Carcinoma of the Lung: A Clinical Review

Transcription

1 Carcinoma of the Lung: A Clinical Review R. Samuel Cromartie, 111, M.D., Edward F. Parker, M.D., James E. May, M.D., John S. Metcalf, M.D., and David M. Bartles, M.S. ABSTRACT Records of 702 patients with carcinoma of the lung seen from 1960 through 1970 were reviewed. The efficacy of various diagnostic and therapeutic procedures was assessed. Salient findings were as follows: Biopsy of nonpalpable ipsilatera1 supraclavicular lymph nodes was positive for carcinoma in 63 of 286 patients (22%). Even more surprising, biopsy of nonpdpable contralateral supraclavicular lymph nodes was positive for carcinoma in 9 of 38 patients (24%). Accordingly, the importance of biopsy of nonpalpable supraclavicular nodes is to be stressed. Squamous cell carcinoma was the most common type, but adenocarcinoma was more common in women and nonsmokers. Among the 702 patients, 48 (6.8%) were nonsmokers. The 5-year survival for 92 patients treated by lobectomy was 21%; the 5-year survival for 77 patients treated by pneumonectomy was 19%; the 5-year survival among 18 patients having resection of the chest wall in addition to resection of the primary lesion was 22%. Of 12 patients with small cell carcinoma of the lung treated by resection, there was 1 5-year survivor. The overall 5-year survival in the 702 patients was 6.6%. During an 11-year period, 702 patients were treated for carcinoma of the lung at two hospitals in Charleston, SC. Here we report our findings in these patients. Material and Methods From 1960 through 1970, 702 patients with carcinoma of the lung were treated at the Medical University Hospital and the Veterans Administration Hospital in Charleston. There were 416 white men (59.3'/0), 197 black men (28.0%), 59 From the Division of Thoracic and Cardiovascular Surgery and the Department of Pathology, the Medical University of South Carolina, Charleston, SC. Presented at the Twenty-sixth Annual Meeting of the Southern Thoracic Surgical Association, Nov 1-3, 1979, San Antonio, TX. Address reprint requests to Dr. Cromartie, Division of Cardiopulmonary Surgery, Indiana University Medical Center, 1100 W Michigan St, Indianapolis, IN white women (8.4%), and 30 black women (4.3%). The age distribution is shown in Table 1. Of the 702 patients, 558 were seen at the Medical University Hospital. There were 311 white men (55.7%), 158 black men (28.3%), 59 white women (lo.6%), and 30 black women (5.4%). Among this group, the ratio of men to women was 5.27: 1. Of the 702 patients, 48 (6.8%) were known to not smoke tobacco. Smoking status was unknown in 190 patients. Of the remaining patients, 464 smoked cigarettes, 134 at least two packs per day, and 7 smoked cigars or pipes. Nine major symptoms were noted among the 702 patients. The incidence was as follows: cough, 451 patients (64.2%); weight loss, 388 (55.3%); pain, 370 (52.7%); sputum, 312 (44.4%); hemoptysis, 199 (28.3%); malaise, 186 (26.5%); fever, 148 (21.1?'0); neuromyopathies, 68 (9.7%); and dizziness, 28 (4.0%). Some patients had more than one symptom. Although cough was the most frequent symptom, it was not necessarily the first one. Eighty-two patients (11.7%) were asymptomatic. Abnormal physical signs varied depending on the presence or absence of complications such as atelectasis, pneumonia, pulmonary abscess, bronchial obstruction, pleural fluid, and chest wall involvement. Certainly, there were no characteristic signs, and in many there were no abnormal signs. Associated diseases included cardiovascular disease in 254 patients (36%), history of tuberculosis in 41 (6%), diabetes mellitus in renal disease in 27 (4%), bronchiectasis in 17 (2%), and other malignancies in 40 (6%). Cytological examination of the sputum was done in 489 patients. The results were positive in 188 patients (38%) and negative in 301 (62%). Bronchoscopy was performed in 503, and bronchial biopsy was positive in 230 (46%). Biopsies of the pleura by needle aspiration or limited thoracotomy in 46 patients were positive in 31 (67%). Pulmonary biopsies by needle aspira by The Society of Thoracic Surgeons

