Stage IB Nonsmall Cell Lung Cancers: Are They All the Same?

doi:10.1016/j.athoracsur.2005.12.054

The Annals of Thoracic Surgery

Volume 81, Issue 6, June 2006, Pages 1958-1962

Presented at the Fifty-first Annual Meeting of the Southern Thoracic Surgical Association, Cancun, Mexico, Nov 2–4, 2004.

https://doi.org/10.1016/j.athoracsur.2005.12.054 Get rights and content

Background

There is renewed interest in adjuvant chemotherapy after complete resection of nonsmall cell lung cancer, including stage IB (T2N0) cancers. Given the heterogeneity of the T2 classification, we hypothesize that there are survival differences in patients with stage IB NSCLC based on specific histopathologic tumor characteristics.

Methods

A retrospective evaluation of 119 consecutive patients from 1999 to 2004 with a pathologic diagnosis of T2N0 nonsmall cell lung cancer was performed. Patient follow-up was 97%. Overall survival and disease-free survival rates were calculated by the Kaplan-Meier method. Univariate analysis was performed using the log rank test and multivariate analysis by Cox’s proportional hazard model. Data were significant if p < 0.05.

Results

The 4-year overall survival and disease-free survival rates were 62% and 60%, respectively. The local and distant recurrence rates were 5% and 18%, respectively. Tumor size (p = 0.001), histologic grade (p = 0.002), the Eastern Cooperative Oncology Group performance status (p = 0.002), angioinvasion (p = 0.03), and visceral pleural involvement (p = 0.02) were predictors of overall survival by univariate analysis. Multivariate analysis demonstrated increasing tumor size (1.26 [95% confidence intervals 1.12, 1.64]) and histologic grade (4.05 [95% confidence intervals 1.38, 11.90]) to be significant independent predictors of a worse overall survival. The 4-year survival of patients without any of these variables was 89% compared with 56% if one or more of these factors were present (p = 0.03).

Conclusions

There is significant heterogeneity in the T2N0 class of nonsmall cell lung cancer. Risk stratification using specific histopathologic variables may help determine which patients will benefit most from adjuvant therapy.

Section snippets

Material and Methods

We performed a retrospective analysis of our general thoracic surgery database for all patients who underwent an R₀ resection for a pT2N0M0 NSCLC at the University of Virginia from July 1999 to January 2004. The project was approved by our institutional review board. A total of 119 consecutive patients undergoing resection for a pathologic stage IB disease were identified. Patients who underwent a nonanatomic wedge resection were excluded. Patients who had a carcinoid tumor and those patients

Results

There were a total of 111 (92%) tumors with a tumor size greater than 3.0 cm, 44 (37%) with visceral pleural involvement, 16 (13%) in which the tumor was greater than or equal to 2.0 cm from the carina, and 12 (10%) with lobar collapse. Tumors were classified as T2 lesions after pathologic analysis based on tumor size alone (n = 63) or visceral pleural involvement alone (n = 9), whereas the remainder of the patients had some combination of criteria (n = 47). No patient was classified as a T2

Comment

Stage IB NSCLC is the most common pathologic stage accounting for 29% of resected pathologic stages IA to IIIA [1]. The incidence of new cases of lung cancer in the United States in 2004 is 174,000, of which approximately 139,000 are NSCLC [6]. Accepting that 25% to 30% of these patients would be offered surgery based on a clinical stage of I, II, and selected IIIA disease [7], this translates into an estimate of 12,000 patients with pathologic stage IB disease annually in the United States.

References (16)

C.F. Mountain
Revisions in the International System for Staging Lung Cancer
Chest
(1997)
M. Brundage et al.
Prognostic factors in non-small cell lung cancer
Chest
(2002)
J. Padilla et al.
Survival and risk model for Stage IB non-small cell lung cancer
Lung Cancer
(2002)
E. Carbone et al.
T2 tumors large than five centimeters in diameter can be upgraded to T3 in non-small cell lung cancer
J Thorac Cardiovasc Surg
(2001)
K. Shimizu et al.
Visceral pleural invasion classification in non-small cell lung cancera proposal on the basis of outcome assessment
J Thorac Cardiovasc Surg
(2004)
R. Molina et al.
Tumor markers (CEA, CA 125, CYFRA 21-1, SCC and NSE) in patients with non-small cell lung cancer as an aid in histological diagnosis and prognosis. Comparison with the main clinical and pathological prognostic factors
Tumour Biol
(2003)
R. Arriagada et al.
Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer
N Eng J Med
(2004)
G.M. Strauss et al.
Randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in stage IB non-small cell lung cancer (NSCLC)report of the cancer and leukemia group B (CALGB) protocol 9633
ASCO Proc
(2004)

There are more references available in the full text version of this article.

