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(Chest. 2000;118:1621-1625.)
© 2000 American College of Chest Physicians

Surgery for Second Lung Cancers*

James W. Asaph, MD, FCCP; John F. Keppel, MD, FCCP; John R. Handy, Jr., MD, FCCP; E. Charles Douville, MD; Andrew C. Tsen, MD and Gary Y. Ott, MD

* From The Oregon Clinic, PC (Drs. Keppel, Handy, Douville, Tsen, and Ott), and the Earle A. Chiles Research Institute (Dr. Asaph), Providence Portland Medical Center, Portland, OR.

Correspondence to: John F. Keppel, MD, FCCP, The Oregon Clinic, PC, 507 N.E. 47th Ave, Portland, OR 97213


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Purpose: To evaluate the outcomes of patients surgically treated for their second primary lung cancer.

Method: In a computerized surgical registry of > 800 consecutive patients treated for primary pulmonary carcinoma since 1980, 37 patients presented with a second lung cancer. These patients were analyzed regarding their original treatment, preoperative evaluation, operative procedures, and long-term follow-up.

Results: Three fifths of the patients were female, and 57% were >= 65 years old at the time of their second operation. One patient originally had two synchronous tumors; another patient had three metachronous neoplasms. The interval between surgeries ranged from 5 to 239 months. In 31 patients, treatment for their original tumor was surgical resection alone. Lobectomy was the most common operation for the original tumor, and 78% were stage I. When the second tumor was diagnosed, 25 patients (68%) were asymptomatic. Eight patients (22%) were current smokers, and 29 patients (78%) were former smokers. The most common operation for the second tumor was a lobectomy. Surgical mortality was 5.4%. Nineteen patients (51%) survived 2 years, and 9 patients (24%) survived >= 5 years. Eleven patients (30%) were still alive at last follow-up, 3 to 198 months postoperatively, and only 13 patients (34%) had died of their cancer.

Conclusion: Surgical treatment of second primary pulmonary neoplasms can be performed in selected patients with acceptable long-term survival.

Key Words: CT • lung cancer • metachronous lung tumors


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Current medical practice extends considerable effort in prevention, early detection, and treatment of primary lung cancer. However, less is written on the continued risk of subsequent primary tumors in survivors of lung cancer. In 1961, LeGal and Bauer1 first reported second primary lung cancers in survivors of previously resected bronchogenic carcinomas. Johnson et al2 reviewed the literature in 1997 and concluded that the rate of developing a second primary lung cancer in patients with initial non-small cell lung cancer ranged from 1 to 2% a year. We have reviewed our experience in a private, tertiary-care environment to determine if our experience reflects that of previous reports.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusion
 References
 
Second primary lung cancers were defined using the criteria outlined by Martini and Melamed3 and modified by Antakli et al4 and Adebonojo et al.5 A computerized registry (Patient Analysis & Tracking System; Axis Software; Portland, OR) was used to track 2,446 consecutive patients undergoing general thoracic surgical procedures between January 1, 1980, and June 30, 1999, by a single group of thoracic surgeons operating in two hospitals. More than 800 of those registered were surgically treated for primary pulmonary carcinoma, of which 35 patients presented with a second lung cancer. In addition, two patients with a diagnosis of small cell lung cancer who were successfully treated with combined medical oncology and radiation therapy and then developed a new, non-small cell carcinoma are included in the study. These 37 patients were analyzed regarding their original treatment, preoperative characteristics, operative procedures, pathology, staging, and long-term follow-up.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusion
 References
 
A majority of patients (56.8%) were >= 65 years old at the time they underwent resection of their second carcinoma, and there was a female predominance (59.5%; Table 1 ).


