Prevalence of Epidermal Growth Factor Receptor and Programmed Death-Ligand 1 testing in a population-based lung cancer surgical resection cohort from 2018-2022.

BACKGROUND: Biomarker-directed therapy requires biomarker testing. We assessed the patterns of Epidermal Growth Factor Receptor (EGFR) and Programmed Death-Ligand 1 (PDL1) testing in a non-small cell lung cancer (NSCLC) resection cohort. We hypothesized that testing would increase but be unevenly distributed across patient-, provider- and institution-level demographics. METHODS: We examined the population-based Mid-south Quality of Surgical Resection (MS-QSR) cohort of NSCLC resections. We evaluated the proportions receiving EGFR and PDL1 testing before and after approval of biomarker-directed adjuvant therapy (2018-2020 versus 2021-2022). We used association tests and logistic regression to compare factors. RESULTS: From 2018-2022, 1687 patients had NSCLC resection across 12 MS-QSR institutions: 1045 (62%) from 2018-2020; and 642 (38%) from 2021-2022. From 2018-2020 11% had EGFR testing, versus 38% in 2021-2022 (56% in those meeting ADAURA trial inclusion criteria, p<0.0001). From 2018-2020, 8% had PDL1 testing, versus 20% in 2021-2022 (p<0.0001). EGFR testing did not significantly differ by age (p=0.07), sex (p=0.99), race (p=0.33), or smoking history (p=0.28); PDL1 testing did not differ significantly by age (p=0.47), sex (p=0.41), race (p=0.51), or health insurance (p=0.07). Testing was significantly less likely in non-teaching and non-Commission on Cancer-accredited hospitals and after resection by cardiothoracic or general surgeons (versus dedicated thoracic surgeons) (all p<0.05). CONCLUSIONS: EGFR and PDL1 testing increased after approval of biomarker-directed adjuvant therapies. However, testing rates were still suboptimal and differed by institutional and provider-level factors. IMPACT: The association of institutional, pathologist, and surgeon characteristics with differences in testing demonstrate the need for more standardization in testing processes.

Two Interventions on Pathologic Nodal Staging in a Population-Based Lung Cancer Resection Cohort.

BACKGROUND: Despite its prognostic importance, poor pathologic nodal staging of lung cancer prevails. We evaluated the impact of 2 interventions to improve pathologic nodal staging. METHODS: We implemented a lymph node specimen collection kit to improve intraoperative lymph node collection (surgical intervention) and a novel gross dissection method for intrapulmonary node retrieval (pathology intervention) in nonrandomized stepped-wedge fashion, involving 12 hospitals and 7 pathology groups. We used standard statistical methods to compare surgical quality and survival of patients who had neither intervention (group 1), pathology intervention only (group 2), surgical intervention only (group 3), and both interventions (group 4). RESULTS: Of 4019 patients from 2009 to 2021, 50%, 5%, 21%, and 24%, respectively, were in groups 1 to 4. Rates of nonexamination of lymph nodes were 11%, 9%, 0%, and 0% and rates of nonexamination of mediastinal lymph nodes were 29%, 35%, 2%, and 2%, respectively, in groups 1 to 4 (P < .0001). Rates of attainment of American College of Surgeons Operative Standard 5.8 were 22%, 29%, 72%, and 85%; and rates of International Association for the Study of Lung Cancer complete resection were 14%, 21%, 53%, and 61% (P < .0001). Compared with group 1, adjusted hazard ratios for death were as follows: group 2, 0.93 (95% CI, 0.76-1.15); group 3, 0.91 (0.78-1.03); and group 4, 0.75 (0.64-0.87). Compared with group 2, group 4 adjusted hazard ratio was 0.72 (0.57-0.91); compared with group 3, it was 0.83 (0.69-0.99). These relationships remained after exclusion of wedge resections. CONCLUSIONS: Combining a lymph node collection kit with a novel gross dissection method significantly improved pathologic nodal evaluation and survival.

Surgeon Quality and Patient Survival After Resection for Non-Small-Cell Lung Cancer.