Cited by (47)

The modification of T description according to visceral pleural invasion and tumor size from 3.1 cm to 4.0 cm in non-small cell lung cancer: A retrospective analysis based on the SEER database
2021, Lung Cancer
Citation Excerpt :
Yip indicated VPI was not a risk factor for OS of patients with TS less than 3 cm and patients can’t be upstaged to T2 without further large and multicenter studies [18]. Rare number of studies had showed that VPI was not a predictive factor of survival for small size tumor or all types of NSCLC [19]. According to the above studies, it’s still remaining controversy that the correlation between VPI and survival of patients with TS less than 5.0 cm.
As a poor prognostic factor, visceral pleural invasion (VPI) was incorporated into non-small cell lung cancer (NSCLC) staging system. For modifying the T description of NSCLC, the prognostic value of VPI was assessed.
From 2010–2015, data on stage pT2N0M0 NSCLC patients with tumor size (TS) from 3.1 cm to 5.0 cm who received surgery from the Surveillance, Epidemiology, and End Results (SEER) database were enrolled retrospectively. Propensity score matching was utilized to balance the baseline factors according to different TS intervals. Overall survival (OS) was assessed by the Kaplan-Meier method and log-rank test. Univariate and multivariate analysis were applied to identify the prognostic factors. The risk factors of VPI were calculated by logistic regression model.
The sum of 4005 resected stage pT2N0M0 NSCLC patients with TS from 3.1 cm to 5.0 cm were recruited, which had 1084 patients with VPI and 2921 patients without VPI respectively. As TS interval of 3.1−4.0 cm, the 5-year OS of patients without VPI was significantly better than those with VPI (62.6 % vs 58.7 %, P = 0.015), while the 5-year OS of patients with VPI and TS interval of 3.1−4.0 cm had no significant difference compared with patients whose TS interval of 4.1−5.0 cm (58.7 % vs 58.8 %, P = 0.918). Logistic regressive analysis manifested that older age, female, worse differentiation grade and larger TS had higher incidence of VPI (OR = 1.01, 1.25, 1.25, 1.16, respectively; P < 0.05 for all).
This study underlined the prognostic effect of VPI and suggested that early-stage NSCLC with VPI and TS interval of 3.1–4.0 cm could be appropriately upstaged from pT2a (stage pIB) to pT2b (modified stage pIIA).
Oncologic Outcomes of Surgery Versus SBRT for Non–Small-Cell Lung Carcinoma: A Systematic Review and Meta-analysis
2021, Clinical Lung Cancer
The optimal treatment of stage I non–small-cell lung carcinoma is subject to debate. The aim of this study was to compare overall survival and oncologic outcomes of lobar resection (LR), sublobar resection (SR), and stereotactic body radiotherapy (SBRT).
A systematic review and meta-analysis of oncologic outcomes of propensity matched comparative and noncomparative cohort studies was performed. Outcomes of interest were overall survival and disease-free survival. The inverse variance method and the random-effects method for meta-analysis were utilized to assess the pooled estimates.
A total of 100 studies with patients treated for clinical stage I non–small-cell lung carcinoma were included. Long-term overall and disease-free survival after LR was superior over SBRT in all comparisons, and for most comparisons, SR was superior to SBRT. Noncomparative studies showed superior long-term overall and disease-free survival for both LR and SR over SBRT. Although the papers were heterogeneous and of low quality, results remained essentially the same throughout a large number of stratifications and sensitivity analyses.
Results of this systematic review and meta-analysis showed that LR has superior outcomes compared to SBRT for cI non–small-cell lung carcinoma. New trials are underway evaluating long-term results of SBRT in potentially operable patients.
Early Distant Recurrence in Patients With Resected Stage I Lung Cancer: A Case Series of “Blast Metastasis”
2021, Clinical Lung Cancer