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  		Table 1.. Preoperative Status*

 
To treat the first cancer, 30 patients underwent a lobectomy or bilobectomy, 2 patients with en bloc chest wall resections; 5 patients underwent lesser procedures, including 1 patient who originally presented with two synchronous tumors and underwent bilateral apical segmentectomies as a single operation (Table 2 ). Another patient had three operations for three metachronous tumors. In four patients, the first lesion was a small cell carcinoma. Two of those patients were treated with radiation and chemotherapy without surgery, one patient had surgical resection followed by postoperative chemotherapy, and one patient underwent surgical resection without adjunctive therapy. Three patients with non-small cell carcinoma received postoperative radiation after resection. No patient with non-small cell carcinoma had adjunctive chemotherapy for the original lesion.


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  		Table 2.. Operative Findings*

 
The original tumor was on the right in 13 patients (35.1%), on the left in 23 patients (62.2%), and bilateral in 1 patient. The second lesions were on the right in 19 patients (51.4%) and on the left in 18 patients (48.6%). In 16 patients (43.2%), the tumors were on the same side as the original cancer (Table 2) .

Adenocarcinoma was the most common initial pathology (n = 17), followed by squamous cell (n = 7), large cell and bronchioloalveolar (5 each), and small cell (n = 4). Twenty-nine of the first primary tumors (78.4%) were stage I, 4 were stage IIA, and 2 were stage IIB with chest wall invasion. The original stage could not be accurately determined in three patients, including the two patients with small cell carcinoma who did not undergo operation (Table 2) .

The second cancer was diagnosed within 2 years of first tumor in 13 patients (35%), with 1 patient presenting as early as 5 months after the first operation. In 10 patients (27%), the interval was between 2 years and 5 years; in 14 patients (37.8%), the interval was > 5 years. One patient presented > 20 years (253 months) after the original tumor (Table 1) .

Twenty-five patients (68%) were asymptomatic when the second tumor was diagnosed. In most cases, the diagnosis was made because of a routine chest radiograph. Eight patients (22%) were smoking at the time the second cancer was diagnosed; the other 29 patients (78%) were former smokers. Eighteen patients (48.6%) had mass lesions > 2 cm on a follow-up screening chest radiograph, compared to only 13 patients (35.2%) with small nodules. Twenty-eight patients underwent a preoperative bronchoscopy, in which the second neoplasm was confirmed in 15 patients (40.5%; Table 1 ). The diagnosis was also confirmed in all three patients who had a preoperative percutaneous needle biopsy. Preoperative pulmonary function tests were performed on 34 patients. The FEV1 ranged from 22 to 139% predicted, but it was < 50% only in two patients.

All patients in this series underwent operation. A pneumonectomy was performed in 10 patients (27%). The original tumor was on the same side as the second tumor in each of these patients. Seventeen patients (45.9%) underwent a lobectomy, and 1 patient underwent a bilobectomy. The second lesion was on the same side as the first tumor in five patients. Eight patients (21.6%) underwent lesser procedures: four underwent segmentectomy and four had local excisions. Both patients with < 50% FEV1 had a lesser procedure. One patient proved to have an advanced squamous cell carcinoma with mediastinal invasion at operation and underwent simple biopsy and mediastinal lymph node sampling (Table 2) .

Adenocarcinoma (22 patients; 59.5%) was also the most common histology for the second cancers. There were eight squamous cell (21.6%), four large cell (10.8%), two bronchioloalveolar (5.4%), and one small cell (2.7%). Thirteen patients (35.1%) had the same cell type as the original tumor. Of these, 10 were contralateral lesions from the original, and the interval between all these tumors ranged from 13 to 159 months. Staging of the second tumors included 16 stage IA (43.2%), 9 stage IB (24.3%), 5 stage IIA (13.5%), 4 stage IIB (10.8%), and 1 each of stage IIIA (2.7%), stage IIIB (2.7%), and stage IV (2.7%; Table 2 ).

