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Reconsidering the American Joint Committee on Cancer Eighth Edition TNM Staging Manual Classifications for T2b and T3 NSCLC

Open ArchivePublished:July 06, 2021DOI:https://doi.org/10.1016/j.jtho.2021.06.016

      Abstract

      Introduction

      The American Joint Committee on Cancer (AJCC) eighth edition TNM staging manual for NSCLC, derived from the International Association for the Study of Lung Cancer (IASLC) Staging Project, designates tumors with additional nodule(s) in the same lobe as T3. This study sought to externally validate the results of the IASLC, which showed a trend in improved survival for such tumors, but excluded treatment-based adjustment, by assessing whether these tumors have worse survival than T2b NSCLC.

      Methods

      Overall survival of patients with T2b-T3, N0-3, M0 NSCLC (satisfying a single T descriptor of tumors >4 cm but ≤5 cm in greatest dimension [“T2b”], tumors >5 cm but ≤7 cm in greatest dimension [“T3-Size”], or tumors with additional nodule(s) in the same lobe [“T3-Add”]), according to the AJCC eighth edition, in the National Cancer Database (2010–2015), was evaluated using multivariable Cox proportional hazards modeling and propensity score matching.

      Results

      31,563 patients with T2b-T3, N0-3, M0 NSCLC met the study inclusion criteria. In multivariable-adjusted analysis, T3-Add tumors had improved overall survival compared with T3-Size tumors (Hazard Ratio = 0.86, 95% Confidence Interval: 0.82–0.89, p < 0.001) and similar survival compared with T2b tumors (Hazard Ratio = 1.04, 95% Confidence Interval: 0.97–1.12, p = 0.28). A propensity score-matched analysis of 2260 T3-Add and 2,260 T2b patients, well-balanced on 16 common prognostic covariates, including treatment type (surgery, chemotherapy, or radiation), revealed similar 5-year survival (53.4% versus 52.3%, p = 0.30).

      Conclusions

      In this national analysis, T3-Add tumors had better survival than other T3 tumors and similar survival to T2b tumors. These findings may be taken into consideration for the AJCC ninth edition staging classifications.

      Keywords

      Introduction

      Staging for primary NSCLC that presents as a tumor with additional intrapulmonary nodule(s) has been challenging to develop and continues to evolve.
      • Kim A.W.
      • Cooke D.T.
      Additional pulmonary nodules in the patient with lung cancer: controversies and challenges.
      In 2016, the American Joint Committee on Cancer (AJCC) published the eighth edition TNM staging manual and assigned tumors with additional nodule(s) to specific T categories on the basis of the location of the separate nodule(s) (T3 for same lobe, T4 for different ipsilateral lobe, M1a for contralateral lobe).
      These tumors are defined as a solid lung cancer with at least one separate tumor nodule of similar solid appearance and presumed matching histologic appearance; these definitions specifically exclude synchronous primary lung cancers and multifocal lung cancer with ground-glass or lepidic features or pneumonic type.
      ,
      • Rami-Porta R.
      • Asamura H.
      • Travis W.D.
      • Rusch V.W.
      Lung cancer - major changes in the American Joint Committee on Cancer eighth edition cancer staging manual.
      The new eighth edition staging guidelines are derived from analysis conducted by the International Association for the Study of Lung Cancer (IASLC) Staging Project, which uses an international database of 70,967 patients with NSCLC diagnosed between 1999 and 2010, representing 35 different databases from 16 countries on five continents.
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      • Chansky K.
      • Groome P.
      • et al.
      The IASLC lung cancer staging project: methodology and validation used in the development of proposals for revision of the stage classification of NSCLC in the forthcoming (eighth) edition of the TNM classification of lung cancer.
      • Rami-Porta R.
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      • et al.
      The IASLC lung cancer staging project: the new database to inform the eighth edition of the TNM classification of lung cancer.
      • Detterbeck F.C.
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      • et al.
      The IASLC Lung Cancer Staging Project: background data and proposals for the classification of lung cancer with separate tumor nodules in the forthcoming eighth edition of the TNM classification for lung cancer.
      In their reported results, patients with tumors with additional nodules in the same lobe had similar survival as patients with other T3 tumors satisfying either a single or multiple T descriptors. These other T3 descriptors in the eighth edition guidelines include tumors greater than 5 cm but less than or equal to 7 cm in greatest dimension (previously staged as T2b in the seventh edition staging manual) and tumors that invade the parietal pleura, chest wall, pericardium, or phrenic nerve.
      Additional relevant updates to the eighth edition include redefining stage T2b to only consist of tumors greater than 4 cm but less than or equal to 5 cm in greatest dimension.
      In the analysis by the IASLC, results revealed a trend in improved survival among patients with tumors with additional nodules in the same lobe when compared with other types of T3 tumors, though the results were not statistically significant.
      • Detterbeck F.C.
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      The IASLC Lung Cancer Staging Project: background data and proposals for the classification of lung cancer with separate tumor nodules in the forthcoming eighth edition of the TNM classification for lung cancer.
      This finding builds on results from previous single-institution and national studies, which have presented conflicting results on the survival of patients with such tumors. Two single-center studies previously found similar overall survival between tumors with additional nodules in the same lobe and tumors with malignant pleural or pericardial effusion, pleural dissemination, or invasion to adjacent major organ,
      • Okumura T.
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      Intrapulmonary metastasis of non-small cell lung cancer: a prognostic assessment.
      and tumors greater than 7 cm in size.
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      Recommended changes for T and N descriptors proposed by the International Association for the Study of Lung Cancer - Lung Cancer Staging Project: a validation study from a single-centre experience.
      Of note, however, various studies have found that such tumors with additional nodules in the same lobe, mostly when surgically resected and node negative, can have long-term survival comparable with stage I or stage II NSCLC.
      • Bryant A.S.
      • Pereira S.J.
      • Miller D.L.
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      Satellite pulmonary nodule in the same lobe (T4N0) should not be staged as IIIB non-small cell lung cancer.
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      Surgical resection is justified in non-small cell lung cancer patients with node negative T4 satellite lesions.
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      Revisiting stage IIIB and IV non-small cell lung cancer: analysis of the surveillance, epidemiology, and end results data.
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      • Patterson G.A.
      Surgical resection of multifocal non-small cell lung cancer is associated with prolonged survival.
      Since the AJCC eighth edition guidelines were published, the results of one national analysis from the Netherlands by Blaauwgeers et al.
      • Blaauwgeers H.
      • Damhuis R.
      • Lissenberg-Witte B.I.
      • de Langen A.J.
      • Senan S.
      • Thunnissen E.
      A population-based study of outcomes in surgically resected T3N0 non-small cell lung cancer in the Netherlands, defined using TNM-7 and TNM-8; justification of changes and an argument to incorporate histology in the staging algorithm.
      suggested improved survival among patients with additional nodules in the same lobe treated surgically and noted that the subgroup of patients with node-negative adenocarcinoma had survival similar to patients with T2, N0, M0 tumors within the IASLC database.
      The objective of this study is to externally validate the results of the IASLC Staging Project for patients with T3 NSCLC presenting with a primary tumor with additional nodule(s) in the same lobe by comparing the long-term survival of these patients with that of patients with T2b NSCLC. The IASLC encourages external validation of their results against outside databases to account for various potential biases in their analysis, including incomplete global geographic distribution of their data and insufficient diversity in treatment type, the latter of which prevents analysis that accounts for varying treatment modalities.
      • Detterbeck F.C.
      • Chansky K.
      • Groome P.
      • et al.
      The IASLC lung cancer staging project: methodology and validation used in the development of proposals for revision of the stage classification of NSCLC in the forthcoming (eighth) edition of the TNM classification of lung cancer.
      ,
      • Rami-Porta R.
      • Bolejack V.
      • Giroux D.J.
      • et al.
      The IASLC lung cancer staging project: the new database to inform the eighth edition of the TNM classification of lung cancer.
      ,
      • Chansky K.
      • Detterbeck F.C.
      • Nicholson A.G.
      • et al.
      The IASLC lung cancer staging project: external validation of the revision of the TNM stage groupings in the eighth edition of the TNM classification of lung cancer.
      ,
      • Goldstraw P.
      • Chansky K.
      • Crowley J.
      • et al.
      The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer.
      One such data source suggested by the IASLC is the National Cancer Database (NCDB), which includes long-term survival data for patients with lung cancer across the United States, with broad representation from all treatment modalities and range of institution types.
      • Detterbeck F.C.
      • Chansky K.
      • Groome P.
      • et al.
      The IASLC lung cancer staging project: methodology and validation used in the development of proposals for revision of the stage classification of NSCLC in the forthcoming (eighth) edition of the TNM classification of lung cancer.
      Thus far, however, external validation with the NCDB has not evaluated specific T descriptors and has not previously included multivariable modeling adjusting for treatment modality.
      • Chansky K.
      • Detterbeck F.C.
      • Nicholson A.G.
      • et al.
      The IASLC lung cancer staging project: external validation of the revision of the TNM stage groupings in the eighth edition of the TNM classification of lung cancer.
      To that end, this study used the NCDB to test the hypothesis that tumors presenting with additional nodules in the same lobe, currently staged as T3, would be associated with better survival, after adjusting for treatment modality, when compared with other T3 tumors and would be associated with similar survival when compared with T2b NSCLC.