2 ~~ 31 Crornartie et al: Carcinoma of the Lung Table 1. Age Distribution of 702 Patients with Carcinoma of the Lung Aae ($1 Table 2. Results of Biopsy of Ipsilateral Supraclavicular Lymph Nodes of Patients with Carcinoma of the Lung Patients Percent Palpable Nonpalpable (N = 118) (N = 541) 2.3 Under Per- Result Per- Result Biopsy Patients cent (%) Patients cent (%) Positive ' b Negative ' b Not done and over Unknown Total 702 loo'o tion or limited thoracotomy in 115 patients were positive in 104 (90%). Pleural fluid was evident on roentgenographic examination in 176 patients (25%). Cytological examination of =Based on 91 patients with a result. bbased on 286 patients with a result. Table 3. Results of Biopsy of Contralateral SuPraclavicular Lymph Nodes Of Patients with Carcinoma Of the Lung Palpable (N = 55) Nonpalpable the pleural fluid was done on one or more occa- (N = 599) sions in 77 patients and was positive in 32 (42%). Biopsy Patients cent (YO) Patients cent (YO) Per- Result Per- Result There was involvement of the left lung in 273 Positive ' P (38.9%) of the 702 patients and of the right lung Negative b in 397 (56.6%). Upper lobes were involved... Unknown more often than lower. Both lungs - were involved in 17 patients (2.4%). The involvement 'Based on 20 patients with a result. bbased on 38 patients with a result. was not clear in 15 (2.1%). By clinical or roentgenographic examination or both, there was suspected spread of tumor to multiple sites. These sites included the hilar or mediastinal lymph nodes in 350 patients (50%), the chest wall in 97 (14%), the phrenic nerve in 40 (6%), the recurrent laryngeal nerve in 45 (6%), and the superior vena cava in 43 (6%). Some patients had two or more. All these sites were not proved, however. Among 659 patients in whom it was recorded, palpable ipsilateral supraclavicular nodes were present in 118 patients. Biopsies were performed in 91; 64 (70%) had positive 3 (15'/0), negative (Table 3). Contralateral supraclavicular nodes were not palpable in 599 patients. Biopsies in 38 of these 599 revealed that in 9 (24%) the findings were positive and in 29 (76%), negative. The most common sites of proved metastases were as follows: lymph nodes, 232 (33%); bone, 126 (18%); brain, 94 (13%); contralateral lung (or separate primary), 72 (10%); liver, 57 (8%); and adrenal gland, 50 (7%). Some patients had multiple metastases, and many others had probable metastases in various sites. and 27 (30%) negative findings (Table 2). Five hundred forty-one patients had no palpable ipsilateral supraclavicular nodes. Biopsies were performed in 286 of them: in 63 (22%), the Tumor Classification A recent review of the pathological reports revealed that 170 of the patients had tumor types findings were positive for carcinoma and in 223 that were unclassified. Therefore, the mi- (78%), negative. croscopic slides of these 170 patients were Among 654 patients in whom it was re- studied again by one of us (J. S. M.), with a corded, palpable contralateral supraclavicular subsequent decrease in the number of unclasnodes were found in 55 patients. Biopsies were sified cell types. The criteria utilized were, in done in 20: 17 (85%) had positive findings and general, those of the World Health Organiza-

3 ~ ~~ 32 The Annals of Thoracic Surgery Vol 30 No 1 July 1980 Table 4. Tumor Classification in 702 Patients with Carcinoma of the Lung Patients Percent Squamous cell Adenocarcinoma Large cell Small cell 65 9 Bronchioloalveolar 9 1 Other or unclassified Total Table 6. Relationship of Histological Type to Smoking History of 512 Patients with Carcinoma of the Lung 464 Smokers 48 Nonsmokers Patients Percent Patients Percent Squamous cell Adenocarcinoma Large cell Small cell Bronchioloalveolar Other or unclassified Table 5. Tumor Classification by Sex in 702 Patients with Carcinoma of the Lung Men Women Patients Percent Patients Percent Squamous cell Adenocarcinoma Large cell Small cell Bronchioloalveolar Other or unclassified Total tion. The diagnosis of squamous cell (epidermoid) carcinoma was made only if either intracellular bridges (prickles) or evidence of keratin production was seen. The diagnosis of adenocarcinoma required either gland or tubule formation or intracytoplasmic mucin. When the tumor appeared to originate peripherally and when the neoplastic cells grew along the alveolar walls, the diagnosis of bronchioloalveolar carcinoma was made. When there were no clearly defined differentiating features, the diagnosis was undifferentiated carcinoma. These lesions were further divided into two categories: large cell and small cell. No further attempt was made to subclassify the neoplasms. In