Shortened Survival of Lung Cancer Patients Initially Presenting with Pulmonary Tuberculosis

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1 Shortened Survival of Lung Cancer Patients Initially Presenting with Pulmonary Tuberculosis Yuh-Min Chen, Jing-Yi Chao, Chun-Ming Tsai, Pui-Yuen Lee and Reury-Perng Perng 'Chest Department and Cancer Therapy Center, Veterans General Hospital-Taipei, National Yang-Ming University, Taipei, Taiwan It has been reported that the incidence of lung cancer is higher in patients with pulmonary tuberculosis (TB). However, there is little information on the survival and clinical characteristics of these patients. We retrospectively reviewed the medical records of patients with coexisting pulmonary TB and lung cancer covering a period from 9 to 99. There were such patients among a total of 9 lung cancers diagnosed. Lung cancer patients had an increased risk of active pulmonary TB in comparison with the general population in Taiwan. Diabetes mellitus (DM) was found in.% of patients who were diagnosed as having active pulmonary TB within years before, or concurrent with, the diagnosis of lung cancer. However, none of the patients who had developed lung cancer before TB had a history of DM. Epidermoid carcinoma accounted for.% of these cases. The patients who had developed active pulmonary TB before, or concurrently with, the diagnosis of lung cancer survived shorter than those who did not have pulmonary TB at diagnosis of lung cancer (P=.). Survival from diagnosis of pulmonary TB was longer in patients who developed the disease earlier than lung cancer (P=.). Survival from the time of diagnosis of lung cancer was significantly longer in patients who developed cancer earlier than active pulmonary TB (P=.), those without DM (P=.), those with an early tumor stage (P=.), and those given specific cancer treatment (P=.). It is concluded that survival is shorter in lung cancer patients who present initially with active TB than in those who do not have TB. (Jpn J Clin Oncol : -, 99) Key words: Diabetes mellitus Lung cancer Tuberculosis Introduction There has long been an interest in the possible relationship between pulmonary tuberculosis (TB) and lung cancer. " ' Previous reports have mentioned that some cases of lung cancer, usually adenocarcinoma, arising in pulmonary scars were the result of healed tuberculous infection. "" ' There has also been documentation of a higher than expected incidence of lung cancer among pulmonary TB patients. ' ) However, the literature appears to lack similar studies concerning the survival of patients with both pulmonary TB and cancer. The clinical characteristics of cancer patients who de- Received: February 9, 99 Accepted: April, 99 For reprints and all correspondence: Yuh-Min Chen, Chest Department, Veterans General Hospital-Taipei, Shih-pai, Taipei, Taiwan, ROC velop active pulmonary TB after treatment of lung cancer have also been discussed only rarely. We therefore conducted the present retrospective study to determine whether there is a difference in the clinical manifestations between cancer patients who present initially with pulmonary TB and those who develop TB later. Patients and Methods From 9 to 99, 9 cases of lung cancer were diagnosed histocytologically in our hospital. Active pulmonary TB, defined as a consistent chest roentgenographic pattern and demonstration of Mycobacterium tuberculosis in cultured sputum or bronchoscopic specimens, was found to develop within years before or after the diagnosis of lung cancer in of these patients. Serial chest roentgenograms of all patients during the entire disease course were available for Downloaded from by guest on January 9 Jpn J Clin Oncol () 99

2 LUNG CANCER AND TUBERCULOSIS review. The right and left lung fields in each roentgenogram were divided into the upper lung field (upper lobe and middle lobe) and lower lung field (lower lobe) for describing the TB lesions. The extent of pulmonary TB was classified as far advanced, moderately advanced and minimal disease according to the roentgenographic criteria of the National Tuberculosis and Respiratory Disease Association (USA), 99. Patients were considered to have far advanced disease when the total extent of radiologic lesions exceeded the following limits: disseminated lesions of slight to moderate density extending throughout the total volume of one lung or its equivalent in both lungs; dense and confluent lesions occupying