      Materials and Methods

      Data Source

      The data used in this study were from the NCDB. The NCDB is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The NCDB is estimated to capture 80% of all newly diagnosed cases of lung cancer in the United States and Puerto Rico.
      • Bilimoria K.Y.
      • Stewart A.K.
      • Winchester D.P.
      • Ko C.Y.
      The National Cancer Data Base: a powerful initiative to improve cancer care in the United States.

      Study Design

      This study was approved by the Institutional Review Board of Massachusetts General Hospital, and data were analyzed from a deidentified NCDB participant user file.
      All patients with stage T2b, N0-3, M0 (tumors >4 cm but ≤5 cm in greatest dimension [“T2b”]) or T3, N0-3, M0 (exclusively satisfying a single T descriptor of tumors >5 cm but ≤7 cm in greatest dimension [“T3-Size”] or tumors with additional nodule(s) in the same lobe [“T3-Add”]) NSCLC, according to the AJCC eighth edition TNM staging manual, were identified using the International Classification of Diseases for Oncology, third edition histology and topography codes.
      Staging in the NCDB was reclassified using best available data according to the most recent AJCC eighth edition staging criteria.
      ,
      • Detterbeck F.C.
      • Boffa D.J.
      • Kim A.W.
      • Tanoue L.T.
      The eighth edition lung cancer stage classification.
      Other types of T3 tumors were not included because of unavailable data.
      Exclusion criteria consisted of nonmalignant disease and history of previous unrelated malignancy. The study was limited to patients diagnosed beginning in 2010 to most accurately reflect current outcomes for patients with T3-Add tumors given the evolution of diagnostic and treatment guidelines for such patients.
      • Kim A.W.
      • Cooke D.T.
      Additional pulmonary nodules in the patient with lung cancer: controversies and challenges.
      ,
      • Fonseca A.
      • Detterbeck F.C.
      How many names for a rose: inconsistent classification of multiple foci of lung cancer due to ambiguous rules.
      Patients diagnosed after 2015 were excluded owing to cessation of data collection for specific T3 descriptors. Patients with missing tumor descriptor or survival data were also excluded.
      Overall survival from time of diagnosis to time of death or last follow-up was the primary outcome measured.

