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J Thorac Cardiovasc Surg 1994;108:158-161
© 1994 Mosby, Inc.

GENERAL THORACIC SURGERY

Postrecurrent survival of patients with non-small-cell lung cancer undergoing a complete resection

Fukuoka, Japan

Supported in part by a grant in aid for Cancer Research (62-S-1 and 2-S-1) from the Ministry of Health and Welfare, Japan.

Received for publication Oct. 1, 1993. Accepted for publication Dec. 14, 1993. Address for reprints: Y. Ichinose, MD, Department of Chest Surgery, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka 815, Japan.

Abstract

The postrecurrent survival of 215 patients who had undergone a complete resection of non-small-cell lung cancer was examined on the basis of various factors, which included gender (female, male), age (<65,65), the pathologic stage of disease at the time of operation (I, II, III), histologic type (squamous cell, nonsquamous cell carcinoma), type of operation (pneumonectomy, other), the selection of adjuvant treatment before recurrence (no treatment, mild chemotherapy, intensive chemotherapy and/or radiotherapy), recurrent site (local, distant), and the disease-free interval (365, 365 days). A univariate analysis of the postrecurrent survival showed that the significant factors influencing the survival consisted of gender, pathologic stage, recurrent site, selection of adjuvant treatment, and the disease-free interval. Namely, female patients or patients who had pathologic stage I disease, local recurrence, no adjuvant treatment, or a disease-free interval of more than 365 days would be expected to have a prolonged survival after recurrence. Of the five significant factors, only two factors (gender and the selection of the adjuvant treatment) were found to be predominant postrecurrent prognostic factors by multivariate analysis. These observations suggest that the biologic behavior of a recurrent tumor may therefore be influenced by gender and adjuvant treatment before recurrence. (J THORAC CARDIOVASC SURG1994;108:158-61)

The prognosis of patients with non-small-cell lung cancer who undergo complete resection of the tumors is known to depend on the stage of the disease as determined by a pathologic examination. ¹ However, among patients with recurrence after the operation, it is still unclear as to which factor most influences the postrecurrent survival. In fact, little is known even about whether or not the postrecurrent survival of patients whose disease at operation was in pathologic stage I is similar to that of those who had pathologic stage III disease. Therefore, in the present study, we attempted to clarify whether the postrecurrent survival of patients who undergo complete resection of non-small-cell lung cancers is influenced by gender, age, operative procedure, pathologic stage, histologic type, previous adjuvant therapy, recurrent site, or disease-free interval.

PATIENTS AND METHODS

In the period from 1972 to 1989, 468 patients who had had non-small-cell lung cancer were confirmed in the National Kyushu Cancer Center to have undergone complete resection as determined by a pathologic examination. As of August 1992, 215 of these patients had been found to have recurrence.

Follow-up examination was, in general, done every 2 months for the first 2 years and thereafter every 3 to 4 months. The examination included a physical examination, complete blood count, blood chemistry, and chest radiography. Although a few patients routinely received screening examinations by computed tomographic (CT) or radionuclide scans once or twice per year after operation, the majority of patients underwent CT or radionuclide scans only when symptoms related to recurrence appeared. The recurrent disease was then confirmed by biopsy if clinically feasible. In cases in which it was not, radiographic evidence (roentgenography, CT scan, or radionuclide scan) was accepted.

Of 215 patients with recurrence, 148 patients had received adjuvant therapy including radiotherapy to the mediastinum or chemotherapy or both before recurrent diseases were found. For convenience, chemotherapy was classified into two categories labeled mild and intensive chemotherapy. Mild chemotherapy mainly consisted of cyclophosphamide and 5-fluorouracil. Combination chemotherapy based on cisplatin was referred to as intensive chemotherapy.

The number of days from the detection of the first recurrent site until death constituted the length of postrecurrent survival. Postrecurrent survival curves were drawn by means of the Kaplan-Meier method and a statistical evaluation of the curves was done by means of the log-rank test. Differences between the proportions were evaluated by the ² or Student's t test. The parameters for the predominant impact on postrecurrent survival were evaluated by Cox's multivariate regression model. ² The data were considered significant when the p value did not exceed 0.05.

RESULTS

The survivals of all patients with recurrence were 49.3% at 1 year, 25.6% at 2 years, and 11.4% at 5 years after recurrence. The median postrecurrent survival time was 11.5 months. The postrecurrent survivals were classified by eight different factors and are shown in Table I. Of the eight factors, gender, pathologic stage, selection of adjuvant therapy before recurrence, recurrent site, and disease-free interval were all considered to be significant prognostic factors by a univariate analysis of postrecurrent survival curves.

The first recurrent site in our series was distant in 78% of the cases. This figure is similar to that of other reports. ³ However, we have not seen any comparable information on postrecurrent survival.

