Diagnosing Lung Cancer Earlier

Sam Janes London Lung Cancer Pathway Director

Consultant Respiratory Physician Wellcome Senior Fellow

University College Hospital, London

What cancer is the biggest killer of men in the UK?

a. Bowel and prostate cancer

b. Lung cancer

What cancer is the biggest killer of men in the UK?

a. Bowel and prostate cancer ✗

b. Lung cancer ✔

What cancer is the biggest killer of women in the UK?

a. Breast cancer

b. Lung cancer

What cancer is the biggest killer of women in the UK?

a. Breast cancer ✗

b. Lung cancer ✔

Estimated UK Cancer Deaths Men

Women

25% Lung

15% Breast

11% Colon/rectum

6% Pancreas

5% Ovary

4% lymphoma

4% Leukemia

2% Uterine corpus

2% Brain/ONS

25% All other sites

Lung 31%

Prostate 11%

Colon/rectum 10%

Pancreas 5%

lymphoma 5%

Leukemia 4%

Esophagus 3%

Liver/ bile duct 3%

Urinary bladder 3%

All other sites 25%

How many people that have had lung cancer are alive 5 years later?

a. 50%

b. 5%

How many people that have had lung cancer are alive 5 years later?

a. 50% ✗

b. 5% ✔

2%

6%8%

14%

15%23%

35%36%

46%

48%

51%

52%54%

61%73%

77%

87%

2%

6%7%

12%13%

23%

36%

45%

47%47%

47%62%

64%

65%77%

96%

Pancreas

Lung

Oesophagus

Stomach

Brain

Multiple myeloma

Leukaemia

Ovary

Kidney

Colon

Rectum

NHL

Bladder

Cervix

Uterus

Breast

Melanoma

Pancreas

Lung

Oesophagus

Brain

Stomach

Multiple myeloma

Leukaemia

Kidney

NHL

Rectum

Colon

Larynx

Bladder

Prostate

Melanoma

Testis

Wo

men

Me

n

5 year survival

The Problem! 10 yr survival by cancer type

Lung cancer as a % of all UK cancer deaths

(CRUK 2007)

An illustration of why lung cancer survival is so poor despite great

changes between 2007 and 2013

• 67yr male

• Presented Jan 2007

• Cough 2/12

• Blood in sputum

• 4kg wt loss

• 10 pk yrs

Clinical Case

Jan 2007

Clinical Case

•T2N2M1disease (meaning he has metastatic disease) : NSCLC NOS

•(central mediastinal nodes and 2 asymptomatic bone metastases)

•MDT decision: chemotherapy (palliative)

•Started gemcitabine and carboplatin

•4th course assessment

June 2007

Dec 2007

• T2N2M1disease: NSCLC NOS – ADENOCARCINOMA by EBUS

• (central mediastinal nodes and 2 asymptomatic bone metastases)

• EGFR MUTATIONAL ANALYSIS (POSSIBLY ALK)

• MDT decision: chemotherapy

• Started gemcitabine and carboplatin PEMETREXED/CISPLATIN

• 4th course assessment Maintenance?

• IF GOOD PS AND SIGNS OF RELAPSE – ERLOTINIB TKI

What would happen 5 years on in 2013?

Period of rapid change in lung cancer

• New Imaging: PET-CT, newer isotopes, prognosis, whole body MRI

• New Diagnostic tests EBUS/EUS

• New Radiotherapy techniques

• Minimally invasive surgery, sublobar resection

• Personalised systemic treatments (tablets)

So why are we making no inroads to survival? Because we continue to catch lung cancer too late

Five-year survival by TNM status in NSCLC

Stage

IA

IB

IIA

IIB

IIIA

IIIB

IV

TNM classification

T1N0M0

T2N0M0

T1N1M0

T2N1M0 or T3N0M0

T1-3N2M0 orT3N1M0

T4NanyM0 or TanyN3M0

TanyNanyM1

5-year survival

(%)

61

38

34

24

13

5

1

Mountain 1997

85% of

patients

• We need to detect lung cancer earlier

• Stage shift towards early- radically curable disease

• Survival benefit

Lung Cancer screening – where are we?