      Statistical Analysis

      Baseline characteristics were evaluated using Wilcoxon Rank Sum test for continuous variables and Pearson's chi-square or Fisher’s exact test for discrete variables. Overall survival of T3-Add versus T3-Size tumors and T3-Add versus T2b tumors was compared for patients diagnosed with clinical N0-3, M0 NSCLC using the Kaplan-Meier method and multivariable Cox proportional hazards modeling (adjusting for age, sex, race, Charlson-Deyo comorbidity score, median census-tract household income and education level, facility type, insurance type, TNM clinical N status, tumor location, treatment type [i.e., surgery, chemotherapy, or radiation], histologic subtype, grade, and distance from patient’s residence to hospital). Additional Cox proportional hazards modeling comparing survival of T3-Add versus T2b tumors was performed using the exact same covariates as mentioned previously, with the exception of treatment type (treatment type was excluded as one of the covariates). Survival was measured from time of diagnosis to time of death or last follow-up. The selected covariates for the Cox proportional hazards model were chosen on the basis of previously described variables that have a known impact on survival in patients with lung cancer.
      • Ambroggi M.
      • Biasini C.
      • Del Giovane C.
      • Fornari F.
      • Cavanna L.
      Distance as a barrier to cancer diagnosis and treatment: review of the literature.
      • Bryant A.S.
      • Cerfolio R.J.
      Impact of race on outcomes of patients with non-small cell lung cancer.
      • Shi R.
      • Diaz R.
      • Shi Z.
      • Duvall E.
      • Mills G.
      The effect of payer status on survival of patients with Stage I/II non-small cell lung cancer: NCDB 1998–2011.
      • Tannenbaum S.L.
      • Koru-Sengul T.
      • Zhao W.
      • Miao F.
      • Byrne M.M.
      Survival disparities in non-small cell lung cancer by race, ethnicity, and socioeconomic status.
      A matched analysis based on propensity scores using methodology similar to as previously described
      • Yang C.F.
      • Kumar A.
      • Gulack B.C.
      • et al.
      Long-term outcomes after lobectomy for non-small cell lung cancer when unsuspected pN2 disease is found: a National Cancer Data Base analysis.
      was also used to compare overall survival between T3-Add versus T3-Size and T3-Add versus T2b tumors. Propensity scores were assigned using a logistic regression model that calculated the scores on the basis of patient- and disease-related variables determined a priori to most likely act as confounders, including age, sex, race, Charlson-Deyo comorbidity score, median census-tract household income and education level, facility type, insurance type, TNM clinical N status, tumor location, treatment type (i.e., surgery, chemotherapy, or radiation), histologic subtype, grade, and distance from patient’s residence to hospital. Using a greedy nearest neighbor-matching algorithm without replacement, with a caliper of 0.01, we identified the most appropriately matched pairs. Standardized differences were used to evaluate the balance of the match. After propensity score matching, Kaplan-Meier analysis was used to compare overall survival of the groups. A case complete analysis was used to address any potential missing data.
      Additional propensity score-matched analyses, using the same covariates and matching algorithm described previously, comparing overall survival between patients with T3-Add versus T2b tumors who underwent surgical resection and diagnosed with pathologic N0 or N1 disease were conducted as sensitivity analyses to better compare outcomes between patients receiving surgery as primary treatment.
      Model balance and diagnostics were evaluated with no violation of major assumptions observed. All statistical analyses were performed using Stata Statistical Software: Release 13.0 (StataCorp LP, College Station, TX). A two-sided p value of 0.05 was used to define significance.

      Results

      Study Cohort

      Between 2010 and 2015, of the 31,563 patients diagnosed with having T2b-T3, N0-3, M0 NSCLC who met the study inclusion criteria, 19,569 (62.0%) satisfied the criteria exclusively for a single T3 descriptor of T3-Size, whereas 8,546 (27.1%) satisfied the criteria for a single T3 descriptor of T3-Add, and 3,448 (10.9%) satisfied the criteria for T2b (Supplementary Fig. 1, which details schema of study subject selection). Median follow-up was 28.6 months (interquartile range: 10.6–52.5 mo) for the entire cohort.

