Interact CardioVasc Thorac Surg 2008;7:50-53. doi:10.1510/icvts.2007.160846
© 2008 European Association of Cardio-Thoracic Surgery
Institutional report - Thoracic general |
Lung cancer as a second primary malignant tumor: prognostic values after surgical resection
József Furáka,*,
Imre Trojána,
Tamás Szökea,
Antal Wolfárda,
Ernest Nagya,
István Némethb,
László Tiszlaviczb and
György Lázára
a Department of Surgery, University of Szeged, Pécsi u. 4. H-6720, Szeged, Hungary
b Department of Pathology, University of Szeged, Szeged, Hungary
Received 3 June 2007;
received in revised form 24 September 2007;
accepted 25 September 2007
 Presented at the 15th European Conference for General Thoracic Surgery, Leuven, Belgium, June 3–6, 2007.
*Corresponding author. Tel.: +36 30 9955815; fax: +36 62 545 701.
E-mail address: jfurak{at}hotmail.com (J. Furák).
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Abstract
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Prognostic values of lung cancers as second primary malignant tumors (LC-as-SPTs) developed after a different type of first primary malignant tumor were analyzed. Forty-three patients underwent surgery for first primary malignant tumors and later for LC-as-SPTs. The most frequent first primary tumors were: 14 laryngo-pharyngeals; 7 lungs; and 5 colons. Only metachronous cases were included in our study, and the disease-free intervals (DFI) between the first and second primary tumors were divided into two groups: shorter than 36 months (DFI<36), and longer than 36 months (DFI>36). The survival was calculated from the time of surgery for LC-as-SPT. The 5-year overall survival rate was 38%. By univariate analysis, the 5-year survival was significantly lower in cases with DFI<36 months (25%) than in cases with DFI>36 months (43%) (P=0.045), and in male (27%) than in female (62%) (P=0.032), and in N1 (31%) and N2 (0%) cases than in N0 (49%) cases (P=0.001). Using multivariate analysis with the previous factors, only the lymph node metastasis (P=0.001) had a significant impact on survival. The survival after LC-as-SPTs was shorter than after first primary lung cancer cases, and lymph node involvement had a significant impact on the postoperative survival based on uni- and multivariate analysis.
Key Words: Lung cancer; Second primary malignant tumor; Disease-free interval
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1. Introduction
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After the treatment of a malignant tumor, a second primary tumor (SPT) can develop. The incidence of the SPT after gastric cancer was 4.2% [1] and 15 years following breast cancer diagnosis was 20% in smokers and 16% in non-smokers [2], and 36% and 31% after seminomas and non-seminomatous testicular tumors [3]. Regarding the etiology, the SPT risk was significantly associated with chemotherapy in testicular cancer [3], but no significant correlation between chemotherapy and SPT in breast cancer cases [2].
Some SPTs appeared as lung cancer (LC-as-SPT). After gastric cancers, 28.4% of the SPTs were LC-as-SPT [1]. Smoking presented a significant risk factor for developing multiple primary malignancies involving lung cancer [4]. The 15-year risk for LC-as-SPT after surgery and radiotherapy for breast carcinoma was 0.26% for non-smokers and 6% for patients who continued to smoke at the time of their radiation [2]. If LC-as-SPT develops after a first primary lung cancer, it is called second primary lung cancer (SPLC). The incidence of SPLC in stage I NSCLC (non-small cell lung cancer) ranges from 1 to 8.6% [5].
The literature has very few papers presenting clinical data for operable LC-as-SPTs developing after a resection for a first primary malignant tumor other than lung cancer [6].
Thus, in our study we investigated the incidence and clinical data of LC-as-SPT, and studied the prognostic factors impacting survival after the second lesion (removed after the successful resection of the first primary malignant lesion).
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2. Materials and methods
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Between 1997 and 2006, 911 patients were operated on for lung cancer in our clinic. Of these, 43 (4.7%) had lung cancer as a second primary malignant tumor (LC-as-SPT). There were 30 males and 13 females with a mean age of 60.4 (43–75) years. Before the surgery for the LC-as-SPT, all patients underwent a surgical resection for first primary malignant lesion. The distribution of the first malignant tumor is detailed in Table 1.