• Symptoms

• Risk scores

• Chest x-ray

• CT

Symptoms

Symptoms of advanced disease

• Change in cough

• New cough lasting >3 weeks

• Breathlessness

• Chest pain

• Haemoptysis

• Unexplained weight loss in a smoker

• Recurrent infection

• (Suddenly stopped smoking)

QCancer®(Lung) risk calculator: http://qcancer.org/lung

• 55yr old lady

– Heavy smoker

– Normal lung function

– History of breast cancer

– Seen with a cough in the last year

– Loss of appetite

– Coughing blood

0.3%

0.6%

2.5%

44%

• 78 yr old man

– moderate smoker

– History of COPD

– Unintentional weight loss

– Coughing up blood

2.2%

10%

72%

+

+

Again – all these things help pick up advanced cancer earlier: Not a bad thing but will not impact long term survival

Chest x-ray Studies Study Patient

number

Control Intervention Results

MSKCC

(1984)

10040 Annual

CXR

Annual CXR &

sputum

No

benefit

John

Hopkins

(1986)

10384 Annual

CXR

Annual CXR &

4 monthly

sputum

No

benefit

Mayo

(1986)

9211 Annual

CXR

4 monthly CXR

& sputum

No

benefit

Czech

(1990)

6364 CXR years

4, 5, 6

6 monthly CXR

(3yrs), annual

CXR year 4-6

No

benefit

Addition of sputum cytology does not increase sensitivity

Lung Cancer screening – where are we?

• Symptoms

• Risk scores

• Chest x-ray

• CT

CT screening: The Evidence

Population 55-75 years old Smoker (or Ex) of 30 pack years

National Lung Cancer Screening Trial

20% reduction in

lung cancer

deaths. P=0.02

US Chest Physicians and Oncologists recommend CT Screening

• Over diagnosis

• False positive rates

• Patient acceptance/ anxiety/ radiation

• Cost per QALY

Potential Issues

UK Lung Screening Trial (UKLS)

Validation study for CT screening in the UK

UKLS Update

• The investigators have been told their study will not progress beyond the pilot stage

London Cancer and CT Screening: Where do we stand?

• For every 300 scans performed one life will be saved

• We would like London Cancer to be at the forefront of delivering CT screening to the UK population

• We aim to provide the evidence required to decide how CT screening should be delivered to the UK population

The Team

• Lung Physicians

• Radiologists

• Experts in Cancer Screening (Prof Jane Wardle)

• Statisticians (Prof Stephen Duffy)

• The UKLS team (John Field and David Baldwin)

• The US team (NLST) (Dr Christine Berg)

• The Lung Cancer Leaders (Dr Mick Peak)

• The UKLS pilot trial recruited directly via population mailing, sending out 250,000 initial questionnaires to recruit 4000 individuals

Why is this needed?

We propose a demonstration project to:

• Research other models of identification of suitable

subjects for lung cancer screening, such as via primary care

• To build expertise in the screening technique • To investigate the immediate implications of screening

in the UK; (false positive rates etc) • Estimate the human and economic costs of the

screening; and • Investigate the effects of different levels of smoking

cessation support in participants

• We propose comparing invitation techniques in recruiting 2,000 subjects at high risk of lung cancer via primary care

• Subjects would be identified from practice records

• They would be offered a single low-dose CT scan for lung cancer

• In addition, we propose to randomised them to one of two smoking cessation interventions

The Project

The Project: Outcomes

• acceptability to GP’s and patients

• comparison of the recruitment rates and costs

• rates of suspicious findings requiring further workup

• detection rate of lung cancer at screening

• incidence of lung cancer in the three years following screening;

• likely costs of the combined screening and further diagnostic activity generated by the screening

• comparison of smoking cessation rates in the two randomised arms

The Plan: and funding!

• Full design of feasibility of implementation trial

• Understand what this will fund

• Gain funding for the NHS resource that will be used to enable the trial

• Likely scale: 80 practices/2000 patients; two areas in London Cancer

Thank you for listening