Long-term Survival After Resection for Bronchogenic Carcinoma DONALD L. PAULSON, M.D.* JOAN S. REISCH, PH.D.t
From the Baylor University Medical Center and The University of Texas Health Science Center, Dallas, Texas
Of 915 resections for bronchogenic carcinoma over a 25-year period (1945-1969), 249 patients survived over 5 years; 127 of the patients eligible survived over 10 years, 61 over 15 years, and 22 over 20 years. The case material was divided into three time periods: 1945-49, 1950-59 and 1960-69, as well as by extent of resection. Lobectomy became the operation of choice, pneumonectomy being reserved for the more extensive lesions. Observed survival rates at 5, 10 and 15 years for 561 patients in the lobectomy series were 35, 22 and 15%, respectively, but strikingly increased to 41, 28 and 19% in the 1960-69 period. Observed rates for 354 patients having pneumonectomies were similar for three time periods, being 16, 8 and 6% at 5, 10 and 15 years, respectively. Relative survival rates for the lobectomy series at 5, 10 and 15 years rose from 33, 28 and 26%, respectively, in the 1950-59 period to 50, 39 and 35% in the last time period, becoming a near horizontal curve segment after 5 years. Dominant factors in survival were extent of the lesion and stage of nodal involvement, histologic type and location being less significant.
gressively, and the dates and causes of death recorded, with the exception of four patients lost to followup after 10 years. Observed and relative survival rates, or the observed rate adjusted for normal life expectancy, were calculated at 5, 10 and 15 years after resection. Resection, when applicable, is the generally accepted treatment of choice for bronchogenic carcinoma. There is evidence that resections done in the early localized stages of cancer of the lung do actually prolong life and improve physical and mental comfort. In later stages, there is less opportunity for good results, simply due to greater extent of the disease. It must be admitted, TrHE RESULTS of 915 resections for bronchogenic however, that not all resections are beneficial and that carcinoma during a 25-year period (1945-1969) in prolonged survival depends mainly on the natural history a private practice of thoracic surgery provides an oppor- of the lesion, its extent and stage of involvement at the tunity for a review of the efficacy of operation on a time of diagnosis. long-term basis. Through 1975, 249 patients (27%) surSelection of patients for operation is the basis of surgical vived over 5 years after resection; 127 (16%) of the pa- treatment for bronchogenic carcinoma in order to avoid tients eligible survived over 10 years; and 61 (11%) over 15 unwarranted, injudicious exploratory thoracotomy and years. Twenty-two patients have survived over 20 resection, both of which carry significant operative risks years, two for 26 and one for 27 years. Very nearly without benefit to the patient's survival. As previously complete followup information was obtained pro- reported, the basis of surgical treatment has changed, with more complete pretreatment evaluation, resulting in Presented at the Annual Meeting of the American Surgical Associ- improved resection rates and survival figures, as well as ation, New Orleans, Louisiana, April 7-9, 1976. low surgical mortality and increased surgical salvage at * Chief of Thoracic Surgery, Baylor University Medical Center, and Clinical Professor of Thoracic and Cardiovascular Surgery, 5 years.9 University of Texas Health Science Center, Dallas, Texas. t Assistant Professor, Medical Computer Science and Allied Health Sciences, University of Texas Health Science Center, Dallas, Texas. Reprint requests: Donald L. Paulson, M.D., 3600 Gaston Avenue, Dallas, Texas 75246.
Materials and Methods The case material for study is from a total series of 2393 patients with bronchogenic carcinoma seen in a
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25-year period, 1945-1969 (Table 1). Operations were TABLE 1. Distribution of 2,393 Patients 1945 -1969 done for 1156 patients (48%), and 1237 patients (52%) were Patients considered inoperable. Of the patients operated upon, 915 resections (79%) and 241 standard exploratory Number Per cent thoracotomies (21%) were done. Operable 1,156 48 The series of 915 resections was divided into three Resection 915 79 time periods for purposes of statistical analysis: 1945-49, 241 Exploration 21 Inoperable 1950-59 and 1960-69, as well as by extent of resection. 1,237 52 During these three time periods, the indications for Total 2,393 100 resection progressively changed, based upon more objective clinical evidence of resectability with benefit to survival. The resection rates of those patients operated upon polation of the Metropolitan Life Insurance Company, increased as a result, from 61% for 1945-49 to 75% in published by Ederer, Axtell and Cutler.4 The 1965 the period 1950-59 and 90% in the period 1960-69. rates were interpolated from the 1960 and 1970 informaSurgical mortality remained the same. Published results tion. For 1975, 1970 rates were used. of operation for bronchogenic carcinoma tend to be better and the resection rate higher in more recent time Results periods, including those from the same institution, Characteristics of Patients indicating a higher degree of selection for operation.12 The percentage of lobectomies increased from 28% in the 1945-49 period to 57% in the fifties and 74% in the Statistical Analysis sixties. In the entire series, 561 patients (61%) had There were 792 males in the series and 123 females, lobectomies (including 68 segmental resections) and 354 a ratio of about 6:1. Ages ranged from 28 to 80, and had pneumonectomies. The overall surgical patients (39o) predominated in the 55 to 64 age group for both men for all resections was 6%, for lobectomy 4% mortality and women, 63% being over age 55 (Table 2). Race and 9%. pneumonectomy was not considered, since very few patients were NonIn the interest of the quality of survival, lobectomy, Caucasian. when has been considered the operation of Observed survival rates for up to 15 years were cal- choiceapplicable, for both peripheral and central lesions, depending culated directly for the patients undergoing resections in on the location, stage and extent of involvement and the 1945-49 and 1950-59 time periods, including operaevidence of benefit to survival. Pneumonectomy objective tive mortalities. To include all cases, survival rates for has been reserved for the more extensive lesions, with those resected during the 1960-69 period were calculated by the actuarial or life-table method described by TABLE 2. Age Groups and Sex by Extent of Resection in Three Periods Armitage.' Relative survival rates, or the ratio of the observed Pneumosurvival rates to the expected rates for groups of people Lobectomies nectomies similar to the patient groups with respect to sex, age Period Age Groups Male Female Male Female and calendar period of observation, were calculated at 5, 35-44 3 0 10 and 15 years for each of the three time periods. 1945-49 2 1 45-54 8 3 30 0 Expected survival rates were determined according to the 55-64 6 1 19 1 approximate methods of Ederer, Axtell and Cutler.4 65-74 4 1 13 1 75+ 0 0 Patients in the series were divided by sex into age 0 0 Subtotal 21 5 64 3 groups, one under 55 years and the other 55 years and 1950-59 35-44 14 9 over. Average ages were found for each of the four 15 4 45-54 51 6 60 3 sex-age groups, separated by extent of resection for the 55-64 94 14 64 8 three time periods. An average of the four rates for 65-74 38 10 22 4 75+ 6 0 each time period was determined by weighting each age3 0 Subtotal 203 39 164 19 sex rate in proportion to the distribution by age and sex 1960-69 35-44 16 6 at the time of resection. The central points chosen for 7 1 45-54 60 12 26 4 each time period were 1945, 1955 and 1965. The year 55-64 95 15 43 1 1945 was selected as the midpoint for the period 1945-49. 65-74 62 13 19 0 75+ 10 4 Survival rates for 1950, 1960 and 1970 were obtained 2 1 Subtotal 243 50 97 7 from the National Office of Vital Statistics Abridged Grand total 467 94 Life Tables. Rates for 1955 were taken from the inter325 29
