Pathologic N1 Non-small Cell Lung Research Articles

Survival difference between patients with single versus multiple metastatic lymph nodes and the role of histology in pathological stage II-N1 non-small cell lung cancer

Background Previous studies investigating whether metastatic lymph node count is a relevant prognostic factor in pathological N1 non-small cell lung cancer (NSCLC), showed conflicting results. Hypothesizing that outcome may also be related to histological features, we determined the prognostic impact of single versus multiple metastatic lymph nodes in different histological subtypes for patients with stage II-N1 NSCLC. Methods We performed a retrospective cohort study using data from the Netherlands Cancer Registry, including patients treated with a surgical resection for stage II-N1 NSCLC (TNM 7th edition) in 2010-2016. Overall survival (OS) was assessed for patients with single (pN1a) and multiple (pN1b) metastatic nodes. Using multivariable analysis, we compared OS between pN1a and pN1b in different histological subtypes. Results After complete resection of histologically proven stage II-N1 NSCLC, 1309 patients were analysed, comprising 871 patients with pN1a and 438 with pN1b. The median number of pathologically examined nodes (N1 + N2) was 9 (interquartile range 6-13). 5-year OS was 53% for pN1a versus 51% for pN1b. In multivariable analysis, OS was significantly different between pN1a and pN1b (HR 1.19, 95% CI 1.01-1.40). When stratifying for histology, the prognostic impact of pN1a/b was only observed in adenocarcinoma patients (HR 1.44, 95% CI 1.15-1.81). Conclusion Among patients with stage II-N1 adenocarcinoma, the presence of multiple metastatic nodes had a significant impact on survival, which was not observed for other histological subtypes. If further refinement as to lymph node count will be considered for incorporation into a new staging system, evaluation of the role of histology is recommended.

Prognostic significance of extranodal extension in patients with pathologic N1 non-small cell lung cancer undergoing complete resection.

The prognostic significance of extranodal extension (ENE) remains unclear in patients with pathologic N1 (pN1) non-small-cell lung cancer (NSCLC) undergoing surgery. We evaluated the prognostic impact of ENE in patients with pN1 NSCLC. From 2004 to 2018, we retrospectively analyzed the data of 862 patients with pN1 NSCLC who underwent lobectomy and more (lobectomy, bilobectomy, pneumonectomy, sleeve lobectomy). According to their resection status and the presence of ENE, patients were classified into R0 without ENE (pure R0) (n=645), R0 with ENE (R0-ENE) (n=130), and incomplete resection (R1/R2) groups (n=87). The primary and secondary endpoints were 5-year overall survival (OS) and recurrence-free survival (RFS), respectively. The prognosis of the R0-ENE group was significantly worse than the pure R0 group for both OS (5-year rate: 51.6% vs. 65.4%, P=0.008) and RFS (44.4% vs. 53.0%, P=0.04). According to the recurrence pattern, a difference of RFS was found only for distant metastasis (55.2% vs. 65.0%, P=0.02). The multivariable Cox analysis revealed that the presence of ENE was a negative prognostic factor in patients who did not undergo adjuvant chemotherapy [hazard ratio (HR) =1.58; 95% confidence interval (CI): 1.06-2.36; P=0.03], but it was not in those with adjuvant chemotherapy (HR =1.20; 95% CI: 0.80-1.81; P=0.38). For patients with pN1 NSCLC, the presence of ENE was a negative prognostic factor for both OS and RFS, regardless of resection status. The negative prognostic effect of ENE was significantly associated with an increase in distant metastasis and was not observed in patients who underwent adjuvant chemotherapy.

Benefit of adjuvant chemotherapy for resected pathologic N1 non-small cell lung cancer is unrecognized: A subgroup analysis of the JBR10 trial

