Lung cancer Screening

Family Physicians and CancerControl 2018

Alain Tremblay

Division of Respiratory Medicine

University of Calgary

Disclosures

• BD Inc - Consultant / Medical Device development• Olympus Respiratory America - Consultant / Medical Device

development• Olympus Canada – Honoraria for bronchoscopy CME courses• BD Inc. – Patent licensed to BD Inc for device to treat pleural

diseases• Investigator led clinical trials (Alberta Lung Cancer Screening)

Objectives

• To understand recent recommendations on lung cancer screening• To review pros and cons of lung cancer screening• To examine the availability of lung cancer screening in the

Province and across the country

Overview

• Lung Cancer & Smoking trends• LDCT screening • Who to screen?• How to manage nodules?• How to avoid drowning in IFs?• Costs and opportunistic / ad-hoc screening• Implementation of screening in Alberta / Canada

Intro & Background - Smoking

Lung Cancer Rates vs. Cases Alberta 2000-2030

The number of lung cancer cases will continue to rise in Alberta

By Vincent Van Gogh 1885

Reducing Lung Cancer Incidence and Mortality

• Prevention• Smoking Cessation!

• Early Detection and treatment• 5 year survival for early stage lung cancers is

≥70%

• Advances in treatment

Alberta's Cancer Plan to 2030

• VISION: By 2030, Alberta will be a place where most cancersare prevented, more cases of cancer are cured…”

• Strategies (10):• Transform Alberta’s approach to cancer by creating a

comprehensive and coordinated system of prevention, screening…• Find cancer early by using robust data and appropriate screening

activities.• Lung cancer by far the most common cause of cancer

deaths in Alberta. • 2.3x Colon ca, 3.75x Breast ca, 3.9x Prostate ca• Absolute number of lung cancer cases to RISE in AB to 2030

• Achieving this vision impossible without lung cancer screening

Annual PA CXR x3

• 53,464 high risk individuals CXR vs. CT annual x3

• High risk eligibility criteria:

• Ages 55 – 74

• 30 pack year smoking history

• If quit, <15 years

• 48% current smokers

• Fewer Deaths in LDCT arm

• 20% Lung cancer specific mortality reduction (3/1000)

• 6.7% all cause mortality reduction (5/1000)

• Number needed to screen:

• 320 / lung cancer death

• 200 / any cause death

NEJM 2011

NNS 5276 531 415 171 161

• Use of lung cancer risk prediction model more sensitive than NLST criteria

• Applied model vs. NLST criteria to 37,332 PLCO smokers / 678 lung cancers

• 14,144 eligible as per NLST criteria• Corresponds to a 1.3455% risk threshold (PLCOM2012)

Sensitivity Specificity• NLST 71.1% 62.7%• Model 83.0% 62.9%

• Model identifies 12% more cancers than NLST crit

Pan-Canadian Early Detection Study Risk Model Based Recruitment

• N=2537 • Minimum risk 2%/6 years

(PLCOm2007 or PanCan model)• Median follow-up 5.5 yrs•164 cancers (6.5%) detected

NLST 4% after 6.5 yearsNELSON 2.6% after 8.16 years

NEJM 2013;369:920-31Lancet Oncology 2014;15:1342-50

• PanCan (N=152)• NLST (N=1080) • Ontario (2007-2009

N=11,261, age 50-75y)

Lung Cancer Screening: Participant Selection by Risk Model – the Pan-Canadian Study – Lancet Oncol. 2017 Nov;18(11):1523-1531

p<0.001 PanCan vs NLST or Ontario Early (I-II) vs. Late stage (III-IV)

Other advances since NLST: Improve specificity of +screen definitions; improved understanding of indolent lung cancers; Integration of smoking cessation activities; optimal screening intervals

High nodules (>10%) at baseline inthe Alberta Lung Cancer Screening Study

0

1

2

3

4

5

6

Both RPM&NLST (n=304) RPM > 1.5% only (n=114) NLST (n=82)

%

P=0.076

Study Site British Columbia Alberta London Total

No. Screened 318 688 648 1654Age (yrs±SD) 65+6.3 63.5+6.3 66+4.2 64.8+5.7%Current(CS)/Former Smoker(EX)

43%CS:57%EX 50%CS:50%EX 73%CS:27%EX 58%CS:42%EX

Pack Years (mean±SD) 47.3+22 42.4+15.8 47.7+22.3 45.3+19.8

Median Follow-up (mths) 7.5 9.7 12.6 9.9

No. of lung cancers 7 6 21 34

• 34 lung cancers• 100% met the

PLCOm2012 selection criteria

• 67% met NLST- like criteria.