PAULSON AND REISCH
326
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Surg. * September 1976
Relative survival rates for the lobectomy cases at 5 and 10 years in the three time periods reveal progressive Lobectomies Pneumonectomies increases, respectively, from 22 and 15% for 1945-49 No. Stage % % No. to 33 and 28% for 1950-59 and 50 and 39o for 1960-69. At 15 years the relative survival rates for lobectomies N0 400 71 163 46 were 18, 26 and 35%, respectively, for the three periods. N1-2 69 64 13129 18154 N3 92 161 36 127 Presented on a logarithmic scale against survival time at 5, 10 and 15 years (Fig. 1), the relative survival curves Total 561 100 354 100 for the lobectomy patients level off from the fifth year on through the tenth to fifteenth year, becoming a near nodal involvement. Seventy-five per cent of the lobec- horizontal curve segment, indicating the period for excess tomies were done for peripheral lesions and 25% in a mortality due to cancer is no longer operative as it was central location. The reverse was true for the pneumonec- in the first five years. tomy series, 77% being done for central lesions and Relative survival rates for patients undergoing penu23% for peripheral tumors. Nodal involvement was found monectomy were similar for the three time frames, in 39Wo of all resections, 29o of the cases resected being 17% at 5 years, in the range of 9 to 12% at by lobectomy, and in 54% of the pneumonectomies. 10 years and 10 to 13% at 15 years. No nodal involvement was recorded in 71% of the lesions resected by lobectomy, and 46% of the pneumonectomies Factors Affecting Survival (Table 3). The extent of the lesion, stage of nodal involvement, Regional lymph node metastases were divided into location and histologic type are all interrelated factors those cases with no lymph node involvement (NO); those with evidence of metastases in intersegmental affecting survival following resection for bronchogenic or interlobar regions or hilar nodes (NI and 2); and those carcinoma. The dominant factors appear to be the extent with evidence of metastases in the mediastinal nodes of the disease and the stage of nodal involvement at (N3). The stages of nodal involvement were comparable the time of diagnosis. The affect of the extent of the lesion is reflected in for two 10-year time periods, with the exception of 7% more stage 0 lesions in the latter period (Table 4). Twenty- the survival rates presented in Table 5 for the lobectomy four and 23% were stage 3 lesions in the two time and pneumonectomy series, pneumonectomy being reserved for the more extensive lesion with nodal involveperiods. ment in general and lobectomy for the lesser involved more localized lesion. Survival Data Nodal Involvement. Observed survival rates by stage Observed survival rates at 5, 10 and 15 years for the of nodal involvement for the second of two time periods series of patients having lobectomies were 35, 22 and 15%, (1950-59 and 1960-69) were strikingly improved for respectively, and 16, 8 and 6% for those having pneumonectomies (Table 5). Divided into three time TABLE 5. Actual Survival Rates by Extent of periods, actual 5-year survival rates in the lobectomy Resection for Three Time Periods series strikingly increased from 19%o in the period 1945-49 Lobectomies to 29o in the 1950-59 series and 41% for 1960-69. Ten and 15-year rates for the last time period were 28 5 Years 10 Years 15 Years and l9o, respectively. The observed rates for patients No. % No. % No. % undergoing pneumonectomies were similar for the three Period time periods, being in the range of 15% at 5 years, 8% 1945-49 5 19.2 3 11.5 3 11.5 1950-59 69 28.6 49 20.3 35 14.5 at 10 and 6% at 15 years. TABLE 3. Extent of Resection and Stage of Nodal Involvement
1960-69 Total
TABLE 4. Distribution by Stage of Nodal Involvement for Two Ten- Year Periods
1950-59
120 194
1960-69
41.0 34.5
5 Years
50 28.0 102 22.0 Pneumonectomies
7 45
10 Years
19.3 14.8
15 Years
Stage
No.
%
No.
%
Period
No.
%
No.
%
No.
%
N0 N 1-2 N3 Total
242 80
57 19
253 54
64 13
103 425
24 100
90 397
23 100
1945-49 1950-59 1960-69 Total
10 28 17 55
14.9 15.3 16.3 15.5
6 15 4 25
9.0 8.2 6.8 7.5
5 11 0 16
7.5 6.0 0 5.9
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FIG. 1. Observed and relative survival rates for the lobectomy series in three time frames plotted on a logarithmic scale against survival time at 5, 10 and 15 years. Per cent survival is indicated on the charted curves.
-i
49
I.-
z a.
TIME (YEARS)
TIME (YEARS)
stage 0 lesions from 31 and 21% at 5 and 10 years to 45 and 33%, respectively, in the latter time frame. For those with hilar node involvement (stage 1-2), survival rates for these time periods were 22 and 13% at 5 and 10 years for the earlier period and 30 and 11%, respectively, for the 1960-69 period. Patients with mediastinal node involvement (stage 3) had markedly decreased survival rates for both periods, being 6 to 8% at 5 years and 3% at 10 years (Fig. 2). Thirty-three patients with hilar nodes survived 5 years, 15 for 10 years and 8 over 15 years. Only 13 patients with mediastinal nodal involvement survived 5 years, 3 for 10 years and 2 over 15 years.
Location was classified as either central or peripheral, the point of division of the segmental bronchi being the boundary between these two categories. A tumor site somewhere proximal to this division point is defined as central. Tumors in this location are usually in the hilar region of a lung, lobe or segment, frequently producing stenosis or obstruction of the bronchus, and usually are visible by bronchoscopic examination. A tumor with a site of origin distal to the point of division of the segmental bronchi was classified as peripheral. This classification included lesions in the lung presenting as a welldemarcated nodule, often close to the visceral pleura, but also deep in the parenchyma or hilar region, or
SURVIVAL BY STAGE OF DISEASE (1950-1959)
FIG. 2. Observed survival rates by stage of nodal involvement for two 10-year time periods plotted on a
logarithmic scale against survival time up to 10 years. Note low survival rates of 6 and 8% at 5 years and 3% at 10 years for stage 3 (mediastinal nodal involvement).
327 RELATIVE SURVIVAL RATES BY TIME PERIOD
SURVIVAL BY STAGE OF DISEASE (1960-1969)
-i
4
'I
z
IL
TIME (YEARS)
TIME (YEAR)
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TABLE 6. Distribution by Location and Stage of Nodal Involvement
Central
Peripheral
Stage
No.
%
No.