      Comparison of T3-Add Versus T3-Size Tumors

      Baseline and tumor characteristics for patients with tumors that satisfied criteria for T3-Size and T3-Add are found in Table 1. When compared with patients with T3-Size tumors, patients with T3-Add tumors were more likely to be of female sex, white, have more comorbidities, have higher census-tract education and income levels, be treated at academic or research programs, and have Medicare insurance. Patients with T3-Add tumors were also more likely to have tumors located in the right upper lobe, adenocarcinoma histology, tumors of lower grade, clinical N0 disease, and be treated surgically.
      Table 1Baseline Characteristics of Patients With T3, N0-3, M0 NSCLC Satisfying the Criteria for T3-Add Versus T3-Size
      Patient CharacteristicsTotal CohortPropensity Score-Matched Analysis
      T3-Size (N = 19,569)T3-Add (N = 8546)PT3-Size (N = 5670)T3-Add (N = 5670)Standardized Differences (%)
      Age (y, IQR)69 (61–76)69 (62–76)0.9669 (62–77)69 (62–76)−0.2
      Female, n (%)8175 (41.8)4827 (56.5)<0.0012927 (51.6)2942 (51.9)0.5
      Race, n (%)0.038
       White16,639 (85.6)7362 (86.7)4882 (86.7)4886 (86.7)0.2
       Black2226 (11.5)887 (10.5)586 (10.4)586 (10.4)0.0
       Other575 (3.0)240 (2.8)164 (2.9)164 (2.9)0.0
      Charlson-Deyo comorbidity score, n (%)0.019
       010,424 (53.3)4393 (51.4)2918 (51.5)2933 (51.7)0.5
       15895 (30.1)2711 (31.7)1782 (31.4)1777 (31.3)−0.2
       22324 (11.9)1013 (11.9)697 (12.3)695 (12.3)−0.1
       3+926 (4.7)429 (5.0)273 (4.8)265 (4.7)−0.7
      Education: % without HS diploma, n (%)<0.001
       >17.5%4178 (23.0)1608 (20.6)1190 (21.0)1201 (21.2)0.5
       10.9%–17.5%5318 (29.3)2211(28.3)1629 (28.7)1613 (28.5)−0.6
       6.3%–10.8%5118 (28.2)2283 (29.2)1623 (28.6)1630 (28.8)0.3
       <6.3%3559 (19.6)1722 (22.0)1228 (21.7)1226 (21.6)−0.1
      Median household income, n (%)<0.001
       <$40,2274083 (22.5)1548 (19.8)1157 (20.4)1180 (20.8)1.0
       $40,227–$50,3534596 (25.3)1850 (23.7)1374 (24.2)1363 (24.0)−0.5
       $50,354–$63,3324287 (23.6)1846 (23.7)1385 (24.4)1367 (24.1)−0.7
       ≥$63,3335183 (28.6)2557 (32.8)1754 (30.9)1760 (31.0)0.2
      Facility type, n (%)<0.001
       Community cancer program1962 (10.1)712 (8.4)492 (8.7%)492 (8.7%)0.0
       Comprehensive community cancer program8775 (45.1)3580 (42.1)2483 (43.8%)2479 (43.7%)−0.1
       Academic or research program6112 (31.4)3031 (35.6)1950 (34.4%)1944 (34.3%)−0.2
       Integrated network cancer program2611 (13.4)1191 (14.0)745 (13.1%)755 (13.3%)0.5
      Insurance, n (%)<0.001
       Private5169 (26.7)2175 (25.8)1418 (25.3)1445 (25.8)1.1
       Medicaid1249 (6.5)499 (5.9)333 (6.0)335 (6.0)0.1
       Medicare12,023 (62.2)5456 (64.6)3630 (64.9)3619 (64.6)−0.4
       Other government335 (1.7)156 (1.9)96 (1.7)92 (1.6)−0.6
       Uninsured569 (2.9)155 (1.8)120 (2.1)110 (2.0)−1.1
      Received surgery, n (%)8257 (42.4%)4747 (55.8%)<0.0012933 (51.7%)2973 (52.4%)1.5
      Received chemotherapy, n (%)11,489 (60.8)4015 (48.7)<0.0012978 (52.5)2993 (52.8)0.5
      Received radiation therapy, n (%)9082 (47.8)2997 (36.1)<0.0012220 (39.2)2195 (38.7)−1.0
      Tumor location, n (%)<0.001
       Right upper lobe5836 (32.6)3244 (39.5)2243 (39.6)2180 (38.5)−2.3
       Right middle lobe779 (4.4)372 (4.5)230 (4.1)220 (3.9)−0.9
       Right lower lobe3777 (21.1)1391 (16.9)990 (17.5)1007 (17.8)0.8
       Left upper lobe4556 (25.5)2169 (26.4)1460 (25.8)1505 (26.5)1.8
       Left lower lobe2993 (16.4)1038 (12.6)747 (13.2)757 (13.4)0.5
      Histologic subtype, n (%)<0.001
       Adenocarcinoma6374 (35.9)4264 (53.7)3028 (53.4)3155 (55.6)4.5
       Squamous9671 (54.5)2149 (27.1)1785 (31.5)1745 (30.8)−1.5
       Large cell387 (2.2)152 (1.9)115 (2.0)129 (2.3)1.7
       Adenosquamous365 (2.1)131 (1.7)105 (1.9)110 (1.9)0.6
       Neuroendocrine tumors378 (2.1)520 (6.5)229 (4.0)173 (3.1)−5.2
       Bronchioloalveolar585 (3.3)730 (9.2)408 (7.2)358 (6.3)−4.2
      Grade, n (%)<0.001
       Well differentiated999 (5.1)967 (11.3)533 (9.4)477 (8.4)−4.1
       Moderately differentiated5007 (25.6)2541 (29.7)1678 (29.6)1741 (30.7)2.7
       Poorly differentiated7368 (37.7)2465 (28.8)1808 (31.9)1794 (31.6)−0.5
       Undifferentiated or anaplastic301 (1.5)86 (1.0)48 (0.9)54 (1.0)1.0
       Cell type not determined5894 (30.1)2487 (29.1)1603 (28.3)1604 (28.3)0.0
      Clinical N status, n (%)<0.001
       cN09468 (48.4)5322 (62.3)3372 (59.5)3345 (59.0)−1.0
       cN12374 (12.1)838 (9.8)538 (9.5)587 (10.4)2.8
       cN26098 (31.2)1814 (21.2)1336 (23.6)1323 (23.3)−0.5
       cN31629 (8.3)572 (6.7)424 (7.5)415 (7.4)−0.5
      Distance to facility (miles, IQR)10.1 (4.3–24.3)10.1 (4.4–24.1)0.4510.4 (4.4–25)10 (4.3–23.7)1.0
      HS, high school; IQR, interquartile range; T3-Add, tumors with additional nodule(s) in the same lobe; T3-Size, tumors greater than 5 cm but less than or equal to 7 cm in greatest dimension.
      In Kaplan-Meier analysis, T3-Add tumors were associated with better 5-year overall survival than T3-Size tumors (p < 0.001) (Fig. 1A). T3-Add tumors continued to have better overall survival in multivariable-adjusted analysis (hazard ratio [HR] = 0.86, 95% confidence interval [CI]: 0.82–0.89, p < 0.001) (Table 2).
      Figure thumbnail gr1
      Figure 1Overall survival of patients with T3, N0-3, M0 NSCLC satisfying the criteria for T3-Add versus T3-Size (A) in the entire cohort (B) after propensity score matching. CI, confidence interval; T3-Add, tumors with additional nodule(s) in the same lobe; T3-Size, tumors greater than 5 cm but less than or equal to 7 cm in greatest dimension.
      Table 2Independent Predictors of Overall Survival After Cox Proportional Hazards Adjustment for Patients With T3, N0-3, M0 NSCLC Satisfying the Criteria for T3-Add Versus T3-Size
      VariableHR95% CIp
      T3-Add vs. T3-Size0.860.82–0.89<0.001
      Age (per y)1.021.02–1.02<0.001
      Female vs. male0.820.79–0.85<0.001
      Race (ref = white)
       Black0.880.83–0.93<0.001
       Other0.760.68–0.85<0.001
      Charlson-Deyo comorbidity score (ref = 0)
       11.161.12–1.21<0.001
       21.271.20–1.34<0.001
       3+1.331.23–1.43<0.001
      Education: % without HS diploma (ref >17.5%)
       10.9%–17.5%1.061.01–1.120.023
       6.3%–10.8%1.081.02–1.150.009
       <6.3%1.060.98–1.130.13
      Median household income (ref < $40,227)
       $40,227–$50,3530.920.87–0.970.002
       $50,354–$63,3320.910.85–0.960.001
       ≥$63,3330.820.76–0.87<0.001
      Facility type (ref = community)
       Comprehensive0.950.89–1.000.066
       Academic or research0.830.78–0.88<0.001
       Integrated network0.890.83–0.960.002
      Insurance type (ref = uninsured)
       Private0.880.78–1.000.043
       Medicaid1.000.87–1.140.97
       Medicare0.930.83–1.060.27
       Other government0.870.72–1.030.11
      Tumor location (ref = right upper lobe)
       Right middle lobe0.950.86–1.040.26
       Right lower lobe1.161.10–1.21<0.001
       Left upper lobe1.010.97–1.060.55
       Left lower lobe1.141.08–1.21<0.001
      Surgery vs. no surgery0.320.30–0.34<0.001
      Chemotherapy vs. no chemotherapy0.680.65–0.71<0.001
      Radiation therapy vs. no radiation therapy0.750.72–0.78<0.001
      Histologic subtype (ref = adenocarcinoma)
       Squamous1.121.08–1.16<0.001
       Large cell1.321.16–1.49<0.001
       Adenosquamous1.301.15–1.46<0.001
       Neuroendocrine0.600.52–0.69<0.001
       Bronchioloalveolar0.920.84–1.020.12
      Grade (ref = well differentiated)
       Moderately differentiated1.371.25–1.49<0.001
       Poorly differentiated1.471.35–1.60<0.001
       Undifferentiated or anaplastic1.631.34–1.98<0.001
       Cell type not determined1.391.28–1.52<0.001
      Clinical N status (ref = cN0)
       cN11.391.31–1.47<0.001
       cN21.621.55–1.70<0.001
       cN31.721.60–1.83<0.001
      Distance from facility (per mile)1.001.00–1.000.42
      CI, confidence interval; HR, hazard ratio; ref, referent; HS, high school; T3-Add, tumors with additional nodule(s) in the same lobe; T3-Size, tumors greater than 5 cm but less than or equal to 7 cm in greatest dimension.
      A propensity score-matched analysis of these patient cohorts yielded two groups of 5670 patients with T3-Size tumors and 5670 patients with T3-Add tumors (Table 1). Both groups were well-balanced on all baseline characteristics, with standardized differences less than or equal to 5.2%. In this matched analysis, T3-Add tumors were associated with better overall survival when compared with T3-Size tumors (p < 0.001) (Fig. 1B).