The standard of care in the management of stage I non–small-cell lung cancer (NSCLC) has been anatomic lung resection with multistation lymph node sampling of ≥ 10 lymph nodes. The 5-year survival for NSCLC has ranged from 73% to 93% (for stage IB and stage IA, respectively) and will be more favorable for patients with fewer comorbidities and those with a higher state of premorbid functioning and who undergo surgical resection. Despite the positive prognosis for operable stage I NSCLC, a subset of patients will develop metastatic disease within as few as 12 months after resection. Using an institutional database, we have presented the data from 68 patients who had developed distant metastatic recurrence after resection of pathologic stage I NSCLC within 1 year after surgery.
A retrospective study was conducted of a prospectively maintained intuitional database. The final cohort included patients with pathologic stage I NSCLC who had undergone anatomic resection but had subsequently presented with multiple sites of distant recurrence within 1 year. The study period extended from 2003 to 2020. Patients with broad local recurrence or recurrence at a single distant site were excluded. Kaplan-Meier analysis was used to estimate the 5-year survival.
A total of 2827 patients had undergone surgical resection for stage I NSCLC during the 17-year period and 68 met the criteria for inclusion. Most of the patients (n = 48) were smokers, and the dominant histologic type was adenocarcinoma (n = 37). After recurrence, 22 patients (33%) had undergone chemoradiotherapy and 19 (28%) had received chemotherapy alone. The mean and median overall survival were 23.7 and 14 months, respectively. The 5-year survival from recurrence and surgery were both 13.2%.
Limited data are available on the risk factors for early metastasis after resected stage I NSCLC. The results from our cohort have demonstrated poor survival after recurrence. These data might be the basis for determining a phenotype for patients prone to early widespread metastasis despite seemingly curative surgical resection.
Cancer of the Lung: Non-Small Cell Lung Cancer and Small Cell Lung Cancer
2019, Abeloff’s Clinical Oncology
Lung cancer is a highly incident disease, and the major cause of cancer death worldwide. Trends in lung cancer incidence and mortality follow an epidemiological link to the history of tobacco consumption, although a recent increase of cases in never smokers has been observed. Throughout this chapter, readers will have the chance to appreciate the major changes and advances that took place in the presentation, diagnosis, and treatment of lung cancer in the past decades. The pathology and staging classification of lung cancer has evolved over time, as has the knowledge on its genomic landscape. The discovery of driver mutations such as EGFR and ALK has revolutionized the field of targeted therapy. Molecular testing has become a standard in non-squamous NSCLC, and results are now essential to link patients to better-suited therapies. The greater understanding of cancer immunology also impacted lung cancer therapy. Immune checkpoint inhibitors are now a routine in most lung cancer cases, including metastatic and locally advanced NSCLC. The advance in imaging diagnostics and intervention allowed better detection (including screening programs), staging (mainly due to PET-CT), and treatment. Minimally invasive techniques are commonly used to help diagnose and stage lung cancer. Daily examples include CT-guided biopsies, EBUS, EUS, video-assisted and robotic surgery. Modern radiation devices have enabled the application of highly precise doses to localized nodules, adding new treatment opportunities to different disease stages. Altogether, lung cancer control requires multidisciplinary care and continuous research effort.
Recurrence Pattern of Pathologic Stage I Lung Adenocarcinoma With Visceral Pleural Invasion
2017, Annals of Thoracic Surgery
Citation Excerpt :
Although VPI has generally been well known as a worse prognostic factor in pathologic stage I lung adenocarcinoma, it has not been well demonstrated the patterns of postoperative recurrence in lung adenocarcinoma with VPI. In the study by Jones and colleagues [7], VPI was identified in 2 of 6 patients (33%) with locoregional recurrence and 8 of 22 patients (36%) with distant recurrence. In study by Manac’h and colleagues [8], patterns of recurrence were recognized in resected N0 NSCLC with VPI, including local recurrence in 5.1% of patients, single-organ metastasis in 48.7%, multiple-organ metastases in 43.6%, and both local and distant metastasis in 2.6%.
