Lobectomy, sublobar resection, and stereotactic ablative radiotherapy for early-stage non-small cell lung cancers in the elderly.
ABSTRACT: The incidence of early-stage non-small cell lung cancer (NSCLC) among the elderly is expected to rise dramatically owing to demographic trends and increased computed tomographic screening. However, to our knowledge, no modern trials have compared the most common treatments for NSCLC.To determine clinical characteristics and survival outcomes associated with the 3 most commonly used definitive therapies for early-stage NSCLC in the elderly.The Surveillance, Epidemiology, and End Results database linked to Medicare was used to determine the baseline characteristics and outcomes of 9093 patients with early-stage, node-negative NSCLC who underwent definitive treatment consisting of lobectomy, sublobar resection, or stereotactic ablative radiotherapy (SABR) from January 1, 2003, through December 31, 2009.Overall and lung cancer-specific survival were compared using Medicare claims through December 31, 2012. We used proportional hazards regression and propensity score matching to adjust outcomes for key patient, tumor, and practice environment factors.The median age was 75 years, and treatment distribution was 79.3% for lobectomy, 16.5% for sublobar resection, and 4.2% for SABR. Unadjusted 90-day mortality was highest for lobectomy (4.0%) followed by sublobar resection (3.7%; P = .79) and SABR (1.3%; P = .008). At 3 years, unadjusted mortality was lowest for lobectomy (25.0%), followed by sublobar resection (35.3%; P < .001) and SABR (45.1%; P < .001). Proportional hazards regression demonstrated that sublobar resection was associated with worse overall survival (adjusted hazard ratio [AHR], 1.32 [95% CI, 1.20-1.44]; P < .001) and lung cancer-specific survival (AHR, 1.50 [95% CI, 1.29-1.75]; P < .001) compared with lobectomy. Propensity score-matching analysis reiterated these findings for overall survival (AHR, 1.36 [95% CI, 1.17-1.58]; P < .001) and lung cancer-specific survival (AHR, 1.46 [95% CI, 1.13-1.90]; P = .004). In proportional hazards regression, SABR was associated with better overall survival than lobectomy in the first 6 months after diagnosis (AHR, 0.45 [95% CI, 0.27-0.75]; P < .001) but worse survival thereafter (AHR, 1.66 [95% CI, 1.39-1.99]; P < .001). Propensity score-matching analysis of well-matched SABR and lobectomy cohorts demonstrated similar overall survival in both groups (AHR, 1.01 [95% CI, 0.74-1.38]; P = .94).Lobectomy was associated with better outcomes than sublobar resection in elderly patients with early-stage NSCLC. Propensity score matching suggests that SABR may be a good option among patients with very advanced age and multiple comorbidities.
Project description:The incidence of early-stage non-small cell lung cancer (NSCLC) among older adults is expected to increase because of demographic trends and computed tomography-based screening; yet, optimal treatment in the elderly remains controversial. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort spanning 2001-2007, we compared survival outcomes associated with 5 strategies used in contemporary practice: lobectomy, sublobar resection, conventional radiation therapy, stereotactic ablative radiation therapy (SABR), and observation.Treatment strategy and covariates were determined in 10,923 patients aged ? 66 years with stage IA-IB NSCLC. Cox regression, adjusted for patient and tumor factors, compared overall and disease-specific survival for the 5 strategies. In a second exploratory analysis, propensity-score matching was used for comparison of SABR with other options.The median age was 75 years, and 29% had moderate to severe comorbidities. Treatment distribution was lobectomy (59%), sublobar resection (11.7%), conventional radiation (14.8%), observation (12.6%), and SABR (1.1%). In Cox regression analysis with a median follow-up time of 3.2 years, SABR was associated with the lowest risk of death within 6 months of diagnosis (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.38-0.63; referent is lobectomy). After 6 months, lobectomy was associated with the best overall and disease-specific survival. In the propensity-score matched analysis, survival after SABR was similar to that after lobectomy (HR 0.71; 95% CI 0.45-1.12; referent is SABR). Conventional radiation and observation were associated with poor outcomes in all analyses.In this population-based experience, lobectomy was associated with the best long-term outcomes in fit elderly patients with early-stage NSCLC. Exploratory analysis of SABR early adopters suggests efficacy comparable with that of surgery in select populations. Evaluation of these therapies in randomized trials is urgently needed.