      Comparison of T3-Add Versus T2b Tumors

      Table 3 details the baseline and tumor characteristics for the 3448 patients satisfying the criteria for T2b tumors and 8546 patients satisfying the criteria for T3-Add tumors. Compared with patients with T2b tumors, those with T3-Add tumors were more likely to be older, of female sex, black, have fewer comorbidities, have Medicare insurance, and be closer to their treatment facility. T3-Add tumors were also more likely to be located in the right upper lobe, have adenocarcinoma histology, and higher clinical N status.
      Table 3Baseline Characteristics of Patients With T2-3, N0-3, M0 NSCLC Satisfying the Criteria for T3-Add Versus T2b
      Patient CharacteristicsTotal CohortPropensity Score-Matched Analysis
      T2b (N = 3448)T3-Add (N = 8546)PT2b (N = 2260)T3-Add (N = 2260)Standardized Differences (%)
      Age (y, IQR)68 (61–75)69 (62–76)<0.00169 (61–75)68 (62–75)0.5
      Female, n (%)1572 (45.6)4827 (56.5)<0.0011092 (48.3)1042 (46.1)−4.4
      Race, n (%)<0.001
       White3038 (88.7)7362 (86.7)1988 (88.5)1980 (88.1)−1.0
       Black278 (8.1)887 (10.5)182 (8.1)190 (8.4)1.2
       Other110 (3.2)240 (2.8)77 (3.4)77 (3.4)0.0
      Charlson-Deyo comorbidity score, n (%)0.003
       01715 (49.7)4393 (51.4)1130 (50.0)1108 (49.0)−2.0
       11155 (33.5)2711 (31.7)749 (33.1)746 (33.0)−0.3
       2447 (13.0)1013 (11.9)285 (12.6)318 (14.1)4.6
       3+131 (3.8)429 (5.0)96 (4.3)88 (3.9)−1.8
      Education: % without HS diploma, n (%)0.51
       >17.5%672 (21.6)1608 (20.6)474 (21.0)481 (21.3)0.8
       10.9%–17.5%890 (28.6)2211 (28.3)639 (28.3)634 (28.1)−0.5
       6.3%–10.8%877 (28.2)2283 (29.2)646 (28.6)628 (27.8)−1.8
       <6.3%668 (21.5)1722 (22.0)501 (22.2)517 (22.9)1.7
      Median household income, n (%)0.58
       <$40,227627 (20.2)1548 (19.8)437 (19.3)444 (19.7)0.8
       $40,227–$50,353743 (24.0)1850 (23.7)544 (24.1)534 (23.6)−1.0
       $50,354–$63,332757 (24.4)1846 (23.7)559 (24.7)562 (24.9)0.3
       ≥$63,333975 (31.4)2557 (32.8)720 (31.9)720 (31.9)0.0
      Facility type, n (%)<0.001
       Community cancer program204 (6.0)712 (8.4)141 (6.2)136 (6.0)−0.8
       Comprehensive community cancer program1446 (42.4)3580 (42.1)984 (43.5)986 (43.6)0.2
       Academic or research program1253 (36.7)3031 (35.6)814 (36.0)817 (36.2)0.3
       Integrated network cancer program510 (14.9)1191 (14.0)321 (14.2)321 (14.2)0.0
      Insurance, n (%)<0.001
       Private1018 (29.8)2175 (25.8)663 (29.7)655 (29.3)−0.8
       Medicaid182 (5.3)499 (5.9)115 (5.2)121 (5.4)1.2
       Medicare2099 (61.5)5456 (64.6)1394 (62.4)1391 (62.3)−0.3
       Other government40 (1.2)156 (1.9)28 (1.3)28 (1.3)0.0
       Uninsured75 (2.2)155 (1.8)35 (1.6)38 (1.7)0.9
      Received surgery, n (%)3101 (90.0)4747 (55.8)<0.0011995 (88.3)2006 (88.8)1.1
      Received chemotherapy, n (%)1275 (38.5)4015 (48.7)<0.001913 (40.4)910 (40.3)−0.3
      Received radiation therapy, n (%)462 (13.9)2997 (36.1)<0.001356 (15.8)356 (15.8)0.0
      Tumor location, n (%)<0.001
       Right upper lobe1006 (30.3)3244 (39.5)741 (32.8)728 (32.2)−1.2
       Right middle lobe157 (4.7)372 (4.5)107 (4.7)108 (4.8)0.2
       Right lower lobe725 (21.8)1391 (16.9)469 (20.8)459 (20.3)−1.1
       Left upper lobe863 (26.0)2169 (26.4)578 (25.6)598 (26.5)2.0
       Left lower lobe568 (17.1)1038 (12.6)365 (16.2)367 (16.2)0.2
      Histologic subtype, n (%)<0.001
       Adenocarcinoma1414 (43.1)4264 (53.7)1131 (50.0)1119 (49.5)−1.1
       Squamous1324 (40.4)2149 (27.1)726 (32.1)764 (33.8)3.7
       Large cell79 (2.4)152 (1.9)50 (2.2)53 (2.4)0.9
       Adenosquamous82 (2.5)131 (1.7)55 (2.4)59 (2.6)1.3
       Neuroendocrine tumors157 (4.8)520 (6.5)113 (5.0)99 (4.4)−2.9
       Bronchioloalveolar225 (6.9)730 (9.2)185 (8.2)166 (7.4)−3.3
      Grade, n (%)<0.001
       Well differentiated404 (11.7)967 (11.3)293 (13.0)284 (12.6)−1.3
       Moderately differentiated1311 (38.0)2541 (29.7)883 (39.1)870 (38.5)−1.3
       Poorly differentiated1314 (38.1)2465 (28.8)797 (35.3)825 (36.5)2.7
       Undifferentiated or anaplastic68 (2.0)86 (1.0)27 (1.2)30 (1.3)1.1
       Cell type not determined351 (10.2)2487 (29.1)260 (11.5)251 (11.1)−0.9
      Clinical N status, n (%)<0.001
       cN02698 (78.3)5322 (62.3)1756 (77.7)1747 (77.3)−0.8
       cN1358 (10.4)838 (9.8)224 (9.9)235 (10.4)1.6
       cN2347 (10.1)1814 (21.2)248 (11.0)242 (10.7)−0.7
       cN345 (1.3)572 (6.7)32 (1.4)36 (1.6)0.7
      Distance to facility (miles, IQR)12.25 (5.1–29.6)10.1 (4.4–24.1)<0.00112 (5.1–28.3)11.1 (4.8–26.8)0.0
      HS, high school; IQR, interquartile range; T2b, tumors greater than 4 cm but less than or equal to 5 cm in greatest dimension; T3-Add, tumors with additional nodule(s) in the same lobe.
