Early Detection of Lung Cancer & Beyond GUIA ELENA IMELDA R. LADRERA, MD Lung Center of the Philippines

Objectives Present available statistics on Lung Cancer. Present data on the early detection of lung cancer. Present the LCP Algorithm in the approach to lung cancer suspect. Present LCP research results in the treatment & prevention of Lung Cancer.

Incidence of Lung Cancer Lung Cancer is the most common cause of cancer related death worldwide Overall 5 year survival - < 15% CANCER Principles and Practice of Oncology DeVita et al 8th Edition p896 Philippines - 15,881 deaths are expected this year - Median survival of 6 months - Five-year survival of 5.28% & a 10-year survival of 2.68% 2005 Philippine Cancer Facts & Estimates

Estimated Five Leading Cancer Sites in 2005, Both Sexes 2005 Philippine Cancer Facts & Estimates Number of Cases

Five Leading Causes of Cancer Deaths in 2005, Both Sexes 2005 Philippine Cancer Facts & Estimates

Lung Center of the Philippines Tumor Registry 2000 - 2004

Patients with Diagnosis of Bronchogenic Cancer at the Lung Center of the Philippines 2000 - 2004 Histology 2000 2001 2002 2003 2004 BCA Unspecified NSCLC or SCLC 20 21 31 36 57 NSCLC AdenoCA Squamous CA Large cell CA Unspecified Others TOTAL NSCLC 88 50 4 39 181 117 44 54 215 142 87 14 2 * 333 168 65 3 67 1+ 304 167 72 84 326 SCLC 26 40 48 46 TOTAL 227 276 412 386 429 * Adeno-Squamous CA +Neuroendocrine CA

Number of Patients with Lung Cancer (NSCLC & SCLC) 2000 – 2004 Lung Center of the Philippines Tumor Registry

Histopathologic Types of NSCLC Lung Center of the Philippines Tumor Registry

Distribution of Patients with Lung Cancer 2000 – 2004 Lung Center of the Philippines Tumor Registry

Distribution of NSCLC According to Stage of the Disease Lung Center of the Philippines Tumor Registry

Survival of Patients with Lung Cancer Lung Center Tumor Registry

Lung Center of the Philippines Bronchogenic Carcinoma (152 cases) 1986 - 1991 1 Year Survival by Stage Stage 1 (T1-2 N0 M0) 96.8% Stage II (T1-2 N1 M0) 94% Stage IIIA (T1-2 N2 M0) 88.9% LCP Tumor Registry 1994

Average 1 Year Survival for all Types 93.2% Lung Center of the Philippines Bronchogenic Carcinoma (152 cases) 1986 - 1991 Average 1 Year Survival for all Types 93.2% LCP Tumor Registry 1994

Overall 5 year survival is LESS THAN 15% Philippines - 15,881 deaths are expected this year - Median survival of 6 months - Five-year survival of 5.28% & a 10-year survival of 2.68% 2005 Philippine Cancer Facts & Estimates

Diagnostic Algorithm for Lung Cancer Lung Center of the Philippines 2008

ALGORITHM IN THE GENERAL APPROACH IN THE DIAGNOSIS OF SUSPECTED LUNG CANCER SPECIAL SITUATIONS Follow-up every 3 months * Negative or low suspicion of neoplasm Positive for pulmonary mass Establish diagnosis Central lesion TTNAB/ Sputum cytology High risk Bronchoscopy with cytology and biopsy Positive Negative Further testing: TTNA/TBNA EBUS-NA VATS Bronchoscopy with Biopsy / Sputum cytology Confirm diagnosis Negative for malignancy or Non-specific Do staging Low suspicion/ risk High suspicion/ risk Exploratory thoracoscopy other invasive procedures Increase in mass size No change in mass size Repeat biopsy No further testing Unresolved pneumonia of >1 month with abnormal CXR or asymptomatic with abnormal CXR CT of chest/MRI CXR and ENT Exam Normal ENT examination with negative or positive CXR Abnormal ENT examination Refer to ENT Follow-up evaluation B Presence of extrapulmonary lymph node Pleural effusion Multiple pulmonary nodules Atelectasis Biopsy of lymph node, if accessible Diagnostic thoracentesis Pleural fluid cytology or pleural biopsy Thoracoscopy Video-assisted Thoracic Surgery (VATS) Open lung biopsy CT guided biopsy Fiberoptic bronchoscopy (FOB) * * * Definition: *Low risk – age < 40 years old, non-smoker with (-) family History. *High risk – age > 40 years old, smoker/ passive (+) family History. RAD/jbl06 CLINICAL PRESENTATION Peripheral Cough or dyspnea CXR Pulmonary mass A Hemoptysis (1) (2) (3) Treat other diseases as indicated or follow up visit every 1 mo. Low risk Go to B ** Inconclusive Follow-up Appropriate treatment

