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Ann Thorac Surg 1997;63:193-197
© 1997 The Society of Thoracic Surgeons

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Original Articles: General Thoracic

Non–Small Cell Lung Cancer at the Extremes of Age: Impact on Diagnosis and Treatment

Section of Cardiothoracic Surgery, Department of Surgery, and Section of Hematology/Oncology, Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, and Section of Biostatistics and Epidemiology, Department of Community and Family Medicine, Dartmouth Medical School, and Dartmouth College, Hanover, New Hampshire

Accepted for publication July 24, 1996.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Data Collection Statistical Considerations Results Comment Acknowledgments References

 
Background. Early detection and surgical resection offers the highest likelihood of cure for patients with lung cancer. Patients presenting at the extremes of age may fail to benefit maximally from these interventions. To study the impact of age on stage, histology, symptom, and treatment of patients with non–small cell lung cancer, we undertook a retrospective review.

Methods. One thousand eight hundred two patients with non–small cell lung cancer were identified between 1983 and 1993. Patients were selected by age as less than 45 years (55 patients) and 80 years or more (108 patients), and their medical records were reviewed.

Results. Three younger patients (6%) presented with stage I or II disease, yet 15 (32%) underwent thoracic operation. Twenty-seven elderly patients (33%) presented with early stage disease and only 6% underwent operation. The median survival was significantly longer for the younger population with surgically resectable stages of disease (stage I to IIIA) (p < 0.05), whereas no significant difference in survival was seen for the two groups with advanced disease (stage IIIB and IV).

Conclusions. Age significantly affects the presentation and treatment of non–small cell lung cancer patients. Although thoracic operation imparts the greatest survival advantage, this benefit is diminished due to advanced disease in the younger patients and lack of surgical intervention in the elderly.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Data Collection Statistical Considerations Results Comment Acknowledgments References

 
Lung cancer continues to be a leading cause of cancer deaths in the United States. There will be an estimated 177,000 patients with new cases of this disease in 1996, of which only 12% are projected to be alive in 5 years. Lung cancer surpassed coronary heart disease as the leading cause of smoking-related death among white middle-class smokers and alone is responsible for the overall increase in death from all cancer nationwide [1].

Non–small cell lung carcinoma (NSCLC) represents 80% of all cancers of the lung. Twenty-five percent of these patients have resectable disease at the time of diagnosis, and 50% have disease confined to the thorax. Although efforts to improve survival have focused on expanded indications for operation and multimodality therapy, little progress has been made [2]. Complete surgical resection remains the only accepted treatment offering the likelihood of cure [3–5]. Optimal implementation of this treatment strategy demands a diagnosis before the disease is spread beyond the confines of the intended resection, and that the patient be sufficiently robust to survive the operation.

Because NSCLC develops in the majority of patients between the ages of 50 and 80 years, conclusions regarding presentation, treatment, and survival have principally been derived from this age group. It has been our impression that patients presenting outside this age group fail to benefit from surgical intervention. In an effort to understand the impact of age on presentation, treatment, and survival for patients with NSCLC, we compared two contrasting groups of patients with this disease, the very young and the very old, in this retrospective analysis.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Data Collection Statistical Considerations Results Comment Acknowledgments References

 
Patient Selection
The Dartmouth-Hitchcock Tumor Registry identified 1,802 patients with NSCLC from 1983 to 1993. From the cancer registry, patients were selected by age at the time of diagnosis as less than 45 years (young age, 55 patients) and 80 years or older (old age, 108 patients). To ensure complete reporting of the surgical treatment of patients with NSCLC, records from the Section of Cardiothoracic Surgery were also examined over this 10-year period.

	Data Collection

Top Footnotes Abstract Introduction Material and Methods Data Collection Statistical Considerations Results Comment Acknowledgments References

 
A retrospective review of the medical records for these patients was conducted. The dates of NSCLC diagnosis and survival were provided by the cancer registry. Patient demographics, smoking history, cancer-related symptoms, performance status, TNM stage, histologic subtype, treatment, and survival were recorded. Primary care physicians were contacted for survival information for patients not recorded by the cancer registry. For patients without recorded TNM stage at diagnosis, radiologic reports and physician notes were used.

	Statistical Considerations

Top Footnotes Abstract Introduction Material and Methods Data Collection Statistical Considerations Results Comment Acknowledgments References

 
The demographics, cancer-related symptoms, histology, stage, and treatment for the younger and older groups of patients were compared using Pearson's ². The Mantel-Haenszel test was used to compare the groups with respect to operation, controlling for stage. Kaplan-Meier survival analysis for the two groups and their survival was compared using the log-rank test.