PURPOSE: The quality and outcomes of curative-intent lung cancer surgery vary in populations. Surgeons are key drivers of surgical quality. We examined the association between surgeon-level intermediate outcomes differences, patient survival differences, and potential mitigation by processes of care. PATIENTS AND METHODS: Using a baseline population-based surgical resection cohort, we derived surgeon-level cut points for rates of positive margins, nonexamination of lymph nodes, nonexamination of mediastinal lymph nodes, and wedge resections. Applying the baseline cut points to a subsequent cohort from the same population-based data set, we assign surgeons into three performance categories in reference to each metric: 1 (<25th percentile), 2 (25th-75th percentile), and 3 (>75th percentile). The sum of performance scores created three surgeon quality tiers: 1 (4-6, low), 2 (7-9, intermediate), and 3 (10-12, high). We used chi-squared, Wilcoxon-Mann-Whitney, and Kruskal-Wallis tests to compare patient characteristics between the baseline and subsequent cohorts and across surgeon tiers. We applied Cox proportional hazards models to examine the association between patient survival and surgeon performance tier, sequentially adjusting for clinical stage, patient characteristics, and four specific processes. RESULTS: From 2009 to 2021, 39 surgeons performed 4,082 resections across the baseline and subsequent cohorts. Among 31 subsequent cohort surgeons, five were tier 1, five were tier 2, and 21 were tier 3. Tier 1 and 2 surgeons had significantly worse outcomes than tier 3 surgeons (hazard ratio [HR], 1.37; 95% CI, 1.10 to 1.72 and 1.19; 95% CI, 1.00 to 1.43, respectively). Adjustment for specific processes mitigated the surgeon-tiered survival differences, with adjusted HRs of 1.02 (95% CI, 0.8 to 1.3) and 0.93 (95% CI, 0.7 to 1.25), respectively. CONCLUSION: Readily accessible intermediate outcomes metrics can be used to stratify surgeon performance for targeted process improvement, potentially reducing patient survival disparities.

Institution-Level Evolution of Lung Cancer Resection Quality With Implementation of a Lymph Node Specimen Collection Kit.

INTRODUCTION: Lung cancer surgery with a lymph node kit improves patient-level outcomes, but institution-level impact is unproven. METHODS: Using an institutional stepped-wedge implementation study design, we compared lung cancer resection quality between institutions in preimplementation and postimplementation phases of kit deployment and, within implementing institutions, resections without versus with the kit. Benchmarks included rates of nonexamination of lymph nodes, nonexamination of mediastinal lymph nodes, and attainment of American College of Surgeons Operative Standard 5.8. We report institution-level adjusted ORs (aORs) for attaining quality benchmarks. RESULTS: From 2009 to 2020, three preimplementing hospitals had 953 resections; 11 implementing hospitals had 4013 resections, 58% without and 42% with the kit. Quality was better in implementing institutions and with kit cases. Compared with preimplementing institutions, the aOR for nonexamination of lymph nodes was 0.62 (0.49-0.8, p = 0.002), nonexamination of mediastinal lymph nodes was 0.56 (0.47-0.68, p < 0.0001), and attainment of Operative Standard 5.8 was 7.3 (5.6-9.4, p < 0.0001); aORs for kit cases were 0.01 (0.001-0.06), 0.08 (0.06-0.11), and 11.6 (9.9-13.7), respectively (p < 0.0001 for all). Surgical quality was persistently poor in preimplementing institutions but sequentially improved in implementing institutions in parallel with kit adoption. In implementing institutions, resections with the kit had a uniformly high level of quality, whereas nonkit cases had a low level of quality, approximating that of preimplementing institutions. Within implementing institutions, 5-year overall survival was 61% versus 51% after surgery with versus without the kit (p < 0.001). CONCLUSIONS: Surgery with a lymph node specimen collection kit improved institution-level quality of curative-intent lung cancer resection.

Lung Cancer Diagnosed Through Screening, Lung Nodule, and Neither Program: A Prospective Observational Study of the Detecting Early Lung Cancer (DELUGE) in the Mississippi Delta Cohort.

