Our study confirms the previously reported association between the presence of comorbidities and lower likelihood of receiving cancer treatment.4–6 However, conflicting data were found with regard to the association between comorbidities and on survival of lung cancer patients. Luchtenborg et al9found that severe comorbidity had a large detrimental impact on the survival of lung cancer patients who undergo curative lung resection. In contrast, a retrospective cohort study from the Netherlands showed that the negative effect of comorbidity on survival in nonsurgical candidates was present only in patients treated with chemotherapy.10 In an analysis of all cancer cases diagnosed between 1992 and 2005 included in the US SEER database, Edwards et al7 found that the influence of comorbidities on the probability of both cancer-specific and non-cancer-related mortality was smaller for lung cancer compared with other cancers. Our study adds to the body of evidence suggesting that comorbidities influence physicians’ decision to recommend treatment for NSCLC, and that comorbidity levels may correlate with other clinical factors influencing treatment choices, such as performance status.

Despite the role of comorbidity assessments in the choice of treatments, limited data are available about the actual benefit of lung cancer therapy in patients with high comorbidity burden. Patients who are more sick are more likely to be excluded from standard clinical trials, leaving clinicians with little objective assessments of treatment benefits in the setting of high comorbidities. Furthermore, when considering the toxicity profile of chemotherapy, the intensity of treatment is limited by organ function, which can be directly impacted by the presence of comorbidities. Patients with higher burden of comorbidities, as determined by KCI score of 3 or higher, constituted ~15% of our study population. In this group, we observed significantly higher survival among those individuals who received any cancer-specific therapy compared with their equally comorbid counterparts who did not. Although selection bias could have resulted in overestimated measures of treatment effects in this observational study, our data indicate that patients may still derive a survival benefit from cancer treatments in the presence of high comorbidity. Likewise, we recognize that comorbidity is not a sole factor used to decide against treatment in NSCLC patients.

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Not all comorbid conditions are expected to have an equal impact on the treatment. The most common comorbidities in lung cancer patients are chronic obstructive pulmonary disease, coronary artery disease, congestive heart failure, diabetes, and renal insufficiency.4–6 Cardiac comorbidity and chronic obstructive pulmonary disease have been described as independent risk factors affecting the development of toxicity and the effectiveness of cancer therapy.11–13 In contrast, no clear role has been described for other comorbidities (such as liver disease or Alzheimer’s dementia) that are also included in the construction of the KCI. Moving forward, it is important for health care providers and patients to realize that, with newer therapeutic options such as immunotherapy, organ dysfunction and the comorbidity burden should play a lesser role in the decision to treat lung cancer.

There are several limitations to our analysis. The data set is from 2007 to 2011 and may not reflect more current practice patterns. This is particularly important since the recent development of immunotherapy, which is believed to have a more favorable safety profile and might not be affected by comorbidities compared with the safety profile of cytotoxic chemotherapy. Given that the study population is restricted to Kentucky residents, the results may not be generalizable to the US NSCLC population.14–19 The SEER-Medicare database does not provide data on other clinically relevant prognostic factors, including performance status and weight loss, or nonclinical factors, such as access to care and social support. The lack of ability to account for the potential confounding effect of these factors could have biased our results.


NSCLC patients with higher comorbidity burden are less likely to receive cancer-specific treatment and more likely to die. However, it appears that even in individuals with high comorbidity burden, cancer-specific treatments seem to improve survival, independently of their stage at presentation. The treatment benefit observed in the high comorbid population is likely a result of multiple factors, including the treatment itself. The impact of comorbidity along with performance status, medical and social support system, and the presenting stage play an important role in decision to treat lung cancer.


This study was supported by Kentucky Lung Cancer Education and Survivorship Grant (LEADS).


The authors report no conflicts of interest in this work.