Treatment of Lung Cancer Lung Center of the Philippines

Total no. Of 0perations - 152 (4.55%) Lung Center of the Philippines Bronchogenic Carcinoma 1986 - 1991 Total no. Of cases - 3,338 Total no. Of 0perations - 152 (4.55%) LCP Tumor Registry 1994

Lung Center of the Philippines Bronchogenic Carcinoma Resection Rate of Operated cases 1982 – 1986 68.6% 1986 – 1991 92.7% LCP Tumor Registry 1994

Percentage of Patients with Early Stage NSCCA who Underwent Surgery 2000 – 2004 Lung Center of the Philippines Tumor Registry Number of Patients (%) Stage I TOTAL With Surgery 58 22 (38%) Stage II 44 8 (18%) Stage IIIA 128 14 (11%)

Lung Center of the Philippines Early Lung Cancer Detection Program Lung Center OF THE Philippines Program, R. Montevirgen, MD Study period: 1991 -1996 Subjects 120 initial participants enrolled High risk individuals Q 6 months CXR until age 75 Results - 3/120 (+) to have lung cancer. - 2 patients presented with late stage disease upon enrolment. - 1 patient detected with early disease (0.83%)

Controlled Trials of Lung Cancer Screening with Chest Radiography with or without Sputum Cytology L.L. Humphrey MD et al Ann Intern Med 2004;140:740-753 Study Sample Intervention Prevalence n (%) Mortality rate per 1000 Person-Yrs Northwest London Mass Radiography Service (1960) 29,733 Men of >40 yrs; 19% former smokers; 67% current smokers CXR & sputum cytology IG: 31 (0.10) CG: 20 (0.08) 3 yr ff up IG: 0.7 CG: 0.8 Kaiser Permanente Study (1964) 10, 713 Age 35-45 yrs; 17% smokers CXR NR 16 yr ff up IG: 8.6 CG: 7.6 Mayo L ung Project (1971) 10,933 Male smokers age ≥ 45 yrs CXR & sputum cytology vs usual care 91 (0.83) 20 yr ff up IG: 4.4 CG: 3.9 Johns Hopkins Lung Project (1973) 10,387 Male smokers age ≥ 45yrs DSG: 39 (0.75) CxG:40 (0.78) 5 to 8 yr ff up DSG: 3.4 CxG: 3.8

Controlled Trials of Lung Cancer Screening with Chest Radiography with or without Sputum Cytology L.L. Humphrey MD et al Ann Intern Med 2004;140:740-753 Study Sample Intervention Prevalence n (%) Mortality rate per 1000 Person-Yrs Memorial Sloan Kettering Study (1974) 10,040 Male smokers age ≥ 45yrs CXR & sputum cytology DSG:30 (0.6) CxG: 23 (0.46) 5 to 8 yr ff up DSG: 2.7 CxG: 2.7 Czech Study (1975) 6,345 Male smokers 40-64 yrs CXR 19 (0.30) 15 yr ff up

Summary Two RCTs (JHLP & MSKLP) which used sputum cytology for screening. No mortality benefit was found. MLP used CXR & sputum cytology compared to usual care. No mortality benefit was found. CLP used q 6m CXR for 3 years, then yearly CXR for 3 years compared to annual CXR. No mortality benefit was found.