Of the 43 patients who underwent surgery for a first primary tumor, 13 (30.2%) received adjuvant oncological treatment (chemo and/or radiotherapy), before surgery for LC-as-SPT.
The diagnosis of a multiple malignant tumor is well documented in the literature with clinical, genetic and pathological criteria [7, 8]. In our study, the diagnosis of multiple lesions, and the synchronous and metachronous status was based on the Martini–Melamed criteria [8]. In all of our cases, LC-as-SPT had a different pathology (based on hematoxylin-eosin and immunostaining by the same pathologist) from the first malignant lesion, including every lung cancer case.
LC-as-SPTs were divided into two groups, based on whether the first primary malignant lesion was a lung cancer [second primary lung cancer (SPLC) group (7/43)], or another type of malignant tumor (non-second primary lung cancer [(non-SPLC) group (36/43)]. The incidence of the operable SPLC among all lung cancers operated on in our clinic during the investigated period was 7/911 (0.77%).
Cases with synchronous lesions were excluded from this study, and only metachronous tumors were included and investigated.
The DFI (Disease Free Interval) between the appearance of the first and the second primary tumors was created similar to the method in studies with pulmonary metastases: DFI<36 months (10 cases; 23.3%) and DFI>36 months (33 cases; 76.7%) [9]. The mean interval between the first and the second primary tumors was 5.6 years (0.3–20 years).
The preoperative examination focused on the site of the first and second lesions, and for possible metastasis. To determine the site of the first tumor, proper physical examinations with computed tomography (CT), ultrasonography and endoscopy were performed. To determine the LC-as-SPT and possible metastasis, preoperative evaluations included a chest X-ray, chest CT, bone scintigraphy, brain CT, bronchoscopy and spirometry to determine lung capacity. Patients without N2 disease on the chest CT and distant metastases were operated on.
The resections performed for the LC-as-SPTs are presented in Table 2. In SPLC cases, the staging of the first primary lung cancers were as follows: 4 stage IB, 2 stage IIB and 1 stage IIIA. For SPLC cases, there were five contralateral wedge resections after previous lobectomies, 1 contralateral lobectomy and 1 completion pneumonectomy was performed. In every case we performed mediastinal block dissection. After the surgery for LC-as-SPT with lymph node positive cases, adjuvant oncological therapy was included.
The survival rate was calculated from the time of surgery for LC-as-SPT using the Kaplan–Meier method and SPSS statistical software.
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3. Results
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Histology, tumor (T) and lymph node (N) status of the tumor, and LC-as-SPT stages are detailed in Table 3.
The postoperative mortality was 2.3%; we lost one patient who had a pneumonectomy and tracheostomy due to a previous laryngectomy.
The 5-year overall survival from the surgery of the LC-as-SPT was 38%, with a 52 months median survival time (95% CI: 39.8–64.16 months), the different cohort group survivals are detailed in Table 4. By univariate analysis, the 5-year survival was significantly lower after resection of LC-as-SPT if the DFI between the resections of the first and second primary tumors was <36 months (DFI<36) (25%), than in DFI>36 months (43%) (P=0.045) (Fig. 1).
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Fig. 1. DFI<36: disease-free interval between first and second primary tumor was shorter than 36 months. DFI>36: disease-free interval between first and second primary tumor was longer than 36 months.
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When comparing the resection types, there was no significant difference in the 5-year survival between the wedge resections (33%) and lobectomy/pneumonectomy (37%) cases (P=0.221) (two cases with explorations were excluded!).
The 5-year survival of the 13 patients who underwent surgery for a first primary tumor and received adjuvant oncological treatment (chemo and/or radiotherapy) before the surgery for LC-as-SPT, was shorter (31%) than for the 30 patients who did not receive any oncological treatment before surgery for LC-as-SPT (40%) (P=0.705).