PURPOSE: Lung cancer screening saves lives, but implementation is challenging. We evaluated two approaches to early lung cancer detection-low-dose computed tomography screening (LDCT) and program-based management of incidentally detected lung nodules. METHODS: A prospective observational study enrolled patients in the early detection programs. For context, we compared them with patients managed in a Multidisciplinary Care Program. We compared clinical stage distribution, surgical resection rates, 3- and 5-year survival rates, and eligibility for LDCT screening of patients diagnosed with lung cancer. RESULTS: From 2015 to May 2021, 22,886 patients were enrolled: 5,659 in LDCT, 15,461 in Lung Nodule, and 1,766 in Multidisciplinary Care. Of 150, 698, and 1,010 patients diagnosed with lung cancer in the respective programs, 61%, 60%, and 44% were diagnosed at clinical stage I or II, whereas 19%, 20%, and 29% were stage IV (P = .0005); 47%, 42%, and 32% had curative-intent surgery (P < .0001); aggregate 3-year overall survival rates were 80% (95% CI, 73 to 88) versus 64% (60 to 68) versus 49% (46 to 53); 5-year overall survival rates were 76% (67 to 87) versus 60% (56 to 65) versus 44% (40 to 48), respectively. Only 46% of 1,858 patients with lung cancer would have been deemed eligible for LDCT by US Preventive Services Task Force (USPSTF) 2013 criteria, and 54% by 2021 criteria. Even if all eligible patients by USPSTF 2021 criteria had been enrolled into LDCT, the Nodule Program would have detected 20% of the stage I-II lung cancer in the entire cohort. CONCLUSION: LDCT and Lung Nodule Programs are complementary, expanding access to early lung cancer detection and curative treatment to different-risk populations. Implementing Lung Nodule Programs may alleviate emerging disparities in access to early lung cancer detection.

The Relative Survival Impact of Guideline-Concordant Clinical Staging and Stage-Appropriate Treatment of Potentially Curable Non-Small Cell Lung Cancer.

BACKGROUND: Lung cancer management guidelines strive to improve outcomes. Theoretically, thorough staging promotes optimal treatment selection. We examined the association between guideline-concordant invasive mediastinal nodal staging, guideline-concordant treatment, and non-small cell lung cancer survival. RESEARCH QUESTION: What is the current practice of invasive mediastinal nodal staging for patients with lung cancer in a structured multidisciplinary care environment? Is guideline-concordant staging associated with guideline-concordant treatment? How do they relate to survival? STUDY DESIGN AND METHODS: We evaluated patients with nonmetastatic non-small cell lung cancer diagnosed from 2014 through 2019 in the Multidisciplinary Thoracic Oncology Program of the Baptist Cancer Center, Memphis, Tennessee. We examined patterns of mediastinal nodal staging and stage-stratified treatment, grouping patients into cohorts with guideline-concordant staging alone, guideline-concordant treatment alone, both, or neither. We evaluated overall survival with Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Of 882 patients, 456 (52%) received any invasive mediastinal staging. Seventy-four percent received guideline-concordant staging; guideline-discordant staging decreased from 34% in 2014 to 18% in 2019 (P < .0001). Recipients of guideline-concordant staging were more likely to receive guideline-concordant treatment (83% vs 66%; P < .0001). Sixty-one percent received both guideline-concordant invasive mediastinal staging and guideline-concordant treatment; 13% received guideline-concordant staging alone; 17% received guideline-concordant treatment alone; and 9% received neither. Survival was greatest in patients who received both (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.26-0.63), followed by those who received guideline-concordant treatment alone (aHR, 0.60; 95% CI, 0.36-0.99), and those who received guideline-concordant staging alone (aHR, 0.64; 95% CI, 0.37-1.09) compared with neither (P < .0001, log-rank test). INTERPRETATION: Levels of guideline-concordant staging were high, were rising, and were associated with guideline-concordant treatment selection in this multidisciplinary care cohort. Guideline-concordant staging and guideline-concordant treatment were complementary in their association with improved survival, supporting the connection between these two processes and lung cancer outcomes.

