Survival After Mediastinal Node Dissection, Systematic Sampling, or Neither for Early Stage NSCLC

Introduction: The American College of Surgeons Oncology Group Z0030 found no survival difference between patients with early stage NSCLC who had mediastinal nodal dissection or systematic sampling. However, a meta-analysis of 1980 patients in five randomized controlled trials from 1989 to 2007 associated better survival with nodal dissection. We tested the survival impact of the extent of nodal dissection in curative-intent resections for early stage NSCLC in a population-based observational cohort. Methods: Resections for clinical T1 or T2, N0 or nonhilar N1, M0 NSCLC in four contiguous United States Hospital Referral Regions from 2009 to 2019 were categorized into mediastinal nodal dissection, systematic sampling, and “neither” on the basis of of the evaluation of lymph node stations. We compared demographic and clinical characteristics, perioperative complication rates, and survival after assessing statistical interactions and confounding. Results: Of the 1942 eligible patients, 18% had nodal dissection, 6% had systematic sampling, and 75% had an intraoperative nodal evaluation that met neither standard. In teaching hospitals, nodal dissection was associated with a lower hazard of death than “neither” resections (0.57 [95% confidence interval: 0.41–0.79]) but not systematic sampling (0.74 [0.40–1.37]) after adjusting for multiple comparisons. There was no significant difference in hazard ratios at nonteaching institutions (p \u3e 0.3 for all comparisons). Perioperative complication rates were not significantly worse after mediastinal nodal dissection or systematic sampling, compared with “neither,” (p \u3e 0.1 for all comparisons). Conclusions: In teaching institutions, mediastinal nodal dissection was associated with superior survival over less-comprehensive pathologic nodal staging. There was no survival difference between teaching and nonteaching institutions, a finding that warrants further investigation

Association of pathologic nodal staging quality with survival among patients with non-small cell lung cancer after resection with curative intent

IMPORTANCE Pathologic nodal stage is the most significant prognostic factor in resectable non-small cell lung cancer (NSCLC). The International Association for the Study of Lung Cancer NSCLC staging project revealed intercontinental differences in N category-stratified survival. These differencesmay indicate differences not only in cancer biology but also in the thoroughness of the nodal examination. OBJECTIVE To determine whether survival was affected by sequentially more stringent definitions of pN staging quality in a cohort of patients with NSCLC after resection with curative intent. DESIGN This observational study used the Mid-South Quality of Surgical Resection cohort, a population-based database of lung cancer resections with curative intent. A total of 2047 consecutive patients who underwent surgical resection at 11 hospitals with at least 5 annual lung cancer resections in 4 contiguous US Dartmouth hospital referral regions in northern Mississippi, eastern Arkansas, and western Tennessee (\u3e90% of the eligible population) were included. Resections were performed from January 1, 2009, through January 25, 2016. Survival was evaluated with the Kaplan-Meier method and Cox proportional hazards models. EXPOSURES Eight sequentially more stringent pN staging quality strata included the following: All patients (group 1); those with complete resections only (group 2); those with examination of at least 1 mediastinal lymph node (group 3); those with examination of at least 10 lymph nodes (group 4); those with examination of at least 3 hilar or intrapulmonary and at least 3 mediastinal lymph nodes (group 5); those with examination of at least 10 lymph nodes, including at least 1 mediastinal lymph node (group 6); those with examination of at least 1 hilar or intrapulmonary and at least 3 mediastinal nodal stations (group 7); and those with examination of at least 1 hilar or intrapulmonary lymph node, at least 10 total lymph nodes, and at least 3 mediastinal nodal stations (group 8). MAIN OUTCOMES AND MEASURES N category-stratified overall survival. RESULTS Of the total 2047 patients (1046 men [51.1%] and 1001 women [48.9%]; mean [SD] age, 67.0 [9.6] years) included in the analysis, the eligible analysis population ranged from 541 to 2047, depending on stringency. Sequential improvement in the N category-stratified 5-year survival of pN0 and pN1 tumors was found from the least stringent group (0.63 [95% CI, 0.59-0.66] for pN0 vs 0.46 [95%CI, 0.38-0.54] for pN1) to the most stringent group (0.71 [95%CI, 0.60-0.79] for pN0 vs 0.60 [95%CI, 0.43-0.73] for pN1). The pN1 cohorts with 3 or more mediastinal nodal stations examined had the most striking survival improvements. More stringently defined mediastinal nodal examination was associated with better separation in survival curves between patients with pN1 and pN2 tumors. CONCLUSIONS AND RELEVANCE The prognostic value of pN stratification depends on the thoroughness of examination. Differences in thoroughness of nodal stagingmay explain a large proportion of intercontinental survival differences. More thorough nodal examination practice must be disseminated to improve the prognostic value of the TNM staging system. Future updates of the TNM staging system should incorporate more quality restraints