Using univariate analysis (presented in Table 4), indicated that lymph node involvement (P=0.001), DFI (0.045) and sex (P=0.032) had a significant impact on survival. Multivariate analysis with DFI, lymph node metastasis and sex indicated that only lymph node metastasis (P=0.001) had a significant prognostic factor for survival and DFI (P=0.832), sex (P=0.154) had no significant impact on survival. All multivariate data analysis is presented in Table 5.
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4. Discussion
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The incidence of an operable LC-as-SPT was 4.7% among all resected lung cancer patients during the examination period. The most frequent first primary tumors were in the head and neck region, and lung, which is similar to the Dechateau study data [10].
By presented data, there were much more male than female with SPT patients [4, 11]. We found the same tendency in our study. There were 70% males and 30% females among our patients with second primary cancer, but the survival was significantly better for females. The sex distribution rate was 80% male and 20% female after gastric cancers in the Ikeda patients [1].
When considering all of our 43 patients, the mean interval between the first and second primary tumors was 5.6 years (0.3–20 years), and 63% of LC-as-SPT (40% in the Dechateau study [10]) developed within five years after the first lesion.
Because of the follow-up after malignant tumor treatment, the incidence of early stages in SPTs is frequently high, according to the publications. Among gastric cancer patients, early stage SPTs were diagnosed 91% of metachronous cases [1], and 24.5% of non-SPLC and 53.3% in SPLC groups in the Liu study [4]. The incidence of stage I+II SPLC cases after stage I first primary lung cancer cases was 66% in the Rice study [5]. In our patients, the incidence of early stage (I and II) LC-as-SPTs was 31/43 (72%).
The type of pulmonary resection can be an interesting question in multiple malignant cases, and a little similar to the principles of metastasectomy. In our practice, the rate of the wedge resections was 19% respecting all cases (71% for SPLC, and 8% for non-SPLC patients). For SPLC cases, these data were 38.7% in the Rice study [5] and 6.25% after lobectomies in the Aziz study [12]. Despite the high number of wedge resections in our study, the median survival time was 52 months, while the corresponding survival times in the Rice study was 49 months [5], and 61 months in the Aziz study [12]. We found no significant difference in the 5-year survival rates between the wedge resections (33%) and lobectomy/pneumonectomy (37%) groups. Rea et al. stated, that limited resection in multiple primary lung cancer could be accepted [11].
In patients with lung cancer and previous malignancy, the postoperative survival after the surgery for LC-as-SPT was shorter than in ‘simple’ first primary lung cancer cases. Among our patients, the survivals in the different stages of the LC-as-SPT were lower than those published by Montain in ‘simple’ lung cancer cases: stage I 49% vs. stage IA 67% and stage IB 57%; stage II 33% vs. stage IIA 55% and stage IIB 39%, stage III 17% vs. stage IIIA 23% [13].
The lymph node involvement is an important prognostic value in lung cancer cases, as it was in LC-as-SPT cases. Both the univariate and multivariate analysis revealed that lymph node involvement was a significant prognostic factor for survival. In the Rea study, the 5-year survival in N0 cases was 45% [11], and in our patients it was 46%.
In our study, in cases with chemo–radio therapy after the first primary lesions (before the surgery for LC-as-SPT) for advanced first malignant tumor, the survival was lower (31%) than in cases without any oncological therapy for the first lesion (40%). It can mark the aggression of the malignancy, but there was no significant correlation between the previous chemo–radio therapy and the stage of the LC-as-SPT.
To summarize our results, we conclude that after the resection of the second primary malignant lung cancer, the survival is shorter than after a ‘simple’, first primary lung cancer surgery. In lung cancer as a second primary malignant tumor with a resected first malignant lesion, the lymph node status of the lung resection has significant impact on survival, based on multivariate analysis. The disease-free interval between the first and second malignancy has a significant impact on survival after the second resection, by univariate analysis. Chemo and/or radio therapy following the surgery for the first lesion, due to its advanced stage, has no significant impact on survival after the second resection.
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Abstract
1. Introduction