all other instances, the tumors were classified as other or unclassified. Cases of carcinoid were excluded from the study. The resultant cell types are shown in Table 4. It is of note that although squamous cell carcinoma was the most common, adenocarcinoma was more common in women and nonsmokers (Tables 5, 6). Fifty-six (8%) patients had cavitary lesions on roentgenographic examination. Cell types for the cavitary lesions were as follows: squamous cell, 40 (71%); large cell, 6 (11Y0); adenocarcinoma, 5 (9%); bronchioloalveolar, 1 (2%); small cell, 0; and other, 4 (7%). Three (5%) of the 56 survived longer than 5 years. Operative lntervention Of the 702 patients studied, 278 had a standard posterolateral thoracotomy (operability rate, 40%). The mean time from the onset of symptoms until operation was 6.2 months. The operations performed were as follows: exploration only, 41 (diagnosis had been established previously); biopsy only, 46; wedge resection only, 3; lobectomy (or bilobectomy on right), 92; pneumonectomy, 77; pulmonary resection with chest wall resection, 18 (12 with lobectomy, 6 with pneumonectomy); and resection of carina, 1. Results There were several complications associated with operation. These included pneumothorax (21 patients or 7.5%); pneumonia (15 or 5%); bronchopleural fistula (15 or 5%); bleeding (12 or 4%); and wound infection (11 or 4%). An empyema developed in 11 patients (6%) among 187 having lobectomy or pneumonectomy. Ninety patients underwent only exploration, biopsy of tumor, or wedge resection. Of these patients, only 1 who had had wedge resection survived more than 5 years. Of the 104 patients who had a lobectomy (including 12 who had

4 33 Cromartie et al: Carcinoma of the Lung Yo ; Squamous Cell n- 64 a Adeno n= Large Cell n= 19 0 Small Cell n= A Bronchiolo-Alveolar n = OtheriUnclassified n = % Squamous Cell n = 252 Adeno n.90 0 Large Cell n= 50 0 Small Cell n I 52 A Bronchiolo-Alveolar n r 8 w OtheriUnclassified n= Fig 1. Survival by cell type for patients with carcinoma of the lung with cervical lymph node metastases. 1 mo 1 yr 2 yr 3 yr 4 yr 5 yr Fig 2. Survival by cell type for patients with carcinoma of the lung without cervical lymph node metastases. concomitant chest wall resection), 5 died (mortality, 4.8%) and 23 (22%) survived 5 years or longer. Of the 83 patients who had a pneumonectomy (including 6 having concomitant chest wall resection), 5 died (mortality, 6.0%) and 16 (19%) survived 5 years or longer. Of the 18 patients who had chest wall resection, 4 (22%) survived longer than 5 years. The patient who had resection of the carina died in less than thirty days. It may be worthy of note that 3 (25%) of 12 patients having lobectomy after receiving preoperative irradiation survived 5 years or longer and that 5 (24%) of 21 patients having pneumonectomy after preoperative irradiation survived more than 5 years. The total number of rads administered to 7 of 8 of the long-term survivors ranged from 2,750 to 4,000 (average, 3,312). In the remaining patient, 3,500 rads was given over a left temporal lobe metastasis and none over the primary in the lung. Immediate or delayed postoperative irradiation was followed by a 5-year survival of 8% (3 out of 36) for lobectomy and 9.5% (2 out of 21) for pneumonectomy. Radiotherapy alone was administered to 304 patients, 3 of whom (1%) lived longer than 5 years. Chemotherapy as an adjunct to radiation therapy in 32 patients resulted in no 5-year survivors. Chemotherapy alone in 26 patients resulted in no survivors past a year. Regardless of the method of treatment, if any, the survival for the different cell types, with and without supraclavicular lymph node metastasis, is shown in Figures 1 and 2. Of 250 patients with negative ipsilateral supraclavicular node biopsies, 15 (6%) survived longer than 5 years compared with 4 (3%) of the 127 patients with positive biopsies. Of 32 patients with negative contralateral supraclavicular biopsies, 4 (12.5%) survived longer than 5 years. Of 26 patients with positive contralateral supraclavicular node biopsies, none survived longer than 5 years. Comments The age and sex distributions in our series are in rough agreement with a number of previous series [3, 7, 10, 21, 221. Sex and race had no important bearing on survival in this study. The study also affirmed the already established fact that most patients with carcinoma of the lung have been tobacco smokers [3]. The etiology is still unknown [SI. Of the diagnostic studies performed, the simplest, sputum cytology, was diagnostic in 38% of our patients. Of the 503 who underwent bronchoscopy, diagnosis was established by bronchial biopsy in 46%; this was before the flexible bronchoscope and transbronchial biopsy were available. In patients with pleural fluid, cytological examination of the fluid was shown to be a valuable diagnostic test in that 32