	Results

Top Footnotes Abstract Introduction Material and Methods Data Collection Statistical Considerations Results Comment Acknowledgments References

 
One thousand eight hundred two patients with NSCLC were recorded in the Dartmouth-Hitchcock Tumor Registry from 1983 to 1993. Over this 10-year period, 55 patients were found to be less than 45 years of age at the time of diagnosis and 108 patients were 80 years of age or older. Twenty-nine patients were not included in the study. Eight patients from the younger group and 21 patients from the older group had either incomplete medical information or a diagnosis other than NSCLC. The remaining 134 patients-47 patients in the group less than 45 years of age and 87 patients in the group 80 years or older-had complete information on smoking history, cancer-related symptoms, and treatment. TNM staging at diagnosis, tumor histology, and survival information was obtained for 96% of patients. The patient demographics, smoking history, Karnofsky performance status, and initial symptom at presentation are shown in Table 1. The age groups were similar with respect to sex. The male to female ratio was 1.6 to 1 for both groups. Although the majority of patients in both groups were cigarette smokers, the younger patient population had a significantly greater proportion of smokers (p < 0.05). Cancer-related symptoms were common: 91% of the younger patients and 85% of the older patients. However, younger patients were significantly more likely to present with pain (p < 0.05), whereas older patients were more likely to have dyspnea (p < 0.05). Cough (54%) was the most common presenting symptom in the older patients.

View larger version (16K): [in this window] [in a new window]   Fig 1. . Kaplan-Meier survival curves for 47 young patients (solid line) and 81 older patients (dashed line) with non–small cell lung cancer (p < 0.05 by log-rank test).

	Comment

Top Footnotes Abstract Introduction Material and Methods Data Collection Statistical Considerations Results Comment Acknowledgments References

In general, NSCLC typically presents between the ages of 50 and 80 years. Of those patients in whom NSCLC is destined to develop, only 3% will present before the age of 45 years and 9% before the age of 50 years [6–8]. In contrast, 90% of patients with NSCLC will present with this disease before the age of 80 years [9]. Our study population obtained from the Dartmouth-Hitchcock Tumor Registry was similar, with 3% of our patients less than 40 years of age and 6% aged 80 years or older. It is well established that cigarette smoking is the principal cause of lung cancer in both men and women. As the result of longer and greater exposure to cigarette tar, middle-age men are the primary candidates for lung cancer. Over the past decade in the United States, the incidence of lung cancer in men is leveling off, while it continues to rise among women.

Typically, the younger population of patients in whom this disease develops tend to be female and have a higher incidence of adenocarcinoma [8]. An explanation for this may be found by examining some of the changing patterns of lung cancer incidence and histology noticed in the past 30 years [10–12]. Although the overall incidence of lung cancer continues to rise, the relative incidence is changing for men and women. One explanation for this demographic shift may be the slower decline in smoking among women compared with men. However, given the same level of lifelong exposure to cigarette smoke, women have a 1.5-fold higher estimated relative risk of lung cancer than men [13, 14]. A low male to female ratio has also been noted in the elderly population. Smith and colleagues [9] reported on 5,205 patients with lung cancer over the age of 70 in Virginia and found a male to female ratio of 2.2:1. These findings are supported by our study. We have a 1.6:1 male to female ratio in both groups of patients: less than 40 years of age and 80 years and older.

The predominance of adenocarcinoma in the younger population may also be explained by changes in smoking patterns. Zheng and colleagues [12] examined the patterns of lung cancer in the Connecticut Tumor Registry from 1960 to 1989 and found that the incidence of squamous cell carcinoma had stabilized in men whereas adenocarcinoma was increasing significantly in both men and women. The researchers attributed this change, in part, to the increased popularity of filtered cigarettes in women, which have been associated with alterations in the lung distribution of smoke particulate. On the other hand, Devesa and co-workers [11] suggested that adenocarcinoma requires less smoke exposure time to develop than squamous cell carcinoma, and therefore, adenocarcinoma would appear more frequently in a younger population. Certainly, the high proportion of adenocarcinoma (55%) in our younger study population supports these results. Despite a lower male to female ratio, one-third of the older patients in our study had squamous cell carcinoma of the lung. This also supports the time of smoke exposure as an explanation for the change in the distribution of NSCLC histology.

Although we had anticipated a higher incidence of asymptomatic patients in the elderly population, most patients in our study presented with symptoms. The presence of symptoms at the time of diagnosis of lung cancer varies from 40% in a screened population to 98% in a review of hospital records [15]. In our series, cough was the most common presenting symptom in the patients 80 years or older (54%). Similarly a series by Hyde and Hyde [16], reported cough as the most common presenting symptom of men with lung cancer (74%). However, cough is a relatively nonspecfic symptom. Irwin and colleagues [17] noted only 2 cases of lung cancer in 102 consecutive patients presenting for evaluation of chronic cough. Chest pain has been reported to occur in 27% to 49% of patients who present with lung cancer [15, 16]. We recorded a much higher proportion of younger patients presenting with pain (64%). When compared with the older patients, pain was significantly more common in the younger group, which may correlate with the high incidence of mediastinal, pleural, or chest wall involvement and more advanced stage of disease. Dyspnea at the time of diagnosis has been reported in 37% of lung cancer patients [15]. The higher incidence of dyspnea in this elderly population (45%) may represent diminished cardiopulmonary reserve associated with advanced age.