Adjuvant chemotherapy is underutilized in clinical practice, in part, because its anticipated survival benefit is limited. We evaluated the impact of AC on overall and recurrence-free survival among completely resected pN1 NSCLC patients enrolled in the North American Intergroup phase III (JBR10) trial. A post-hoc subgroup analysis of pN1 NSCLC patients was performed. Participants were randomized to cisplatin+vinorelbine (AC) (n = 118) or observation (n = 116) following complete resection. The primary endpoint was overall survival (OS). The secondary endpoint was recurrence free survival (RFS). Kaplan-Meier methods were used to compare OS and RFS between the two treatment groups. Cox regression was used to identify factors associated with OS and RFS endpoints. Both groups had similar baseline characteristics. AC patients had improved 5-year OS (AC 61.4% vs observation 41.0%, log-rank p = .008) and 5-year RFS (AC 56.2% vs observation 39.9%, log-rank p = .011) rates compared to observation. Cox regression analyses confirmed the OS (HR 0.583, 95% CI 0.402-0.846, p = .005) and RFS (HR 0.573, 95% CI 0.395-0.830, p = .003) benefit associated with AC. AC was associated with a lower risk (HR 0.648, 95% CI 0.435-0.965, p = .0326) and a lower cumulative incidence (Subdistribution Hazard Ratio [SHR], 0.67, 95% CI 0.449-0.999, p = .0498) of lung cancer deaths. In the JBR10 trial, treatment with AC conferred a significant OS and RFS advantage over observation for pN1 NSCLC patients. These data suggest that pN1 NSCLC patients may experience a disproportionately greater clinical benefit from AC than the 6% survival advantage estimated by the LACE meta-analysis.

Surgical Results in Pathological N1 Nonsmall Cell Lung Cancer

This retrospective study investigated the prognosis of patients with pathological N1 (pN1) nonsmall cell lung cancer (NSCLC). We included patients with pN1 NSCLC who underwent lobectomy or pneumonectomy with mediastinal lymph node dissection and achieved complete resection (R0) between January 2000 and December 2012. Patients who received neoadjuvant therapy were excluded. A total of 249 patients were included. The mean age was 63.2 years, and 172 patients were males. Of the 249 patients, 200, 20, and 29 underwent lobectomy, bilobectomy, and pneumonectomy, respectively. The median observation period was 5.5 years. The 5-year overall survival (OS) rate was 64.6% (95% confidence interval: 58.3-70.4). Five-year OS rates were 79.8% for positive lymph nodes at station 13 or 14 (n = 57), 59.6% at station 12 (n = 72), 62.7% at station 11 (n = 69), and 56.9% at station 10 (n = 51) (log-rank test; p = 0.016); furthermore, the 5-year OS rate was 75.2% for patients with positive lymph nodes at a single station (n = 160) and 45.4% for patients with positive lymph nodes at multiple stations (n = 89) (log-rank test; p < 0.001). Five-year cumulative incidences of recurrence were equivalent between patients who received adjuvant chemotherapy and patients who did not (45.9 vs. 55.1%; Gray's test; p = 0.366). Distant recurrence was the most frequent mode of recurrence in both groups (70.8 and 67.3%). The locations and the number of stations of the positive lymph nodes were identified as prognostic factors in patients with pN1 NSCLC. The primary mode of recurrence was distant recurrence irrespective of postoperative adjuvant chemotherapy.

Disparities in Guideline-Concordant Treatment for Pathologic N1 Non-Small Cell Lung Cancer

Socioeconomic status (SES) disparities in the surgical management of patients with non-small cell lung cancer (NSCLC) are well described. Disparities in the receipt of adjuvant chemotherapy are poorly understood. We assessed the influence of SES on adjuvant chemotherapy after resection in patients with pN1 NSCLC. The National Cancer Database was queried for cN0/N1 NSCLC patients who underwent surgical resection and had demonstrated pN1 disease. This cohort was further divided into those who received multiagent adjuvant chemotherapy (MAAC) vs surgery-only treatment. Factors associated with treatment assignment were examined, and long-term survival was compared. Of the 14,892 patients who underwent resection for pN1 disease, 8061 (54.1%) received MAAC. Patients were less likely to receive MAAC if they resided in rural areas (odds ratio, 1.23; 95% confidence interval [CI], 1.11-1.37; P < .001), or were uninsured or on Medicaid (odds ratio, 1.23; 95% CI, 1.07-1.41; P= .004). The propensity score-weighted 5-year survival was significantly higher for those receiving MAAC compared with surgery only (53.6% vs 39.5%, log-rank P < .001). Lower income (hazard ratio, 1.06; 95% CI, 1.00-1.12; P= .044) and uninsured or Medicaid insurance status (hazard ratio, 1.22; 95% CI, 1.13-1.31; P < .001) were independently associated with increased mortality by Cox regression in the propensity score-weighted cohort. pN1 NSCLC patients living in rural areas or who are uninsured or on Medicaid insurance are at increased risk of not receiving MAAC. Treatment with MAAC significantly improves long-term survival of pN1 patients. Efforts should be made to ensure these at-risk groups receive guideline-concordant care.

Prognostic Factors of Pathological N1 Non-small Cell Lung Cancer After Curative Resection Without Adjuvant Chemotherapy.

