Informing Patient Surveillance for the Growing Number of Survivors of Lung Cancer

Abstract

Lung cancer remains the major cause of cancer-related death worldwide, with only 10% to 20% of patients surviving more than 5 years.1Sung H. Ferlay J. Siegel R.L. et al.Global cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin. 2021; 71: 209-249Google Scholar Fortunately, improvements in therapies have improved lung cancer survival rates in recent years.2Howlader N. Forjaz G. Mooradian M.J. et al.The effect of advances in lung-cancer treatment on population mortality.N Engl J Med. 2020; 383: 640-649Google Scholar Furthermore, the potential implementation of lung cancer screening programs is likely to further improve survival rates.3Ten Haaf K. van der Aalst C.M. de Koning H.J. Kaaks R. Tammemägi M.C. Personalising lung cancer screening: an overview of risk-stratification opportunities and challenges.Int J Cancer. 2021; 149: 250-263Google Scholar However, survivors of cancer are known to be at increased risk for developing second primary cancers (SPCs).4Sung H. Hyun N. Leach C.R. Yabroff K.R. Jemal A. Association of first primary cancer with risk of subsequent primary cancer among survivors of adult-onset cancers in the United States.JAMA. 2020; 324: 2521-2535Google Scholar Therefore, studies on the risk of SPC in survivors of lung cancer will become increasingly relevant to inform patient surveillance. The study by Eberl et al.5Eberl M. Tanaka L.F. Kraywinkel K. Klug S.J. Incidence of smoking-related second primary cancers after lung cancer in Germany: an analysis of nationwide cancer registry data.J Thorac Oncol. 2022; 17: 388-398Google Scholar reported in this issue of the journal provides a number of insights in the risk of SPC in survivors of lung cancer. Their study considered 11 population-based cancer registries in Germany, covering about 50% of the German population. Overall, almost 136,000 survivors of lung cancer (who survived at least 6 mo) were considered in the analyses. To evaluate the increase in risk for developing an SPC, the authors compared the standardized incidence ratios (SIRs) among survivors of lung cancer with those of the general German population. Overall, the most frequently occurring SPC were prostate, colorectal, lung, urinary tract, and breast cancers, accounting for 51.8% of all SPCs (51.6% in men, 52.4% in women). The authors found that the risk for developing nonsmoking-related SPC (according to the definition of the International Agency for Research on Cancer) was not elevated in men and elevated by 1.36-fold in women.6Secretan B. Straif K. Baan R. et al.A review of human carcinogens--part E: tobacco, areca nut, alcohol, coal smoke, and salted fish.Lancet Oncol. 2009; 10: 1033-1034Google Scholar The elevation in risk for nonsmoking-related SPC in women may be primarily attributed to breast cancers, which had a SIR of 1.35 compared with women in the general German population and accounted for 26.9% of all SPC in women. However, the risk for developing a smoking-related SPC was elevated by 1.41-fold for men and 1.81-fold for women. In particular, the risks for developing SPC in the urinary tract (SIRs: 2.27 in men, 2.68 in women), esophagus (SIRs: 2.49 in men, 4.66 in women), and the head and neck regions (SIRs: oral cavity: 2.86 in men, 3.14 in women; pharynx: 3.17 in men, 3.32 in women; larynx: 3.70 in men, 7.19 in women) were elevated for both sexes, accounting for 19.9% of all SPCs (24.1% in men, 9.5% in women). The authors found similar SPC risks across lung cancer histologies. This indicates that differences in lung cancer histology distributions between sexes do not account for the sex differences in smoking-related SPC risks.7Meza R. Meernik C. Jeon J. Cote M.L. Lung cancer incidence trends by gender, race and histology in the United States, 1973-2010.PLoS One. 2015; 10e0121323Google Scholar Furthermore, this finding provides information on whether lung cancer screening programs may affect future SPC risks. Computed tomography screening is more likely to detect and yield favorable outcomes for adenocarcinomas compared with other histologies.8Ten Haaf K. van Rosmalen J. de Koning H.J. Lung cancer detectability by test, histology, stage, and gender: estimates from the NLST and the PLCO trials.Cancer Epidemiol Biomarkers Prev. 2015; 24: 154-161Google Scholar,9Pinsky P.F. Church T.R. Izmirlian G. Kramer B.S. The National Lung Screening Trial: results stratified by demographics, smoking history, and lung cancer histology.Cancer. 2013; 119: 3976-3983Google Scholar Although screening programs may increase the proportion of survivors diagnosed with an adenocarcinoma, the shift in histology distribution among survivors of lung cancer may thus not necessarily affect the SPC risks. However, lung cancer screening has been suggested to be more beneficial for women than for men.9Pinsky P.F. Church T.R. Izmirlian G. Kramer B.S. The National Lung Screening Trial: results stratified by demographics, smoking history, and lung cancer histology.Cancer. 2013; 119: 3976-3983Google Scholar, 10de Koning H.J. van der Aalst C.M. de Jong P.A. et al.Reduced lung-cancer mortality with volume CT screening in a randomized trial.N Engl J Med. 2020; 382: 503-513Google Scholar, 11Becker N. Motsch E. Trotter A. et al.Lung cancer mortality reduction by LDCT screening—results from the randomized German LUSI trial.Int J Cancer. 2020; 146: 1503-1513Google Scholar Consequently, screening programs may further increase the overall number of female survivors of lung cancer at risk for developing a SPC. The authors suggest that the promotion of smoking cessation in patients with lung cancer who still smoke may play a role in the prevention of smoking-related SPC.5Eberl M. Tanaka L.F. Kraywinkel K. Klug S.J. Incidence of smoking-related second primary cancers after lung cancer in Germany: an analysis of nationwide cancer registry data.J Thorac Oncol. 