Segmentectomy versus lobectomy in patients with stage I pulmonary carcinoma

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1 Segmentectomy versus lobectomy in patients with stage pulmonary carcinoma Five-year survival and patterns of intrathoracic recurrence One hundred seventy-three patients with stage (Tl NO, T2 NO) non-small-cell lung cancer underwent either a segmental pulmonary resection (n = 68) or lobectomy (n = 105) from 1980 to Four patients were lost to follow-up, but the remaining 169 patients were followed up for 5 years. Survival and the prevalence of local/regional recurrence were assessed. Although no survival advantage of lobectomy over segmental resection was noted for patients with tumors 3.0 cm in diameter or smaller, a survival advantage was apparent f6r patients undergoing lobectomy for tumors larger than 3.0 cm. The rate of local/regional recurrence was 22.7 % (15/66) after segmental resection versus 4.9% (5/103) after lobectomy. A review of histologic tumor type, original tumor diameter, and segment resected revealed no risk factors that were predictive of recurrence. An additional resection for recurrence was performed in four patients. Lobectomy is the preferred operative procedure for patients with stage tumors larger than 3.0 cm. Because the rate of local/regional recurrence was high after segmental resections, diligent follow-up of these patients is mandatory. (J THORAC CARDOVASC SURG 1994;107: ) William H. Warren, MD, and L. Penfield Faber, MD, Chicago, ll. Oer the past 30 years, considerable controversy has arisen over the role of segmental resections in the management of stage (Tl NO, T2 NO) lung carcinoma. Although segmental lung resection has been described as a reasonable option for patients with compromised pulmonary reserve,-3 others have advocated it for patients believed to be able to tolerate a lobectomy.4-9 The appropriateness of segmental pulmonary resections must be measured by the perioperative morbidity and mortality, the 5-year survival, and the prevalence oflocally recurrent disease. Despite guidelines suggested to distinguish a local From the Department of Cardiovascular-Thoracic Surgery, Rush Presbyterian-St. Luke's Medical Center, Chicago ll. Supported in part by the John and June Antalek Foundation, the Kole Foundation, and contributors to the Thoracic Disease Research Fund. Read at the Seventy-third Annual Meeting of The American Association for Thoracic Surgery, Chicago, ll., April 25-28, Address for reprints: William H. Warren, MD, Suite 218,1725 West Harrison St., Chicago, L Copyright@ 1994 by Mosby-Year Book, nc /94 $ /6/53214 recurrence from a second primary pulmonary carcinoma or a solitary pulmonary metastasis,lo, 11 problems of interpretation persist. For the purposes of this clinical retrospective study, we defined a local/regional recurrence as the development of an additional carcinoma in the ipsilateral hemithorax (lung and mediastinum) within 5 years of the resection, regardless of the histologic assessment and the exact location within the hemithorax. Although this definition is entirely arbitrary and does not attempt to distinguish incompletely resected tumors from solitary metastases or second primary carcinomas, it is, nevertheless, objective and unambiguous. The prevalence of localjregional recurrence was also compared with the prevalence of carcinoma developing in the contralateral hemithorax. The purposes of this clinical review were (1) to evaluate survival after segmentectomy and standard lobectomy in the management of stage pulmonary carcinomas, (2) to determine the prevalence of local/regional and contralateral recurrence, and (3) to identify prognostic factors relating to survival and to the development of localj regional recurrence. 1087