%
N0 N 1-2 N3 Total
219 74 120 413
53 18 29 100
344 59 99 502
68 12 20 100
extending through the pleura to the chest wall, diaphragm or mediastinum, or secondarily invading a central bronchus. In this series, 413 lesions were classified as central and 502 as peripheral. Pneumonectomies were done for 66% of the central lesions and 16% of the peripherally located tumors. In contrast, lobectomies were done for 34% of the central lesions and 84% of those in a peripheral location. Forty-seven per cent of the central lesions had nodes involved, 29% mediastinal. Peripherally located lesions differed in that fewer cases, 32%, were found to have nodes involved, 20% mediastinal (Table 6). Ninetyone per cent of the peripheral lesions without nodal involvement were resected by lobectomy. Pneumonectomies were done for 60% of the centrally located lesions without nodal involvement, and 78% of those with mediastinal nodes involved (N3). There is no significant difference in survival rates at 5 or 10 years, however, for patients with central or peripheral lesions, either in the total series of resections or those done in the time perilod 1960-69 (Fig. 3).
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In patients with no nodes involved and having lobectomies, survival rates at 5 years were 45% for those with central lesions and 42% for those with peripherally located lesions. For those having pneumonectomies,
the rates were 21% for central lesions and 16% for the peripheral location. The survival rates by location were similar for those patients with nodal involvement as well.
Histologic Types Epidermoid carcinomas predominated, constituting 61% of the series; adenocarcinoma and large cell carcinoma each 12%; and bronchioalveolar and small cell undifferentiated carcinomas each 5%. The influence of cell type on long-term survival, examined separately, reveals similar survival rates for epidermoid, adenocarcinoma and large cell undifferentiated carcinomas, but significantly differing survival rates for bronchioalveolar and small cell undifferentiated carcinomas (Table 7). Twenty-one of 48 patients (48%) having bronchioalveolar carcinomas survived 5 years, 8 (27%) for 10 years and 3 (21%) for 15 years. None of the 45 patients undergoing resections for small cell undifferentiated carcinomas survived 5 years. Formerly, three patients classified as having this cell type survived 5 years, but on recent review, these have been diagnosed as atypical carcinoid tumors.10 Causes of Death
Causes of death for 127 patients who died after 5, 10 and 15 years were determined, in so far as possible, 100 through personal knowledge, physician's reports, autopsy -LOBECTOMIES - CENTRAL or death certificates. Deaths occuring before 5 years were mainly due to metastases from the original lesion. 60 _ LOBECTOMIES-PERIPHERAL From 5 through 10 years, 23 patients died of metastases 40 (39) (29) from the original lesion, but second primary carcinomas of the lung accounted for deaths of 7 patients. Causes \N,,,^.. PNEUMONECTOMIES .so PERIPHERAL -J (27) of death other than lung cancer in this period were other 4t 20 -.j1S) cancers in 5, cardiovascular disease in 19, pulmonary A (16) >^,, disease in 10 and miscellaneous diseases in 3 patients. cn 10 _ Causes of death could not be definitely determined in z w 10 patients (Table 8). w After 10 years, 9 of 50 patients (18%) died of lung 0. PINEUMONECTOMIES CENTRAL and of these, only 2 died of metastases from cancer, 4 the original lesion. A second primary carcinoma of the (4)' lung caused the death of 14 patients, one of whom, at age 78, died of a second undifferentiated carcinoma 2 of the right lung 25 years after undergoing a left lower lobectomy for an epidermoid carcinoma. A second patient 1,i _ II lO 12 died at age 71 of a small cell undifferentiated carciI4' 2 4 6 8 noma of the left lung 15 years after a right upper TIME (YEARS FIG. 3. Actual survival rates computed by t:he actuarial method for lobectomy with a sleeve resection of the right main location and extent of resection (1960-69) Iplotted on a logarithmic bronchus for an epidermoid carcinoma. The death of the scale against survival time up to 15 years. third patient, age 71, after 15 years survival following 1
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TABLE 7. Survivors by Cell Type (1945-1969) resection of the original epidermoid carcinoma, was due to an undifferentiated carcinoma of the lung. 5 Years 10 Years Division by age groups at the time of death reNumber Cell Type Patients No. % No. % veals competing causes to predominate over deaths due to lung cancer in at least a 2:1 ratio for those over the Epidermoid 562 153 27 87 17 age of 55. Cancer deaths ranged among 30% in the 55-64 Adenocarcinoma 113 23 20 14 14 age group, 28% for the 65 to 74 group and 26% over Large cell undifferentiated 40 36 10 111 13 age 75. Bronchioalveolar 48 21 48 8 27
Discussion Several factors were studied for their effect on survival in a review of the results of 915 resections for bronchogenic carcinoma over a 25-year period. Observed and relative survival rates were strongly affected by the extent of the resection and the stage of nodal involvement. Location of the lesion and histologic type were less important factors. The concept of selectivity for operation, based on complete pretreatment evaluation of the patient, has resulted in improved resection rates and survival figures, with a low surgical mortality and increased surgical salvage in the long term. Resection rates improved from 61 to 90% and the percentage of lobectomies from 28% to 74%. Increased resection rates, with increased proportions of lobectomies, lessen the overall mortality risks of operation and improve the quality of survival with greater physical and mental comfort to the patient. The extent of the lesion is reflected in the extent of resection necessary for its removal. Selected, extended resections are justified, but only on the basis of pretreatment evaluation for the stage of nodal involvement. The greater the extent of the lesion, the higher is the incidence of positive mediastinal nodes.68 No patients requiring extended resections for lesions with mediastinal nodes involved survive much over a year, and the operative mortality exceeds surgical salvage.2 Pretreatment investigation of nodal involvement provides information regarding operability, and also the extent of the resection necessary. The data regarding nodal involvement provides important correlative information for survival, and emphasizes the concept of selection of patients for operation. The stage, the location and type of nodal involvement are all important considerations in survival.2'5'6 Without exception, in reported series in which there is documented invasion of mediastinal nodes, 5-year survival rates are less than 10%.2,7,9,11 Unfortunately confusion still exists, both as to the significance of localization and the extent of invasion of the lymph nodes. Bergh and Schersten2 and Larsson5 have distinguished between ipsilateral and contralateral spread and perinodal and intranodal involvement. Perinodal involvement was found to be predominant in all of the histologic types. Intranodal