      Comparing treatment modalities in these two groups of patients reveals that those with T3-Add tumors were less likely to undergo surgery in both the entire cohort (55.8% versus 90.0%, p < 0.001) and when stratified by clinical N status (N0: 72.8% versus 94.0%, p < 0.001; N1: 54.9% versus 91.3%, p < 0.001; N2: 22.3% versus 66.6%, p < 0.001) (Supplementary Fig. 2, which compares rates of surgical resection for T3-Add versus T2b tumors). Among the 44.2% of patients with T3-Add tumors who did not receive surgery, 81.4% did not receive surgery because the patients' treating physicians did not include surgery as part of the planned first course of treatment. In addition, 14.7% of patients did not receive surgery because it was contraindicated owing to patient risk factors, including severely comorbid conditions, advanced age, or progression of the tumor before surgery, and 3.0% of patients refused surgery after it was recommended to them.
      Kaplan-Meier analysis revealed that patients with T3-Add tumors had worse 5-year overall survival than those with T2b tumors (p < 0.001) (Fig. 2A). T3-Add tumors were also associated with worse survival than T2b tumors after multivariable-adjusted Cox proportional hazards modeling without treatment modality (i.e., surgery, chemotherapy, or radiation) as a covariate (HR = 1.30, 95% CI: 1.21–1.39, p < 0.001) (Supplementary Table 1, which compares overall survival for patients with T3-Add versus T2b tumors). Nevertheless, after multivariable-adjusted Cox proportional hazards modeling including treatment modality as a covariate, no significant differences were found between the overall survival of the two groups (HR = 1.04, 95% CI: 0.97–1.12, p = 0.28) (Table 4).
      Figure thumbnail gr2
      Figure 2Overall survival of patients with T2-3, N0-3, M0 NSCLC satisfying the criteria for T3-Add versus T2b (A) in the entire cohort (B) after propensity score matching. CI, confidence interval; T2b, tumors greater than 4 cm but less than or equal to 5 cm in greatest dimension; T3-Add, tumors with additional nodule(s) in the same lobe.
      Table 4Independent Predictors of Overall Survival After Cox Proportional Hazards Adjustment for Patients With T2-3, N0-3, M0 NSCLC Satisfying the Criteria for T3-Add Versus T2b
      VariableHR95% CIp
      T3-Add vs. T3-Size1.040.97–1.120.28
      Age (per y)1.021.01–1.02<0.001
      Female vs. male0.730.69–0.77<0.001
      Race (ref = white)
       Black0.960.87–1.060.45
       Other0.720.60–0.870.001
      Charlson-Deyo comorbidity score (ref = 0)
       11.141.07–1.22<0.001
       21.241.14–1.36<0.001
       3+1.291.14–1.47<0.001
      Education: % without HS diploma (ref >17.5%)
       10.9%–17.5%1.020.93–1.110.72
       6.3%–10.8%0.990.90–1.090.83
       <6.3%0.910.81–1.020.10
      Median household income (ref < $40,227)
       $40,227–$50,3530.970.89–1.060.47
       $50,354–$63,3320.990.90–1.090.89
       ≥$63,3330.920.82–1.020.11
      Facility type (ref = community)
       Comprehensive0.880.79–0.970.013
       Academic or research0.760.68–0.85<0.001
       Integrated network0.830.73–0.940.003
      Insurance type (ref = uninsured)
       Private0.870.69–1.090.23
       Medicaid0.920.72–1.190.54
       Medicare1.000.79–1.250.99
       Other government0.910.66–1.240.55
      Tumor location (ref = right upper lobe)
       Right middle lobe0.850.72–1.000.052
       Right lower lobe1.161.07–1.26<0.001
       Left upper lobe1.050.98–1.130.19
       Left lower lobe1.020.93–1.120.61
      Surgery v no surgery0.350.32–0.39<0.001
      Chemotherapy vs. no chemotherapy0.780.73–0.84<0.001
      Radiation therapy vs. no radiation therapy0.860.80–0.93<0.001
      Histologic subtype (ref = adenocarcinoma)
       Squamous1.141.07–1.21<0.001
       Large cell1.611.34–1.94<0.001
       Adenosquamous1.311.08–1.600.007
       Neuroendocrine0.610.51–0.73<0.001
       Bronchioloalveolar0.990.88–1.120.86
      Grade (ref = well differentiated)
       Moderately differentiated1.391.23–1.56<0.001
       Poorly differentiated1.491.32–1.68<0.001
       Undifferentiated or anaplastic1.571.16–2.140.004
       Cell type not determined1.341.18–1.52<0.001
      Clinical N status (ref = cN0)
       cN11.541.40–1.69<0.001
       cN21.731.59–1.88<0.001
       cN31.981.75–2.24<0.001
      Distance from facility (per mile)1.001.00–1.000.46
      CI, confidence interval; HR, hazard ratio; ref, referent; HS, high school; T2b, tumors greater than 4 cm but less than or equal to 5 cm in greatest dimension; T3-Add, tumors with additional nodule(s) in the same lobe.
      Furthermore, a propensity score-matched analysis was conducted of 2260 patients with T2b tumors and 2260 patients with T3-Add tumors, well-balanced on all baseline characteristics (Table 3). Standardized differences were less than or equal to 4.6%. Kaplan-Meier analysis of 5-year overall survival yielded no significant differences between patients with T3-Add tumors and those with T2b tumors (p = 0.30) (Fig. 2B).