• No lung cancer found in participants who met NLST-like criteria alone.

Optimal Selection Criteria for LDCTLung Cancer Screening – WCLC 2017

Bach et al. JAMA. 2012;307(22):doi:10.1001/jama.2012.5521

Screening Positivity Rate in NLST

• Positive Screen = nodule ≥4mm or other findings potentially related to lung cancer

• 39% of NLST CT participants had at least 1 positive scan

• 72% of positive scans had diagnostic workup (mostly CTs…)

Bach et al. JAMA. 2012;307(22):doi:10.1001/jama.2012.5521

False Positives

• 7% of patients with false positive / 2% overall will have invasive procedure

• Ann Int Med 2010; 152:505-512

• Surgical procedure for benign disease not infrequent

Mayo BCCA PLuSS DANTE LCSS NLSTVATS or thoracotomy for benign disease

0.70% 1% 1% 1% 0.5% 0.6%

ACRLungRADS

• Size• Nodule

character

• Adopted in US programs

Comparison of the PanCan model, Lung-RADSand NCCN guidelines

• Danish Lung Cancer Screening dataset

• PanCan performed superiorly to Lung-RADS and NCCN

• (AUC 0.874 vs. 0.813, p = 0.003; 0.874 vs. 0.836, p = 0.010)

Martin C Tammemagi, and Stephen Lam BMJ 2014;348:bmj.g2253

©2014 by British Medical Journal Publishing Group

Probabilistic approach to guide clinical decisions using the Pan Canadian model

12 month f/u

3 month f/u

Clinical assessment

Baseline nodulesALCSP (N=649)

• 9.2% positive screen / require other than annual scan

• 5.7% have a nodule with >=10 risk

• Lung-RADS >=3 (10.6%)

Cancer diagnosis

Participant Nod risk Path Stage Treatment Comment

88JW_A 0.522 adenoCa Ib VATS wedge Outside NLST (age)

Herder: 93.3%

Under investigation

Risk Type/size Location Follow-up Plan

326JG_A 0.31 Solid 10mm LUL PETCT-Resolving Return to annual

Incidental findings

• Thyroid nodules• Adrenal nodules• Coronary calcifications• Breast lesions• Interstitial lung disease• Pleural effusions• Pericardial effusions• Renal lesions• Mediastinal adenopathy• Anterior mediastinal lesions

Incidentals – Other Cancers

• 191MP_A: Invasive ductal carcinoma left breast.

• 87GS_A: Invasive ductal carcinoma left breast.

• 610AS_A: Mesothelioma

• 666KL_A: Esophageal cancer

• 1332DG_A: ?Ovarian cancer

• 75% of participants at least 1 IF• Only 8.5% possibly clinically relevant

• 6% underwent addition evaluation• 1% determined to have IF with clinical implication

Findings were located most frequently in• liver (n=76, 53%) • kidneys (n=53, 37%)

less common in:• thyroid, mediastinum, adrenals, breast,• colon, and spine

< 0.5 cm ≥ 0.5cm

≥ 1.5 cm

Incidental Liver Mass

Suspicious imaging features

Benign imaging features

One or more liver lesions (0.5-1.5cm) are detected as described above. Follow-up imaging (CT, U/S or MRI) is recommended in 6 months.

One or more liver lesions (<0.5 cm) are detected as described above. No further work-up is required unless risk factors are present (prior malignancy, cirrhosis, or other hepatic risk factors) in which case follow-up imaging (CT, U/S or MRI) is recommended in 6 months.