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 < 0.0001). Kit cases were 66% R0 and 29% R-uncertain, compared to 14% R0 and 79% R-uncertain in non-kit cases (p < 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 < 0.0001) and non-examination of mediastinal lymph nodes, 8% vs. 35% (p < 0.0001). With the kit, more R-uncertain cases had examination of stations 7 (43% vs. 22%, p < 0.0001) and 10 (67% vs. 45%, p < 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 < 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.

Trends in Accuracy and Comprehensiveness of Pathology Reports for Resected NSCLC in a High Mortality Area of the United States.

INTRODUCTION: Complete and accurate pathology reports are vital to postoperative prognostication and management. We evaluated the impact of three interventions across a diverse group of hospitals on pathology reports of postresection NSCLC. METHODS: We evaluated pathology reports for patients who underwent curative-intent surgical resection for NSCLC, at 11 institutions within four contiguous Dartmouth Hospital Referral Regions in Arkansas, Mississippi, and Tennessee from 2004 to 2020, for completeness and accuracy, before and after the following three quality improvement interventions: education (feedback to heighten awareness); synoptic reporting; and a lymph node specimen collection kit. We compared the proportion of pathology reports with the six most important items for postoperative management (specimen type, tumor size, histologic type, pathologic [p] T-category, pN-category, margin status) across the following six patient cohorts: preintervention control, postintervention with four different combinations of interventions, and a contemporaneous nonintervention external control. RESULTS: In the postintervention era, the odds of reporting all key items were eight times higher than those in the preintervention era (OR = 8.3, 95 % confidence interval [CI]: 6.7-10.2, p < 0.0001). There were sixfold and eightfold increases in the odds of accurate pT- and pN-category reporting in the postintervention era compared with the preintervention era (pT OR = 5.7, 95 % CI: 4.7-6.9; pN OR = 8.0, 95 % CI: 6.5-10.0, both p < 0.0001). Within the intervention groups, the odds of reporting all six key items, accurate pT category, and accurate pN-category were highest in patients who received all three interventions. CONCLUSIONS: Gaps in the quality of NSCLC pathologic reportage can be identified, quantified, and corrected by rationally designed interventions.

Outcomes After Use of a Lymph Node Collection Kit for Lung Cancer Surgery: A Pragmatic, Population-Based, Multi-Institutional, Staggered Implementation Study.

INTRODUCTION: Suboptimal pathologic nodal staging prevails after curative-intent resection of lung cancer. We evaluated the impact of a lymph node specimen collection kit on lung cancer surgery outcomes in a prospective, population-based, staggered implementation study. METHODS: From January 1, 2014, to August 28, 2018, we implemented the kit in three homogeneous institutional cohorts involving 11 eligible hospitals from four contiguous hospital referral regions. Our primary outcome was pathologic nodal staging quality, defined by the following evidence-based measures: the number of lymph nodes or stations examined, proportions with poor-quality markers such as nonexamination of lymph nodes, and aggregate quality benchmarks including the National Comprehensive Cancer Network criteria. Additional outcomes included perioperative complications, health care utilization, and overall survival. RESULTS: Of 1492 participants, 56% had resection with the kit and 44% without. Pathologic nodal staging quality was significantly higher in the kit cases: 0.2% of kit cases versus 9.8% of nonkit cases had no lymph nodes examined; 3.2% versus 25.3% had no mediastinal lymph nodes; 75% versus 26% attained the National Comprehensive Cancer Network criteria (p < 0.0001 for all comparisons). Kit cases revealed no difference in perioperative complications or health care utilization except for significantly shorter duration of surgery, lower proportions with atelectasis, and slightly higher use of blood transfusion. Resection with the kit was associated with a lower hazard of death (crude, 0.78 [95% confidence interval: 0.61-0.99]; adjusted 0.85 [0.71-1.02]). CONCLUSIONS: Lung cancer surgery with a lymph node collection kit significantly improved pathologic nodal staging quality, with a trend toward survival improvement, without excessive perioperative morbidity or mortality.