2 1 088 Warren and Faber The Journal of Thoracic and April 1994 Table. Histologic description of tumors Group! (segmentectomy) Group (lobectomy) Tumor type No. % No. % Adenocarcinoma 44/ / Squamous carcinoma 15/ / "Mixed" phenotypes 5/66 8 6/103 6 Large cell carcinoma 2/66 3 9/103 9 Methods and patients n this retrospective, nonrandomized study, the clinical and pathology files from 1980 to 1988 were reviewed for patients who had undergone either a standard lobectomy or a segmental resection (defined as the resection of one or more anatomic segments of a single lobe but less than a lobe) for a pathologic stage (T NO, T2 NO) non-small-cell carcinoma. The choice of the operation was at the discretion of the surgeon. Patients believed to be able to tolerate a lobectomy underwent a segmentectomy if the tumor was small and peripheral. Anatomic segmental resections were performed. These operations involved dissecting out the hilar structures and securing the branches of the pulmonary artery, pulmonary vein, and segmental bronchus individually as previously described'; patients having nonanatomic "wedge" resections were not eligible. All tumors were limited to one lobe and patients with tumor at the resection margin were excluded. All patients had a regional nodal dissection. Patients having a segmentectomy were included in group and those having a lobectomy in group. Patients were excluded if they had synchronous tumors, had had a previous malignant tumor at any site, or had received preoperative or postoperative adjuvant therapy. All other patients were eligible irrespective of their operative risk factors, pulmonary function, or cardiac status. Patients were seen and examined at regular intervals, and chest radiographs were routinely obtained. Whenever possible, pathologic confirmation of recurrent tumor was done before treatment. The prevalence of local/regional recurrence was compared with the prevalence of carcinoma developing in the contralaterallung in both groups in the 5 years of follow-up. Tumors that recurred as simultaneous bilateral carcinomas were recorded separately. Tumors,that recurred simultaneously both in the ipsilateral hemithorax and distantly were considered to be distant recurrences. No attempt was made to assess operative risk factors of these patients. t is acknowledged that some of the group patients had limited cardiopulmonary reserve and were poor candidates for a lobectomy. The survival statistics and the prevalence of local/regional recurrence of the two groups were analyzed with respect to tumor diameter as measured by the pathologist, histologic examination, time interval between resection and appearance of the recurrence, and management of the recurrent carcinoma. Because tumor diameter was considered to be potentially significant, results were analyzed by tumor size: 2.0 cm or smaller, 2.1 cm to 3.0 cm, and larger than 3.0 cm. To compare the frequencies of the various categorical outcomes in the two groups, we used X 2 tests when all expected cell counts were five or more and Fisher's exact test otherwise. To compare the tumor size distributions of the two groups, we used the two-sample t test. To examine the effects of single variables on survival, on time-until-recurrence, and on disease-free interval, we used log rank tests. To check for multivariate effects on these same event times, we performed stepwise fitting of Cox proportional hazards models on the following prognostic variables: age, sex, maximum tumor diameter, histologic type, and location of the tumor (upper, middle, lower lobes) (right versus left). For all statistical tests, the significance level was The plots show Kaplan-Meier estimates of the proportion in each group alive as a function of time after the operation. All statistical analyses were performed in the SAS statistical package (SAS nstitute, nc., SAS Language and Procedures: Usage, Version 6, 1st ed., Cary, N.C., SAS nstitute nc., 1989). Results Case histories of 173 patients were reviewed. Four patients were lost to follow-up. Of the remaining 169 patients, 66 had undergone a segmentectomy (group ) and 103 had undergone a lobectomy (group ). The ages of group patients ranged from 36 to 81 years (mean years); 66.7% were male. The ages of group patients ranged from 31 to 87 years (mean 63.