The aim of this study was to evaluate the outcomes of patients with pathological N1 non-small cell lung cancer who did not receive adjuvant chemotherapy. We attempted to identify those patients for whom adjuvant chemotherapy would be indispensable. Among 132 patients who were diagnosed with pathological N1 lung cancer at a single institution from January 2010 to December 2016 were 32 patients who did not receive adjuvant treatment after curative surgical resection. The surgical and oncological outcomes of these patients were analyzed. Candidate factors for predicting recurrence were analyzed to identify patients at high risk of recurrence. The median follow-up time for all 32 patients was 1044days. The 5-year recurrence-free survival (RFS) and disease-specific survival rates of the patients without adjuvant therapy were 50.3% and 77.6%, respectively. By multivariate analysis, tumors with a lepidic growth pattern [hazard ratio (HR) 0.119, p = 0.024] and extralobar lymph node metastasis (HR 6.848, p = 0.015) were significant factors predicting recurrence. The difference between the 5-year RFS rates of patients with tumors with or without a lepidic growth pattern was statistically significant (63.5% vs 40.0%, respectively; p = 0.050). The 5-year RFS rates of patients with intralobar lymph node metastasis versus those with extralobar lymph node metastasis were 63.3% and 18.8%, respectively (p = 0.002). Patients with tumors without a lepidic growth pattern or with extralobar lymph node metastasis who do not receive adjuvant chemotherapy have a high recurrence rate after surgery. Therefore, these patients should be encouraged to undergo adjuvant chemotherapy if their overall condition is not a contraindication for chemotherapy.

Segmentectomy vs Lobectomy for Pathological N1 Non-Small Cell Lung Cancer

Segmentectomy vs Lobectomy for Pathological N1 Non-Small Cell Lung Cancer

Prognostic value of lymph node ratio in patients with pathological N1 non-small cell lung cancer: a systematic review with meta-analysis.

Non-small cell lung cancer (NSCLC) patients with N1 disease have variable outcomes, and additional prognostic factors are needed. The number of positive lymph nodes (LNs) has been proposed as a prognostic indicator. However, the number of positive LNs depends on the number of LNs examined from the resection specimen. The lymph node ratio (LNR) can circumvent this limitation. The purpose of this study is to evaluate LNR as a predictor of survival and recurrence in patients with pathologic N1 NSCLC. We systematically reviewed studies published before March 17, 2016, on the prognostic value of LNR in patients with pathologic N1 NSCLC. The hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to combine the data. We also evaluated heterogeneity and publication bias. Five studies published between 2010 and 2014 were eligible for this systematic review with meta-analysis. The total number of patients included was 6,130 ranging from 75 to 4,004 patients per study. The combined HR for all eligible studies evaluating the overall survival (OS) and disease-free survival (DFS) of N1 LNR in patients with pathologic N1 NSCLC was 1.53 (95% CI: 1.22-1.85) and 1.64 (95% CI: 1.19-2.09), respectively. We found no heterogeneity and publication bias between the reports. LNR is a worthy predictor of survival and cancer recurrence in patients with pathological N1 NSCLC.

Prognostic analysis of patients with unsuspected pathologic N1 non-small cell lung cancer

To investigate the prognosis of patients with N1 non-small cell lung cancer, and to compare the clinicopathological features and survival between patients with unexpected N1 (cN0-pN1) and expected N1 disease (cN1-pN1) after operation for non-small cell lung cancer. This study retrospectively reviewed and analyzed the medical records of 183 patients who underwent surgery and pathologically diagnosed with N1 non-small cell lung cancer between January 2006 and December 2010. Among them, 78 patients had negative findings before surgery (cN0-pN1 group), and 105 patients had positive findings before surgery (cN1-pN1 group). The clinicopathological features, median survival time and 5-year survival rates between the two groups were analyzed. Patients in the cN1-pN1 group had greater pathologic T stage, larger tumors, greater number and stations of positive N1 lymph nodes, and greater percentage of pneumonectomy than those in the cN0-pN1 group (P < 0.05). For the patients with cN0-pN1, the MST was 47.0 months and the 1-, 3-, and 5-year OS were 85.9%, 57.4%, and 42.5%, respectively. For the patients with cN1-pN1, the MST was 30.0 months and the 1-, 3-, and 5-year OS were 74.3%, 44.6%, and 28.8%, respectively. There were significant differences in survival between the two groups (P < 0.05). The locoregional recurrence rate of cN0-pN1 group was lower than in the cN1-pN1group (P < 0.05). The multivariate analysis showed that T staging and N staging before surgery, lymph node metastasis to multiple N1 stations and adjuvant chemotherapy were independent prognostic factors. Different clinical features of N1 non-small cell lung cancer has certain heterogeneity. Patients with unexpected N1 disease show better survival and lower locoregional recurrence rate than did those with expected N1 disease.