Project description:Stereotactic ablative radiation (SABR) is a promising alternative to lobectomy or sublobar resection for early lung cancer, but the value of SABR in comparison to surgical therapy remains debated. We examined the cost-effectiveness of SABR relative to surgery using SEER-Medicare data.Patients age ?66 years with localized (<5 cm) non-small cell lung cancers diagnosed from 2003-2009 were selected. Propensity score matching generated cohorts comparing SABR with either sublobar resection or lobectomy. Costs were determined via claims. Median survival was calculated using the Kaplan-Meier method. Incremental cost-effectiveness ratios (ICERs) were calculated and cost-effectiveness acceptability curves (CEACs) were constructed from joint distribution of incremental costs and effects estimated by non-parametric bootstrap.In comparing SABR to sublobar resection, 5-year total costs were $55,120 with SABR vs. $77,964 with sublobar resection (P<0.001) and median survival was 3.6 years with SABR vs. 4.1 years with sublobar resection (P=0.95). The ICER for sublobar resection compared to SABR was $45,683/life-year gained, yielding a 46% probability that sublobar resection is cost-effective. In comparing SABR to lobectomy, 5-year total costs were $54,968 with SABR vs. $82,641 with lobectomy (P<0.001) and median survival was 3.8 years with SABR vs. 4.7 years with lobectomy (P=0.81). The ICER for lobectomy compared to SABR was $28,645/life-year gained, yielding a 78% probability that lobectomy is cost-effective.SABR is less costly than surgery. While lobectomy may be cost-effective compared to SABR, sublobar resection is less likely to be cost-effective. Assessment of the relative value of SABR versus surgical therapy requires further research.
Project description:OBJECTIVES: To compare cancer specific survival after thoracoscopic sublobar lung resection and stereotactic ablative radiotherapy (SABR) for tumors ?2 cm in size and thoracoscopic resection (sublobar resection or lobectomy) and SABR for tumors ?5 cm in size. DESIGN: National population based retrospective cohort study with propensity matched comparative analysis. SETTING: Surveillance, Epidemiology, and End Results (SEER) registry linked with Medicare database in the United States. PARTICIPANTS: Patients aged ?66 with lung cancer undergoing SABR or thoracoscopic lobectomy or sublobar resection from 1 Oct 2007 to 31 June 2012 and followed up to 31 December 2013. MAIN OUTCOME MEASURES: Cancer specific survival after SABR or thoracoscopic surgery for lung cancer. RESULTS: 690 (275 (39.9%) SABR and 415 (60.1%) thoracoscopic sublobar lung resection) and 2967 (714 (24.1%) SABR and 2253 (75.9%) thoracoscopic resection) patients were included in primary and secondary analyses. The average age of the entire cohort was 76. Follow-up of the entire cohort ranged from 0 to 6.25 years, with an average of three years. In the primary analysis of patients with tumors sized ?2 cm, 37 (13.5%) undergoing SABR and 44 (10.6%) undergoing thoracoscopic sublobar resection died from lung cancer, respectively. The cancer specific survival diverged after one year, but in the matched analysis (201 matched patients in each group) there was no significant difference between the groups (SABR v sublobar lung resection mortality: hazard ratio 1.32, 95% confidence interval 0.77 to 2.26; P=0.32). Estimated cancer specific survival at three years after SABR and thoracoscopic sublobar lung resection was 82.6% and 86.4%, respectively. The secondary analysis (643 matched patients in each group) showed that thoracoscopic resection was associated with improved cancer specific survival over SABR in patients with tumors sized ?5 cm (SABR v resection mortality: hazard ratio 2.10, 1.52 to 2.89; P<0.001). Estimated cancer specific survival at three years was 80.0% and 90.3%, respectively. CONCLUSIONS: This propensity matched analysis suggests that patients undergoing thoracoscopic surgical resection, particularly for larger tumors, might have improved cancer specific survival compared with patients undergoing SABR. Despite strategies used in study design and propensity matching analysis, there are inherent limitations to this observational analysis related to confounding, similar to most studies in healthcare of non-surgical technologies compared with surgery. As the adoption of SABR for the treatment of early stage operable lung cancer would be a paradigm shift in lung cancer care, it warrants further thorough evaluation before widespread adoption in practice.