5 34 The Annals of Thoracic Surgery Vol30 No 1 July 1980 (42%) of the 77 studied had positive results. The presence of pleural fluid was an ominous prognostic sign: only 1 of 45 who had a negative cytological examination survived more than 5 years. No patients with positive pleural fluid cytological examination survived for 5 years. The presence of cavitation had no influence on survival in our patients since the 5% 5-year survival of patients with cavitation is comparable with 5% (27 out of 521) of patients without cavitary lesions (excluding 125 patients in whom the presence or absence of cavitation was not recorded). It was noted by Mittman and Bruderman [121 that cavitary carcinomas usually are squamous cell and seldom oat cell. None of our 56 patients with cavitary lesions had small cell carcinoma. The most common sites of metastases in order of frequency were lymph nodes, bone, brain, contralateral lung, liver, and adrenal glands. No evaluation of routine isotopic scans was made in this review, but Ramsdell and co-workers [15] evaluated 100 patients with lung carcinoma (excluding oat cell) by routine liver, brain, and bone scans. Of 131 scans performed on patients with no clinical evidence of involvement, only 1 was a correct positive. Conversely, of 17 positive scans in these patients, 16 were false positives. Biopsy was diagnostic in 70% (64 out of 91) of the patients with palpable ipsilateral supraclavicular nodes and in 85% (17 out of 20) of the patients with palpable contralateral supraclavicular nodes (see Tables 2,3). The practice of supraclavicular node biopsy in the absence of palpable nodes has been questioned by many surgeons [2, 4, 231, but in this study positive nodes were found in 22% (63 out of 286) of the patients with nonpalpable ipsilateral nodes and in 24% (9 out of 38) of patients with nonpalpable contralateral nodes. These results are similar to those of Brantigan and colleagues [5] who evaluated 341 consecutive patients with carcinoma of the lung by bilateral supraclavicular node biopsies. Positive biopsies were found in 68 (23.8%) of 286 patients with nonpalpable nodes [5]. In light of the ease and safety of this procedure, which can be performed under local anesthesia, it should be performed routinely in patients with nonpalpable nodes for accurate staging before deciding on the optimal methods of treatment. Mediastinoscopy was not evaluated in this review, but it has been shown to be a valuable and safe method for both diagnosis and determination of resectability [8, 9, 14, 191. It has been reported that postoperative empyema may prolong survival after resection for carcinoma of the lung [16, 181. This was not the case with our 11 patients in whom an empyema developed after lobectomy or pneumonectomy, with or without concomitant chest wall resection. Only 1 survived longer than 5 years. Preoperative irradiation apparently did not have an adverse effect on survival of patients undergoing resection; 24% of those undergoing pneumonectomy and 25% of those having lobectomy survived more than 5 years. This survival after resection following preoperative irradiation is contradictory to the results of Baker and co-workers [ll who followed 17 patients with no tumors found in the surgical specimen after irradiation with cobalt 60. All but 1 were dead at the time of follow-up. Shields [17] evaluated 331 patients with biopsy-proved bronchial carcinoma in a randomized study in which one group received preoperative irradiation and resection, and the other group resection only. He found no advantage in preoperative irradiation and probable harmful effects on survival at 4 years. The patients requiring chest wall resection had a reasonable survival with 21% (4 out of 19) living more than 5 years. Geha and associates [6] reported that 12 out of 41 patients (29%) survived 5 years after en bloc excision of the chest wall for curative resection with and without postoperative irradiation. For superior sulcus carcinoma, Paulson and Urschel [13] reported survival longer than 5 years for 16 out of 46 (35%) patients who underwent preoperative irradiation combined with extended resection. These results support the thesis that chest wall involvement is not a contraindication to resection of pulmonary carcinoma if the chest wall involvement is a direct extension and not a distant metastasis. In agreement with previous series [lo, 20,