one third of the volume of one lung; total diameter of cavitation more than cm. Minimal disease was defined as restriction of TB lesion(s) to within the boundary formed by the apex and the line between the second costosternal junction and the vertebral body of T or the spinal process of T, and included only TB lesion(s) without cavity formation. Patients in whom the extent of roentgenographically evident lesions was intermediate between minimal disease and far advanced disease were defined as having moderately advanced disease. All the patients received antituberculosis treatment after the diagnosis of pulmonary TB. This included isoniazid ( mg/kg/day), ethambutol ( mg/kg/day for months, followed by mg/kg/day) and rifampicin ( mg/kg/day), with/without pyrazimide ( mg/kg/day for months) for 9 months or until their death. The patient survival time for pulmonary TB was calculated from the date of clinical diagnosis or positive acid-fast bacilli smear, to death or last follow-up. Patient survival for lung cancer was calculated from the date of cytopathologic diagnosis of lung cancer to death or last follow-up. Survival analysis was based on the Kaplan-Meier method and log-rank test. Statistical analysis was performed using the SAS software package. Results In 99, the prevalence of active pulmonary TB (Mycobacterium tuberculosis-positive sputum culture) in the general population without lung cancer was.% in Taiwan. The prevalence of active pulmonary TB within years before or after diagnosis of lung cancer was.9% (/9) in our hospital. Lung cancer patients had an increased risk of active pulmonary tuberculosis with an odds ratio of. (9% CI:.-.). The mean age of the patients who developed active pulmonary TB within years before or after diagnosis of lung cancer was years, with a range of to yr. Sixteen patients had active pulmonary TB diagnosed before, or concurrently with, lung cancer (mean age years, range - yr). Fifteen patients had pulmonary TB diagnosed after they had developed lung cancer (mean age years, range - yr). Twenty-seven of the patients had smoked. Diabetes mellitus was found in of the (.%) patients who were diagnosed as having pulmonary TB before, or concurrently with lung cancer, but not in any of the patients who developed pulmonary TB after lung cancer diagnosis. All cancer patients who developed active pulmonary TB later had a history of receiving various treatments for lung cancer including chemotherapy in, radiotherapy in, chemoand radiotherapy in, surgery in, and surgery followed by chemotherapy and radiotherapy in. Among those in whom pulmonary TB had been diagnosed before, or concurrently with lung cancer, radiotherapy was the primary treatment modality for lung cancer in, surgery in, and the remaining patients received only supportive care because the lung cancer was at the terminal stage. The primary lung cancer was located on the same side as the main pulmonary TB lesion in patients, and in patients the cancer and the main TB lesion was located in the contralateral lungs. The remaining patients underwent surgical removal of the primary lung cancer. The histologic classification of lung cancer included epidermoid carcinoma in patients, adenocarcinoma in, and small cell lung cancer in. Pulmonary TB was far advanced in of the patients (.%), moderately advanced in and minimal in. Thirty patients had their main pulmonary lesions in the upper lung field and only one had lower lung field TB. The primary lung cancer was located in the right upper lobe in patients, the right lower lobe in, the left upper lobe in, the left lower lobe in, the right main bronchus in and the left main bronchus in. Patients' clinical characteristics are shown in Table I. The patients who had active pulmonary TB concurrently with or before the diagnosis of lung cancer survived for a shorter period than those who did not (P=., Fig. ). Survival from diagnosis of pulmonary TB was longer in patients who developed TB earlier than, or concurrently with lung cancer than in those who developed active pulmonary TB later (P=., Fig. ). Survival from diagnosis of lung cancer was longer in patients whose cancer developed earlier than active pulmonary TB (P=., Fig. ). Among these patients, those who did not have diabetes mellitus (DM) survived longer than those who did (P=.). Cancer staging and whether or not the patients had received specific treatment were also significant prognostic factors (P=. and. Downloaded from by guest on January 9