Small cell undifferentiated Other Total
45 36 915
0 12 249
27
0 8 127
16
15 Years No.
%
41 8
11 9
3 3
8 21
0 6 61
11
metastases were found in
only 15% of the patients. No patient with perinodal involvement was alive two years after resection. Survival at three years for those with ipsilateral intranodal growth was better than 50% in a small group of patients. There is also a highly significant association between histologic type and mediastinal node metastases. In both small cell undifferentiated and adenocarcinoma, a much higher percentage of mediastinal node involvement was found than in epidermoid carcinomas, providing important information regarding both diagnosis of histologic type and operability. Carlens3 has suggested, on the basis of these findings regarding the stage, location and extent of nodal involvement, that those patients with contralateral spread or perinodal extent be excluded from operation. Among patients with invaded mediastinal nodes, there will remain 12% located ipsilaterally, with intranodal involvement only. Taking into account the surgical mortality of resection for these lesions, a figure results which corresponds well with the survival figures for stage 3 lesions. The improved survival rates in the 1960-69 time frame over the 1950-59 period can be explained on the basis of both prereferral and postreferral selection. In the latter TABLE 8. Causes of Death in Patients Surviving Over Five Years
Cause
5- 10 yr
Metastases from 10 carcinoma Second 1° carcinoma lung Subtotal Other cancer Cardiovascular Pulmonary Miscellaneous Unknown Total
23 7 30 5 19 10 3 10 77 Age Groups at Death
Lung cancer Other causes
10- 15 yr
Over 15 yr
2 7 15 1 0 6 35
0 3 3 0 7 2 0 3 15
4
6
75
5 3
12 28
16 40
6 17
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PAULSON AND REISCH
period, 64% were found to have no nodal invasion, compared to 57% in the earlier time frame. Whereas 43% of the lesions were central lesions in the period 1950-59, only 28% were so located in the latter period, and the percentage of lobectomies for centrally located lesions increased from 35 to 65%, suggesting lesions of lesser extent in the 1960-69 time period. For stage 0 lesions, 5-year survival rates for the lobectomy series were the same for central and peripheral lesions, being in the range of 40-45%. For the same stage, but of such extent as to require a pneumonectomy, 5-year rates were 16-21%. Larsson found in his series that 73% of the peripheral lesions were confined to one lobe and 26% asymptomatic, in contrast to central lesions, 55% of which had extended beyond the confines of a lobe of the lung at the time of diagnosis.5 Although there are individual differences in natural history, histologic type is significant in relation to survival only with respect to the undifferentiated small cell carcinomas and in relation to nodal involvement. No significant differences have been found in survival at 5 years between squamous cell, adenocarcinomas or other undifferentiated carcinomas in patients with negative lymph nodes."' The efficacy of resection for bronchogenic carcinoma improves with selection and may be judged on a longterm basis by calculation of relative survival rates. The slopes of these curves, presented on a semi-log plot, suggest that after 5 years, they level off, assuming a near horizontal curve segment. Causes of death indicate that from 5 to 10 years, only 23 of 77 patients (30O) died of metastases from the original lesion. After 10 years, 41 of 50 patients (82%) died of competing risks other than lung cancer. Conclusions Observed survival rates at 5, 10 and 15 years in a series of 561 lobectomies for bronchogenic carcinoma over a 25-year period were 35, 22 and 15%, respectively, but strikingly increased to 41, 28 and 19%o in the 1960-69 period. Observed rates for the series of 354 pneumonectomies were similar for three time periods, being 16, 8 and 6 per cent at 5, 10 and 15 years, respectively. Relative survival rates for the lobectomy series at 5, 10, and 15 years rose from 33, 28 and 26%, respectively, in the 1950-59 period to 50, 39 and 35% in the last time period. Relative survival curves for the lobectomy patients level off from the fifth year on through the tenth and fifteenth year, becoming a near horizontal curve segment, indicating the period of excess mortality due to cancer is no longer operative as it was in the first five years. Relative survival rates for patients having pneumonectomies were similar for three time frames,
Ann. Surg. * September 1976
being 17% at 5 years, from 9 to 12% at 10 years and 10 to 13% at 15 years. Dominant factors in survival appear to be the extent of the disease, reflected in the extent of resection necessary, and the stage of nodal involvement. Observed survival rates by stage of nodal involvement for the second of two time periods (1950-59 and 1960-69) were strikingly improved for stage 0 lesions from 31 and 21% at 5 and 10 years to 45 and 33%, respectively, in the latter time period. For patients with hilar nodes involved, survival rates for those time periods were similarly improved from 22 to 30Wo at 5 years. Patients with mediastinal node involvement (stage 3) had markedly decreased survival rates for both periods, being 6 to 8% at 5 years and 3% at 10 years. The data regarding nodal involvement provide important correlative information for survival, and emphasizes the concept of selection of patients for operation. For stage 0 lesions, 5-year survival rates for the lobectomy series were the same for central and peripheral lesions, being in the range of 40-45%, but for those of such extent as to require pneumonectomy, 5-year rates were 16-21%. Although individual differences in natural history are recognized, histologic type is significant in relation to survival only with respect to the small cell undifferentiated carcinomas and in relation to nodal involvement. Causes of death indicate that from 5 to 10 years, only 23 of 77 patients (30 per cent) died of metastases from the original lesion and after 10 years, 41 of 50 patients (82%) died of competing risks other than lung cancer.
Acknowledgments We would like to thank Doctors Robert R. Shaw, John L. Kee and Harold C. Urschel, Jr., for allowing us to include their patients in this series.
References 1. Armitage, P.: Statistical Methods in Medical Research, John Wiley, New York, 1971; pp. 408-414. 2. Bergh, N. P. and Schersten, T.: Bronchogenic Carcinoma. Acta. Chir. Scand. Suppl., 347:1-42, 1965. 3. Carlens, E.: Appraisal of Choice and Results of Treatment for Bronchogenic Carcinoma. Chest, 65:442, 1974. 4. Ederer, F., Axtell, L. M. and Cutler, S. J.: The Relative Survival Rate: A Statistical Methodology in End Results and Mortality Trends in Cancer, Bethesda, National Cancer Institute Monograph No. 6, 1961; pp. 101-121. 5. Larsson, S.: Pretreatment Classification and Staging of Bronchogenic Carcinoma. Scand. J. Thorac. Cardiovasc. Surg., Suppl.
10, 1973. 6. Maassen, W.: Results of Routine Mediastinoscopy in Bronchial Carcinoma. In Mediastinoscopy. Denmark, Odense University Press, 1971; pp. 31-35. 7. Nohl, H. C.: The Spread of Carcinoma of the Bronchus. London, Lloyd-Luke, 1962.
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8. Nohl-Oser, H. C.: The Lymphatic Spread of Carcinoma of the Bronchus. In Mediastinoscopy. Denmark, Odense University Press, 1971; pp. 15-18. 9. Paulson, D. L. and Urschel, H. C., Jr.: Selectivity in the Surgical Treatment of Bronchogenic Carcinoma. J. Thorac. Cardiovasc. Surg., 62:554, 1971. 10. Rosai, J.: Personal Communication, 1975.
11. Shields, T. W., Yee, J., Conn, H. J. and Robinette, C. D.: Relationship of Cell Type and Lymph Node Metastasis to Survive after Resection of Bronchial Carcinoma. Ann. Thorac. Surg., 20: 501, 1975. 12. Weiss, W., Cooper, D. A. and Boucot, K. R.: Operative Mortality and 5-Year Survival Rates in Men with Bronchogenic Carcinoma. Ann. Intern. Med., 71:59, 1969.