      Sensitivity Analysis: Stratification by Pathologic N Status

      Two additional propensity score-matched analyses were conducted, specifically comparing survival of patients with T3-Add versus T2b tumors who underwent surgical resection and diagnosed with pN0 or pN1 disease.
      3134 patients (36.7%) with T3-Add tumors and 2229 patients (64.6%) with T2b tumors underwent surgical resection and were diagnosed with pN0 disease, respectively. A propensity score-matched analysis yielded two groups of 1419 patients in each arm. Kaplan-Meier analysis revealed no significant difference in 5-year overall survival between T3-Add and T2b tumors in patients with pN0 disease (p = 0.76) (Supplementary Fig. 3A, which demonstrates overall survival for patients with T3-Add versus T2b tumors and pN0 disease in a propensity score-matched analysis).
      Similarly, when evaluating the frequency of pN1 disease, 668 patients (7.8%) with T3-Add tumors and 534 patients (15.5%) with T2b tumors received surgery and were diagnosed with having pN1 disease. Propensity score matching of these patients generated a cohort of 580 patients (290 in each arm). Comparison of 5-year overall survival between each arm revealed that there were no significant differences in survival for T3-Add tumors and T2b tumors (p = 0.18) (Supplementary Fig. 3B, which demonstrates overall survival for patients T3-Add versus T2b tumors and pN1 disease in a propensity score-matched analysis).