3 CHEN ET AL. Table I. Clinical Characteristics of Lung Cancer Patients with Active Pulmonary Tuberculosis Patient number Mean age (range) Diabetes mellitus (%) Cancer treatment Chemotherapy (C/T) Radiotherapy (R/T) Surgery (S/T) C/T + R/T S/T + R/T + C/T Supportive care alone Histology of lung cancer Epidermoid carcinoma Small cell lung cancer Adenocarcinoma Poorly differentiated carcinoma Non-small cell lung cancer, type? Lung cancer staging I II Ilia Illb VI Unknown Location of lung cancer and TB* Ipsilateral (same lobe only) Contralateral Cancer removed Extent of pulmonary TB Far advanced Moderately advanced Minimal Main TB lesion Upper lung field Lower lung field Location of lung cancel RUL RLL LUL, upper division LUL, lingular division LLL RMB LMB Group A (-) (.) 9 () 9 Group B (-) () Total (-) (9.) () Group A, active pulmonary TB occurred within years before, or concurrently with cancer; Group B, active pulmonary TB developed within years after diagnosis of lung cancer; *: Ipsilateral, the main lesion of TB lay in the same hemithorax as that of lung cancer; contralateral, the main lesion of TB was located in the hemithorax contralateral to that of cancer; same lobe only, TB only affected the same lobe as that of lung cancer; : RUL, right upper lobe; RLL, right lower lobe, LUL, left upper lobe; LLL, left lower lobe, RMB, right main bronchus; LMB, left main bronchus. Downloaded from by guest on January 9 Jpn J Clin Oncol () 99

4 LUNG CANCER AND TUBERCULOSIS Month Fig.. Survival from diagnosis of lung cancer with/without concurrent or prior active pulmonary tuberculosis (P=.)., patients without concurrent or prior pulmonary tuberculosis (9 patients, median months); A A, patients with concurrent or prior pulmonary tuberculosis ( patients, median months). Fig.. Survival from diagnosis of lung cancer (P=.)., lung cancer patients with concurrent or prior pulmonary tuberculosis ( patients, median months); A A, lung cancer patients who developed pulmonary tuberculosis later ( patients, median months). respectively) in single variable analysis. The causes of death patients who developed TB earlier than, or concurrently with lung cancer were tumor death in, disseminated TB in, tumor and TB in, pneumonia with sepsis in, and unknown Month Fig.. Survival from diagnosis of pulmonary tuberculosis (i»=.)., lung cancer patients with concurrent or prior pulmonary tuberculosis ( patients, median months); A -A, lung cancer patients who developed pulmonary tuberculosis later ( patients, median months). Table II. Causes of Death in Lung Cancer Patients with Active Pulmonary Tuberculosis Causes of death Group A Group B Total Tumor death Disseminated TB Tumor+ TB Pneumonia with sepsis Unknown Group A, active pulmonary TB occurred within years before, or concurrently with cancer; Group B, active pulmonary TB developed within years after diagnosis of lung cancer. in. The causes of death in patients whose lung cancer developed earlier than active pulmonary TB were tumor death in, disseminated TB in, cancer and TB in, and unknown in (Table II). Tumor death was the main cause of mortality in those who developed TB earlier than, or concurrently with lung cancer, in contrast to disseminated TB, which was the main cause of death in those whose lung cancer developed earner than active pulmonary TB. Discussion Our results show that the incidence of active pulmonary TB within years of diagnosis of lung cancer was.9%. Active pulmonary TB can occur Downloaded from by guest on January 9

5 CHEN ET AL. in lung cancer patients from the time of diagnosis or later. Our finding that lung cancer patients had a higher risk of developing pulmonary TB than the general population was similar to previous reports. 9 - ) DM is a risk factor for tuberculosis infection or reactivation, with a relative risk of.