Prognosis of Unexpected and Expected Pathologic N1 Non-Small Cell Lung Cancer

This study was undertaken to compare clinicopathologic features and survival between patients with unexpected N1 (clinical N0-pathologic N1) and expected N1 disease (clinical N1-pathologic N1) after operation for non-small cell lung cancer. From 2003 to 2009, 305 patients who were found to have pathologic N1 disease after complete resection were retrospectively analyzed. Among these, 177 patients had negative findings for both computed tomography (CT) and positron emission tomography (PET)/CT (group cN0). Sixty-eight patients had negative CT and positive PET/CT or positive CT and negative PET/CT findings (group cN0-1). Sixty patients had positive findings for both CT and PET/CT (group cN1). Patients in the cN1 group had larger tumors (p<0.001), greater pathologic T stage (p=0.018), and greater percentage of squamous cell carcinoma (p<0.001) than did those in the other groups. Patients in the cN1 group had a greater number of positive N1 lymph nodes (p=0.004) and more frequent extracapsular nodal invasion (p<0.001). The 5-year overall survival was 66%, 63%, and 58% in groups cN0, cN0-1, and cN1, respectively (cN0 vs cN0-1, p=0.958; cN0 vs cN1, p=0.038). The 5-year disease-free survival was 54%, 52%, and 39% in groups cN0, cN0-1, and cN1, respectively (cN0 vs cN0-1, p=0.862; cN0 vs cN1, p=0.01). Patients with unexpected N1 disease showed better survival than did those with expected N1 disease, which seemed to be related to the pathologically minimal extent of the primary tumor and nodal involvement.

Nonexamination of Lymph Nodes and Survival After Resection of Non-Small Cell Lung Cancer

Nonexamination of lymph nodes is an extreme example of the variability of pathologic nodal staging of non-small cell lung cancer. We compared the prevalence, characteristics, and survival of patients without lymph nodes (pNX) to patients with documented pathologic N0 and pathologic N1 non-small cell lung cancer. A retrospective analysis was done of non-small cell lung cancer resections in the US Surveillance, Epidemiology, and End Results database from 1998 to2009. Thirteen percent of all resections (18% of node negative resections) were pNX, including 6% of all node-negative lobar or greater resections and 51% of sublobar resections. Thirty-five percent of pNX resections were lobar or greater compared with 90% of pathologic N0 (p < 0.0001). Advanced age and surgery in rural locations were also significantly associated with pNX resection. The median duration of survival was 3 years in the pNX cohort, 6.4yearsin the N0 cohort (p < 0.0001), and 2.8 years in the N1group, with respective 5-year survival rates of 47%, 67%, and 45%(p < 0.0001). These survival differences remained afteradjustment for potentially confounding factors. Patients with pNX resections are a high-risk subset, with survival approximating pathologic N1, not N0. They should have further attempts at retrieving lymph nodes for examination or be offered postoperative adjuvant chemotherapy. We predict that treatment modalities that fail to address lymph nodes are likely to yield inferior survival in comparison to surgery with proper lymph node examination. The proportion of pNX lung resections may be a sentinel quality indicator for lung cancer programs.

Pathologic N1 Non-small Cell Lung Cancer: Identifying Subsets of Patients at High Risk of Local Failure

Pathologic N1 Non-small Cell Lung Cancer: Identifying Subsets of Patients at High Risk of Local Failure

Lymph node ratio as a prognostic factor in elderly patients with pathological N1 non-small cell lung cancer

BackgroundLymph node (LN) metastasis is an important predictor of survival for patients with non-small cell lung cancer (NSCLC). However, the prognostic significance of the extent of LN involvement among patients...

