The status of Lung Cancer Screening Guidelines. Peter B. Bach, MD, MAPP Memorial Sloan Kettering Cancer Center

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1 The status of Lung Cancer Screening Guidelines Peter B. Bach, MD, MAPP Memorial Sloan Kettering Cancer

2 Homogeneity of guidelines But what about these?

3 Outside the box guidelines requires extrapolation from NLST What do we know about unstudied groups and interventions? What do we know about harm minimization? In these groups? Overall? Are safeguards in place? Can we rely on surrogate endpoints to expand who is screened? Where does individualized decision making fit in?

4 NLST shows efficacy of LDCT screening for lung cancer in protocol driven study

5 Partial overlap with overall at-risk group: demographics

6 Modest overlap: Age when people die of lung cancer 30% % of total lung cancer deaths by age 25% 20% 15% 10% 5% 0% SEER (CSR ) NLST

7 Care settings: not typical

8 What to do about unstudied groups? Unstudied durations? Where we have no data: Screening over 74 Screening for longer duration Screening in real world settings But what can we infer?

9 Inference: older age groups NLST: fewer than 9% of subjects over age 69 at entry, none over 74 Rising age and its tradeoffs: Good: Risk of lung cancer rises (lowers number needed to screen) Large differences: 80 yr old with 50 pyrs is at 11-times the 6- year risk of death from lung cancer compared to a 55 year old with 30 pyrs (4.5% vs 0.4%) Bad: Risk of false positives rises (more harm to those not benefitting) Life expectancy falls (less benefit per saved life ) Risk of surgical death rises (reduces net benefit)

10 Years of life remaining False positive rate & surgical mortality Bad trends with advancing age Age Expected Life Years Remaining (CISNET models for smokers) Observed false positive rate (NLST data) Extrapolated false positive rate Surgical Mortality (SEER-Medicare analysis) Extrapolated surgical mortality

11 Harm minimization Reasons for optimism: Numerous efforts to codify approach to false positives ( LungRADS ) Efforts underway to create standards for follow-up and biopsies But some caution: Trusted lists of screening sites?? Trusted guidelines Using surrogates to expand population

12 List of trusted sites (n=78)* (Lung Cancer Alliance 2014) 19% ACCP/ASCO/ATS/ACS USPSTF Neither (age too low) 13% 59% 3% 1% Neither (smoking or quit duration too liberal) Neither (non-smokers eligible) 5% *Sample was 1 st half of listed US States Neither (multiple reasons)

13 NCCN guidelines

14 NCCN not even NCCN Consensus? UCSF

15 What about surrogates? CT screening according to the I-ELCAP regimen can detect clinical stage I lung cancer in a high proportion of persons when it is curable by surgery. In a population at risk for lung cancer, such screening could prevent some 80% of deaths from lung cancer.

16 Surrogate markers for expanding population Surrogate should be early and accurate predictors of true outcomes True outcome: lung cancer mortality change Surrogates used: Proportion of lung cancers that are early stage: Early interception of lung cancer means diversion to better outcome Survival of those diagnosed through screening: Assumed to be (1-mortality)

17 We addressed surrogate value with data Natural variation between sites of NLST Study had 33 sites Each has data on surrogate endpoints and true outcomes Conducted correlation analyses that are part of the Prentice Criteria for surrogate markers

18 A Surrogates NOT predictive of OUTCOME Favors CT Favors CT Favors CXR

19 Real World example: DLCST results Increase in early stage lung cancers found Increase in survival following CT diagnosis True Outcome: HR = 1.03; ( ; P = 0.9)

20 Risk and individual decision making Every guideline recommends shared decision making: Why? Risk varies predictably, so does benefit Decision tools are in development

21 Guidelines recommending shared decision making

22 Risk variation in the NLST Kovalchik SA, et al. Targeting of low-dose CT screening according to the risk of lung-cancer death. N Engl J Med. 2013;369(3):

23 Benefit travels with risk of disease

24 Decision tools under piloting

25 Thank you