6 35 Cromartie et al: Carcinoma of the Lung 211, the most frequent cell type among our patients was squamous (46%) and the second, adenocarcinoma (17%). Many physicians believe that the pathological finding of small cell carcinoma of the lung is a contraindication to resection. Jones and colleagues [lo] reported no 5-year survivors among 21 patients who underwent resection of oat cell carcinoma, and Miller and co-workers [113 found superior survival with radiotherapy compared with resection for oat cell carcinoma. In our study, patients with small cell carcinoma who underwent thoracotomy and resection had a 5-year survival of 8% (1 of 12). The overall 5-year survival for the entire 702 patients was 6.6%. References 1. Baker NH, Cowley RA, Linberg E: A follow-up in patients with bronchogenic carcinoma locally cured by preoperative irradiation. J Thorac Cardiovasc Surg 46:298, Baker RR, Stitik FP, Summer WR: Preoperative evaluation of patients with suspected bronchogenic carcinoma. Curr Probl Surg: 1, Dec, Bergh NP, Schersten T: Bronchogenic carcinoma: a follow-up study of a surgically treated series with special reference to the prognostic significance of lymph node metastases. Acta Chir Scand [Suppl] 347:1, Boyd AD: Mediastinoscopy : comparison with scalene fat-pad biopsy. NY State J Med 71:445, Brantigan JW, Brantigan CO, Brantigan OC: Biopsy of nonpalpable scalene lymph nodes in carcinoma of the lung. Am Rev Respir Dis 107:962, Geha AS, Bernatz PE, Wooher LB: Bronchogenic carcinoma involving the thoracic wall: surgical treatment and prognostic significance. J Thorac Cardiovasc Surg 54:394, Green N, Kurohara SS, George FW: Cancer of the lung: an in-depth analysis of prognostic factors. Cancer 28:1229, Gross L: Cancer and slow virus diseases-some common features. N Engl J Med 301:432, Hutchinson CM, Mills NL: The selection of patients with bronchogenic carcinoma for medias- tinoscopy. J Thorac Cardiovasc Surg 71:768, Jones JC, Kern WH, Chapman ND, et al: Longterm survival after surgical resection for bronchogenic carcinoma. J Thorac Cardiovasc Surg 54:383, Miller AB, Fox W, Tall R: Five year follow up of the Medical Research Council comparative trial of surgery and radiotherapy for the primary treatment of small celled or oat-celled carcinoma of the bronchus. Lancet 2:501, Mittman C, Bruderman I: Lung cancer: to operate or not? Am Rev Respir Dis 116:477, Paulson DL, Urschel HC: Superior sulcus carcinomas, in Gibbon s Surgery of the Chest. Third edition. Edited by DC Sabiston, FC Spencer. Philadelphia, Saunders, 1976, chap 18, p Pearson FG, Nelems JM, Henderson RD, et al: The role of mediastinoscopy in the selection of treatment for bronchial carcinoma with involvement of superior mediastinal lymph nodes. J Thorac Cardiovasc Surg 64:382, Ramsdell JW, Peters RM, Taylor AT Jr, et al: Multiorgan scans for staging lung cancer: correlation with clinical evaluation. J Thorac Cardiovasc Surg 73:653, Ruckdeschel JC, Codish SD, Stranahan A, et al: Postoperative empyema improves survival in lung cancer: documentation and analysis of a natural experiment. N Engl J Med 287:1013, Shields TW: Preoperative radiation therapy in the treatment of bronchial carcinoma. Cancer 30:1388, Takita H: Effect of postoperative empyema on survival of patients with bronchogenic carcinoma. J Thorac Cardiovasc Surg 59542, Trinkle JK, Bryant LR, Hiller AJ, et al: Mediastinoscopy: experience with 300 consecutive cases. J Thorac Cardiovasc Surg 60:297, Vincent RG, Takita H, Lane WW, et al: Surgical therapy of lung cancer. J Thorac Cardiovasc Surg 71:581, Weiss W: Operative mortality and five-year survival rate in men with bronchogenic carcinoma. Chest 66:483, Weiss W: Operative mortality and five-year survival rate in patients with bronchogenic carcinoma. Am J Surg 128:799, Yashar J: Transdiaphragmatic exploration of the upper abdomen during surgery for bronchogenic carcinoma. J Thorac Cardiovasc Surg 52:599, 1966