~ years); 65.0% were male. Tumors in group were classified histologically as adenocarcinoma (44 cases), squamous carcinoma (15 cases), "mixed" phenotypes (5 cases), and large cell carcinoma (2 cases). Tumors in group were assessed to be adenocarcinoma (53 cases), squamous carcinoma (35 cases), "mixed" phenotypes (6 cases), and large cell carcinoma (9 cases) (Table ). The composition of the two groups was not statistically significantly different with respect to histologic type (p = 0.16, Fisher's exact test). Overall, carcinomas in group were smaller than those in group (p < , Student's two-tailed two-sample t test) (Table ). Ofthe 66 carcinomas in group, 38 were 2.0 cm or smaller, 13 were 2.1 to 3.0 em, and 15 were larger than 3.0 em in diameter(3.l to 6.5 em). Of the 103 carcinomas in group tumors, 34 were 2.0 em or smaller, 10 were 2.1 to 3.0 em, and 59 were larger than 3.0 in diameter (3.1 to 16.0 em). Three patients (2 lobectomy, 1 segmentectomy) died in the perioperative period of pulmonary embolus (n = 1), myocardial infarction (n = 1), or adult respiratory distress syndrome (n = O. At 5 years, considering tumors of all diameters, patients undergoing lobectomy (group ) have a statistically significant survival advantage over patients undergoing segmentectomy (group ) (p = 0.Q35) (Fig. 1). However, a comparison of patients with tumors 2.0 em or smaller and patients with tumors 2.1 to 3.0 em in diameter showed no statistically significant difference between groups and (p = 0.24 and 0.58, respectively, log rank test) at 5 years (Figs. 2 and 3). The most common cause

3 The Journal of Thoracic and Volume 107, Number 4 Warren and Faber ,0 C) c.s;.s; :::l en -0 ~ :c C\l.c 0 D Group (66 pis) Group (103 pis) p = o Time in Years Fig. 1. Kaplan-Meier survival plot for group (solid line) (66 patients) and group (dashed line) (103 patients) with carcinomas of all diameters. Vertical bars indicate ± 1 standard error (p = 0.035, log rank test) , - C) c.s;.s; 0.8 :::l en >- :: 0.4 :c C\l.c D- Group (38 pis) Group (34 pis) p = Time in Years Fig. 2. Kaplan-Meier survival plot for group (solid line) (38 patients) and group (dashed line) (34 patients) with carcinomas 2.0 cm or less in diameter. Vertical bars indicate ± 1 standard error (p = 0.024, log rank test). of death in these two groups was distant recurrence of lung carcinoma (14/1,9 group deaths versus 10/16 group deaths). Among patients with tumors larger than 3.0 em in diameter, group had a significantly better survival than group patients (p = 0.006, log rank test) (Fig. 4). However, of those patients with tumors larger than 3 em who died within 5 years of resection, 59% (16/27) died without evidence of recurrent carcinoma (6/9 in group, 10/18 in group ). No statistically significant difference was detected in the 5-year survival in either group on comparing adenocarcinoma versus all other histologic types and squamous carcinoma versus all other histologic types. The patterns of tumor recurrence are presented in Table. The risk of development of local/regional recurrence was signficantly higher in group patients (22.7%) than in group patients (4.9%). This likelihood of local/regional recurrence was further studied according to histologic type, size of the original tumor, and time interval to recurrence. Among the 15 group patients with local/regional recurrence, the histologic description of the original tumor was adenocarcinoma in nine, squamous carcinoma in four, and "mixed" phenotypes in two. n 10 patients, the histologic classifications of the local/regional recurrent tumors were the same as that of the original tumor; in the remaining five patients, a biopsy of the recurrent tumor was not done. Among the five group patients who had local/ regional recurrent carcinoma, the histologic type was

4 1090 Warren and Faber The Journal of Thoracic and April Cl c.s: 0.8.s: :::l U) >- :: 0.4 :c CS.c l Group (13 pts) Group (10 pts) p = 0.58 o Time in Years Fig. 3. Kaplan-Meier survival plot for group (solid line) (3 patients) and group (dashed line) (Opatients) with carcinomas 2.1 to 3.0 cm in diameter. Vertical bars indicate ± 1 standard error (p = 0.58, log rank test). Cl c.s:.s: :::l U) -0 >- :!:: :c CS.c 0 l L~ --'-- i : w==-~- ~--.,-.,t o -- Group (15 pts) Group (59 pts) p =.006 '-'---"----"-cf Time in Years Fig. 4. Kaplan-Meier survival plot for group (15 patients) and group (59 patients) with carcinomas 3.0 cm or larger in diameter. Vertical bars indicate ± 1 standard error(p = 0.006, log rank test). consistent with the original in two patients. A biopsy of the tumor was not obtained in the remaining three. The pattern of local/regional recurrence was further studied according to the site of the recurrence within the ipsilateral hemithorax. n 11 of the group