DISCUSSION
The survival after thoracotomy, after craniotomy, was >95% and the symptom-free interval in this group of 22 patients was excellent. Among the Group I cases there are currently only three survivors, but of interest is the fact that the survival time and the symptomfree time in these patients after removal of their single cranial metastasis has been quite encouraging, and has afforded them a much better quality of life. Several of these patients have had a second craniotomy, with additional survival. Three patients are alive as long as 4 years and 3 months after thoracotomy, 3h years after craniotomy, and symptom-free, in one case, 3½ years after craniotomy; the other two for lesser intervals but significant periods of symptom-free life. I would like to point out that the surgical mortality rate in these 22 craniotomies has been very low (
From the Baylor University Medical Center and The University of Texas Health Science Center, Dallas, Texas
Of 915 resections for bronchogenic carcinoma over a 25-year period (1945-1969), 249 patients survived over 5 years; 127 of the patients eligible survived over 10 years, 61 over 15 years, and 22 over 20 years. The case material was divided into three time periods: 1945-49, 1950-59 and 1960-69, as well as by extent of resection. Lobectomy became the operation of choice, pneumonectomy being reserved for the more extensive lesions. Observed survival rates at 5, 10 and 15 years for 561 patients in the lobectomy series were 35, 22 and 15%, respectively, but strikingly increased to 41, 28 and 19% in the 1960-69 period. Observed rates for 354 patients having pneumonectomies were similar for three time periods, being 16, 8 and 6% at 5, 10 and 15 years, respectively. Relative survival rates for the lobectomy series at 5, 10 and 15 years rose from 33, 28 and 26%, respectively, in the 1950-59 period to 50, 39 and 35% in the last time period, becoming a near horizontal curve segment after 5 years. Dominant factors in survival were extent of the lesion and stage of nodal involvement, histologic type and location being less significant.
gressively, and the dates and causes of death recorded, with the exception of four patients lost to followup after 10 years. Observed and relative survival rates, or the observed rate adjusted for normal life expectancy, were calculated at 5, 10 and 15 years after resection. Resection, when applicable, is the generally accepted treatment of choice for bronchogenic carcinoma. There is evidence that resections done in the early localized stages of cancer of the lung do actually prolong life and improve physical and mental comfort. In later stages, there is less opportunity for good results, simply due to greater extent of the disease. It must be admitted, TrHE RESULTS of 915 resections for bronchogenic however, that not all resections are beneficial and that carcinoma during a 25-year period (1945-1969) in prolonged survival depends mainly on the natural history a private practice of thoracic surgery provides an oppor- of the lesion, its extent and stage of involvement at the tunity for a review of the efficacy of operation on a time of diagnosis. long-term basis. Through 1975, 249 patients (27%) surSelection of patients for operation is the basis of surgical vived over 5 years after resection; 127 (16%) of the pa- treatment for bronchogenic carcinoma in order to avoid tients eligible survived over 10 years; and 61 (11%) over 15 unwarranted, injudicious exploratory thoracotomy and years. Twenty-two patients have survived over 20 resection, both of which carry significant operative risks years, two for 26 and one for 27 years. Very nearly without benefit to the patient's survival. As previously complete followup information was obtained pro- reported, the basis of surgical treatment has changed, with more complete pretreatment evaluation, resulting in Presented at the Annual Meeting of the American Surgical Associ- improved resection rates and survival figures, as well as ation, New Orleans, Louisiana, April 7-9, 1976. low surgical mortality and increased surgical salvage at * Chief of Thoracic Surgery, Baylor University Medical Center, and Clinical Professor of Thoracic and Cardiovascular Surgery, 5 years.9 University of Texas Health Science Center, Dallas, Texas. t Assistant Professor, Medical Computer Science and Allied Health Sciences, University of Texas Health Science Center, Dallas, Texas. Reprint requests: Donald L. Paulson, M.D., 3600 Gaston Avenue, Dallas, Texas 75246.
Materials and Methods The case material for study is from a total series of 2393 patients with bronchogenic carcinoma seen in a
324
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25-year period, 1945-1969 (Table 1). Operations were TABLE 1. Distribution of 2,393 Patients 1945 -1969 done for 1156 patients (48%), and 1237 patients (52%) were Patients considered inoperable. Of the patients operated upon, 915 resections (79%) and 241 standard exploratory Number Per cent thoracotomies (21%) were done. Operable 1,156 48 The series of 915 resections was divided into three Resection 915 79 time periods for purposes of statistical analysis: 1945-49, 241 Exploration 21 Inoperable 1950-59 and 1960-69, as well as by extent of resection. 1,237 52 During these three time periods, the indications for Total 2,393 100 resection progressively changed, based upon more objective clinical evidence of resectability with benefit to survival. The resection rates of those patients operated upon polation of the Metropolitan Life Insurance Company, increased as a result, from 61% for 1945-49 to 75% in published by Ederer, Axtell and Cutler.4 The 1965 the period 1950-59 and 90% in the period 1960-69. rates were interpolated from the 1960 and 1970 informaSurgical mortality remained the same. Published results tion. For 1975, 1970 rates were used. of operation for bronchogenic carcinoma tend to be better and the resection rate higher in more recent time Results periods, including those from the same institution, Characteristics of Patients indicating a higher degree of selection for operation.12 The percentage of lobectomies increased from 28% in the 1945-49 period to 57% in the fifties and 74% in the Statistical Analysis sixties. In the entire series, 561 patients (61%) had There were 792 males in the series and 123 females, lobectomies (including 68 segmental resections) and 354 a ratio of about 6:1. Ages ranged from 28 to 80, and had pneumonectomies. The overall surgical patients (39o) predominated in the 55 to 64 age group for both men for all resections was 6%, for lobectomy 4% mortality and women, 63% being over age 55 (Table 2). Race and 9%. pneumonectomy was not considered, since very few patients were NonIn the interest of the quality of survival, lobectomy, Caucasian. when has been considered the operation of Observed survival rates for up to 15 years were cal- choiceapplicable, for both peripheral and central lesions, depending culated directly for the patients undergoing resections in on the location, stage and extent of involvement and the 1945-49 and 1950-59 time periods, including operaevidence of benefit to survival. Pneumonectomy objective tive mortalities. To include all cases, survival rates for has been reserved for the more extensive lesions, with those resected during the 1960-69 period were calculated by the actuarial or life-table method described by TABLE 2. Age Groups and Sex by Extent of Resection in Three Periods Armitage.' Relative survival rates, or the ratio of the observed Pneumosurvival rates to the expected rates for groups of people Lobectomies nectomies similar to the patient groups with respect to sex, age Period Age Groups Male Female Male Female and calendar period of observation, were calculated at 5, 35-44 3 0 10 and 15 years for each of the three time periods. 1945-49 2 1 45-54 8 3 30 0 Expected survival rates were determined according to the 55-64 6 1 19 1 approximate methods of Ederer, Axtell and Cutler.4 65-74 4 1 13 1 75+ 0 0 Patients in the series were divided by sex into age 0 0 Subtotal 21 5 64 3 groups, one under 55 years and the other 55 years and 1950-59 35-44 14 9 over. Average ages were found for each of the four 15 4 45-54 51 6 60 3 sex-age groups, separated by extent of resection for the 55-64 94 14 64 8 three time periods. An average of the four rates for 65-74 38 10 22 4 75+ 6 0 each time period was determined by weighting each age3 0 Subtotal 203 39 164 19 sex rate in proportion to the distribution by age and sex 1960-69 35-44 16 6 at the time of resection. The central points chosen for 7 1 45-54 60 12 26 4 each time period were 1945, 1955 and 1965. The year 55-64 95 15 43 1 1945 was selected as the midpoint for the period 1945-49. 65-74 62 13 19 0 75+ 10 4 Survival rates for 1950, 1960 and 1970 were obtained 2 1 Subtotal 243 50 97 7 from the National Office of Vital Statistics Abridged Grand total 467 94 Life Tables. Rates for 1955 were taken from the inter325 29
PAULSON AND REISCH
326
Ann.
