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Comparison of the Effects of the Sixth and Seventh TNM Staging on Survival in Operable Non-Small Cell Lung Cancer.

INTRODUCTION

Lung cancer is the most common cancer in the world in terms of both incidence and mortality, accounting for 12.4% of newly diagnosed cancers. The incidence of lung cancer in Turkey is 75.8 per 100,000 among men and 9.6 per 100,000 among women (1, 2).

Tumor, node, and metastasis (TNM) staging was first proposed by Denoix in 1946 and was adapted to lung cancer by the Union for International Cancer Control (UICC) in 1968 and the American Joint Committee on Cancer (AJCC) in 1973. These two different approaches were re-examined in 1986 at the annual meeting of AJCC and UICC and converted into a single system under the name of the International Staging System for Lung Cancer (3).

Changes in TNM stage were made at the annual meetings, and the International Association for the Study of Lung Cancer (IASLC) proposed changes in the 7th TNM staging of malignant lung tumors, which was published in the Journal of Thoracic Oncology in 2007 (4). The TNM staging system was discussed, and a number of changes were proposed in the 12th World Lung Cancer Conference held in South Korea in September 2007; some updates were implemented in the T and M descriptors, whereas no significant change was made in the N identifier (5). Thus, the pathological stage of many patients has shifted to an upper or lower group. This situation was statistically significant when survival analysis was performed. The published 7th TNM staging system has been started to be used in daily clinical practice since 2009 (6).

The aim of the present study was to re-stage patients who underwent resection with the diagnosis of non-small cell lung cancer (NSCLC) according to the 7th TNM staging system and to determine the effect of the new system on survival.

MATERIAL and METHODS

The clinicopathological stages of 136 patients who underwent resection due to NSCLC between January 1, 2000 and January 1, 2010 in our clinic were retrospectively reviewed and re-classified according to the 7th TNM staging system to investigate its effect on survival. Of the patients, 9 (6.6%) were females, and 127 (93.4%) were males. The mean age of the patients was 59.4 (min-max: 30-76) years. Age, gender, type and location of the tumor and its diameter, clinical stage of the disease according to the 6th TNM staging system, and resection type were noted from the patient files, and the survival data were obtained from the outpatient clinic records and telephone interviews. Oral consent was obtained from the relatives of all the patients who participated in the study.

Ethics committee approval was received for this study from the ethics committee of Trakya University School of Medicine. (TUBADK 2011/46, 23.02.2011)

The mean ages of the patients were 54.0 (min-max: 38-66) years in female cases and 59.8 (min-max: 30-76) years in male cases when the age distribution of cases was examined according to sex.

Lobectomy was performed in 81 (59.6%) cases, pneumonectomy in 44 (32.4%) cases, wedge resection in 7 (5.1%) cases, and mediastinal lymph node sampling concomitant with bilobectomy in 4 (2.9%) cases with NSCLC diagnosis.

Cases were followed up for 1-60 (average: 30.7) months. Of the cases, 56 (41.2%) died within this follow-up period.

Statistical Analysis

Results were expressed as mean. Statistical analysis of data was made using the STATISTICA 7.0 (serial no.: AXF003C-775430FAN2) software (StatSoft; TIBCO Software, CA, USA). The Kaplan-Meier method was used to determine the mean life span and the log-rank test statistic for comparison of life span in different variables. The Cox regression model was used to determine the effects of independent variables on survival. A p<0.05 was accepted as statistically significant.

RESULTS

According to histopathological examination, squamous cell carcinoma was determined in 88 (64.7%) cases, adenocarcinoma in 41 (30.1%) cases, adenosquamous cell carcinoma in 4 (2.9%) cases, large cell carcinoma in 2 (1.5%) cases, and bronchoalveolar carcinoma in 1 (0.8%) case. There was no statistically significant relationship between survival and histopathological type of tumor (p=0.184). In addition, there was no significant relationship between tumor resection type and survival (p=0.169).

Cases were followed up for 1-60 (average:30.7) months. Of the cases, 56 (41.2%) died within this follow-up period, with 54 of them males. No statistically significant relationship was found between gender and survival (p=0.323).

