Pneumonectomy for non-small cell lung cancer. A National Cancer Database analysis of geographic and temporal trends, outcomes, and associated factors.

BACKGROUND: The circumstances under which pneumonectomy should be performed are controversial. This study aims to investigate national trends in pneumonectomy use to determine which patients, in what geographic areas, and under what clinical circumstances pneumonectomy is performed in the United States. METHODS: We queried the National Cancer Database and included all patients undergoing anatomic surgical resection for non-small cell lung cancer (2015-2020). The association between demographic and clinical factors and the use of pneumonectomy were investigated. RESULTS: Who: A total of 128,421 patients were identified, of whom 738 (0.6%) underwent pneumonectomy. Those patients were younger (median 65 vs 68 years, P < .001), more often male (59.9% vs 44.9%, P < .001), more likely to be below median income level (44.2% vs 38.6%, P = .002), and more likely to have lower education indicators (53% vs 48.6%, P = .02) than those who underwent other anatomic resections. Notably, there was a decreasing trend in pneumonectomy use during the study period (0.9% down to 0.4%, P < .001). Where: Patients undergoing pneumonectomy were less likely to live in metropolitan areas (77.9% vs 81.7%, P = .008) and to live closer (<12 miles) to their treating facility (45% vs 49%, P = .02). Regional geographic differences also were identified (P < .001). Why: Patients who underwent pneumonectomy were more likely to have received neoadjuvant therapy (20.6% vs 5.3%, P < .001), to be clinically N (+) (39.3% vs 12.3%, P < .001), and to have more advanced tumors (cT3-4: 46.3% vs 11.3%, P < .001). CONCLUSION: Although primarily driven by advanced oncologic features, socioeconomic and geographic factors also were associated independently with the use of pneumonectomy. Standardizing pneumonectomy indications nationwide is crucial to prevent widening outcome gaps for patients with lung cancer.

Resection of the Primary Tumor and Survival in Patients with Single-Site Synchronous Oligometastatic Non-Small Cell Lung Cancer: Propensity-Matched Analysis of the National Cancer Database.

BACKGROUND: Local therapy for the primary tumor is postulated to remove resistant cancer cells as well as immunosuppressive cells from the tumor microenvironment, potentially improving response to systemic therapy (ST). We sought to determine whether resection of the primary tumor was associated with overall survival (OS) in a multicentric cohort of patients with single-site synchronous oligometastatic non-small cell lung cancer. STUDY DESIGN: Using the National Cancer Database (2018 to 2020), we evaluated patients with clinical stage IVA disease who received ST and stratified the cohort based on receipt of surgery for the primary tumor (S). We used multivariable and propensity score-matched analysis to study factors associated with S (logistic regression) and OS (Cox regression and Kaplan-Meier), respectively. RESULTS: Among 12,215 patients identified, 2.9% (N = 349) underwent S and 97.1% (N = 11,886) ST (chemotherapy or immunotherapy) without surgery. Patients who underwent S were younger, more often White, had higher income levels, were more likely to have private insurance, and were more often treated at an academic facility. Among those who received S, 22.9% (N = 80) also underwent resection of the distant metastatic site. On multivariable analysis, metastasis to bone, N+ disease, and higher T-stages were independently associated with less S. On Cox regression, S and resection of the metastatic site were associated with improved survival (hazard ratio 0.67, 95% CI 0.56 to 0.80 and hazard ratio 0.80, 95% CI 0.72 to 0.88, respectively). After propensity matching, OS was improved in patients undergoing S (median 36.8 vs 20.8 months, log-rank p < 0.001). CONCLUSIONS: Advances in ST for non-small cell lung cancer may change the paradigm of eligibility for surgery. This study demonstrates that surgical resection of the primary tumor is associated with improved OS in selected patients with single-site oligometastatic disease.

Minimally invasive surgery for clinical T4 non-small-cell lung cancer: national trends and outcomes.