Jorge Rios,1 Rahul Gosain,1 Bernardo HL Goulart,2 Bin Huang,3 Margaret N. Oechsli,1 Jaclyn K. McDowell,4 Quan Chen,4 Thomas Tucker,4 Goetz H. Kloecker1

1James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 2Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, 3Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, 4Markey Cancer Center, University of Kentucky, Lexington, KY, USA 


1. Raz DJ, Zell JA, Ou SH, Gandara DR, Anton-Culver H, Jablons DM. Natural history of stage I non-small cell lung cancer: implications for early detection. Chest. 2007;132(1):193–199.

2. Goulart BH, Reyes CM, Fedorenko CR, et al. Referral and treatment patterns among patients with stages III and IV non-small-cell lung cancer. J Oncol Pract. 2013;9(1):42–50.

3. Small AC, Tsao CK, Moshier EL, et al. Prevalence and characteristics of patients with metastatic cancer who receive no anticancer therapy. Cancer. 2012;118(23):5947–5954.

4. Islam KM, Jiang X, Anggondowati T, Lin G, Ganti AK. Comorbidity and survival in lung cancer patients. Cancer Epidemiol Biomarkers Prev. 2015;24(7):1079–1085.

5. Tammemagi CM, Nesulund-Dudas C, Simoff M, Kvale P. Impact of comorbidity on lung cancer survival. Int J Cancer. 2003;103(6):792–802.

6. Grose D, Devereux G, Milroy R. Comorbidity in lung cancer: important but neglected. a review of the current literature. Clin Lung Cancer. 2011;12(4):207–211.

7. Edwards BK, Noone AM, Mariotto AB, et al. Annual report to the nation on the status of cancer, 1975–2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer. Cancer. 2014;120(9):1290–1314.

8. Klabunde CN, Potosky AL, Legler JM, Warren JL. Development of a comorbidity index using physician claims data. J Clin Epidemiol. 2000;53(12):1258–1267.

9. Luchtenborg M, Jakobsen E, Krasnik M, Linklater KM, Mellemgaard A, Møller H. The effect of comorbidity on stage-specific survival in resected non-small cell lung cancer patients. Eur J Cancer. 2012;48(18):3386–3395.

10. Mellemgaard A, Luchtenborg M, Iachina M, et al. Role of comorbidity on survival after radiotherapy and chemotherapy for nonsurgically treated lung cancer. J Thorac Oncol. 2015;10(2):272–279.

11. Nalbantov G, Kietselaer B, Vandecasteele K, et al. Cardiac comorbidity is an independent risk factor for radiation-induced lung toxicity in lung cancer patients. Radiother Oncol. 2013;109(1):100–106.

12. Zhai R, Yu X, Shafer A, Wain JC, Christiani DC. The impact of coexisting COPD on survival of patients with early-stage non-small cell lung cancer undergoing surgical resection. Chest. 2014;145(2):346–353.

13. Lee SJ, Lee J, Park YS, et al. Impact of chronic obstructive pulmonary disease on the mortality of patients with non-small-cell lung cancer. J Thorac Oncol. 2014;9(6):812–817.

14. Gadgeel SM, Kalemkerian GP. Racial differences in lung cancer. Cancer Metastasis Rev. 2003;22(1):39–46.

15. Patel JD, Socinski MA, Garon EB et al. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013;31(34):4349–4357.

16. Barlesi F, Scherpereel A, Gorbunova V, et al. Maintenance bevacizumab-pemetrexed after first-line cisplatin-pemetrexed-bevacizumab for advanced nonsquamous nonsmall-cell lung cancer: updated survival analysis of the AVAPERL (MO22089) randomized phase III trial. Ann Oncol. 2014;25(5):1044–1052.

17. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008;26(21):3543–3451.

18. Zhou C, Wu YL, Chen G, et al. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015;26(9):1877–1883.

19. Rosell R, Carcereny E, Gervais R, et al; Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239–246.

Source: Cancer Management and Research.

Originally published January 24, 2018.