When the patients were re-classified according to the 7th staging system, 21 (15.4%) cases were T1 according to the 6th staging system, whereas 25 (18.4%) cases were T1 according to the 7th staging system; 89 (65.4%) cases were T2 according to the 6th staging system, whereas 70 (51.5%) cases were T2 according to the 7th staging system; 23 (16.9%) cases were T3 according to the 6th staging system, whereas 39 (28.7%) cases were T3 according to the 7th staging system; 3 (2.2%) cases were T4 according to the 6th staging system, whereas 2 (1.4%) cases were T4 according to the 7th staging system. Changes in the T stage were statistically significant (p<0.01) (Table 1).

The number of cases with stage 1a was 17 (12.5%), and there was no change. There were 56 (41.2%) cases in stage 1b according to the 6th staging system, 41 (30.1%) of which remained as stage 1b when they were re-classified according to the 7th staging system. Nine of the remaining 15 cases shifted into stage 2a, and 6 of them to stage 2b according to the 7th staging system. The most obvious change was observed in the stage 2a group. Three (2.2%) cases were classified as stage 2a according to the 6th staging system, whereas 22 (16.2%) cases were classified as stage 2a according to the 7th staging system. Ten cases had shifted from stage 2b group into stage 2a, and 9 cases from stage 1b. The number of cases in stage 2b decreased to 33 (24.3%) from 41 (30.1%) with the 7th staging system. In the stage 3a group, the number of cases increased from 15 (11%) to 23 (16.9%) with the 7th staging system.

There were a total of 3 (2.2%) cases in stage 3b and 4 cases in the 6th staging system, whereas no cases were classified in these stages according to the new staging system. Changes between stages were statistically significant (p<0.01) (Table 2).

When the relationship between the 6th staging system and survival was analyzed, as the disease stage increased, survival decreased significantly (p=0.017) (Figure 1). Similarly, it was determined that the disease stage according to the 7th staging system was statistically significantly related with survival (p=0.028) (Figure 2).

DISCUSSION

A convenient staging system in lung cancer is essential to determine the prognosis and decision in treatment strategy. The 6th TNM staging system, which was revised in 1997, was not suitable for evaluating all patients with lung cancer because it included a limited number of patients. Patients were composed of only one geographical region, and only surgical treatment was applied to the majority of the patients. Since tumors of similar clinical and pathological characteristics were included in this staging system, tumor subgroups could not be studied, and the validity of the classification was not investigated. Then, IASLC carried out a project named "Lung Cancer Staging Project" and performed survival analysis for different cases of T, N, and M descriptors, and their effects on prognosis were determined. The established 7th staging system was introduced in 2009 (1, 5-7).

The most important changes in the new staging system were in the T and M evaluations. Statistical evaluation of the obtained data on survival revealed that a tumor size of 2, 3, 5, and 7 cm affected the prognosis significantly. Tumors were classified as T1a ([less than or equal to]2 cm), T1b (>2 cm-[less than or equal to]3 cm), T2a (>3 cm-[less than or equal to]5 cm), T2b (>5 cm-[less than or equal to]7 cm), and T3 (>7 cm) according to their size; meanwhile, the prognosis of the satellite nodules in the same lobe was shown to be better than that of the other T4 tumors, thus these tumors were considered as T3. According to the same data, T4 tumors with malignant pleural effusion had been demonstrated to have worse prognosis than others, thus these tumors were classified as M1a (6, 7).

During the new staging trials, though the effects of single zone N1 and multiple zone N1 or single zone N2 involvement on survival had been shown to be different, there was no proposal for change in the N classification since validity assessment could not be performed (6, 7). Considering the case migrations between the old and new staging systems, Strand et al. (8) showed that most migrated cases are in the stage 2a and 3a groups, and in their study, the number of stage 2a cases in the patient population changed from 4.1% to 20.4%, and cases in stage 3a changed from 8.4% to 16.4%. The decrease in the number of cases was mostly observed in the stage 1b and 2b groups. The number of cases decreased from 38.6% to 27.4% in stage lb and from 17.8% to 11.9% in stage 2b. The only group with no change was identified as stage 1a.

In the study by Suzuki et al. (9), it was shown that the greatest increase in the number of cases is in stage 2a, which increased from 3.1% to 10.2% after re-staging. The group with the most decrease is in stage 3b. The number of cases in this group decreased from 17.4% to 4.6%. It has been determined that the vast majority of cases in this group have been displaced to stage 3a. In their study, stage la was the only group with no change.