OBJECTIVES: Recent randomized data support the perioperative benefits of minimally invasive surgery (MIS) for non-small-cell lung cancer (NSCLC). Its utility for cT4 tumours remains understudied. We, therefore, sought to analyse national trends and outcomes of minimally invasive resections for cT4 cancers. METHODS: Using the 2010-2019 National Cancer Database, we identified patients with cT4N0-1 NSCLC. Patients were stratified by surgical approach. Multivariable logistic analysis was used to identify factors associated with use of a minimally invasive approach. Groups were matched using propensity score analysis to evaluate perioperative and survival end points. RESULTS: The study identified 3715 patients, among whom 64.1% (n = 2381) underwent open resection and 35.9% (n = 1334) minimally invasive resection [robotic-assisted in 31.5% (n = 420); and video-assisted in 68.5% (n = 914)]. Increased MIS use was noted among patients with higher income [≥$40 227, odds ratio (OR) 1.24; 95% confidence interval (CI) 1.01-1.51] and those treated at academic hospitals (OR 1.25; 95% CI 1.07-1.45). Clinically node-positive patients (OR 0.68; 95% CI 0.55-0.83) and those who underwent neoadjuvant therapy (OR 0.78; 95% CI 0.65-0.93) were less likely to have minimally invasive resection. In matched groups, patients undergoing MIS had a shorter median length of stay (5 vs 6 days, P < 0.001) and no significant differences between 30-day readmissions or 30/90-day mortality. MIS did not compromise overall survival (log-rank P = 0.487). CONCLUSIONS: Nationally, the use of minimally invasive approaches for patients with cT4N0-1M0 NSCLC has increased substantially. In these patients, MIS is safe and does not compromise perioperative outcomes or survival.

Association of socioeconomic factors with the receipt of neoadjuvant therapy for patients with non-small cell lung cancer.

BACKGROUND: Neoadjuvant therapy (NT) will be increasingly used for patients with non-small cell lung cancer (NSCLC), particularly given the recent approval of neoadjuvant chemoimmunotherapy. Several barriers may prevent the uptake of NT and should be identified and addressed. We queried the National Cancer Database (NCDB) to determine predictors of the use of NT. METHODS: Using the NCDB (2006-2019), we identified 80,707 patients who underwent surgery for clinical stage II and III NSCLC. Sociodemographic and clinical factors were reviewed, and univariable and multivariable analyses were performed to identify associations with the uptake of NT. In propensity score-matched groups, survival was determined using the Kaplan-Meier method. RESULTS: Among 80,707 eligible patients, 17,262 (21.4%) received NT. Clinical stage and node positivity were associated with receipt of NT. On multivariable analysis, factors associated with lower rates of NT included black race (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.67-0.90), Charlson Comorbidity Index ≥2 (OR, 0.75; 95% CI, 0.67-0.85), Medicaid/Medicare insurance (OR, 0.82; 95% CI, 0.75-0.90), lower income level (OR, 0.79; 95% CI, 0.71-0.87), and treatment at a community center (OR, 0.81; 95% CI, 0.67-0.96). In an exploratory analysis, those patients who received NT had longer 5-year overall survival compared with those who did not (48.3% vs 46.0%; P < .001). CONCLUSIONS: Rates of NT are relatively low for patients with clinical stage II/III NSCLC treated prior to recent chemoimmunotherapy trials. Socioeconomic barriers to the uptake of NT include race, insurance status, income, and area of residence. As NT becomes more widely offered, accessibility for vulnerable populations must be assured.

The Effect of Neoadjuvant Therapy on Esophagectomy for cT2N0M0 Esophageal Adenocarcinoma.