Project description:BACKGROUND:Lobectomy has been compared with sublobar resection for the treatment of stage IA non-small cell lung cancer (NSCLC). Accurate long-term data are lacking on the risk of recurrence in routine clinical practice. This study used a unique and representative dataset to compare recurrence, overall survival (OS), and lymph node staging between lobectomy and sublobar resection. METHODS:The American College of Surgeons performed a Special Study of the National Cancer Data Base, by reabstracting records to augment NSCLC data with enhanced information on preoperative comorbidity and cancer recurrence from 2007 to 2012. For patients treated with lobectomy or sublobar resection (wedge resection or segmentectomy) for clinical stage IA NSCLC, propensity matching and competing risks models compared 5-year OS and risk of cancer recurrence. Secondary measures included lymph nodes collected, pathologic upstaging, and surgical margin status. RESULTS:A total of 1,687 patients with stage IA NSCLC were identified (1,354 who underwent lobectomy, and 333 who had sublobar resections). Propensity matching yielded 325 pairs. Lobectomy and sublobar resection groups had similar 5-year OS (61.8% vs 55.6%, p = 0.561). The sublobar group had a 39% increased risk of NSCLC recurrence (hazard ratio, 1.39; 95% confidence interval, 1.04 to 1.87). Median lymph node counts were higher for lobectomy-treated patients (7 [3, 10] vs 1 [0, 4], p < 0.001)]. CONCLUSIONS:In an enhanced national dataset representative of outcomes for stage IA NSCLC, sublobar resection was associated with a 39% increased risk of cancer recurrence. The majority of patients treated with sublobar resection had an inadequate lymph node assessment. These real-world results must be considered when existing clinical trial results comparing these treatments are extrapolated for clinical use.
Project description:Lung cancer in the right middle lobe has a poorer prognosis than tumors located in other lobes. The optimal surgical procedure for early-stage non-small cell lung cancer (NSCLC) in the right middle lobe has not yet been elucidated. The aim of this study was to compare survival rates after lobectomy and sublobar resection for early-stage right middle lobe NSCLC.Patients who underwent lobectomy or sublobar resection for stage IA right middle lobe NSCLC tumors ? 2 cm between 2004 and 2014 were identified from the Surveillance, Epidemiology and End Results database of 18 registries. Cox regression model analysis was used to evaluate the prognostic factors. The lung cancer-specific survival (LCSS) and overall survival (OS) rates between the two groups were compared.A total of 861 patients met our criteria, including 662 (76.9%) patients who underwent lobectomy and 199 (23.1%) patients who underwent sublobar resection. No statistical differences in LCSS and OS rates were identified between the groups of patients with stage IA right middle lobe NSCLC ? 1?cm. For tumors > 1-2 cm, lobectomy was associated with more favorable LCSS and OS rates compared to sublobar resection.Lobectomy and sublobar resection deliver a comparable prognosis for patients with stage IA right middle lobe NSCLC ? 1?cm. For tumors > 1-2 cm, lobectomy showed better survival rates than sublobar resection.
Project description:BACKGROUND:To date, few studies have evaluated the impact of lobectomy versus sublobar resection for early small cell lung cancer (SCLC). We investigated the survival rates of patients with pathological stage T1-2N0M0 SCLC who underwent lobectomy or sublobar resection. METHODS:We identified 548 SCLC patients in the Surveillance, Epidemiology, and End Results database who underwent lobectomy or sublobar resection. Propensity score matching (PSM) and Cox regression analysis were used to adjust for baseline characteristics. RESULTS:The three-year overall survival (OS) of patients treated with lobectomy (n?=?376, 60%) was significantly higher than those treated with sublobar resection (n?=?172, 38%). PSM and Cox multivariable analysis further confirmed this result (hazard ratio [HR] 0.543, 95% confidence interval [CI] 0.421-0.680; P?<?0.001). The three-year OS of patients treated with segmentectomy (n?=?24, 54%) and wedge resection (n?=?148, 36%) was not significantly different (HR 0.639, 95% CI 0.393-1.039; P?=?0.071). Based on PSM analysis, segmentectomy conferred a superior survival advantage to patients relative to wedge resection (HR 0.466, 95% CI 0.221-0.979; P?=?0.040). CONCLUSION:Lobectomy correlated with superior survival. For patients in which lobectomy is unsuitable, prognosis following segmentectomy appears to be better than after wedge resection.