Similar to other previous studies, there were migrations between the groups observed in our study. The most increase in the number of cases occurred in stage 2a, which increased from 3 (2.1%) in the old system to 22 (16.1%) according to the new staging system that started to be used in 2009. It was seen that the number of cases also increased in the stage 3a group according to the new staging system. The number of cases decreased in both stages 1b and 2b.

The number of cases decreased from 41.2% to 30.1% in stage 1b and from 30.1% to 24.2% in stage 2b. As in all previous studies, there was no change in the number of cases in stage 1a. The case migration between the groups was statistically significant. The main factor affecting the shift between stages was the changes in the T system.

In the study conducted by Chansky et al. (10), the median survival of cases staged according to the new staging system was found as 95 (66%) months for stage 1a, 75 (56%) months for stage 1b, 44 (43%) months for stage 2a, 29 months for stage 2b, and 19 (23%) months for stage 3a. The relationship between disease stage and survival was shown to be statistically significant.

In the study by Rami-Porta et al. (6), a 5 year survival analysis of the patients was conducted according to the pathology results and new staging system, and the 5 year survival rate was found as 73% for patients in stage 1a, 58% for stage 1b, 46% for stage 2a, 36% for stage 2b, 24% for stage 3a, 9% for stage 3b, and 14% for stage 4.

In the study by Strand et al. (8), a similar relationship was found between new staging system and survival of the patients. The 5 year survival rates were 60.3% in stage 1a, 57.9% in stage 1b, 37.9% in stage 2a, 31.2% in stage 2b, 17.7% in stage 3a, 13.3% in stage 3b, and 14.4% in stage 4. Based on the subgroups of the 6th and 7th TNM staging, many studies have reported that a 5 year survival did not significantly change between the subgroups.

Goldstraw et al. (4) found that the expected 5year survival rates are 73% for stage 1a, 58% for stage 1b, 46% for stage 2a, 36% for stage 2b, 24% for stage 3a, 9% for stage 3b, and 13% for stage 4. According to the 6th TNM staging system, the 5-year survival rates were determined as 50% for stage 1a, 43% for stage 1b, 36% for stage 2a, 25% for stage 2b, 19% for stage 3a, 7% for stage 3b, and 2% for stage 4. They found a 5 year survival for each group to be statistically significant when the 6th and 7th TNM grading systems were compared within their subgroups with a lower and an upper group.

Detterbeck et al. (11) stated that the new staging system proposed brings many innovations, but that the innovations introduced are still controversial, and that new subgroups created by the new staging system are more prognostic.

In our study, the 5 year survival rate decreased as the stage increased, both in the 6th and in the 7th grading systems. The relationship between disease stage and survival rate was found to be statistically significant in both staging systems. However, there were no statistically significant migrations between the subgroups.

In conclusion, the 7th TNM grading system, which was introduced in 2009, has provided guidance on the correctness of the survival analysis in terms of the T and M classifications and the selection of appropriate patients for surgical treatment. However, no changes have been done in the N classification with regard to surgical decision making or per-operative patient management, thus it still cannot fully meet the expectation. The expectation from the updated advanced staging systems is to reveal the survival differences between the single focus N1 and the multifocus N1 together with more effective guidance in patient selection by performing survival analyses of multifocus N1, single focus N2, and multifocus N2 patients.

Ethics Committee Approval: Ethics committee approval was received for this study from Trakya University School of Medicine Scientific Research Ethics Committee. (Approval Date: 23.02.2011, Approval Number: TUBADK 2011/46).

Informed Consent: Written informed consent was obtained from patients and the family of the patients who participated in this study.

Peer-review: Externally peer-reviewed.

Author contributions: Concept - M.K., Y.A.K.; Design - M.K., Y.A.K.; Supervision - M.K., Y.A.K.; Resource - M.K., Y.A.K., Y.Y.; Materials - M.K., Y.A.K., Y.Y.; Data Collection and/or Processing - M.K., Y.A.K., Y.Y.; Analysis and/or Interpretation - M.K., Y.A.K.; Literature Search - M.K.; Writing - M.K.; Critical Reviews - Y.A.K., Y.Y.

Conflict of Interest: The authors have no conflicts of interest to declare.

Financial Disclosure: The author declared that this study has received no financial support.