patients and four ofthe group patients, the local/regional recurrence was within the remaining ipsilateral lung (Table V). n the 11 group (segmentectomy) patients with local/ regional recurrence within the lung parenchyma as determined by roentgenography and bronchoscopy, eight of the recurrences were in close proximity to the area of the previous operation. The size of the original tumor in these 15 group patients with local/ regional recurrence was as follows: 2.0 em or smaller, 9 of 38 patients (24%); 2.l to 3.0 em, 4 of 13 patients (31%); larger than 3.0 em, 2 of 15 patients (13%) (Table V). n the five group patients with localj regional recurrence, the size of the original carcinoma was as follows: 2 em or smaller, 1 of 34 patients (2.9%); 2.l to 3.0 em, 1 of 10 patients (10.0%); larger than 3.0 em, 3 of 59 patients (5.l %). The size of the original tumor did not correlate with the risk of local/regional recurrent carcinoma developing in either group or group (p = 0.75 and p = 0.60, respectively, Fisher's exact test). The interval from initial resection to the appearance of the localjregional recurrence ranged from 15 to 58 months (median of 24 months) in group and 8 to 54 months (median 22 months) in group (Fig. 5). Among the 15 patients in group with local/regional recurrence, four successfully underwent an additional

5 The Journal of Thoracic and Volume 107, Number 4 Warren and Faber 1091 Table. Distribution of carcinomas according to diameter >3.0 Totals Tumor size (em) Mean Standard deviation Group (segmentectomy) No. % 38/66 13/66 15/ cm No. 34/103 10/103 59/103 Group (lobectomy) % Totals cm 1.71 Table. Sites of intrathoracic recurrent carcinoma in group (66 patients) and group (103 patients) psilateral recurrences No. % Group (segmentectomy) 15/ Group (lobectomy) 5/ Bilateral recurrences Contralateral recurrences No. % No. % 1/ / / / Table V. Site of local/regional recurrence within the hemithorax in group (segmentectomy) and group (lobectomy) Group Group (15 local/regional (5 local/regional Location recurrences) recurrences) ntrapulmonary 11 4 Mediastinal 3 0 Not specified Table V. Relative risk of local/regional recurrence in group and group according to tumor diameter Group Group/ Tumor (segmentectomy) (lobectomy) diameter (em) No. % No. % / / / /10 10 >3.0 3/ /59 5 complete resection. Five years after the original resection, two of these patients had died of recurrent carcinoma, and two were alive and free of cancer. The remaining 11 patients were deemed to be in inoperable condition because of prohibitive risk factors. These patients all received radiotherapy or no therapy and all died from 3 to 63 months (median 10 months) after the appearance of the local/regional recurrence. Of the five group patients with local/regional recurrence, one underwent curative resection but died 17 months later with distant metastases. The remaining four died from 3 to 14 months (median 11 months) from the time the local/regional recurrence was identified despite adjunctive treatment. Discussion Segmental resections have become an acceptable surgical option for patients with compromised pulmonary reserve. Previous studies have documented that segmental resections can be performed with less morbidity and operative mortality than lobectomy. 1-6 Segmentectomies have also been proposed as the procedure of choice for stage carcinoma of the lung whenever the anatomic location is favorable. 4-8 The Lung Cancer Study Group (LCSG) has conducted a prospective randomized study to assess the role of conservative pulmonary resections in the surgical management of patients with stage carcinomas who are able to tolerate a lobectomy.9 Our review differs from the LCSG study in two important aspects. n our retrospective study, all patients were considered regardless of their physiologic ability to tolerate a lobectomy. Because many of our patients had poor cardiopulmonary reserve, a lower 5-year survival can be anticipated. Second, in our series, 23% (15/66) of patients undergoing segmentectomy had tumors greater than 3.0 cm, whereas the LCSG study is limited to patients with T1 NO carcinomas. We have demonstrated a 5-year survival advantage in performing a lobectomy rather than a segmentectomy when the carcinoma is larger than 3.0 cm in diameter.