2022; 17: 388-398Google Scholar In general, smoking cessation should be promoted for patients with lung cancer, as continued smoking negatively affects survival for their first primary lung cancer.12Tammemagi C.M. Neslund-Dudas C. Simoff M. Kvale P. Smoking and lung cancer survival: the role of comorbidity and treatment.Chest. 2004; 125: 27-37Google Scholar Furthermore, continued smoking after treatment for the first primary lung cancer increases the risk for developing a second primary lung cancer, which accounted for 10.3% of all SPC (10.2% in men, 10.5% in women) in the analyses of Eberl et al.5Eberl M. Tanaka L.F. Kraywinkel K. Klug S.J. Incidence of smoking-related second primary cancers after lung cancer in Germany: an analysis of nationwide cancer registry data.J Thorac Oncol. 2022; 17: 388-398Google Scholar,13Aredo J.V. Luo S.J. Gardner R.M. et al.Tobacco smoking and risk of second primary lung cancer.J Thorac Oncol. 2021; 16: 968-979Google Scholar Lung cancer screening has been suggested to be a potential “teachable moment” that could aid in promoting smoking cessation before the diagnosis of the first lung cancer.14Moldovanu D. de Koning H.J. van der Aalst C.M. Lung cancer screening and smoking cessation efforts.Transl Lung Cancer Res. 2020; 10: 1099-1109Google Scholar Research on integrating smoking cessation interventions in lung cancer screening has primarily focused on the prevention of the first primary lung cancer and reducing all-cause mortality.15Cao P. Jeon J. Levy D.T. et al.Potential impact of cessation interventions at the point of lung cancer screening on lung cancer and overall mortality in the United States.J Thorac Oncol. 2020; 15: 1160-1169Google Scholar However, future studies may consider incorporating the effects of successfully promoting smoking cessation on improving the survival for the first primary lung cancer and the prevention of smoking-related SPCs. Although the importance of smoking cessation cannot be understated, a large proportion of lung cancers occur in those who have already ceased smoking. Estimates for the United States suggest that over half of all lung cancer deaths in the next decades will occur in former smokers.16Jeon J. Holford T.R. Levy D.T. et al.Smoking and lung cancer mortality in the United States from 2015 to 2065: a comparative modeling approach.Ann Intern Med. 2018; 169: 684-693Google Scholar Even in high-risk populations, such as the NLST (National Lung Screening Trial) and NELSON (Dutch-Belgian Lung Screening Trial), approximately half of the participants had already ceased smoking at randomization.10de Koning H.J. van der Aalst C.M. de Jong P.A. et al.Reduced lung-cancer mortality with volume CT screening in a randomized trial.N Engl J Med. 2020; 382: 503-513Google Scholar,17Aberle D.R. Adams A.M. et al.National Lung Screening Trial Research TeamReduced lung-cancer mortality with low-dose computed tomographic screening.N Engl J Med. 2011; 365: 395-409Google Scholar However, former smokers remain at elevated risk for developing lung cancer for decades after smoking cessation.18Peto R. Darby S. Deo H. Silcocks P. Whitley E. Doll R. Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies.BMJ. 2000; 321: 323Google Scholar Similar long-term elevations in risks after smoking cessation have been found for other smoking-related first primary cancers, such as head and neck cancers.19International Agency for Research on CancerTobacco Control: Reversal of Risk After Quitting Smoking.in: IARC Handbooks of Cancer Prevention. Vol 11. International Agency for Research on Cancer, Lyon, France2007Google Scholar Consequently, the risk for developing a smoking-related SPC may remain elevated for a prolonged period after smoking cessation. Indeed, Eberl et al.5Eberl M. Tanaka L.F. Kraywinkel K. Klug S.J. Incidence of smoking-related second primary cancers after lung cancer in Germany: an analysis of nationwide cancer registry data.J Thorac Oncol. 2022; 17: 388-398Google Scholar report that the risk for developing a smoking-related SPC remains elevated for at least a decade after treatment for their initial lung cancer, suggesting that the long-term surveillance of patients with lung cancer should be investigated. Guidelines for the follow-up of patients with early-stage lung cancer and those treated with curative intent generally focus on providing recommendations for 2- to 3-year follow-up periods, emphasizing a general paucity of studies on lung cancer surveillance.20Schneider B.J. Ismaila N. Aerts J. et al.Lung cancer surveillance after definitive curative-intent therapy: ASCO guideline.J Clin Oncol. 2020; 38: 753-766Google Scholar, 21Postmus P.E. Kerr K.M. Oudkerk M. et al.Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2017; 28: iv1-iv21Google Scholar, 22Colt H.G. Murgu S.D. Korst R.J. Slatore C.G. Unger M. Quadrelli S. Follow-up and surveillance of the patient with lung cancer after curative-intent therapy: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2013; 143: e437S-e454SGoogle Scholar Given this paucity of evidence, analyses such as those of Eberl et al.5Eberl M. Tanaka L.F. Kraywinkel K. Klug S.J. Incidence of smoking-related second primary cancers after lung cancer in Germany: an analysis of nationwide cancer registry data.J Thorac Oncol. 2022; 17: 388-398Google Scholar are of great importance to inform future studies on surveillance for the growing number of survivors of lung cancer. Kevin ten Haaf: Conceptualization, Writing - original draft preparation. Incidence of Smoking-Related Second Primary Cancers After Lung Cancer in Germany: An Analysis of Nationwide Cancer Registry DataJournal of Thoracic OncologyVol. 17Issue 3PreviewApproximately 80% of lung cancer cases in Germany are attributable to smoking. Patients with a lung cancer diagnosis may remain at increased risk of developing smoking-related second primary cancers (SPCs). Full-Text PDF