Predictors of Survival and Disease-Free Survival in Patients With Resected N1 Non-Small Cell Lung Cancer

Factors that predict poor survival or increased risk of recurrence for patients with N1 disease may be dependent on tumor characteristics. This study was a retrospective review of a prospective database of consecutive patients who had clinical or pathologic N1 non-small cell lung cancer (NSCLC) who underwent preoperative 2-[18F] fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) scans and complete resection with thoracic lymphadenectomy. There were 135 patients (88 men). The 5-year disease-free rate was 55%. Kaplan-Meier analysis showed that poor differentiation (p = 0.036), multiple N1 stations (p = 0.010), and the lack of adjuvant chemotherapy (p = 0.039) were all associated with a shorter 5-year disease-free rate. Multivariate disease-free analysis demonstrated that only multiple stations (p = 0.002) were independently associated with recurrence. The overall 5-year survival was 48%. Univariate analysis showed that multiple nodes within one station (p = 0.016), multiple station involvement (p = 0.041), and lack of adjuvant chemotherapy (p = 0.039) and moderate-to-poor tumor differentiation (p = 0.046) were associated with decreased survival. Multivariate analysis found that multiple stations, multiple nodes, and lack of adjuvant chemotherapy were independent predictors of poor survival. Integrated PET-computed tomography (CT) was significantly more sensitive for staging N1 disease than dedicated FDG-PET (p = 0.032). Neoadjuvant chemotherapy given to 48 nonrandomized patients did not seem to impact disease recurrence or overall 5-year survival rates (p = 0.349). Factors that predict a poor outcome in patients with resected N1 NSCLC are the involvement of multiple N1 stations, multiple N1 nodes, and the lack of adjuvant chemotherapy. Integrated PET-CT is more sensitive for detecting N1 disease then dedicated PET. These data may influence preoperative or postoperative therapy, or both.

Prognostic variability among nonsmall cell lung cancer patients with pathologic N1 lymph node involvement

Patients who have nonsmall cell lung cancer with N1 lymph node status are an intermediate group of patients who have a variable prognosis. Differences in lymph node level (hilar or pulmonary lymph nodes) may influence patient survival. The authors retrospectively analyzed the factors that influenced prognosis, including the level of N1 lymph node involvement. The authors used the Tuscan Cancer Registry archives to retrieve records on 2523 patients who had lung tumors diagnosed during the period from 1996 and 1998 in the provinces of Florence and Prato, central Italy. To analyze the survival of patients according to the level of lymph node involvement, the prognoses of patients with nonsmall cell lung cancer who had N1 lymph node status were compared in a population-based case series. Among 112 patients with pathologic N1 status, the following variables were analyzed for their influence on postoperative survival: gender, age, cell type, pathologic tumor status, the number of metastatic lymph nodes, the level of metastatic lymph nodes (hilar or pulmonary), and the type of surgical resection. The 5-year survival rates for patients who had involvement of pulmonary and hilar lymph nodes were 41.2% and 21.8%, respectively (P =.005). A Cox proportional hazards model analysis indicated that the presence of hilar lymph node involvement was an independent prognostic factor. N1 pathologic lymph node status was identified in a combination of subgroups with different prognoses, and the presence of hilar lymph node disease had prognostic significance. This difference in survival may lead to the use of different therapies for these subgroups of patients with pathologic N1 non-small cell lung cancer.

Pathologic N1 non-small cell lung cancer: Correlation between pattern of lymphatic spread and prognosis

Objectives: Patients with N1 non-small cell lung cancer represent a heterogeneous population with varying long-term survivals. Prognosis and pattern of recurrence seem to be particularly affected by the level of lymph node involvement. Methods: From 1990 to 1995, a total of 1954 consecutive patients underwent surgical resection for non-small cell lung cancer: 549 (28%) had ipsilateral pulmonary lymph node metastases (N1). The hospital survivors (n = 535) were reviewed. Three levels of lymph node metastases (hilar, interlobar, and lobar) were identified according to the new Regional Lymph Node Classification for Lung Cancer Staging and differentiated from lymph node involvement on the basis of direct invasion. Results: 1 The overall 5-year survival of patients with N1 disease was 40%. Survival was related in the univariate analysis to T classification, level-type of N1 involvement, number of involved nodes, multilevel involvement, Karnofsky Index, R status, and adjuvant therapy. In the multivariate analysis, only T classification and level-type of N1 involvement clearly showed statistical power (P =.000 and P =.001, respectively). The pattern of cancer relapse according to level-type of N1 involvement differed significantly: hilar N1 disease recurred at distant sites in 41% of patients and locoregionally in 12% of patients, whereas N1 disease by direct invasion occurred in 24% and 17% of patients, respectively (P =.030). Conclusions: Metastases to ipsilateral hilar, interlobar, or both, lymph nodes are associated with a poorer prognosis compared with metastases in intralobar lymph nodes or with lymph node involvement by means of direct invasion. Although surgical resection remains the mainstay of treatment, the high rate of tumor recurrence in both groups mandates further randomized studies with multimodality therapy approaches.J Thorac Cardiovasc Surg 2003;125;543-53