AJCC … nomogram is unlikely to improve clinical decision making or patient outcomes”,[object Object]
Nam nomogram (AUC 0.68) Biopsy all (AUC 0.5) PCPT (AUC 0.61)
Prediction models vs. risk groups Have the benefits of prediction models really been demonstrated? BUT: Prediction modeling allows rational decision making.
Rational decision making Prostate biopsy if: PSA > 4 ng / ml? Risk of prostate cancer > 20%? Harms and benefits of biopsy can be considered to choose a risk threshold Risk threshold can be individualized

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NY Prostate Cancer Conference - A. Vickers - Session 8: Debate 2: Categorical staging versus continuous prediction: How can we integrate predictive models into the staging systems? (Categorical staging vs prediction models: what is the evidence?)

  • 1. Categorical staging vs. prediction models: what is the evidence? Andrew J. Vickers, Ph.D. Assistant Attending Research Methodologist Memorial Sloan-Kettering Cancer Center
  • 2. How do we normally assess risk in cancer? We don’t do so explicitly We use stage as an approximate surrogate
  • 3. Clinical decisions based on stage Adjuvant chemotherapy for stage II but not stage I gastric cancer Why is chemotherapy effective if “tumor invades into the muscularis propria layer” but not if it “extends only into the muscularis mucosa”?
  • 4. Some basic decision theory We want to know a patient’s risk to help determine treatment e.g.: High risk of recurrence: adjuvant therapy Low risk of recurrence: no adjuvant therapy The more accurately we estimate risk, the better our decisions
  • 5. Statistical model vs. AJCC: Gastric cancer AJCC IV (32) IIIB (24) IIIA (69) II (117) IB (115) IA (102)
  • 6. Statistical model vs. AJCC: Melanoma IIC 53% IIB 34% IIA 24% IB 9% IA 2%
  • 7. As the man on the Clapham ominbus would tell you… More information => better prediction A man with low grade cancer might have positive lymph nodes and high PSA suggesting metastases A man with high grade cancer might have very localized disease curable by prostatectomy
  • 8. Risk group approach Based on features, we make a crude tree. Most cancer staging systems do this. High grade N Y High PSA & high stage Y HIGH RISK LOW RISK N
  • 9. Kattan MW, et al., J Clin. Oncol., 2000.
  • 10. Theory vs. Practice Risk modeling sounds like a great idea, but what data do we have that it actually helps? Typical study: Obtain a data set with predictors and outcome Compare predictive accuracy of model and AJCC stage or other risk grouping
  • 11. Comparison of prediction models vs. risk grouping
  • 12.
  • 14. “In this single institution study that involved data dependent variable selection, a small change in effect size is unlikely to withstand external validation.”
  • 15.
  • 16. Nam nomogram (AUC 0.68) Biopsy all (AUC 0.5) PCPT (AUC 0.61)
  • 17. Prediction models vs. risk groups Have the benefits of prediction models really been demonstrated? BUT: Prediction modeling allows rational decision making.
  • 18. Rational decision making Prostate biopsy if: PSA > 4 ng / ml? Risk of prostate cancer > 20%? Harms and benefits of biopsy can be considered to choose a risk threshold Risk threshold can be individualized
  • 19. Ultimately, we must towards prediction modeling To facilitate optimal decision making