Defining Cancer Recurrence in a Population-Based Cancer Surveillance Study

1. Defining Cancer Recurrence in a Population-Based Cancer Surveillance Study Trevor D. Thompson Mathematical Statistician Cancer Surveillance Branch NAACCR Conference 2019 June 13, 2019 Vancouver, British Columbia, Canada

2. Background • Cancer recurrence is an important outcome not routinely captured by population-based registries • Difficult time to event outcome to define • Who is eligible for a recurrence? • When to start the time to event clock (i.e. when are patients at risk)? • When to censor? • Assume disease-free through active follow-up date (last review of medical records) unless otherwise documented? • At last documented disease-free date – clinical follow-up schedules vary • Should cause of death information figure in?

3. NPCR Patient-Centered Outcomes Research (PCOR) • Five US states (CO, LA, ID, NH, RI) • Outcomes of interest – disease-free (DF) status, recurrence, and progression • Active follow-up of medical records for a minimum of 32 months post-diagnosis with the majority followed at least 60 months • N=17,802 breast and colorectal cancer cases diagnosed in 2011

4. NPCR Patient-Centered Outcomes Research (PCOR) • Recurrence Status • Coding: • 0 = Patient never found to be DF • 1 = Found to be DF and remained DF till the end of study • 2 = Documented Recurrence • 3 = Uncertain if recurrence based on incomplete documentation • 4 = Uncertain if recurrence based on conflicting documentation • 9 = Unknown; patient was DF but unclear if remained DF or recurred • First recurrence date • Type of recurrence (in situ, local, regional, distant) • Recurrence source

5. Study Population • Include only: • First primary diagnosed in study period • Surgery patients • Achieved DF status (at risk for recurrence) • Known stage • Exclude patients with no follow-up time: • Missing surgery or recurrence date • Unknown recurrence status and last DF date = surgery date • N=9826 female breast cancers and N=3770 colorectal cancers

6. Methods • Outcomes: • Time from surgery to recurrence • Time from surgery to death or recurrence • Censoring Methods/Assumptions: • Assume no recurrence through active follow-up (AFU) date • Censor at last documented DF date • Used SEER Cause-Specific Death Classification as part of outcome algorithm • Uses ICD codes to define cancer deaths for first primaries • 0=Alive or dead of other cause, 1=Dead attributable to cancer DX • We used cancer-specific COD only for sequence numbers 02+

7. Methods • Discrete variables presented as frequencies and percentages; continuous variables presented as 25th / 50th / 75th percentiles • Freedom from recurrence and recurrence-free survival presented as Kaplan-Meier estimates/figures • Estimates censored at 4-years where follow-up was relatively complete

8. Events Algorithm – AFU Assumption • Patients with a documented recurrence classified as both events at date of recurrence • Patients classified as DF until end of study according to abstractor • Patients that were DF but unclear if remained DF until end of study • R = Recurrence, DR = Death or Recurrence * According to SEER Cause-Specific Death algorithm

9. Events Algorithm – Documented DF • Patients with a documented recurrence classified as both events at date of recurrence • Patients classified as DF until end of study according to abstractor • Patients that were DF but unclear if remained DF until end of study • R = Recurrence, DR = Death or Recurrence * According to SEER Cause-Specific Death algorithm

10. Study Population - Demographics

11. Study Population – AJCC Stage

12. 4-year Freedom from Breast Cancer Recurrence by AJCC Stage

13. 4-year Freedom from Colorectal Cancer Recurrence by AJCC Stage

14. Summary: 4-Year Recurrence-Free Survival

15. Summary • PCOR dataset provides a unique opportunity to analyze cancer recurrence in a population-based setting • Active follow-up of medical records with directly coded disease-free, recurrence, and progression status • Recurrence is a difficult outcome to define • Important to weigh the pros/cons of definitions/algorithms and acknowledge limitations • Recurrence-free survival presents additional challenge of shorter follow-up for recurrence compared to death (via linkages)

16. Summary • Recommend using active follow-up date in definitions rather than last DF date • Logically makes sense given the nature of the PCOR data collection (abstractors reviewing records and directly coding recurrence status) • Results in less censoring - increases % with complete follow-up • Yielded similar results for recurrence and recurrence-free survival compared to documented DF dates • Recommend using cause of death information as part of algorithms

17. Funding: This work was supported by the Patient Centered Outcome Research Trust Fund through CDC Cooperative Agreements of the National Program of Cancer Registries: in conjunction with the participating states and a CDC Patient Centered Outcome Research contract to ICF Acknowledgements