Surg. * September 1976
Relative survival rates for the lobectomy cases at 5 and 10 years in the three time periods reveal progressive Lobectomies Pneumonectomies increases, respectively, from 22 and 15% for 1945-49 No. Stage % % No. to 33 and 28% for 1950-59 and 50 and 39o for 1960-69. At 15 years the relative survival rates for lobectomies N0 400 71 163 46 were 18, 26 and 35%, respectively, for the three periods. N1-2 69 64 13129 18154 N3 92 161 36 127 Presented on a logarithmic scale against survival time at 5, 10 and 15 years (Fig. 1), the relative survival curves Total 561 100 354 100 for the lobectomy patients level off from the fifth year on through the tenth to fifteenth year, becoming a near nodal involvement. Seventy-five per cent of the lobec- horizontal curve segment, indicating the period for excess tomies were done for peripheral lesions and 25% in a mortality due to cancer is no longer operative as it was central location. The reverse was true for the pneumonec- in the first five years. tomy series, 77% being done for central lesions and Relative survival rates for patients undergoing penu23% for peripheral tumors. Nodal involvement was found monectomy were similar for the three time frames, in 39Wo of all resections, 29o of the cases resected being 17% at 5 years, in the range of 9 to 12% at by lobectomy, and in 54% of the pneumonectomies. 10 years and 10 to 13% at 15 years. No nodal involvement was recorded in 71% of the lesions resected by lobectomy, and 46% of the pneumonectomies Factors Affecting Survival (Table 3). The extent of the lesion, stage of nodal involvement, Regional lymph node metastases were divided into location and histologic type are all interrelated factors those cases with no lymph node involvement (NO); those with evidence of metastases in intersegmental affecting survival following resection for bronchogenic or interlobar regions or hilar nodes (NI and 2); and those carcinoma. The dominant factors appear to be the extent with evidence of metastases in the mediastinal nodes of the disease and the stage of nodal involvement at (N3). The stages of nodal involvement were comparable the time of diagnosis. The affect of the extent of the lesion is reflected in for two 10-year time periods, with the exception of 7% more stage 0 lesions in the latter period (Table 4). Twenty- the survival rates presented in Table 5 for the lobectomy four and 23% were stage 3 lesions in the two time and pneumonectomy series, pneumonectomy being reserved for the more extensive lesion with nodal involveperiods. ment in general and lobectomy for the lesser involved more localized lesion. Survival Data Nodal Involvement. Observed survival rates by stage Observed survival rates at 5, 10 and 15 years for the of nodal involvement for the second of two time periods series of patients having lobectomies were 35, 22 and 15%, (1950-59 and 1960-69) were strikingly improved for respectively, and 16, 8 and 6% for those having pneumonectomies (Table 5). Divided into three time TABLE 5. Actual Survival Rates by Extent of periods, actual 5-year survival rates in the lobectomy Resection for Three Time Periods series strikingly increased from 19%o in the period 1945-49 Lobectomies to 29o in the 1950-59 series and 41% for 1960-69. Ten and 15-year rates for the last time period were 28 5 Years 10 Years 15 Years and l9o, respectively. The observed rates for patients No. % No. % No. % undergoing pneumonectomies were similar for the three Period time periods, being in the range of 15% at 5 years, 8% 1945-49 5 19.2 3 11.5 3 11.5 1950-59 69 28.6 49 20.3 35 14.5 at 10 and 6% at 15 years. TABLE 3. Extent of Resection and Stage of Nodal Involvement
1960-69 Total
TABLE 4. Distribution by Stage of Nodal Involvement for Two Ten- Year Periods
1950-59
120 194
1960-69
41.0 34.5
5 Years
50 28.0 102 22.0 Pneumonectomies
7 45
10 Years
19.3 14.8
15 Years
Stage
No.
%
No.
%
Period
No.
%
No.
%
No.
%
N0 N 1-2 N3 Total
242 80
57 19
253 54
64 13
103 425
24 100
90 397
23 100
1945-49 1950-59 1960-69 Total
10 28 17 55
14.9 15.3 16.3 15.5
6 15 4 25
9.0 8.2 6.8 7.5
5 11 0 16
7.5 6.0 0 5.9
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BRONCHOGENIC CARCINOMA OBSERVED SURVIVAL RATES BY TIME PERIOD
FIG. 1. Observed and relative survival rates for the lobectomy series in three time frames plotted on a logarithmic scale against survival time at 5, 10 and 15 years. Per cent survival is indicated on the charted curves.
-i
49
I.-
z a.
TIME (YEARS)
TIME (YEARS)
stage 0 lesions from 31 and 21% at 5 and 10 years to 45 and 33%, respectively, in the latter time frame. For those with hilar node involvement (stage 1-2), survival rates for these time periods were 22 and 13% at 5 and 10 years for the earlier period and 30 and 11%, respectively, for the 1960-69 period. Patients with mediastinal node involvement (stage 3) had markedly decreased survival rates for both periods, being 6 to 8% at 5 years and 3% at 10 years (Fig. 2). Thirty-three patients with hilar nodes survived 5 years, 15 for 10 years and 8 over 15 years. Only 13 patients with mediastinal nodal involvement survived 5 years, 3 for 10 years and 2 over 15 years.
Location was classified as either central or peripheral, the point of division of the segmental bronchi being the boundary between these two categories. A tumor site somewhere proximal to this division point is defined as central. Tumors in this location are usually in the hilar region of a lung, lobe or segment, frequently producing stenosis or obstruction of the bronchus, and usually are visible by bronchoscopic examination. A tumor with a site of origin distal to the point of division of the segmental bronchi was classified as peripheral. This classification included lesions in the lung presenting as a welldemarcated nodule, often close to the visceral pleura, but also deep in the parenchyma or hilar region, or
SURVIVAL BY STAGE OF DISEASE (1950-1959)
FIG. 2. Observed survival rates by stage of nodal involvement for two 10-year time periods plotted on a
logarithmic scale against survival time up to 10 years. Note low survival rates of 6 and 8% at 5 years and 3% at 10 years for stage 3 (mediastinal nodal involvement).
327 RELATIVE SURVIVAL RATES BY TIME PERIOD
SURVIVAL BY STAGE OF DISEASE (1960-1969)
-i
4
'I
z
IL
TIME (YEARS)
TIME (YEAR)
328
PAULSON AND REISCH
TABLE 6. Distribution by Location and Stage of Nodal Involvement
Central
Peripheral
Stage
No.
%
No.