Cohort Trials of Low Dose CT Screening CANCER Principles and Practice of Oncology DeVita et al 8th Edition p 685 Table III Project name Enrolled Baseline Annual Lung Cancer Prevalence Baseline Annual % of Stage I Survival Rate ELCAP (1993- 1999) >60y, >10Pk-yr 1000 1184 2.9% 0.6% 85% 86% Nagano, Japan (1996-1998) >40y, Pk-yr not req’d 5,483 8,303 0.4% 100% ALCA-NCC,Japan (1993 – 2000) 1,611 7,891 0.9% 0.3% 79% 82% 5 yr OS baseline : 71% Hitachi, Japan (2001 – 2002) >40 y Pk-yr not req’d 7,956 5,568 0.5% 0.1%

Cohort Trials of Low Dose CT Screening CANCER Principles and Practice of Oncology DeVita et al 8th Edition p 685 Table III Project name Enrolled Baseline Annual Lung Cancer Prevalence Baseline Annual % of Stage I Survival Rate Mayo Clinic (1999 – 2004) Age>50,Pk yrs >20, quit < 10 y 1520 4,472 2.0% 0.8% 77% 71% 72% Instituto Tumori, Italy (2000 – 2001) Age >50y,Pk yrs >20 1,035 996 1.7% 0.5% 100% 85% I-ELCAP (1993-2006) Age>40y, Pk yrs not req’d 31, 567 27,456 1.3% 0.3% 86% 10yr OS : 80%

Summary The lung cancer prevalence rate depends on risk characteristics. The ratio of baseline to annual cancers is much higher for CT scan than it was for CXR. Or sputum cytology. High proportion of finding Stage I disease.

No major medical professional organization currently recommends screening for lung cancer

Alternatives to Lung Cancer Screening ?????

National Smoking Prevalence Study Research & Development, Lung Center of the Philippines Phil. Journal Int. Medicine 27: 133 – 156, May – June 1989 Adult population - 46.52% smokers Urban population – 40.92% Rural population – 49.94% Young Population - 22.70% Urban population – 18.98% Rural population – 26.20%

Manila, Philippines Prevalence of ever smoking in population1 ages >40 by sex Men Women 83% 31% 1 Unweighted data for the sample of responders Overall = 55% Philippine BOLD Study . AS Buist et al, The Lancet 2007, Vol 370 pp 741 - 50 21 February 2008

Cigarette Smoking Among Hospitalized Patients in Metro Manila JCAlonzo MD, I.Fabic, MD Scientific Proceedings (LCP) 1996 Vol.4 pp65 - 73 Results : 1. 34% current smokers 43% former smokers 2. Of all current smokers <30y, 65% NEVER thought of attempting to quit. For those >30y, 66% attempted to quit 3. Of those who attempted to quit, 52% had 5-10x attempts.

Attitudes & Beliefs of Smokers More than half of population thought seriously about quitting. 2.5-3x serious attempts to quit – Urban group 1 serious attempt to quit - Rural group Cigarette Smoking Among Hospitalized Patients in Metro Manila JCAlonzo MD, I.Fabic, MD Scientific Proceedings (LCP) 1996 Vol.4 pp65 - 73

Young People as Smokers Overall – 22.70% - Urban : 18.98% - Rural : 26.20% Mean age for starting is 11 – 12 y Major reason for starting – Peer group pressure Cigarette Smoking Among Hospitalized Patients in Metro Manila JCAlonzo MD, I.Fabic, MD Scientific Proceedings (LCP) 1996 Vol.4 pp65 - 73

Teaching Lung Cancer Prevention to the Filipinos: an Inter-Agency Collaboration Department of Research & Development, Lung Center of the Philippines Scientific Proceedings 1995 Vol 3 pp47- 52 Aim is to develop a curriculum material on both elementary and HS levels on Lung Cancer prevention. Modules are designed to develop awareness among students of the health hazards of smoking and its direct link to lung cancer.

SUMMARY Lung cancer is the leading cause of cancer diagnosis and deaths worldwide and locally. Lung cancer screening is currently not advocated even for high risk population. Standardization of diagnostic evaluation for patients with suspected lung cancer is recommended. Prevention of smoking through education, implementation of tobacco regulation law may help curb the incidence of lung cancer.