Visceral pleural invasion (VPI) is well known to be a poor prognostic factor in lung adenocarcinoma. There were few studies reporting postoperative recurrence pattern in lung adenocarcinoma with VPI. This study was to evaluate the clinical effect of VPI on recurrence pattern in pathologic stage I lung adenocarcinoma after curative resection.
Among 574 patients with pathologic stage I lung adenocarcinoma after complete resection between 2003 and 2012, the clinicopathologic characteristics of 89 patients (16%) who had recurrence were retrospectively reviewed. The pathologic findings, postrecurrence survival, and patterns of recurrence were compared between patients with VPI and without VPI.
Median follow-up duration was 53.6 months. The VPI was found in 43 patients (group I) and not found in 46 patients (group II). Both total tumor size and invasive size were larger in group I (3.2 versus 2.7 cm and 2.5 versus 2.1 cm; p < 0.05). The median duration of overall survival was 58 months in group I and 76 months in group II. As patterns of recurrence, pleural seeding was found in 25 patients, and the percentage of pleural seeding was significantly higher in group I than group II (44.2% versus 13.0%; p = 0.001). In group I, bilateral lung metastasis was significantly common (39.5% versus 13.0%; p = 0.004), and increasing percentage of pleural seeding was observed as the invasive tumor size grows.
The presence of VPI was a significant predictable factor for pleural seeding and bilateral lung metastasis as patterns of recurrence after complete resection in pathologic stage I lung adenocarcinoma.
Visceral pleural invasion impacts the prognosis of non-small cell lung cancer: A meta-analysis
2016, European Journal of Surgical Oncology
In the 7th tumor, node, metastasis (TNM) classification, T1 tumors with visceral pleural invasion (VPI) are upgraded to T2a. The objective of this study was to evaluate the prognostic impact of VPI among patients with NSCLC and to propose a method of incorporating VPI into T-status classification in future staging systems.
A systematic electronic search was conducted from each database's date of inception to October 2015. The included studies were selected according to predefined inclusion criteria. The hazard ratio (HR) was used as the outcome measure for data combining.
A total of 22 studies, published from 2003 to 2015, were included in this meta-analysis. In the subgroup analysis, we identified that VPI was a poor prognostic factor for tumor size ≤2 cm (2.34 [95% confidence interval (CI) 1.55–3.54; P < 0.0001]), 2–3 cm (1.81 [95% CI 1.56–2.10; P < 0.0001]), 3–5 cm (1.61 [95% CI 1.38–1.87; P < 0.0001]) and 5–7 cm (1.50 [95% CI 1.24–1.82; P < 0.0001]). In addition, we also found that there were no significant differences for the following comparisons of OS: tumor size ≤2 cm with VPI versus 3–5 cm without VPI (1.04 [95% CI 0.83–1.31; P = 0.34]); 2–3 cm with VPI versus 3–5 cm without VPI (1.04 [95% CI 0.96–1.13; P = 0.30]); 3–5 cm with VPI versus 5–7 cm without VPI (0.95 [95% CI 0.78–1.17; P = 0.66]); and 5–7 cm with VPI versus T3 status (1.03 [95% CI 0.93–1.14; P = 0.57]).
In addition to the current TNM classification recommendations, consideration should be given to classifying the T2a tumors with VPI as T2b and classifying T2b with VPI as T3 in the next edition of the TNM Classification for Lung cancer.

View all citing articles on Scopus

View full text

Original articleGeneral thoracicStage IB Nonsmall Cell Lung Cancers: Are They All the Same?

Background

Methods

Results

Conclusions

Section snippets

Material and Methods

Results

Comment

Chest

Chest

Lung Cancer

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Tumor markers (CEA, CA 125, CYFRA 21-1, SCC and NSE) in patients with non-small cell lung cancer as an aid in histological diagnosis and prognosis. Comparison with the main clinical and pathological prognostic factors

Tumour Biol

Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer

N Eng J Med

Randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in stage IB non-small cell lung cancer (NSCLC)report of the cancer and leukemia group B (CALGB) protocol 9633

ASCO Proc

Original article
General thoracic
Stage IB Nonsmall Cell Lung Cancers: Are They All the Same?