There were two operative deaths (5.4%), one following pneumonectomy and the other associated with a lobectomy. Overall, 27 patients had no pulmonary complications (73.0%), 3 patients required bronchoscopy for postoperative atelectasis (8.1%), 4 patients experienced air leaks > 7 days or space/reexpansion complications, 2 patients required prolonged mechanical ventilation, and 1 patient developed an empyema. Two patients experienced wound infections (5.4%), six patients developed postoperative atrial fibrillation (16.2%), one patient had a myocardial infarction, and one patient had a cerebral vascular accident. Two patients required reoperation for postoperative bleeding. The mean length of postoperative hospital stay was 8.3 days (Table 3 ).


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  		Table 3.. Second Cancer Postoperative Data*

 
Follow-up after resection of the second cancer was up to 198 months, with a mean follow-up of 36.1 months. Eighteen patients (48.6%) have survived 2 years, and 9 of the 32 patients (28.1%) operated on > 5 years ago have survived >= 5 years (Fig 1 ). Eight of the patients (25%) were still alive at their last follow-up, and only 14 patients (38%) died of their neoplasm. The remainder died of causes not directly related to their cancer or treatment.



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  		Figure 1.. Survival of all cases up to 16 years following surgery for second primary lung cancer. Dotted lines represent one SD.

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusion
 References
 
Our results for surgical treatment of second primary lung cancers are similar to those of other reports.4 5 6 7 8 9 Previous surgery for lung cancer identifies a population at risk for subsequent lung cancers, justifying intensive, prolonged surveillance. Patients who have new cancers that are resectable, with no evidence of extrathoracic metastatic disease and acceptable physiology, should undergo surgical treatment of their tumor. Indeed, there are reports of long-term survival in patients undergoing resection of a second primary from the contralateral lung after previous pneumonectomy.10 11 12

As the incidence of new primary lung cancers continues to increase, the risk of developing metachronous second lung cancers becomes a significant problem. Of particular concern is the need to differentiate new primary lung cancers from recurrence of the original disease, for the results of surgical intervention are far better with new primaries compared to recurrence of the original tumor.13 14 Martini and Melamed3 and Antakli et al4 have defined metachronous, second primary carcinomas as being tumors of different histology or, if of the same histology, having at least two of the following characteristics: a tumor-free interval of at least 2 years, an origin from a separate premalignant lesion, an anatomic distinction in different lobes with no carcinoma in the lymphatics common to both lesions, a different DNA ploidy, or no extrapulmonary metastases at the time of the second diagnosis. Adebonojo et al5 have noted that new pulmonary nodules >= 2 years after initial treatment are most likely new primaries and not metastases of original cancer.

The issue of postoperative surveillance following resection of primary lung cancers is becoming more relevant in this era of increasing managed care. A review by Johnson et al2 noted the risk of a new primary tumor in smokers with a history of previous lung cancer is 10-fold greater than with smokers without such a history. Our experience, with 78% of our cases being former smokers, suggests that this incidence remains high even for patients who successfully stop smoking after or even before their first operation. Johnson et al14 discussed the rationale for follow-up of patients treated for primary lung cancer. In an editorial addressing that article, Shields15 wrote that a major reason for follow-up was to be able to find second primaries, since these are more amenable to surgical resection (and cure) than is recurrent disease.

How often and by what means this surveillance should be done is unclear. However, over two thirds of our second cancer patients were asymptomatic, and the vast majority had stopped smoking long before the diagnosis of their second tumor. Nevertheless, clinical and subsequent surgical staging showed that nearly 50% were advanced lesions when they were diagnosed. In our practice environment, primary-care providers render long-term postoperative follow-up and there is no community standard regarding frequency of follow-up. It was disappointing, however, that so many patients were at a late stage of their second tumor at the time of referral to a surgeon. Since the patient data in this report were collected from a surgical registry, we have no information regarding patients who had second lung cancers diagnosed but were at an advanced clinical stage, precluding surgical referral. This information does suggest, however, that follow-up could be improved in this patient population.