BACKGROUND: For cT2N0M0 esophageal adenocarcinomas, the effects of neoadjuvant chemoradiotherapy (NT) on surgical outcomes and the oncological benefits to the patients are debatable. In this study, we investigated the optimal management for cT2N0M0 adenocarcinoma (1) assessing the perioperative impact of NT on esophagectomy and (2) evaluating the oncologic effect of NT in a homogeneous group of patients with clinical stage IIA. We hypothesized that NT does not negatively affect perioperative outcomes and provides an oncologic benefit to selected patients with cT2N0M0 disease. METHODS: The National Cancer Database was queried (2010-2019) for patients with cT2N0M0 esophageal adenocarcinoma undergoing esophagectomy. After propensity-matching to adjust for differences in patient and tumor characteristics, we compared postoperative outcomes (logistic regression) and survival (Kaplan-Meier and Cox regression) among those who underwent NT vs upfront surgery (S). RESULTS: This study included 3413 patients, of whom 2359 (69%) received NT, and 1054 (31%) S. In contrast to those who underwent S, in the matched cohort, patients treated with NT had comparable conversion rates (8% vs11.1%, p = 0.06), length of stay (9 vs 10 days, p = 0.078), unplanned readmission (5.4% vs 8.8%, p = 0.109), and 30- (3.9% vs 3.7%, p = 0.90) and 90-day mortality (5.7% vs 4.7%, p = 0.599). In addition, NT associated with improved survival in patients with cT2N0M0 tumors > 5 cm (HR 0.30, 95% CI 0.17-0.36). CONCLUSIONS: NT does not appear to increase technical complexity or to adversely affect postoperative outcomes after esophagectomy. Furthermore, minimally invasive esophagectomy is feasible following NT, with comparable conversion rates to those who had upfront surgery. Lastly, NT was selectively associated with improved survival in patients with cT2N0M0 esophageal cancer.

Sublobar resection is associated with less lymph nodes examined and lower delivery of adjuvant therapy in patients with 1.5- to 2.0-cm clinical IA2 non-small-cell lung cancer: a retrospective cohort study.

OBJECTIVES: CALGB140503, in which nodal sampling was mandated, reported non-inferior disease-free survival for patients undergoing sublobar resection (SLR) compared to lobectomy (L). Outside of trial settings, the adequacy of lymphadenectomy during SLR has been questioned. We sought to evaluate whether SLR is associated with suboptimal lymphadenectomy, differences in pathologic upstaging and survival in patients with 1.5- to 2.0-cm tumours using real-world data. MATERIALS AND METHODS: Using the National Cancer Database(2018-2019), we evaluated patients with 1.5- to 2.0-cm non-small-cell lung cancer who underwent resection (sublobar versus lobectomy). We studied factors associated with nodal upstaging (logistic regression) and survival (Cox regression and Kaplan-Meier method) after propensity matching to adjust for differences among groups. RESULTS: Among 3196 patients included, SLR was performed in 839 (26.3%) (of which 588 were wedge resections) and L was performed in 2357 (73.7%) patients. More patients undergoing SLR (21.7%) compared to L (2.1%) had no lymph nodes sampled (P < 0.001). Those undergoing SLR had fewer total lymph nodes examined (4 vs 11, P < 0.001) and were less likely to have pathologic nodal metastases (4.7% vs 9%, P < 0.001) compared to L. Multivariable analysis identified L [adjusted odds ratio (aOR) 2.21, 95% confidence interval, 1.47-3.35] to be independently associated with pathologic N+ disease. Overall survival was not associated with the type of procedure but was significantly decreased in those with N+ disease. CONCLUSIONS: Despite comparable overall survival to L, SLR is associated with suboptimal lymphadenectomy in patients with 1.5-2.0 cm non-small-cell lung cancer. Surgeons should be careful to perform adequate lymphadenectomy when performing SLR to mitigate nodal under-staging and to identify appropriate patients for systemic therapy.

Is underutilization of adjuvant therapy in resected non-small-cell lung cancer associated with socioeconomic disparities?