6 1092 Warren and Faber The Journal of Thoracic and April 1994 Group m Will i i i i ii 60 Mo. Group i i ~ i 60 Mo. Fig. 5. Disease-free time interval until local/ regional recurrence in group ( 66 patients) and group (l 03 patients). However, when we analyzed the data for tumors 3.0 cm in diameter or smaller, we found no statistically significant difference in 5-year survival. The LCSG results are similar. 9 This result is significant because patients with marginal cardiopulmonary reserve were more likely to undergo a segmental resection and more likely to die of other causes in 5 years. Stair,lO Read,ll, 12 and their associates reported that T1 NO tumors 2.0 cm in diameter or smaller have a better prognosis than tumors 2.1 to 3.0 cm. Our data support this observation; in both groups, patients with tumors that were 2 cm or smaller had a better survival than those with tumors 2.1 to 3.0 cm. However, a comparison of T1 tumors with similar diameters showed no survival advantage for patients who underwent lobectomy rather than segmentectomy. The survival advantage for patients with tumors larger than 3.0 cm undergoing lobectomy versus segmentectomy may reflect, in part, the marginal pulmonary reserve of the patients rather than the operative procedures per se, because in both groups diseases other than recurrent lung carcinoma accounted for the majority of the deaths. According to our statistics, the likelihood of a local/regional recurrence developing over the 5-year period after lobectomy for stage carcinoma is 4.9%. This figure is somewhat higher than the 2.9% likelihood of carcinoma developing in the contralateral lung, but it is in accordance with the likelihood of a local/regional recurrence or a second primary lung cancer developing, as described by others Despite the fact that the 5-year survival was not significantly different among patients with carcinomas that were 3.0 cm or smaller in the two groups, it was disappointing to find a 4.6-fold increased prevalence of localjregional recurrence in group versus group patients. Previous reports from this institution identified the likelihood of local recurrence after segmental resection to be 9.5% to 12.4%.1,5,6 n these reports, an attempt was made to distinguish local recurrence from a second lung primary or a solitary metastasis. Our current figure of 22.7% reflects, in large part, our broader definition of local/regional recurrence. f local/regional recurrences are redefined to be limited to occur only within 2 years after resection, as suggested by others, 16, 17 the prevalence drops to 13.6% (group ) versus 3.9% (group ). Preliminary data from the LCSG with a minimum of 2 years' follow-up support this observation with a 2.7-fold increased prevalence in local/regional recurrence identified after limited pulmonary resections versus lobectomies. 9 Because conservative pulmonary resections leave more lung at risk for the development of a new primary pulmonary carcinoma, one may suggest that segmental resections should be expected to have a higher local/regional recurrence rate. The prevalence in our series, however, is far higher than one could explain on this basis alone. No correlation exists between the size of the tumor and the risk of local/ regional recurrence developing in either of the two groups. Even in tumors measuring 2.0 cm or smaller, the risk of local/regional recurrence was greater after segmentectomy versus lobectomy according to our data. Although others have identified a correlation between histologic type and risk of recurrence,13, 14, 18, 19 no such correlation was apparent in this study. Bronchioloalveolar carcinomas, however, were not distinguished from adenocarcinomas in this retrospective study. Considering that, among segmentectomies, (1) the median time to the development of a 10calJregionai recurrence was 24 months, (2) the majority of the localj regional recurrences were within the remaining lung, (3) the likelihood of a carcinoma developing in the contralaterallung was only 4.5%, and (4) whenever studied, the histologic features of the local/regional recurrence were