Clearly younger patients with NSCLC present with more extensive disease [6, 8, 18]. This fact is not easily explained. The rare nature of bronchogenic carcinoma in the young population may limit both public and professional awareness, thus delaying diagnosis while ineffectual treatment is rendered for nonspecific complaints. Pembertom and colleagues [6] found patients less than 40 years of age waited an average of 4.2 months between onset of symptoms and diagnosis, yet they could not compare this time interval with the population at large [6]. In contrast, Antkowiak and colleagues [7] reviewed 89 patients with lung cancer younger than 40 years and found 94% presented with stage III or IV disease with a median interval from onset of symptom to diagnosis of 1.5 months. DeCaro and co-workers [18] reviewed a similar population of young lung cancer patients and found no evidence that the interval between the onset of symptoms and the establishment of a definitive diagnosis was different from the population at large. Although chest radiographic screening of the general population has been shown to be ineffectual in lowering mortality rates from lung cancer, screening of high-risk populations has been shown to detect cancers in earlier stages [6]. Perhaps young patients with extensive smoking histories should be identified as a high-risk population and considered for routine screening.

Treatment strategies for patients with NSCLC are clearly determined by the age at presentation. Despite presenting with more advanced disease, younger patients are more likely to be offered surgical resection than elderly patients. Pemberton and colleagues [6] reported on 113 patients less than 40 years of age. Eighty-seven percent had stage III NSCLC and 50% underwent surgical resection. In the series of 102 young patients from Barnes Hospital, Kyriakos and colleagues found that 76% underwent thoracotomy, and 57% of the patients had a curative resection. This series did not present information regarding stage at presentation [19]. In contrast, Smith and co-workers [9] found increasing age in lung cancer patients with local-regional disease was associated with either not undergoing operation or with receiving no therapy, and that age had no influence on whether patients were offered radiation therapy. Although older patients carry a higher risk of surgical mortality than their younger counterparts, as longevity increases within the general population, surgical therapy for cancer assumes the same relative importance for the elderly as for younger patients [20]. The younger patients presented here clearly had a higher performance status than the elderly group, in part explaining the higher likelihood of surgical resection in this group. Smith and colleagues [9] found higher comorbidity score predicted an absence of surgical resection, regardless of stage, but they did not directly link age to comorbidity.

Overall survival was better in the younger population. Although this is not surprising, considering the older population included only those equal to or greater than 80 years of age, the younger patients presented with significantly more advanced disease. It is likely that despite the advanced status of the younger population, the aggressive use of surgical resection may explain the difference in outcomes. In fact, when comparing median survival in only stage IIIB and stage IV disease, there is no difference between the old and young patients. Although some have argued that lung cancer in the very young is a more aggressive disease, this observation would argue against that being true [21].

In conclusion, NSCLC remains a particularly deadly disease when it presents at either pole of its typical age spectrum. In younger patients, it tends to be strongly associated with smoking and to attack women more frequently than in the general population. Young patients are very likely to be symptomatic, have adenocarcinoma, and present with advanced disease. The elderly population also has a lower male to female ratio than the general population, but otherwise presents with a more typical histologic and clinical staging picture. Both groups, the young and the old, fail to maximally benefit from surgical resection. Young patients seem to benefit from an aggressive surgical approach, yet present too late in the course of disease to be offered high likelihood of cure. This outcome could be improved by detecting disease earlier and by reducing the incidence of smoking in the adolescent and young adult population. Routine chest radiography in patients who are heavy smokers might be considered.

In the elderly population, the benefit of operation is likely to be lost either due to associated comorbidities making operation prohibitively dangerous or due to pervasive customs and beliefs within the medical community that chronologic age automatically excludes an aggressive surgical approach to this disease. As the percentage of the population older than 80 years increases, the benefit potential of surgical cure in an otherwise fatal illness begins to match the benefit seen in younger patients. Increased application of less invasive surgical techniques and improvement in the perioperative care of this elderly population will offer the greatest opportunity for improvement.

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods Data Collection Statistical Considerations Results Comment Acknowledgments References

 
This study was supported by grant number 5R25 CA 19379–18, Cancer Education Project, National Cancer Institute, DHHS. James R. Rigas is the recipient of the American Cancer Society Clinical Oncology Career Development Award.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Data Collection Statistical Considerations Results Comment Acknowledgments References

 
Address reprint requests to Dr Nugent, Section of Cardiothoracic Surgery, Dartmouth-Hitchcock Medical Center, One Medical Center Dr, Lebanon, NH 03756-0001.

	References

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): William C. Nugent Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nugent, W. C. Articles by Rigas, J. R. Search for Related Content PubMed PubMed Citation Articles by Nugent, W. C. Articles by Rigas, J. R.