OBJECTIVES: Although adjuvant systemic therapy (AT) has demonstrated improved survival in patients with resected non-small-cell lung cancer (NSCLC), it remains underutilized. Recent trials demonstrating improved outcomes with adjuvant immunotherapy and targeted treatment imply that low uptake of systemic therapy in at-risk populations may widen existing outcome gaps. We, therefore, sought to determine factors associated with the underutilization of AT. METHODS: The National Cancer Database (2010-2018) was queried for patients with completely resected stage II-IIIA NSCLC and stratified based on the receipt of AT. Logistic regression was used to identify factors associated with AT delivery. The Kaplan-Meier method was applied to estimate survival after propensity-matching to adjust for confounders. RESULTS: Of 37 571 eligible patients, only 20 616 (54.9%) received AT. While AT rates increased over time, multivariable analysis showed that older age [adjusted odds ratio (aOR) 0.45, 95% confidence interval (CI) 0.43-0.47], male sex (aOR 0.88, 95% CI 0.85-0.93) and multiple comorbidities (aOR 0.86, 95% CI: 0.81-0.91) were associated with decreased AT. Socioeconomic factors were additionally associated with underutilization, including public insurance (aOR 0.70, 95% CI: 0.66-0.74), lower education indicators (aOR 0.93, 95% CI: 0.88-0.97) and living more than 10 miles from a treatment facility (aOR 0.89, 95% CI: 0.85-0.93). After propensity matching, receipt of adjuvant therapy was associated with improved overall survival (median 76.35 vs 47.57 months, P ≤ 0.001). CONCLUSIONS: AT underutilization in patients with resected stage II-III NSCLC is associated with patient, institutional and socioeconomic factors. It is critical to implement measures to address these inequities, especially in light of newer adjuvant immunotherapy and targeted therapy treatment options which are expected to improve survival.

Building a Lung Cancer Screening Program.

Lung cancer screening improves lung-cancer specific and potentially overall survival; however, uptake rates are concerningly low. Several barriers to screening exist and require a systemic approach to address. The authors describe their approach toward building a centralized lung cancer screening program at an urban academic center along with lessons learned. To this end, the identification of involved stakeholders, evaluation of community barriers and needs, optimization of the electronic health system, and implementation of system of standardized follow-up for patients are processes for consideration. Perhaps most important to undertaking this endeavor is the need to customize each program and maintain adaptability.

Underutilization of Systemic Therapy in Patients With NSCLC Undergoing Pneumonectomy: A Missed Opportunity for Survival.

Introduction: Recent trials have reported promising results with the addition of immunotherapy to chemotherapy for patients with locally advanced NSCLC, but in practice, the proportion of patients who receive systemic therapy (ST) has historically been low. Underutilization of ST may be particularly apparent in patients undergoing pneumonectomy, in whom the physiologic insult and surgical complications may preclude adjuvant therapy (ADJ). We, therefore, evaluated the use of ST for patients with NSCLC undergoing pneumonectomy. Methods: We queried the National Cancer Database, including all patients with NSCLC who underwent pneumonectomy between 2006 and 2018. Logistic regression was used to identify associations with ST and neo-ADJ (NEO). Overall survival was compared after propensity score matching (1:1) patients undergoing ST to those undergoing surgery alone using Kaplan-Meier and Cox regression methods. Results: A total of 2619 patients were identified. Among these, 12% received NEO, 43% received ADJ, and 45% surgery alone. Age younger than 65 years (adjusted odds ratio [aOR] = 1.53, 95% confidence interval; [CI]: 1.10-2.11), Asian ethnicity (aOR = 2.68, 95% CI: 1.37-5.23), treatment at a high-volume center (aOR = 1.39, 95% CI: 1.06-1.81), and private insurance (aOR = 1.42, 95% CI: 1.05-1.94) were associated with NEO, whereas age younger than 65 years (aOR = 1.95, 95% CI: 1.61-2.38), comorbidity index less than or equal to 1 (aOR = 1.66, 95% CI: 1.29-2.16), and private insurance (aOR = 1.47, 95% CI: 1.20-1.80) were associated with any ST. In the matched cohort, ST was associated with better survival than surgery (adjusted hazard ratio = 0.67, 95% CI: 0.58-0.78). Conclusions: A high proportion of patients who undergo pneumonectomy do not receive ST. Patient and socioeconomic factors are associated with the receipt of ST. Given its survival benefit, emphasis should be placed on multimodal treatment strategies, perhaps with greater consideration given to neoadjuvant approaches.

Operative Time is Associated With Postoperative Complications After Pulmonary Lobectomy.