Rurality, Stage-Stratified Use of Treatment Modalities, and Survival of Non-small Cell Lung Cancer

Background: To eliminate them, non-small cell lung cancer (NSCLC) care and outcome disparities need to be better understood. Research Question: How does rurality interact with NSCLC care and outcome disparities? Study Design and Methods: We examined guideline-concordant use of active treatment for NSCLC across five institutions in one community-based health care system spanning 44% of the Delta Regional Authority catchment area from 2011 to 2017. Institution- and patient-level rurality were based on Rural-Urban Commuting Area codes. Chi-squared, F-tests, and logistic regressions were used to analyze differences across institutions and rurality; survival was examined using log-rank tests and Cox regression. Results: Of 6,259 patients, 47% resided in rural areas; two of five institutions were rurally located and provided care for 20% of patients. Compared with rural residents at rural institutions, urban and rural residents attending urban institutions were more likely to receive stage-preferred treatment: OR 1.68 (95%CI, 1.44-1.96), and 1.33 (1.11-1.61), respectively, after adjusting for insurance, age, and clinical stage. Urban and rural residents attending urban institutions had a lower hazard of death compared with rural residents attending rural institutions: hazard ratio (HR) 0.69 (0.64-0.75) and 0.61 (0.55-0.67), respectively. Among recipients of stage-preferred treatment, care at urban institutions remained less hazardous: HR 0.7 (0.63-0.79). When further stratified by stage, care for late-stage patients at urban institutions remained less hazardous: HR 0.8 (0.71-0.91). Interpretation: Rurality-associated treatment and survival disparities were present at the patient and institution levels, but the institution-level disparity was greater. Rural residents receiving care at urban institutions had similar outcomes to urban residents receiving care at urban hospitals. To overcome rurality-associated NSCLC survival disparity, interventions should preferentially target the institution level, including expanding access to higher-quality guideline-concordant care

Invasive mediastinal staging for resected non–small cell lung cancer in a population-based cohort

Objectives: Invasive mediastinal nodal staging is recommended before curative-intent resection in patients with non–small cell lung cancer deemed at risk for mediastinal lymph node involvement. We evaluated the use and survival effect of preoperative invasive mediastinal nodal staging in a population-based non–small cell lung cancer cohort. Methods: We analyzed all curative-intent resections for non–small cell lung cancer from 2009 to 2018 in 11 hospitals in 4 contiguous Dartmouth Hospital Referral Regions, comparing patients who did not have invasive mediastinal nodal staging with those who did. Results: Preoperative invasive nodal staging was used in 22% of 2916 patients, including mediastinoscopy only in 13%, minimally invasive procedures only in 6%, and both approaches in 3%. Sixty-three percent of patients at risk for nodal disease (tumor size ≥3.0 cm/T2-T4; N1-N3 by computed tomography or positron-emission tomography-computerized tomography criterion) did not undergo invasive staging; among those who did not have invasive testing, 47% had at least 1 of the 3 clinical indications. Mediastinoscopy yielded a median of 3 lymph nodes and 2 nodal stations; 17% of mediastinoscopies and 31% of endobronchial ultrasound procedures yielded no lymph node material. Patients not invasively staged were more likely to have no nodes (6% vs 2%; P \u3c .0001) and no mediastinal nodes (20% vs 11%; P \u3c .0001) examined at surgery. Invasive staging was associated with significantly better survival (P = .0157). Conclusions: More than a decade after the 2001 American College of Surgeons Patient Care Evaluation report, preoperative invasive nodal staging remains underused and of variable quality, but was associated with survival benefit in high-risk patients