Risk = average, unless known malignancy, hepatic dysfunction, abnormal liver function tests or hepatic malignancy risk factors (hepatitis, chronic active hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemochromatosis, hemosiderosis, oral contraceptive use, anabolic steroid use) or symptoms attributable to the liver.Benign imaging features: Typical hemangioma eg sharply marginated, homogenous low attenuation (up to 20 HU). May have sharp, but irregular margins.Suspicious imaging features: Ill defined margins, enhancement (more than 20 HU), heterogeneous, enlargement. To evaluate--> prefer multiphasic MRI.

Benign, No follow-up

One or more liver lesions (>1.5cm) are detected as described above. Further evaluation is required with MRI or biopsy according to patient risk factors (prior malignancy, cirrhosis, or other hepatic risk factors).

0.5-1.5 cm

Screening Management Platform

Part 1 http://www.screencast.com/t/J60ttVB4Part 2 http://www.screencast.com/t/KKeCiFqsIqAPart 3 http://www.screencast.com/t/6fpxIv1nfll

Is lung cancer screening cost-effective

• Data from NLST (US system) $81,000 per quality-adjusted life-year. (N Engl J Med Volume 371(19):1793)

• Canadian Modeling $52 000/QALY, $C24 000/QALY with effective smoking cessation (J Thorac Oncol. 2014 Oct;9(10):1449)

• PANCAN high hisk screening model $C20,724 per QALY gained (J ThoracOncol. 2017 Aug;12(8):1210)

• screening may even offer cost savings if noncurative treatment costs for advanced cancer continue to rise

Opportunistic vs. Organized Screening (CPAC)

• Opportunitsic screening will very likely be more costly and less cost-effective than organized screening

• If indirect costs and costs of harms were included, opportunistic screening would be even less cost-effective than projected

Access to CT Services

90.4% of Alberta’s population lives within a 60 minute drive of a CT Scanner

Stage Distribution:Impact to Surgery/Oncology in AB

Funding for Lung Cancer Screening

• No Provincial funding to date in Canada• 10,000 participant pilot initiated in Ontario• BC/Vancouver cohort (private donor)• In AB study funded to 800 participants (enrolment complete)• Request submitted to expand to 3,000 and propose a full scale program to AH/AHS –

DECLINED!• Discussions ongoing…

• USA• Under Affordable Care Act, private insurers must cover USPSTF grade B recommendations• Medicare coverage in place

• Discordance in Canada between CTFPHC and Provincial funding for programs

Current AHS Policy on lung cancer screening

• October 2017 memo“…we will not presently offer LDCT examinations for Lung Cancer

Screening at AHS facilities.”

• Would not recommend obtaining CT outside of a formal program• Outside criteria for screening• Likely full dose even contrast• No systematic reporting of findings• Variable management approaches

Why bother?

• More than 50% of new lung cancers diagnosed today are in either ex-smokers or never-smokers

• Screening programs can incorporate smoking cessation support for those who still smoke

• A large number of common health conditions we face today are at least in part heavily impacted by individual behaviors or habits, be it smoking, alcohol, diet or inactivity. This is not a reason to shun interventions that may help these individuals, in particular for such a devastating disease as lung cancer.

• While smoking remains an individual choice, the majority of smokers are hooked at a young age, often before age 18

• Society must share the responsibility for their addiction and associated consequence to a legal product in the past heavily marketed to our population, and for which we all draw (through our governments) substantial revenue even today (1 billion $/year AB).

• Never-smokers would also benefit from a reduction in death and suffering from our deadliest cancer in their parents, grand-parents, sisters, brothers, spouses and other loved ones.

Conclusions

• LDCT screening reduces mortality from #1 cancer killer • Several organizations have recommended screening (NLST criteria)• Well defined programs should proceed, preferably with close

monitoring and research components to ensure proper inclusion and management, as well as increase knowledge

• Inclusion criteria, definition & management of positive tests, incidental findings, cost, integration of smoking cessation activities, quality metrics

• Potential for ineffective and costly opportunistic screening in the absence of an organized program

Thank you!

alain.tremblay@ucalgary.ca