      Discussion

      In this national analysis, patients with T3 NSCLC presenting with a primary tumor with additional nodule(s) in the same lobe (“T3-Add”) were found to have better long-term survival than those with T3 tumors greater than 5 cm and less than or equal to 7 cm (“T3-Size”) and were found to have similar long-term survival to those with T2b tumors in both multivariable Cox proportional hazards modeling and propensity score-matched analysis. We also found that in the United States, T3-Add tumors were much less likely to be surgically resected when compared with T2b tumors, even though the National Comprehensive Cancer Network (NCCN) guidelines recommend similar treatment for both types of tumors.
      This study is the first national analysis to externally validate the T2b and T3 results drawn by the IASLC Staging Project,
      • Detterbeck F.C.
      • Bolejack V.
      • Arenberg D.A.
      • et al.
      The IASLC Lung Cancer Staging Project: background data and proposals for the classification of lung cancer with separate tumor nodules in the forthcoming eighth edition of the TNM classification for lung cancer.
      which suggested that tumors with additional nodules in the same lobe be classified as T3 in the AJCC eighth edition TNM staging manual.
      A primary finding of this study—that T3-Add tumors are associated with better survival than other types of T3 tumors—builds on results from the IASLC analysis, which revealed a trend in improved survival among T3-Add tumors compared with tumors satisfying other T3 descriptors, but found no significant differences.
      • Detterbeck F.C.
      • Bolejack V.
      • Arenberg D.A.
      • et al.
      The IASLC Lung Cancer Staging Project: background data and proposals for the classification of lung cancer with separate tumor nodules in the forthcoming eighth edition of the TNM classification for lung cancer.
      The 5-year overall survival for T3-Add tumors, in this study, of 42.5% was similar to the survival rates observed in the IASLC database, with such tumors having 47% 5-year overall survival when clinically staged and 42% 5-year survival when pathologically staged. Older population-based studies have reported survival between 23% and 35%,
      • Kim A.W.
      • Cooke D.T.
      Additional pulmonary nodules in the patient with lung cancer: controversies and challenges.
      ,
      • Detterbeck F.C.
      • Bolejack V.
      • Arenberg D.A.
      • et al.
      The IASLC Lung Cancer Staging Project: background data and proposals for the classification of lung cancer with separate tumor nodules in the forthcoming eighth edition of the TNM classification for lung cancer.
      though most of these studies primarily used data collected before 2003. A more recent national study of 683 patients diagnosed with having pT3, N0, M0 NSCLC between 2010 and 2013 from the Netherlands reported 5-year survival of 62.8% for patients with T3-Add, N0, M0 who underwent surgery. Smaller, single-institution studies have reported 5-year survival for all T3-Add tumors in the range of 20% to 57%.
      • Kim A.W.
      • Cooke D.T.
      Additional pulmonary nodules in the patient with lung cancer: controversies and challenges.
      ,
      • Detterbeck F.C.
      • Bolejack V.
      • Arenberg D.A.
      • et al.
      The IASLC Lung Cancer Staging Project: background data and proposals for the classification of lung cancer with separate tumor nodules in the forthcoming eighth edition of the TNM classification for lung cancer.
      This study has the following strengths. The NCDB serves as a valuable database to use for external validation of the IASLC results owing to its size and scope of inclusion. The IASLC previously used the NCDB for external validation of the eighth edition revision for the TNM stage groupings, citing the original database's underrepresentation of both North American patients and nonsurgical patients.
      • Detterbeck F.C.
      • Chansky K.
      • Groome P.
      • et al.
      The IASLC lung cancer staging project: methodology and validation used in the development of proposals for revision of the stage classification of NSCLC in the forthcoming (eighth) edition of the TNM classification of lung cancer.
      ,
      • Rami-Porta R.
      • Bolejack V.
      • Giroux D.J.
      • et al.
      The IASLC lung cancer staging project: the new database to inform the eighth edition of the TNM classification of lung cancer.
      ,
      • Chansky K.
      • Detterbeck F.C.
      • Nicholson A.G.
      • et al.
      The IASLC lung cancer staging project: external validation of the revision of the TNM stage groupings in the eighth edition of the TNM classification of lung cancer.
      ,
      • Goldstraw P.
      • Chansky K.
      • Crowley J.
      • et al.
      The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer.
      In the IASLC database, 15.5% of patients were treated without surgery. The NCDB not only accounts for both of these potential limitations but also offers detailed information on patients' treatment sequence and breakdown of treatment type by stage.
      In this study, unlike previous related studies, we were also able to adjust for treatment modality (surgery, chemoradiation, or radiation) in our multivariable analysis. According to the NCCN treatment guidelines, primary treatment for T3-Add tumors is as follows: (1) surgery followed by adjuvant chemotherapy for clinical N0 or N1 disease (stages IIB–IIIA); (2) concurrent chemoradiation or induction chemotherapy followed by surgery or radiation depending on progression for N2 disease (stage IIIB); and (3) concurrent chemoradiation only for N3 disease (stage IIIC).
      • Ettinger D.S.
      • Wood D.E.
      • Aggarwal C.
      • et al.
      NCCN guidelines insights: non-small cell lung cancer, version 1.2020.
      These differences in treatment recommendations highlight not only the association between treatment type and long-term survival but also the importance of adjusting for treatment in multivariable Cox proportional hazards analyses. For example, in the IASLC database, patients with T3-Add, N0, M0 NSCLC who received surgery had much better estimated 5-year survival than those treated nonsurgically (68% surgical versus 0% nonsurgical).
      • Detterbeck F.C.
      • Bolejack V.
      • Arenberg D.A.
      • et al.
      The IASLC Lung Cancer Staging Project: background data and proposals for the classification of lung cancer with separate tumor nodules in the forthcoming eighth edition of the TNM classification for lung cancer.
      The difference between the findings in this study, that T3-Add tumors were associated with better survival than T3-Size tumors, and the results in the IASLC analysis, which found no significant differences between the survival of these two groups, could be due to the fact that the IASLC analysis did not account for treatment type.
      Current NCCN treatment guidelines for T2b tumors are similar to T3-Add tumors.
      • Ettinger D.S.
      • Wood D.E.
      • Aggarwal C.
      • et al.
      NCCN guidelines insights: non-small cell lung cancer, version 1.2020.
      In practice, however, T3-Add tumors are far less likely to be treated surgically than T2b tumors, as reflected by our results, which revealed that only 55.8% of patients with T3-Add tumors received surgery as compared with 90.0% of patients with T2b tumors—a finding consistent regardless of clinical N status. In addition, of the patients with T3-Add tumors who did not receive surgery, 81.4% did not receive surgery because their primary treating physician did not include it as part of the planned first course of treatment. This is in contrast to only 14.7% of patients whose physicians considered surgical resection but eventually decided the patients would not be candidates owing to severely comorbid conditions, advanced age, or tumor progression before surgery.
      The difference between the incorporation of surgery during treatment for T3-Add and T2b tumors is especially important given our finding that T3-Add and T2b tumors have similar long-term overall survival after both multivariable adjustment accounting for treatment type and propensity score matching on treatment type. At present, patients with T3-Add tumors are far less likely to receive surgery as compared with patients with T2b tumors, primarily owing to a lack of their consideration as surgical candidates. In light of these findings, we believe that reevaluating whether T3-Add tumors should be grouped together with T2b tumors in the same category for the upcoming AJCC ninth edition guidelines would be valuable in the long-term care of these patients. This reevaluation of staging may simplify treatment guidelines and promote a multidisciplinary treatment approach for patients with such tumors, thereby leading to more guideline-concordant surgical treatment of T3-Add tumors.
      This study has several limitations. First, due to its retrospective nature, unobserved confounding and selection bias may persist despite our use of multivariable modeling and propensity score matching to account for confounding factors. Second, due to the method of coding for specific T descriptors in the NCDB, this study was unable to accurately identify patients exclusively satisfying the final T3 descriptor of tumors invading the parietal pleura, chest wall, pericardium, or phrenic nerve. Third, this study only analyzed patients satisfying a single T3 descriptor. Patients who satisfy multiple T descriptors may potentially have worse survival than those who satisfy a single T descriptor,
      • Detterbeck F.C.
      • Bolejack V.
      • Arenberg D.A.
      • et al.
      The IASLC Lung Cancer Staging Project: background data and proposals for the classification of lung cancer with separate tumor nodules in the forthcoming eighth edition of the TNM classification for lung cancer.
      ,
      • Blaauwgeers H.
      • Damhuis R.
      • Lissenberg-Witte B.I.
      • de Langen A.J.
      • Senan S.
      • Thunnissen E.
      A population-based study of outcomes in surgically resected T3N0 non-small cell lung cancer in the Netherlands, defined using TNM-7 and TNM-8; justification of changes and an argument to incorporate histology in the staging algorithm.
      and future studies should incorporate such patients as well. Fourth, information on recurrence, disease-free survival, and disease-specific survival is unavailable in the NCDB. Finally, the NCDB only captures data from Commission on Cancer-accredited hospitals in the United States and Puerto Rico, which may not accurately reflect cancer incidence, treatment rates, or outcomes in the various other countries represented in the IASLC database.
      In conclusion, in this national, population-based analysis, patients with T3 NSCLC owing to the presence of additional nodules in the same lobe, according to the AJCC eighth edition TNM staging classifications, were found to have better long-term survival than those with T3 tumors that are greater than 5 cm and less than or equal to 7 cm in greatest dimension and found to have similar long-term survival as patients with T2b tumors that are greater than 4 cm and less than or equal to 5 cm in greatest dimension, in both multivariable Cox proportional hazards modeling and propensity score-matched analysis. In addition, we found that, nationally, T3 tumors consisting of a primary tumor with additional nodules were much less likely to be surgically resected when compared with T2b tumors. The results of this study suggest that tumors with additional nodules in the same lobe, which are currently classified as T3, should be considered for restaging as T2b when determining criteria for the upcoming ninth edition of the AJCC staging manual for lung cancer that is due to be developed and published by 2024.

      CRediT Authorship Contribution Statement

      Arvind Kumar: Conceptualization, Methodology, Formal Analysis, Investigation, Writing—original draft preparation, Visualization.
      Sanjeevani Kumar: Formal Analysis, Investigation, Writing—original draft preparation, Visualization.
      Shivee Gilja: Investigation, Writing—original draft preparation.
      Alexandra Potter: Investigation, Visualization.
      Vignesh Raman: Formal Analysis.
      Ashok Muniappan, Douglas Liou: Writing—review and editing, Supervision.
      Chi-Fu Jeffrey Yang: Conceptualization, Methodology, Data Curation, Writing—review and editing, Supervision.

      Acknowledgments

      The data used in the study are derived from a deidentified NCDB file. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methodology used or the conclusions drawn from these data by the investigators.

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      Linked Article

      • Could T3Satell Tumors Be Considered Reclassified as T2b?
        Journal of Thoracic OncologyVol. 16Issue 12
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          We read with great interest the study by Kumar et al.,1 reporting their national analysis and suggesting that tumors with additional nodules in the same lobe, which are currently classified as T3, should be considered for reclassification as T2b in the next edition of the staging system.
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