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 < 0.001 for all, except pNX rate baseline versus HA). Survival rate was significantly higher for both interventions compared with baseline (p < 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.

Beyond Margin Status: Population-Based Validation of the Proposed International Association for the Study of Lung Cancer Residual Tumor Classification Recategorization.

INTRODUCTION: The International Association for the Study of Lung Cancer's (IASLC's) proposal to recategorize the residual tumor (R) classification for resected NSCLC needs validation. METHODS: Using a 2009 to 2019 population-based multi-institutional NSCLC resection cohort from the United States, we classified resections by Union for International Cancer Control (UICC) and IASLC R criteria and compared the distribution of R classification variables and their survival associations. RESULTS: Of 3361 resections, 95.3% were R0, 4.3% were R1, and 0.4% were R2 by UICC criteria; 33.3% were R0, 60.8% were R-uncertain, and 5.8% were R1/2 by IASLC criteria; 2044 patients (63.8%) migrated from UICC R0 to IASLC R-uncertain. Median survival was not reached, 69 (95% confidence interval [CI]: 64-77), and 25 (95% CI: 18-36) months, respectively, for patients with IASLC R0, R-uncertain, and R1 or R2 resections. Failure to achieve nodal dissection criteria caused 98% of migration to R-uncertainty, metastasis to the highest mediastinal node station, 5.8%. Compared with R0, R-uncertain resections with mediastinal nodes, no mediastinal nodes, and no nodes had adjusted hazard ratios of 1.28 (95% CI: 1.10-1.48), 1.47 (95% CI: 1.24-1.74), and 1.74 (95% CI: 1.37-2.21), respectively, suggesting a dose-response relationship between nodal R-uncertainty and survival. Accounting for mediastinal nodal involvement, the highest mediastinal station involvement was not independently prognostic. The incomplete resection variables were uniformly prognostic. CONCLUSIONS: The proposed R classification recategorization variables were mostly prognostic, except the highest mediastinal nodal station involvement. Further categorization of R-uncertainty by severity of nodal quality deficit should be considered.

Survival Before and After Direct Surgical Quality Feedback in a Population-Based Lung Cancer Cohort.

BACKGROUND: Surgical resection is the main curative modality for non-small cell lung cancer (NSCLC), but variation in the quality of care contributes to suboptimal survival rates. Improving surgical outcomes by eliminating quality deficits is a key strategy for improving population-level lung cancer survival. We evaluated the long-term survival effect of providing direct feedback on institutional performance in a population-based cohort. METHODS: The Mid-South Quality of Surgical Resection cohort includes all NSCLC resections at 11 hospitals in four contiguous Dartmouth Hospital Referral Regions in Arkansas, Mississippi, and Tennessee. We evaluated resections from 2004 to 2013, before and after onset of a benchmarked performance feedback campaign to surgery and pathology teams in 2009. RESULTS: We evaluated 2,206 patients: 56% preintervention (pre-era) and 44% postintervention (post-era). Preoperative positron emission tomography/computed tomography (46% vs 82%, p < 0.0001), brain scans (6% vs 21%, p < 0.0001), and bronchoscopy (8% vs 27%, p < 0.0001) were more frequently used in the post-era. Patients had 5-year survival of 47% (44% to 50%) in the pre-era compared with 53% (50% to 56%) in the post-era (p = 0.0028). The post-era had an adjusted hazard ratio of 0.85 (95% confidence interval [CI], 0.75 to 0.97; p = 0.0158) compared with the pre-era. This differed by extent of resection (p = 0.0113): compared with the pre-era, the post-era adjusted hazard ratio was 0.49 (95% CI, 0.33 to 0.72) in pneumonectomy, 0.91 (95% CI, 0.79 to 1.05) in lobectomy/bilobectomy, and 0.85 (95% CI, 0.63 to 1.15) in segmentectomy/wedge resections. CONCLUSIONS: Overall survival after surgical resection improved significantly in a high lung cancer mortality region of the United States. Reasons may include better selection of patients for pneumonectomy and more thorough staging.