7 The Journal of Thoracic and Volume 107, Number 4 Warren and Faber 1093 the same as those of the original tumor, we must concede the possibility that the majority of these local/regional recurrences arise from "incomplete" resections. The majority of patients with local/regional recurrence eventually died of distant metastases, but this did not affect the 5-year survival in the two groups. t is possible that longer follow-up will demonstrate a survival advantage for lobectomy versus segmentectomy in patients with carcinomas 3.0 em or smaller. We recognize that patients undergoing segmental pulmonary resections have a 4.6-fold increased risk of local/ regional recurrence over lobectomy for stage carcinomas over a 5-year period. This increased risk is maintained for both squamous and 'l-denocarcinoma and even in tumors 2.0 em or less in diameter. Most local/regional recurrences occur within 3 years, and therefore a vigilant follow-up over this period is especially important. n the absence of distant metastases, patients with a local/regional recurrence should undergo an additional resection whenever possible rather than palliative radiotherapy. We thank Dr. Sue Leurgans, PhD, for her invaluable assistance in the statistical analysis of the data. REFERENCES l. Jensik RJ, Faber LP, Milloy FJ, Monson DO. Segmental resection for lung carcinoma. J THoRAc CARDOV ASC SURG 1973;66: Hoffman TH, Ransdell HT. Comparison oflobectomy and wedge resection for carcinoma of the lung. J THoRAc CAR. 00VASC SURG 1980;79: Errett LE, Wilson J, Chiu RC-J, Munro DD. Wedge resection as an alternative procedure for peripheral bronchogenic carcinoma in poor-risk patients. J THORAC CAR. 00V ASC SURG 1985;90: Shields TW, Higgins GA. Minimal pulmonary resection in treatment of carcinoma of the lung. Arch Surg 1974; 108: Jensik RJ. Miniresection of small peripheral carcinomas of the lung. Surg Clin North Am 1987;67: Jensik RJ, Faber LP, Kittle CF. Segmental resection for bronchogenic carcinoma. Ann Thorac Surg 1979;28: Crabbe MM, Patrissi GA, Fontenelle LJ. Minimal resection for bronchogenic carcinoma: Should this be standard therapy? Chest 1989;95:968-7l. 8. Crabbe MM, Patrissi GA, Fontenelle LJ. Minimal resection for bronchogenic carcinoma: an update. Chest 1991;99: Ginsberg RJ, Rubenstein L. A randomized comparative trial of lobectomy vs. segmentectomy for patients with TlNO non-sclc lung cancer. Lung Cancer 1991; 7(Suppl):83A. 10. Stair JM, Womble J, Schaefer RF, Read R. Segmental pulmonary resection for cancer. Am J Surg 1985;150: Read RC, Schaeffer R, Neshe N, Walls R. Diameter, cell type, and survival in Stage primary non-small cell lung cancer. Arch Surg 1988;123: Read RC, Yoder G, Schaeffer RC. Survival after conservative resection for TNOMO non-small cell lung cancer. Ann Thorac Surg 1990;49: Thomas P, Rubinstein L, Lung Cancer Study Group. Cancer recurrence after resection: TNO non-small cell lung cancer. Ann Thorac Surg 1990;49: thomas P A, Piantadosi S, Lung Cancer Study Group. Postoperative Tl NO non-small cell lung cancer: squamous versus nonsquamous recurrences. J THORAC CAROOV ASC SURG 1987;94: mmerman SC, Vanecko RM, Fry W A, Head LR, Shields TW. Site of recurrence in patients with Stage and carcinoma of the lung resected for cure. Ann Thorac Surg 1981 ;32: Faber LP. Resection for second and third primary lung cancer. Semin Surg OncoJ993;9:l35-4l. 17. Martini N, Melamed MR. Multiple primary lung cancers. J THoRAc CAROOVASC SURG 1975;70: Gail MH, Eagan RT, Feld R, et al Prognostic factors in patients with resected Stage non-smallcell cancer: a report from the Lung Cancer Study Group. Cancer 1984;54: l Feld R, Rubinstein LV, Weisenberger TH, Lung Cancer Study Group. Sites of recurrence in resected Stage nonsmall-cell lung cancer: a guide for future studies. J Clin Oncol 1984;2: Discussion Dr. Valerie W. Rusch (New York, N.Y.). This is a large and important series from a group that has extensive experience with limited pulmonary resection. As Dr. Warren points out in the manuscript, his data are consistent with those generated from a prospective randomized trial performed by the LCSG. This trial randomized patients who had intraoperatively staged T NO lung cancers to undergo either lobectomy or limited resection by wedge resection or segmentectomy. Patients were stratified according to the intended resection and according to their pulmonary function. No difference in survival was identified between the patients who underwent lobectomy and those who had a limited resection. However, there was an increased rate of local recurrence in patients undergoing limited resection, and this was primarily confined to patients who had a wedge resection. The difference in local recurrence between lobectomy and segmentectomy does not reach statistical significance. Local recurrence was also confined to the patients who had nonsquamous tumors. Thus both of these studies, one of which is retrospective and the other prospective, confined to Tl NO lesions, indicate that limited resection should be considered a compromise operation.