%
N0 N 1-2 N3 Total
219 74 120 413
53 18 29 100
344 59 99 502
68 12 20 100
extending through the pleura to the chest wall, diaphragm or mediastinum, or secondarily invading a central bronchus. In this series, 413 lesions were classified as central and 502 as peripheral. Pneumonectomies were done for 66% of the central lesions and 16% of the peripherally located tumors. In contrast, lobectomies were done for 34% of the central lesions and 84% of those in a peripheral location. Forty-seven per cent of the central lesions had nodes involved, 29% mediastinal. Peripherally located lesions differed in that fewer cases, 32%, were found to have nodes involved, 20% mediastinal (Table 6). Ninetyone per cent of the peripheral lesions without nodal involvement were resected by lobectomy. Pneumonectomies were done for 60% of the centrally located lesions without nodal involvement, and 78% of those with mediastinal nodes involved (N3). There is no significant difference in survival rates at 5 or 10 years, however, for patients with central or peripheral lesions, either in the total series of resections or those done in the time perilod 1960-69 (Fig. 3).
Ann. Surg.
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September 1976
In patients with no nodes involved and having lobectomies, survival rates at 5 years were 45% for those with central lesions and 42% for those with peripherally located lesions. For those having pneumonectomies,
the rates were 21% for central lesions and 16% for the peripheral location. The survival rates by location were similar for those patients with nodal involvement as well.
Histologic Types Epidermoid carcinomas predominated, constituting 61% of the series; adenocarcinoma and large cell carcinoma each 12%; and bronchioalveolar and small cell undifferentiated carcinomas each 5%. The influence of cell type on long-term survival, examined separately, reveals similar survival rates for epidermoid, adenocarcinoma and large cell undifferentiated carcinomas, but significantly differing survival rates for bronchioalveolar and small cell undifferentiated carcinomas (Table 7). Twenty-one of 48 patients (48%) having bronchioalveolar carcinomas survived 5 years, 8 (27%) for 10 years and 3 (21%) for 15 years. None of the 45 patients undergoing resections for small cell undifferentiated carcinomas survived 5 years. Formerly, three patients classified as having this cell type survived 5 years, but on recent review, these have been diagnosed as atypical carcinoid tumors.10 Causes of Death
Causes of death for 127 patients who died after 5, 10 and 15 years were determined, in so far as possible, 100 through personal knowledge, physician's reports, autopsy -LOBECTOMIES - CENTRAL or death certificates. Deaths occuring before 5 years were mainly due to metastases from the original lesion. 60 _ LOBECTOMIES-PERIPHERAL From 5 through 10 years, 23 patients died of metastases 40 (39) (29) from the original lesion, but second primary carcinomas of the lung accounted for deaths of 7 patients. Causes \N,,,^.. PNEUMONECTOMIES .so PERIPHERAL -J (27) of death other than lung cancer in this period were other 4t 20 -.j1S) cancers in 5, cardiovascular disease in 19, pulmonary A (16) >^,, disease in 10 and miscellaneous diseases in 3 patients. cn 10 _ Causes of death could not be definitely determined in z w 10 patients (Table 8). w After 10 years, 9 of 50 patients (18%) died of lung 0. PINEUMONECTOMIES CENTRAL and of these, only 2 died of metastases from cancer, 4 the original lesion. A second primary carcinoma of the (4)' lung caused the death of 14 patients, one of whom, at age 78, died of a second undifferentiated carcinoma 2 of the right lung 25 years after undergoing a left lower lobectomy for an epidermoid carcinoma. A second patient 1,i _ II lO 12 died at age 71 of a small cell undifferentiated carciI4' 2 4 6 8 noma of the left lung 15 years after a right upper TIME (YEARS FIG. 3. Actual survival rates computed by t:he actuarial method for lobectomy with a sleeve resection of the right main location and extent of resection (1960-69) Iplotted on a logarithmic bronchus for an epidermoid carcinoma. The death of the scale against survival time up to 15 years. third patient, age 71, after 15 years survival following 1
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0
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TABLE 7. Survivors by Cell Type (1945-1969) resection of the original epidermoid carcinoma, was due to an undifferentiated carcinoma of the lung. 5 Years 10 Years Division by age groups at the time of death reNumber Cell Type Patients No. % No. % veals competing causes to predominate over deaths due to lung cancer in at least a 2:1 ratio for those over the Epidermoid 562 153 27 87 17 age of 55. Cancer deaths ranged among 30% in the 55-64 Adenocarcinoma 113 23 20 14 14 age group, 28% for the 65 to 74 group and 26% over Large cell undifferentiated 40 36 10 111 13 age 75. Bronchioalveolar 48 21 48 8 27
Discussion Several factors were studied for their effect on survival in a review of the results of 915 resections for bronchogenic carcinoma over a 25-year period. Observed and relative survival rates were strongly affected by the extent of the resection and the stage of nodal involvement. Location of the lesion and histologic type were less important factors. The concept of selectivity for operation, based on complete pretreatment evaluation of the patient, has resulted in improved resection rates and survival figures, with a low surgical mortality and increased surgical salvage in the long term. Resection rates improved from 61 to 90% and the percentage of lobectomies from 28% to 74%. Increased resection rates, with increased proportions of lobectomies, lessen the overall mortality risks of operation and improve the quality of survival with greater physical and mental comfort to the patient. The extent of the lesion is reflected in the extent of resection necessary for its removal. Selected, extended resections are justified, but only on the basis of pretreatment evaluation for the stage of nodal involvement. The greater the extent of the lesion, the higher is the incidence of positive mediastinal nodes.68 No patients requiring extended resections for lesions with mediastinal nodes involved survive much over a year, and the operative mortality exceeds surgical salvage.2 Pretreatment investigation of nodal involvement provides information regarding operability, and also the extent of the resection necessary. The data regarding nodal involvement provides important correlative information for survival, and emphasizes the concept of selection of patients for operation. The stage, the location and type of nodal involvement are all important considerations in survival.2'5'6 Without exception, in reported series in which there is documented invasion of mediastinal nodes, 5-year survival rates are less than 10%.2,7,9,11 Unfortunately confusion still exists, both as to the significance of localization and the extent of invasion of the lymph nodes. Bergh and Schersten2 and Larsson5 have distinguished between ipsilateral and contralateral spread and perinodal and intranodal involvement. Perinodal involvement was found to be predominant in all of the histologic types. Intranodal