OBJECTIVE: To investigate the association between operative time and postoperative outcomes. BACKGROUND: The association between operative time and morbidity after pulmonary lobectomy has not been characterized fully. METHODS: Patients who underwent pulmonary lobectomy for primary lung cancer at our institution from 2010 to 2018 were reviewed. Exclusion criteria included clinical stage ≥IIb disease, conversion to thoracotomy, and previous ipsilateral lung treatment. Operative time was measured from incision to closure. Relationships between operative time and outcomes were quantified using multivariable mixed-effects models with surgeon-level random effects. RESULTS: In total, 1651 patients were included. The median age was 68 years (interquartile range, 61-74), and 63% of patients were women. Median operative time was 3.2 hours (interquartile range, 2.7-3.8) for all cases, 3.0 hours for open procedures, 3.3 hours for video-assisted thoracoscopies, and 3.3 hours for robotic procedures ( P =0.0002). Overall, 488 patients (30%) experienced a complication; 77 patients (5%) had a major complication (grade ≥3), and 5 patients (0.3%) died within 30 days of discharge. On multivariable analysis, operative time was associated with higher odds of any complication [odds ratio per hour, 1.37; 95% confidence interval (CI), 1.20-1.57; P <0.0001] and major complication (odds ratio per hour, 1.41; 95% CI, 1.21-1.64; P <0.0001). Operative time was also associated with longer hospital length of stay (ß, 1.09; 95% CI, 1.04-1.14; P =0.001). CONCLUSIONS: Longer operative time was associated with worse outcomes in patients who underwent lobectomy. Operative time is a potential risk factor to consider in the perioperative phase.

Implementing a High-Value Care Discharge Protocol in Patients Undergoing CABG Reduces Readmission.

BACKGROUND: Readmission after coronary artery bypass grafting (CABG) is associated with adverse outcomes and increased cost. We evaluated the impact of a high-value care discharge protocol on readmission, length of stay (LOS), and discharge destination in patients undergoing isolated CABG. METHODS: In 2016, a comprehensive, patient-centered discharge protocol was implemented. A nurse practitioner was the fulcrum of this program, which focused on improving health literacy, disease management, and rigorous follow-up. All patients undergoing isolated CABG between 2012 and 2019 were retrospectively analyzed with regard to 30-day readmission, LOS, and discharge disposition. Differences were analyzed by Mann-Whitney, chi-square, and t tests. Analyses were repeated using propensity matching. RESULTS: A total of 910 consecutive patients undergoing isolated CABG were included in the analyses: 353 preprotocol and 557 postprotocol. Preprotocol patients had a readmission rate of 14.4% (n = 51), compared with 6.8% (n = 38) in the postprotocol patients (P < .001). Median postoperative LOS before implementation was 6 (interquartile range, 5-8) days compared with 5 (interquartile range, 4-6) days postimplementation (P < .001). Postimplementation, a higher proportion of patients were discharged to home compared with a skilled nursing facility (82.7% [n = 461] vs 73.9% [n = 261]; P = .002). After propensity matching, 298 well-balanced patients were included for analysis and these significant reductions in LOS, readmission, and discharge destination persisted. CONCLUSIONS: Implementation of a new discharge protocol was significantly associated with reduced readmission and LOS, along with higher rates of discharge to home in isolated CABG patients. Importantly, the results were sustainable and did not require additional resources, delivering high-value care.

Performance Comparison Between SURPAS and ACS NSQIP Surgical Risk Calculator in Pulmonary Resection.

BACKGROUND: Accurate preoperative risk assessment is critical for informed decision making. The Surgical Risk Preoperative Assessment System (SURPAS) and the National Surgical Quality Improvement Program (NSQIP) Surgical Risk Calculator (SRC) predict risks of common postoperative complications. This study compares observed and predicted outcomes after pulmonary resection between SURPAS and NSQIP SRC. METHODS: Between January 2016 and December 2018, 2514 patients underwent pulmonary resection and were included. We entered the requisite patient demographics, preoperative risk factors, and procedural details into the online NSQIP SRC and SURPAS formulas. Performance of the prediction models was assessed by discrimination and calibration. RESULTS: No statistically significant differences were found between the 2 models in discrimination performance for 30-day mortality, urinary tract infection, readmission, and discharge to a nursing or rehabilitation facility. The ability to discriminate between a patient who will develop a complication and a patient who will not was statistically indistinguishable between NSQIP and SURPAS, except for renal failure. With a C index closer to 1.0, the NSQIP performed significantly better than the SURPAS SRC in discriminating risk of renal failure (C index, 0.798 vs 0.694; P = .003). The calibration curves of predicted and observed risk for each model demonstrate similar performance with a tendency toward overestimation of risk, apart from renal failure. CONCLUSIONS: Overall, SURPAS and NSQIP SRC performed similarly in predicting outcomes for pulmonary resections in this large, single-center validation study with moderate to good discrimination of outcomes. Notably, SURPAS uses a smaller set of input variables to generate the preoperative risk assessment. The addition of thoracic-specific input variables may improve performance.

