This document summarizes research evaluating a risk prediction tool called PLCOm2012 for identifying high-risk individuals for lung cancer screening in Australia. The tool was validated using data from the 45 and Up Study, an ongoing cohort study of over 260,000 Australians aged 45 and older. Results showed PLCOm2012 predicted lung cancer incidence well and identified more high-risk individuals than the criteria used in the National Lung Screening Trial. Further modeling is still needed to fully assess the effectiveness and cost-effectiveness of using PLCOm2012 to target lung cancer screening in Australia.

1. Identifying individuals at high
risk for lung cancer in
Australia using a validated
risk prediction tool
Dr Marianne Weber
with
Karen Canfell, David Goldsbury, Sarsha Yap, Yoon-Jung Kang,
Michael Caruana, Emily Banks, Annette McWilliams, David
Manners, Martin Tammemagi, & Kwun Fong
45 and Up Study Collaborator’s Meeting,
Sydney
6th Sept, 2016

2. Background
• Lung cancer is the leading cause of cancer mortality in Australia,
with 5-yr relative survival: 11% men,15% women
• Reasons for poor survival include:
– relatively high proportion of diagnoses at an advanced stage
– adverse effects of smoking-related comorbidities
• ~85% of lung cancers are non-small cell lung cancers, which are
screen-detectable, and survival for these cancers can potentially be
improved if caught early.
• Screening can be controversial: lives saved weighed against
adverse events, invasive follow-up testing, over-diagnosis, and over-
treatment of indolent tumours
• Targeting high-risk individuals can reduce the harms and increase
cost-effectiveness of screening

3. Lung cancer screening is on the horizon
• Low dose computed tomography (LDCT) was shown to reduce
mortality from lung cancer in the National Lung Screening Trial
(NLST) in the USA by 20%
N = 53,454
55 to 74 years
≥ 30 pack-years, <
15 years quit
Median follow-up 6.5
years
20% relative
reduction in mortality

4. Optimising the target population through risk
assessment tools
• Risk assessment tools are a mathematical combination of risk
factors that aim to predict lung cancer incidence
• Tammemagi et al., PLCOm2012 is a logistic regression model that
predicts 6-yr risk of lung cancer
– In addition to smoking/age, incorporates sociodemographic and health factors.
– Was developed in the PLCO trial dataset and validated on the NLST
• How does it translate to an Australian population?
• Based on the Busselton Health Study*, 17.9% of ever smokers in
Australia would be screened according to PLCOm2012
• We examined how well it predicted lung cancer incidence in the 45
and Up Study
*Manners, et al. (2016) Estimating eligibility for lung cancer screening in an Australian cohort, including
the effect of spirometry. MJA 204: 406

5. PLCOm2012
• Designed for ‘ever smokers’ and includes:
– Age; Education; Ethnicity; BMI; Personal history of cancer;
Family history of lung cancer; Presence of COPD (ascertained
from APDC/PBS records);
– Smoking status/intensity/duration/years quit
• Applied the tool to participants at baseline
– Excluded those with: prior lung cancer, missing information for
any variable, linkage errors, recruitment date > June 30, 2008
• Followed-up for incident lung cancer censored at
6 years or death
• Lung cancers ascertained from NSWCR (to
2010) and APDC (2011-2014)

6. Distribution of PLCOm2012 risk scores
Current smokers Ex-smokers

7. Predictive performance: calibration
Results not yet published: edited for web

8. Predictive performance: Discrimination
Results not yet published: edited for web

9. Assess model thresholds
• NLST participants with PLCOm2012 scores ≥0.0151 were
those who benefited from LDCT screening
– i.e. mortality was 4-fold lower in the LDCT arm for participants
with scores higher than 0.0151
– PLCOm2012 ≥0.0151 is the critical cut-point to sort participants
into those who should or shouldn’t be screened
– had higher sensitivity than the NLST eligibility criteria, with no
loss in specificity (i.e. ages 55-74 years)
*Manners, et al. (2016) MJA 204: 406

10. PLCOm2012 ≥0.0151: 45 and Up cohort
Results not yet published: edited for web

11. PLCOm2012 vs. NLST
Ages 55-74
Results not yet published: edited for web

12. Conclusions
• PLCOm2012 is good at predicting lung cancer incidence
within 6 years
• These results on their own are not enough to
recommend LDCT screening using PLCOm2012 criteria
• The next step is to use microsimulation modelling to
integrate PLCOm2012 findings with:
– LDCT screening trial data
– Smoking history data
– Health services utilisation data
– Lung cancer incidence and mortality data
• Assess the effectiveness and cost-effectiveness of LDCT
screening for the whole of the high risk population

13. Acknowledgements
This research was completed using data collected through the 45 and Up Study
(www.saxinstitute.org.au). The 45 and Up Study is managed by the Sax
Institute in collaboration with major partner Cancer Council NSW; and partners:
the National Heart Foundation of Australia (NSW Division); NSW Ministry of
Health; NSW Government Family & Community Services – Carers, Ageing and
Disability Inclusion; and the Australian Red Cross Blood Service. We thank the
many thousands of people participating in the 45 and Up Study.
We thank the Centre for Health Record Linkage for the data linkage and the
NSW Ministry of Health and Cancer Institute NSW for the use of their data.