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J Thorac Cardiovasc Surg 1994;107:8-12
© 1994 Mosby, Inc.

GENERAL THORACIC SURGERY

Local recurrence after complete resection for non-small-cell carcinoma of the lung: Significance of local control by radiation treatment

Fukuoka, Japan

Received for publication Jan. 13, 1993. Accepted for publication March 30, 1993. Address for reprints: Tokujiro Yano, MD, Department of Chest Surgery, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka 815, Japan.

Abstract

Of 471 patients undergoing a complete resection for non-small-cell carcinoma of the lung between 1972 and 1989, 40 patients (8.5%) had local recurrences without extrathoracic distant metastasis. Excluding 8 patients who had malignant pleural effusion, we selected 32 patients (24 with hilar-mediastinal lymph node, 6 with bronchial stump, and 2 with chest wall recurrence) from the 40 patients and assessed the significance of local control by radiotherapy. The median length of survival after disease recurrence for these 32 patients was 19 months. Of 29 patients given radiation treatment, 16 who responded to the treatment survived significantly longer than nonresponders (median survival time 27 months versus 6 months, p < 0.01). Univariate analyses of survival after recurrences in relation to various factors revealed that sex and disease-free intervals were significant prognostic factors (p < 0.05) other than the effect of radiotherapy. A multivariate analysis showed that the effect of radiotherapy was the predominant prognostic factor. From these results, we conclude that local control with radiation is beneficial in patients with solely locally recurrent tumors in terms of improved survival. (J THORAC CARDIOVASC SURG 1994;107:8-12)

Operation is the therapy of choice for resectable primary non-small-cell carcinoma of the lung. Unfortunately, the long-term results of operation still remain poor, largely because of the frequent development of distant metastases. Furthermore, despite performance of a radical operation, locoregional recurrences, that is, recurrences in the mediastinum, bronchial stump, and chest wall occur with an incidence of about 30% of the disease recurrences. ^1-4

Does local control of locoregional recurrent disease contribute to the prolongation of survival? In this study, we analyzed the clinical features of local recurrences without extrathoracic distant metastases and identified the effectiveness of radiation treatment on these diseases.

PATIENTS AND METHODS

We reviewed the hospital charts of 471 patients with non-small-cell carcinoma of the lung that was completely resected at the National Kyushu Cancer Center during the period from April 1972 until December 1989. Complete resections consisted of either a lobectomy or a pneumonectomy together with resection of the regional lymph nodes (ipsilateral hilar and mediastinal system). In all cases, the resection margin was microscopically proved negative for tumor cells. Of the 471 patients, 277 had pathologic stage I disease, 71 had stage II disease, and 123 had stage IIIA disease. A total of 241 patients (51.2%) received postoperative adjuvant chemotherapy with various regimens, whereas 64 patients (13.6%) received radiation treatment to the mediastinum postoperatively. The staging of all patients is reported according to the new International Staging System for Lung Cancer. ⁵

Postoperative follow up was done at our outpatient clinic, with patients seen at monthly intervals for the first year, at bimonthly intervals during the second year, and then at 3-month intervals thereafter. Evaluation included a physical examination, chest roentgenography, computed tomographic scans, bone scintigraphy, and bronchoscopy.

In patients treated with either radiation therapy or chemotherapy, tumor response was evaluated at the completion of the therapy. A complete response was defined as complete disappearance of all clinical evidence of the disease. A partial response was defined as a greater than 50% reduction in the sum of the products of the shortest and longest dimensions of all measured lesions for at least 4 weeks. No change indicated neither an objective progression nor regression of the tumor, and progressive disease was classified as a definite progression of the disease.

The Beccel Mark-II statistical package program (version 4.0, Tokyo, Japan) was used in all statistical analyses. Survival after local recurrences was estimated by the method of Kaplan and Meier. ⁶ The influence of variables on survival was analyzed with the log-rank test. ⁷ The Cox proportional hazards modeling technique was used to identify which independent factors had a jointly significant influence on survival. ⁸ All reported p values are two-sided.