REFERENCES

(1.) Yurdakul AS. The new lung cancer staging system. Tur Toraks Der 2010; 11: 173-80. [CrossRef]

(2.) Ministry of Health Cancer Control Department. 2004-2006 Turkey cancer incidence report. Ankara: 2006.

(3.) Mountain CF. Revisions in the international system for staging lung cancer. Chest 1997; 111: 1710-7. [CrossRef]

(4.) Goldstraw P, Crowley J, Chansky K, Giroux DJ,Groome PA, Rami-Porta R, et al. The IASLC Lung Cancer Staging Project: Proposals for the Revision of the TNM Stage Groupings in the Forthcoming (Seventh) Edition of the TNM Classification of Malignant Tumours. J Thorac Oncol 2007; 2: 706-714. [CrossRef]

(5.) Aydiner A, Ece T, Topuz E. Lung cancer diagnosis-treatment-follow up: Antakya consensus report. Istanbul: Nobel Tip Kitabevleri, 2010.

(6.) Rami-Porta R, Crowley JJ, Goldstrow P. The revised TNM staging system for lung cancer. Ann Cardiovasc Surg 2009; 15: 4-9.

(7.) Duzgun Y, Saygi A, Levent E, Yilmaz HO, Koksal H, Soylu AC, Kutlu CA. Comparison of the sixth and seventh editions of the TNM staging systems with regard to non-small cell lung carcinoma. Turk Gogus Kalp Dama 2012; 20: 536-43. [CrossRef]

(8.) Strand TE, Rostad H, Wentzel-Larsen T, Von Plessen C. A population-based evaluation of the seventh edition of the TNM system for lung cancer. Eur Respir J 2010; 36: 401-407. [CrossRef]

(9.) Suzuki M, Yoshida S, Tamura H, Wada H, Moriya Y, Hoshino H, et al. Applicability of the revised International Association for the Study of Lung Cancer staging system to operable non-small-cell lung cancers. Eur J Cardiothorac Surg 2009; 36: 1031-1036. [CrossRef]

(10.) Chansky K, Sculier JP, Crowley JJ, Giroux D, Van Meerbeeck J, Goldstraw P, et al. The International Association for the Study of Lung Cancer Staging Project: Prognostic Factors and Pathologic TNM Stage in Surgically Managed Non-small Cell Lung Cancer. J Thorac Oncol. 2009; 4: 792-801. [CrossRef]

(11.) Detterbeck FC, Boffa DJ, Tanoue LT. The New Lung Cancer Staging System. Chest 2009; 136; 260-271. [CrossRef]

Mustafa Kuzucuoglu (1), Yekta Altemur Karamustafaoglu (2), Yener Yoruk (2)

(1) Department of Thoracic Surgery, Balikesir University School of Medicine, Balikesir, Turkey

(2) Department of Thoracic Surgery, Trakya University School of Medicine, Edirne, Turkey

ORCID IDs of the authors: M.K. 0000-0001-9889-0061; Y.A.K. 0000-0002-5491-1219; Y.Y. 0000-0001-6309-3054

This study was presented at the 7th Turkish Thoracic Surgery Congress, April 25-28, 2013, Antalya, Turkey.

Corresponding Author: Mustafa Kuzucuoglu

E-mail: mustafakuzucuoglu@hotmail.com

Received: 04.04.2018

Accepted: 20.05.2018

DOI: 10.5152/cjms.2018.482
TABLE 1. Change table between old T and new T

                           New T
          T1a  T1b  T2a  T2b  T3  T4  Total

T  T1      10   11    0    0   0   0    21
   T2       0    4   56   14  14   1    89
   T3       0    0    0    0  23   0    23
   T4       0    0    0    0   2   1     3
   Total   10   15   56   14  39   2   136

TABLE 2. Change table between old stage and new stage

                   New stage
              1a  1b  2a  2b  3a  Total

Stage  1a     17   0   0   0   0    17
       1b      0  41   9   6   0    56
       2a      0   0   3   0   0     3
       2b      0   0  10  26   5    41
       3a      0   0   0   0  15    15
       3b      0   0   0   1   2     3
       4       0   0   0   0   1     1
       Total  17  41  22  33  23   136
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Title Annotation:Original Article
Author:Kuzucuoglu, Mustafa; Karamustafaoglu, Yekta Altemur; Yoruk, Yener
Publication:Cyprus Journal of Medical Sciences
Date:Aug 1, 2018
Words:3051
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