External Validation of Surgical Risk Preoperative Assessment System in Pulmonary Resection.

BACKGROUND: Accurate preoperative risk assessment is necessary for informed decision making for patients and surgeons. Several preoperative risk calculators are available but few have been examined in the general thoracic surgical patient population. The Surgical Risk Preoperative Assessment System (SURPAS), a risk-assessment tool applicable to a wide spectrum of surgical procedures, was developed to predict the risks of common adverse postoperative outcomes using a parsimonious set of preoperative input variables. We sought to externally validate the performance of SURPAS for postoperative complications in patients undergoing pulmonary resection. METHODS: Between January 2016 and December 2018, 2514 patients underwent pulmonary resection at our center. Using data from our institution's prospectively maintained database, we calculated the predicted risks of 12 categories of postoperative outcomes using the latest version of SURPAS. Performance of SURPAS against observed patient outcomes was assessed by discrimination (concordance index) and calibration (calibration curves). RESULTS: The discrimination ability of SURPAS was moderate across all outcomes (concordance indices, 0.640 to 0.788). Calibration curves indicated good calibration for all outcomes except infectious and cardiac complications, discharge to a location other than home, and mortality (all overestimated by SURPAS). CONCLUSIONS: SURPAS demonstrates outcomes for pulmonary resections with reasonable predictive ability. Discretion should be applied when assessing risk for postoperative infectious and cardiac complications, discharge to a location other than home, and mortality. Although the parsimonious nature of SURPAS is one of its strengths, its performance might be improved by including additional factors known to influence outcomes after pulmonary resection, such as sex and pulmonary function.

BRMS1 Expression in Surgically Resected Lung Adenocarcinoma Predicts Future Metastases and Is Associated with a Poor Prognosis.

INTRODUCTION: Expression of breast cancer metastasis suppressor 1 gene (BRMS1) is decreased in NSCLC cells and tumors. We hypothesized that intratumoral breast cancer metastasis suppressor 1 (BRMS1) expression is associated with lung adenocarcinoma (LUAD) histologic subtypes and overall survival (OS) and disease-free survival (DFS) in patients undergoing resection for early-stage LUAD. METHODS: Patients (N = 1030) who underwent complete resection for LUAD with tissue available for histologic evaluation were identified. Tissue microarrays were constructed, and immunostaining was performed and scored for intensity of BRMS1 expression. OS and DFS were estimated (by the Kaplan-Meier method) and compared between groups (by the log-rank test), stratified by stage. Hazard ratios (HRs) for hazard of death and recurrence were estimated using univariable and multivariable Cox proportional hazards models. OS and DFS nomograms were created, and model performance was examined. RESULTS: Intratumoral BRMS1 expression was high in 632 patients (61%) and low in 398 (39%). Low BRMS1 expression was associated with higher pathologic T stage (p = 0.001), larger tumor size (p ≤ 0.0001), greater lymphatic (p = 0.032) and vascular (p = 0.001) invasion, LUAD histologic subtype (p = 0.001), and intermediate and high architectural tumor grade (p = 0.003). Low BRMS1 expression was an independent predictor of worse OS (HR = 1.35, 95% confidence interval: 1.10-1.65, p = 0.004) and DFS (HR = 1.27, 95% confidence interval: 1.05-1.54, p = 0.012). OS and DFS nomograms showed excellent predictive performance based on discrimination and calibration. CONCLUSIONS: Among patients with surgically resected LUAD, OS and DFS were significantly worse in cases with low intratumoral BRMS1 expression. Our findings suggest that BRMS1 is an independent biomarker with prognostic significance in surgically resected LUAD.