-.. "~ l) It was found in more than one third of our patients who were diagnosed as having active pulmonary TB earlier than, or concurrently with cancer. However, DM is not a risk factor for lung cancer. ) The peak incidence of DM with reactivation of pulmonary TB occurs among the elderly. ) Reactivation or worsening of the tuberculous lesions often overlaps the peak age for development of lung cancer. ) The high incidence of DM in our patients with active pulmonary TB diagnosed earlier than, or concurrently with lung cancer also indirectly supports the notion that DM is a risk factor of reactivation of pulmonary TB. Another important finding was that DM was a poor prognostic factor for patients who had TB and lung cancer. Immunosuppression is another risk factor for tuberculosis infection. - ) All of our patients who were diagnosed as having lung cancer before reactivation of TB had received treatment for lung cancer. Twelve of patients had received radiotherapy and/or chemotherapy, a well-known cause of immunosuppression. Cellular immunity has been found to be compromised in cancer patients, and also in patients with progressive TB, who seem to have a defective Thl component. - ) This defect in the cellular immunity of cancer patients can partly explain their increased risk of pulmonary TB. Immunosuppression, whether due to cancer treatment or cancer itself, was the main cause of reactivation of pulmonary TB in our cancer patients, especially those who developed active TB later. In these patients, immunosuppression played a more important role in the development of pulmonary TB than DM, which was not found in this group of patients. Pulmonary TB occurring after antineoplastic therapy, resulting in more severe infection with a higher mortality rate, has been reported previously. 9 - ) The histologic classification of lung cancer shows that the majority of cases are epidermoid carcinoma. ) This is true even in patients who have had active TB prior to, or concurrently with cancer. Scar cancer, of which the predominant histologic type is adenocarcinoma, - ) was less common in our patients. Nevertheless, the major location of pulmonary TB lesions was the same lobe or on the same side as the lung cancer. This condition was noted even in patients who were found to have active TB before the diagnosis of cancer. Pulmonary TB and primary lung cancer thus showed a close association, as reported previously. ' Our survival analysis showed that patients with active pulmonary TB at the time of diagnosis of lung cancer survived for a shorter period than those without pulmonary TB. Pulmonary TB, as well as systemic diseases such as DM, can possibly delay the diagnosis and complicate the treatment of lung cancer. Another possibility is that pulmonary TB tends to occur in lower socio-economic classes who are less accustomed to seeking medical resources. The survival calculated from the time of diagnosis of lung cancer showed that patients who developed pulmonary TB later than cancer survived longer than those who developed TB before cancer. However, a converse phenomenon was noted when survival time was calculaulated from the time of diagnosis of TB. This was possibly because the patients who developed TB later than cancer had received cancer treatment and survived long enough to develop reactivation of pulmonary TB. Such TB reactivation is probably less likely in those who survived shorter only because of the time factor. It would have been better if we had made a survival comparison between groups with similar characteristics, such as those of the same tumor stage and given the same treatment modalities. However, this would have limited the number of patients available for comparison, and thus statistical analysis would not have been possible or appropriate. Therefore the survival analysis of patients who developed pulmonary TB earlier or later than lung cancer was confounded by the fact that the patient characteristics, such as stage and treatment methods, were not equal between the groups. In conclusion, epidermoid carcinoma was present in the majority of lung cancer patients with pulmonary TB. Both lung cancer and TB tended to occur in the upper lung fields. DM appeared to be an important risk factor in those who developed TB earlier than or concomitantly with cancer, and was also a poor prognostic factor. Immunosuppression related to cancer treatment played an important role in the reactivation of pulmonary TB in lung cancer patients. Survival was poor in lung cancer patients with active pulmonary TB as compared with those without TB. These findings indicate that a diagnosis of active pulmonary TB in patients with suspected bronchogenic carcinoma should not delay the institution of appropriate studies for diagnosis of lung cancer. ' References ) Bender F: Primary pulmonary carcinoma associated with active pulmonary tuberculosis. Dis Chest : -, 9 ) Greenberg SD, Jenkens DE, Bahar D, Schweppe HI, Downloaded from by guest on January 9 Jpn J Clin Oncol () 99

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