Plain chest radiographs have been the standard for surveillance of patients with a history of lung cancer. However, a recent lung cancer screening study suggests that low-radiation-dose spiral computerized axial tomograms may be a better and more cost-effective way of following up these patients.16


   Conclusion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
References
 
Aggressive surgical resection is indicated in selected patients with second lung cancers and can result in good long-term survival. Our results are similar to those of previous reports from oncologically specialized academic centers of surgical treatment of second primary lung cancer. The possibility of surgical cure is enhanced by a regular follow-up policy for all patients with a history of primary lung cancer to screen for potentially curable, early stage, second primary cancers.


   Footnotes
 
This project was financed entirely by the author physicians from The Oregon Clinic, PC, and given nonfinancial support by Providence Portland Medical Center and The Earle A. Chiles Research Institute. No outside financial support was sought or utilized for this study.

Received for publication December 15, 1999. Accepted for publication May 9, 2000.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 

  1. LeGal, Y, Bauer, WC (1961) Second primary bronchogenic carcinoma. J Thorac Cardiovasc Surg 41,114-121
  2. Johnson, BE, Cortazar, P, Chute, JP (1997) Second lung cancers in patients successfully treated for lung cancer. Semin Oncol 24,492-499[ISI][Medline]
  3. Martini, N, Melamed, MR (1975) Multiple primary lung cancers. J Thorac Cardiovasc Surg 70,606-612[Abstract]
  4. Antakli, T, Schaefer, RF, Rutherford, JE, et al (1995) Second primary lung cancer. Ann Thorac Surg 59,863-867[Abstract/Free Full Text]
  5. Adebonojo, SA, Moritz, DM, Danby, CA (1997) The results of modern surgical therapy for multiple primary lung cancers. Chest 112,693-701[Abstract/Free Full Text]
  6. Martini, N, Bains, MS, Burt, ME, et al (1995) Incidence of local recurrence and second primary tumors in resected stage I lung cancer. J Thorac Cardiovasc Surg 109,120-129[Abstract/Free Full Text]
  7. Jensik, RJ, Faber, LP, Kittle, CF, et al (1981) Survival following resection for second primary bronchogenic carcinoma. J Thorac Cardiovasc Surg 82,658-668[Abstract]
  8. Mathisen, DJ, Jensik, RJ, Faber, LP, et al (1984) Survival following resection for second and third primary lung cancers. J Thorac Cardiovasc Surg 88,502-510[Abstract]
  9. Deschamps, C, Pairolero, PC, Trastek, VF, et al (1990) Multiple primary lung cancers. J Thorac Cardiovasc Surg 99,769-778[Abstract]
  10. Kittle, CF, Faber, LP, Jensik, RJ, et al (1985) Pulmonary resection in patients after pneumonectomy. Ann Thorac Surg 40,294-299[Abstract]
  11. Spaggiari, L, Gruenwald, D, Girard, P, et al (1996) Cancer resection on the residual lung after pneumonectomy for bronchogenic carcinoma. Ann Thorac Surg 62,1598-1602[Abstract/Free Full Text]
  12. Terzi, T, Furlan, F, Gorla, A, et al (1997) Lung resection on single residual lung after pneumonectomy for bronchogenic carcinoma. Thorac Cardiovasc Surg 45,273-276[Medline]
  13. Pairolero, PC, Williams, DE, Bergstralh, EJ, et al (1984) Postsurgical stage I bronchogenic carcinoma: morbid implications of recurrent disease. Ann Thorac Surg 38,331-338[Abstract]
  14. Johnson, FE, Naunheim, KS, Coplin, MC, et al (1997) How tumor stage affects surgeons’ surveillance strategies after lung cancer surgery. Chest 111,99-102[Abstract/Free Full Text]
  15. Shields, TW (1997) Postoperative lung cancer surveillance: who, what, when, and why [editorial]? Chest 111,11-12[Free Full Text]
  16. Henschke, CI, McCauley, DI, Yankelevitz, DF, et al (1999) Early Lung Cancer Action Project: overall design and findings from baseline screening. Lancet 354,99-105[CrossRef][ISI][Medline]



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