8 1094 Warren and Faber The Journal of Thoracic and April 1994 One important feature of the LCSG trial was an assessment of pulmonary function carried out 3 months and year after the operation. Three months after the operation patients who had a limited resection had significantly better pulmonary function than those who had a lobectomy but that difference was no longer evident year after the operation. Therefore, think we can conclude that patients should be considered for a limited resection if they have severely limited pulmonary function that precludes a lobectomy, but they must be kept under close surveillance during the first 2 to 3 years after the operation. have three questions for the authors. The first pertains to the calculation of overall survival. Did you exclude from the survival calculations patients who died shortly after the operation? Such patients would be excluded from the calculation of recurrence rates, but excluding patients who died immediately after the operation from the survival calculation may alter your results. The second point with respect to survival relates to the inclusion of individuals who had neuroendocrine carcinomas and small-cell lung cancers. Although the absolute numbers of patients in this study with those types of cancers is small, the inclusion of such tumors in survival calculations will alter your results because of their biological behavior. Have you analyzed your results both with and without the inclusion of small-cell cancers and neuroendocrine tumors? n addition, have you evaluated the causes of death in the patients who had T2 tumors? Finally, have you looked at the margins of resections on the patients who had segmentectomies? Were these margins indeed histologically normal at the time of resection? Dr. William S. Blakemore (Birmingham, Ala.). would like to ask you to look further at some of the related factors. On evaluating breast cancers, we had a much different distribution of ploidy studies in Tl /T2 NO MO cancers than in more advanced stages of the disease. Similarly, about 6 years ago we did a limited study on ploidy studies oftl NO MO cancer of the lung with very good survival. By using the ploidy studies we found a marked difference. Survival was excellent with euploid tumors and poor with aneuploidy. Such studies can be done on archival tumors, and would suggest that you consider doing such studies if you have not already done so. A number of other studies would be of interest on archival tumors, for example, studies for oncogenes and suppressor genes. Do you have any information on this type of finding? f you could give some information about the biologic potential of these tumors, you might separate prognostic factors. One such factor would be to separate small-cell tumors. Dr. James B. D. Mark (Stanford, Calif). Realizing that there was not statistical significance between segmental resection and lobectomy, still, every patient between those two curves is a survivor after lobectomy but not after segmental resection. t is antiintuitive, it seems to me, to recommend an operation in which there is a 20% chance of having localj regional recurrence if the patient could withstand a little more extensive operation, that is, lobectomy. What is your definition of segmental resection? s this our old style anatomic segmental resection or is it use of staplers and what we would normally call wedge resection? Dr. Thomas Egan (Chapel Hill, N.c.). have one question about the types of segmentectomies, specifically, a superior segmentectomy of a lower lobe: Did it produce the same kind of local recurrence rate as segmentectomies elsewhere? One sometimes gets the impression that an appropriate dissection similar to a lobectomy can be done on a superior segment lesion. f you did a superior segmentectomy, did it indeed have the same risk of local recurrence? Dr. Ralph J. Lewis (New Brunswick, N.J.). am not clear on the metastases. Local recurrence does not always occur separate from metastases. Were there combinations in your series? When you say local recurrence, was there also a simultaneous metastasis in that patient? Dr. Warren. want to thank the discussants for their very pertinent questions. Dr. Rusch, we excluded patients who died in the 30-day perioperative period. Other than that, these data are actual, not actuarial. Every patient was followed up for 5 years; patients were not excluded if they died from other causes. However, if the surgical resection margins were assessed to be involved, those cases were excluded. You asked a question about neuroendocrine carcinoma. There were three small cell neuroendocrine carcinomas in each of the two groups. All six patients died of distant metastases; none of them had a local recurrence before the development of their distant metastases. We believed this number was sqlall and did not significantly influence the overall survival. n patients with tumors greater than 3 cm, approximately 50% died from recurrent carcinoma, locally or distally, and 50% died from other causes. Dr. Mark, these patients all underwent a formal segmentectomy. The branches of the pulmonary artery and pulmonary vein, as well as the segmental bronchus, were all dissected out and divided. The intersegmental plane was then completed with either digital dissection or a stapler. For the purpose of this study, the segmentectomy was considered to be the resection of one or more segments, but limited to one lobe. We did not assess our segmentectomies according to which segment was resected, but do recall several patients undergoing superior segmentectomies who had a local/regional recurrence. hope this will be the first in a short series of papers studying these tumors in more detail with respect to their histology, their flow cytometric profile, and the presence of various tumor markers. Dr. Lewis, patients who had both local/regional recurrence and distant metastases simultaneously were considered to have simply distant recurrence. t is true that we found no difference in our 5-year survival of patients undergoing segmentectomy versus lobectomy, although we found a higher local/regional recurrence rate among tumors resected by segmentectomies. At least one scenario could explain this apparent paradox: more aggressive tumors, when resected by local resection, may develop localjregional recurrence before the clinical identification of distant metastasis. When that same patient with an aggressive tumor undergoes a lobectomy, there is a lower likelihood of localjregional recurrence, but the patient dies at about the same time from distant metastases. Therefore, overall survival may be more a function of the biology of a tumor than the adequacy of two operations as curative cancer procedures. Further studies will attempt to address this possibility.