Small cell undifferentiated Other Total
45 36 915
0 12 249
27
0 8 127
16
15 Years No.
%
41 8
11 9
3 3
8 21
0 6 61
11
metastases were found in
only 15% of the patients. No patient with perinodal involvement was alive two years after resection. Survival at three years for those with ipsilateral intranodal growth was better than 50% in a small group of patients. There is also a highly significant association between histologic type and mediastinal node metastases. In both small cell undifferentiated and adenocarcinoma, a much higher percentage of mediastinal node involvement was found than in epidermoid carcinomas, providing important information regarding both diagnosis of histologic type and operability. Carlens3 has suggested, on the basis of these findings regarding the stage, location and extent of nodal involvement, that those patients with contralateral spread or perinodal extent be excluded from operation. Among patients with invaded mediastinal nodes, there will remain 12% located ipsilaterally, with intranodal involvement only. Taking into account the surgical mortality of resection for these lesions, a figure results which corresponds well with the survival figures for stage 3 lesions. The improved survival rates in the 1960-69 time frame over the 1950-59 period can be explained on the basis of both prereferral and postreferral selection. In the latter TABLE 8. Causes of Death in Patients Surviving Over Five Years
Cause
5- 10 yr
Metastases from 10 carcinoma Second 1° carcinoma lung Subtotal Other cancer Cardiovascular Pulmonary Miscellaneous Unknown Total
23 7 30 5 19 10 3 10 77 Age Groups at Death
Lung cancer Other causes
10- 15 yr
Over 15 yr
2 7 15 1 0 6 35
0 3 3 0 7 2 0 3 15
4
6
75
5 3
12 28
16 40
6 17
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PAULSON AND REISCH
period, 64% were found to have no nodal invasion, compared to 57% in the earlier time frame. Whereas 43% of the lesions were central lesions in the period 1950-59, only 28% were so located in the latter period, and the percentage of lobectomies for centrally located lesions increased from 35 to 65%, suggesting lesions of lesser extent in the 1960-69 time period. For stage 0 lesions, 5-year survival rates for the lobectomy series were the same for central and peripheral lesions, being in the range of 40-45%. For the same stage, but of such extent as to require a pneumonectomy, 5-year rates were 16-21%. Larsson found in his series that 73% of the peripheral lesions were confined to one lobe and 26% asymptomatic, in contrast to central lesions, 55% of which had extended beyond the confines of a lobe of the lung at the time of diagnosis.5 Although there are individual differences in natural history, histologic type is significant in relation to survival only with respect to the undifferentiated small cell carcinomas and in relation to nodal involvement. No significant differences have been found in survival at 5 years between squamous cell, adenocarcinomas or other undifferentiated carcinomas in patients with negative lymph nodes."' The efficacy of resection for bronchogenic carcinoma improves with selection and may be judged on a longterm basis by calculation of relative survival rates. The slopes of these curves, presented on a semi-log plot, suggest that after 5 years, they level off, assuming a near horizontal curve segment. Causes of death indicate that from 5 to 10 years, only 23 of 77 patients (30O) died of metastases from the original lesion. After 10 years, 41 of 50 patients (82%) died of competing risks other than lung cancer. Conclusions Observed survival rates at 5, 10 and 15 years in a series of 561 lobectomies for bronchogenic carcinoma over a 25-year period were 35, 22 and 15%, respectively, but strikingly increased to 41, 28 and 19%o in the 1960-69 period. Observed rates for the series of 354 pneumonectomies were similar for three time periods, being 16, 8 and 6 per cent at 5, 10 and 15 years, respectively. Relative survival rates for the lobectomy series at 5, 10, and 15 years rose from 33, 28 and 26%, respectively, in the 1950-59 period to 50, 39 and 35% in the last time period. Relative survival curves for the lobectomy patients level off from the fifth year on through the tenth and fifteenth year, becoming a near horizontal curve segment, indicating the period of excess mortality due to cancer is no longer operative as it was in the first five years. Relative survival rates for patients having pneumonectomies were similar for three time frames,
Ann. Surg. * September 1976
being 17% at 5 years, from 9 to 12% at 10 years and 10 to 13% at 15 years. Dominant factors in survival appear to be the extent of the disease, reflected in the extent of resection necessary, and the stage of nodal involvement. Observed survival rates by stage of nodal involvement for the second of two time periods (1950-59 and 1960-69) were strikingly improved for stage 0 lesions from 31 and 21% at 5 and 10 years to 45 and 33%, respectively, in the latter time period. For patients with hilar nodes involved, survival rates for those time periods were similarly improved from 22 to 30Wo at 5 years. Patients with mediastinal node involvement (stage 3) had markedly decreased survival rates for both periods, being 6 to 8% at 5 years and 3% at 10 years. The data regarding nodal involvement provide important correlative information for survival, and emphasizes the concept of selection of patients for operation. For stage 0 lesions, 5-year survival rates for the lobectomy series were the same for central and peripheral lesions, being in the range of 40-45%, but for those of such extent as to require pneumonectomy, 5-year rates were 16-21%. Although individual differences in natural history are recognized, histologic type is significant in relation to survival only with respect to the small cell undifferentiated carcinomas and in relation to nodal involvement. Causes of death indicate that from 5 to 10 years, only 23 of 77 patients (30 per cent) died of metastases from the original lesion and after 10 years, 41 of 50 patients (82%) died of competing risks other than lung cancer.
Acknowledgments We would like to thank Doctors Robert R. Shaw, John L. Kee and Harold C. Urschel, Jr., for allowing us to include their patients in this series.
References 1. Armitage, P.: Statistical Methods in Medical Research, John Wiley, New York, 1971; pp. 408-414. 2. Bergh, N. P. and Schersten, T.: Bronchogenic Carcinoma. Acta. Chir. Scand. Suppl., 347:1-42, 1965. 3. Carlens, E.: Appraisal of Choice and Results of Treatment for Bronchogenic Carcinoma. Chest, 65:442, 1974. 4. Ederer, F., Axtell, L. M. and Cutler, S. J.: The Relative Survival Rate: A Statistical Methodology in End Results and Mortality Trends in Cancer, Bethesda, National Cancer Institute Monograph No. 6, 1961; pp. 101-121. 5. Larsson, S.: Pretreatment Classification and Staging of Bronchogenic Carcinoma. Scand. J. Thorac. Cardiovasc. Surg., Suppl.
10, 1973. 6. Maassen, W.: Results of Routine Mediastinoscopy in Bronchial Carcinoma. In Mediastinoscopy. Denmark, Odense University Press, 1971; pp. 31-35. 7. Nohl, H. C.: The Spread of Carcinoma of the Bronchus. London, Lloyd-Luke, 1962.
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8. Nohl-Oser, H. C.: The Lymphatic Spread of Carcinoma of the Bronchus. In Mediastinoscopy. Denmark, Odense University Press, 1971; pp. 15-18. 9. Paulson, D. L. and Urschel, H. C., Jr.: Selectivity in the Surgical Treatment of Bronchogenic Carcinoma. J. Thorac. Cardiovasc. Surg., 62:554, 1971. 10. Rosai, J.: Personal Communication, 1975.
11. Shields, T. W., Yee, J., Conn, H. J. and Robinette, C. D.: Relationship of Cell Type and Lymph Node Metastasis to Survive after Resection of Bronchial Carcinoma. Ann. Thorac. Surg., 20: 501, 1975. 12. Weiss, W., Cooper, D. A. and Boucot, K. R.: Operative Mortality and 5-Year Survival Rates in Men with Bronchogenic Carcinoma. Ann. Intern. Med., 71:59, 1969.
DISCUSSION
The survival after thoracotomy, after craniotomy, was >95% and the symptom-free interval in this group of 22 patients was excellent. Among the Group I cases there are currently only three survivors, but of interest is the fact that the survival time and the symptomfree time in these patients after removal of their single cranial metastasis has been quite encouraging, and has afforded them a much better quality of life. Several of these patients have had a second craniotomy, with additional survival. Three patients are alive as long as 4 years and 3 months after thoracotomy, 3h years after craniotomy, and symptom-free, in one case, 3½ years after craniotomy; the other two for lesser intervals but significant periods of symptom-free life. I would like to point out that the surgical mortality rate in these 22 craniotomies has been very low (