Comparative Effectiveness of a Lymph Node Collection Kit Versus Heightened Awareness on Lung Cancer Surgery Quality and Outcomes

Introduction: The adverse prognostic impact of poor pathologic nodal staging has stimulated efforts to heighten awareness of the problem through guidelines, without guidance on processes to overcome it. We compared heightened awareness (HA) of nodal staging quality versus a lymph node collection kit. Methods: We categorized curative-intent lung cancer resections from 2009 to 2020 in a population-based, nonrandomized stepped-wedge implementation study of both interventions, into preintervention baseline, HA, and kit subcohorts. We used differences in proportion and hazard ratios across the subcohorts to estimate the effect of the interventions on poor quality (nonexamination of nodes [pNX] or nonexamination of mediastinal lymph nodes) and attainment of quality recommendations of the National Comprehensive Cancer Network, the Commission on Cancer, and the proposed complete resection definition of the International Association for the Study of Lung Cancer across the three cohorts. Results: Of 3734 resections, 39% were preintervention, 40% kit, and 21% HA cases. Cohort proportions were the following: pNX, 11% (baseline) versus 0% (kit) versus 9% (HA); nonexamination of mediastinal lymph nodes, 27% versus 1% versus 22%; Commission on Cancer benchmark attainment, 14% versus 77% versus 30%; International Association for the Study of Lung Cancer-defined complete resection, 11% versus 58% versus 24%; National Comprehensive Cancer Network attainment, 23% versus 79% versus 35% (p \u3c 0.001 for all, except pNX rate baseline versus HA). Survival rate was significantly higher for both interventions compared with baseline (p \u3c 0.0001). Conclusions: Resections with HA or the kit significantly improved surgical quality and outcomes, but the kit was more effective. We propose to conduct a prospective, institutional cluster-randomized clinical trial comparing both interventions

Impact of a Lymph Node Specimen Collection Kit on the Distribution and Survival Implications of the Proposed Revised Lung Cancer Residual Disease Classification: A Propensity-Matched Analysis

Importance: The International Association for the Study of Lung Cancer (IASLC) has proposed a revision of the residual disease (R-factor) classification, to R0, ‘R-uncertain’, R1 and R2. We previously demonstrated longer survival after surgical resection with a lymph node specimen collection kit, and now evaluate R-factor redistribution as the mechanism of its survival benefit. Objective: We retrospectively evaluated surgical resections for lung cancer in the population-based observational ‘Mid-South Quality of Surgical Resection’ cohort from 2009-2019, including a full-cohort and propensity-score matched analysis. Results: Of 3,505 resections, 34% were R0, 60% R-uncertain, and 6% R1 or R2. The R0 percentage increased from 9% in 2009 to 56% in 2019 (p \u3c 0.0001). Kit cases were 66% R0 and 29% R-uncertain, compared to 14% R0 and 79% R-uncertain in non-kit cases (p \u3c 0.0001). Compared with non-kit resections, kit resections had 12.3 times the adjusted odds of R0 versus R-uncertainty. Of 2,100 R-uncertain resections, kit cases had lower percentages of non-examination of lymph nodes, 1% vs. 14% (p \u3c 0.0001) and non-examination of mediastinal lymph nodes, 8% vs. 35% (p \u3c 0.0001). With the kit, more R-uncertain cases had examination of stations 7 (43% vs. 22%, p \u3c 0.0001) and 10 (67% vs. 45%, p \u3c 0.0001). The adjusted hazard ratio (aHR) for kit cases versus non-kit cases was 0.75 (confidence interval [CI]: 0.66–0.85, p \u3c 0.0001). In 2,100 subjects with R-uncertain resections, kit cases had an aHR of 0.79 versus non-kit cases ([CI: 0.64–0.99], p=0.0384); however, in the 1,199 R0 resections the survival difference was not significant (aHR: 0.85[0.68–1.07], p = 0.17). Conclusions and Relevance: A lymph node kit increased overall survival by increasing R0, reducing the probability of R-uncertain resections, and diminishing extreme R-uncertainty