Our primary question was whether or not the postrecurrent survival of patients who had pathologic stage I disease at the time of operation was similar to that of those who had pathologic stage III disease. The postoperative survival of patients with non-small-cell lung cancer is known to be correlated with the pathologic stage. This means that the frequency of occult metastases that cannot be detected by preoperative examination is higher in pathologic stage III disease than in pathologic stage I. As for the extent of occult metastases, when the tumor burden of occult metastases in stage III is larger than that in stage I, the disease-free interval of patients with recurrence in stage III is thought to be shorter than that in stage I. This presumption might be true on the basis of the information provided in Table II. The disease-free interval in stage I and III was 644 ± 619 and 403 ± 419 days, respectively, and this difference was statistically significant (p < 0.01).

In our previous study on a randomized trial of postoperative adjuvant chemotherapy, we showed that the postrecurrent survival of patients undergoing cisplatin-based chemotherapy after operation was significantly shorter than that of the control patients. ⁴ The median survivals after recurrence in the control and adjuvant chemotherapy groups were 18.5 and 7.5 months, respectively. The first recurrent site and selection of treatment modality after recurrence in both groups were similar. This trial was done during the period from 1983 to 1987.

Therefore we investigated whether or not the selection of adjuvant treatment after operation also influences the postrecurrent survival in this retrospective study of patients with recurrence. As a result of a multivariate analysis of postrecurrent survival, we found this assumption to be true. Namely, patients with recurrence who underwent previous radiotherapy or cisplatin based-chemotherapy, or both, had a shorter postrecurrent survival than those who had no previous adjuvant treatment. It is usually seen that tumors in patients who received such treatment as chemotherapy or radiotherapy show resistance to a new set of treatments as compared with those in patients without prior treatment. Therefore there is a possibility that once recurrence occurs in patients who receive adjuvant treatment recurrent tumors do not respond as well to treatment; thus the postrecurrent survival of the patients is shorter than that of the nontreated patients. In fact, some trials evaluating adjuvant chemotherapy have shown that the survival of patients who received treatment was somewhat impaired compared with that of the control patients. ^5,6 However, we do not have enough information on the responsiveness of treatment for the recurrent tumors in this retrospective study to support this hypothesis. The other possibility is that the cancer cells left after the adjuvant treatment possess a more aggressive character.

Many reports show that women have better prognostic results in lung cancer. ⁷ We also found gender to be a predominant prognostic factor in postrecurrent survival determined by a multivariate analysis. In our series, 54 (78.3%) of 69 female patients with recurrence had adenocarcinoma as the histologic type. Our previous study showed that female patients with stage IV adenocarcinoma had a significantly longer survival than male patients with adenocarcinoma in the same stage. ⁸ Therefore we think that it is of interest to study the biologic characteristics of adenocarcinoma in women even further.

In the present study, we found that gender and the selection of the adjuvant treatment were predominant prognostic factors in the postrecurrent survival of patients who underwent complete resection of non-small-cell lung cancer. Because these observations were, however, based on a retrospective analysis, the results still need to be reconfirmed in a prospective study.

Acknowledgments

We thank Dr. Katsuro Yagawa for his help with the statistical analysis, Mr. B.T. Quinn, Kyushu University, for the critical review, and Misses Yumiko Oshima and Yuko Ishibashi for their help in the preparation of the manuscript.

References

1. Mountain CF. A new international staging system for lung cancer. Chest 1986;89(Suppl):225s-33s.
   
2. Cox DR. Regression models and life-tables. J R Stat Soc (B) 1972;34:187-220.
   
3. Homes CE, Gail M, Lung Cancer Study Group. Surgical adjuvant therapy for stage II and stage III adenocarcinoma and large-cell undifferentiated carcinoma. J Clin Oncol 1986;4:710-5.[Abstract/Free Full Text]
   
4. Ichinose Y, Hara N, Ohta M, Motohiro A, Kuda T, Asoh H. Postoperative adjuvant chemotherapy in non-small cell lung cancer: prognostic value of DNA diploidy and postrecurrent survival. J Surg Oncol 1991;46:15-20.[Medline]
   
5. Brunner KW, Marthaler T, Muller W. Effects of long term adjuvant chemotherapy with cyclophosphamide (NSC-26271) for radically resected bronchogenic carcinoma. Cancer Chemother Rep 1973;4:125-32.
   
6. Shields TW, Higgins GA, Humphrey EW, Matthews MJ, Keehn RJ. Prolonged intermittent adjuvant chemotherapy with CCNU and hydroxyurea after resection of carcinoma of the lung. Cancer 1982;50:1713-21.[Medline]
   
7. Ruckdeschel JC. Chemotherapy of disseminated non-small cell lung cancer. In: Bitran JD, Golomb HM, Little AG, Weichselbaum RR, eds. Lung cancer: a comprehensive treatise. Orlando, Fla.: Grune & Stratton, 1988:233-41.
   
8. Takanashi N, Hara N, Ichinose Y, et al. Clinicopathological studies of female lung cancer (in Japanese). Lung Cancer 1993;33:373-81.
   

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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 Ichinose, Y. Articles by Takanashi, N. Search for Related Content PubMed PubMed Citation Articles by Ichinose, Y. Articles by Takanashi, N.