RESULTS

Postoperative cancer recurrence was observed in 211 of the 471 patients. Locoregional recurrences occurred in 40 of the 211 patients (19.0%), distant metastases in 155 patients (73.4%), and combined recurrences in 16 patients (7.6%). The mode of recurrence was not different among the various stages of the disease (Table I). As shown in Table II, the 40 patients with local disease recurrences had hilar-mediastinal lymph node metastases (24 patients), bronchial stump recurrences (6), chest wall extensions (2), and carcinomatous pleuritis (8). Excluding the 8 patients with carcinomatous pleuritis, we selected the 32 patients with local disease recurrences for a retrospective evaluation in this study. Of those, 17 patients had received postoperative adjuvant chemotherapy and 6 patients had received radiation treatment postoperatively.

View larger version (10K): [in this window] [in a new window]   Fig. 1. Survival curve after local recurrences for completely resected non-small-cell carcinoma of lung. Numbers in parentheses indicate number of patients still being followed up at each time point; bars indicate standard errors.

View larger version (16K): [in this window] [in a new window]   Fig. 2. Effect of radiotherapy on survival after local disease recurrences. CR, Complete response; PR, partial response; NC, no change; PD, progressive disease.

View larger version (16K): [in this window] [in a new window]   Fig. 3. Influence of chemotherapy on survival after local disease recurrences.

View larger version (16K): [in this window] [in a new window]   Fig. 4. Influence of extrathoracic distant metastases on survival after local disease recurrences.

In our series, solely local recurrences, including malignant effusion, occurred in 8.5% of 471 patients undergoing a complete resection for non-small-cell lung cancer and accounted for 19.0% of all postoperative recurrences. The incidence of local recurrences seemed slightly lower than that in other series, ^{1-4, 9} but is not so different. As in other reports, lymph node metastases in the hilum and mediastinum were the most common mode of local recurrences. ^{2, 9} This implies a possibility that despite systematic lymph node dissection, occult residual disease was persistent in the hilar and mediastinal tissues, probably in the small lymphatic vessels. Iascone and associates ¹ reported that local recurrences accounted for 75% of all recurrences in N0 disease, 28.6% in N1 disease, and 15.4% in N2 disease. However, we did not observe any differences in the modes of recurrences among the initial stages of the disease (Table I).

The present study demonstrates that local treatment with radiation is beneficial in patients with locoregional recurrent disease after a complete resection. Half of the patients who received radiation treatment achieved a good local response and a prolonged survival with a median survival time of 27 months. On the other hand, the median survival time of patients with uncontrolled disease was only 6 months. The subsequent appearance of extrathoracic metastases did not affect the survival time after local recurrences. This implies that locoregional spreading of the disease is likely to be critical and that local control is important even if temporary. As far as we know, there has been only one report referring to the treatment results of postoperative local recurrences. Green and Kern ⁹ observed a propensity for locally recurrent tumors to remain limited to the site of origin and an improved survival of patients with such disease with radiotherapy. Similarly in our series, 19 of 32 patients were disease-free for more than 2 years until local recurrence finally manifested itself. Such patients also had a longer survival than others.

From the present results, we do not mean to suggest that there is advantage in postoperative adjuvant radiotherapy. In fact, The Lung Cancer Study Group demonstrated that postoperative adjuvant radiotherapy could reduce local recurrence but that the effect did not translate into a survival benefit, largely because most of the recurrences were systemic. ^{10, 11} In terms of improved survival, local control by radiation seems to benefit only patients with solely locally recurrent tumors.

At present, we surgeons must carefully consider the necessity for radiotherapy when we find local recurrences after resection.

Acknowledgments

We thank Mr. B. T. Quinn, Kyushu University, for his critical reading of the manuscript.

Footnotes

From the Departments of Chest Surgery and Radiology,^a National Kyushu Cancer Center, Fukuoka, Japan.

References

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10. The Lung Cancer Study Group. Effects of postoperative mediastinal radiation on completely resected stage II and stage III epidermoid cancer of the lung. N Engl J Med 1986;315:1377-81.[Abstract]
    
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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Yukito Ichinose Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yano, T. Articles by Hata, K. Search for Related Content PubMed PubMed Citation Articles by Yano, T. Articles by Hata, K.