Project description:The appropriateness of lobectomy for all elderly patients is controversial. Meanwhile, sublobar resection is associated with reduced operative risk, better preservation of pulmonary function, and a better quality of life, constituting a potential alternative to standard lobectomy for elderly patients with early-stage non-small cell lung cancer (NSCLC). To date, no randomized trial comparing sublobar resection and lobectomy focusing on elderly patients has been reported. We hypothesized that for patients at least 70 years old with clinical stage T1N0M0 NSCLC, sublobar resection is non-inferior to lobectomy for 3-year disease-free survival (DFS).This is a prospective, randomized, controlled multicenter non-inferiority trial with two study arms: sublobar resection and lobectomy groups. Comprehensive geriatric assessments will be acquired for each patient. A total of 339 subjects will be enrolled on the basis of power calculations, and participants followed up every 6 months post-operation for 3 years. In case of relapse, survival follow-up will be continued until 5 years or death. Pulmonary function testing will be performed at 6, 12, and 36 months post-operation. The primary outcome is 3-year DFS; secondary endpoints include peri-operative complications and mortality, hospitalization time, post-operative ventilator time, overall survival, 3-year recurrence rates, post-operative pulmonary function, quality of life, geriatric assessment data, and 4-year mortality index.The present study is the only prospective, multicenter, randomized controlled trial comparing sublobar resection and lobectomy for elderly patients. The therapeutic outcomes of sublobar resection will be evaluated in comparison with lobectomy for elderly patients (?70 years) with early-stage NSCLC.NCT02360761 : 01/24/2015 (ClinicalTrials.gov).
Project description:Lobectomy is considered the standard treatment for early-stage non-small cell lung cancer (NSCLC); however, more limited resections are commonly performed. We examined patient and surgeon factors associated with limited resection and compared postoperative and long-term outcomes between sublobar and lobar resections.A population- and health system-based sample of patients newly diagnosed with stage I or II NSCLC between 2003 and 2005 in five geographically defined regions, five integrated health-care delivery systems, and 15 Veterans Affairs hospitals was observed for a median of 55 months, through May 31, 2010. Predictors of limited resection and postoperative outcomes were compared using unadjusted and propensity score-weighted analyses. All P values are from two-sided tests.One hundred fifty-five (23%) patients underwent limited resection and 524 (77%) underwent lobectomy. In adjusted analyses of patient-specific factors, smaller tumor size (P = .004), coverage by Medicare or Medicaid, no insurance or unknown insurance (P = .02), more severe lung disease (P < .001), and a history of stroke (P = .049) were associated with receipt of limited resection. In adjusted analyses of surgeon characteristics, thoracic surgery specialty (P = .02), non-fee-for-service compensation (P = .008), and National Cancer Institute cancer center designation (P = .006) were associated with higher odds of limited resection. Unadjusted 30-day mortality was higher with limited resection than with lobectomy (7.1% vs 1.9%, difference = 5.2%, 95% confidence interval [CI] = 1.5% to 10.8%, P = .003), and the adjusted difference was not statistically significant (6.5% vs 2.9%, difference = 3.6%, 95% CI = -.1% to 9.2%, P = .09). Postoperative complications did not differ by type of surgery (all P > .05). Over the course of the study, a non-statistically significant trend toward improved long-term survival was evident for lobectomy, compared with limited resection, in adjusted analyses (hazard ratio of death = 1.35 for limited resection, 95% CI = 0.99 to 1.84, P = .05).Evidence is statistically inconclusive but suggestive that lobectomy, compared with limited resection, is associated with increased long-term survival for early-stage lung cancer. Clinical, socioeconomic, and surgeon factors appear to be associated with the choice of surgical resection.
Project description:BACKGROUND:There is debate regarding the use of stereotactic ablative radiotherapy (SABR) or surgery for patients with early stage non-small cell lung cancer (NSCLC). This meta-analysis compared the clinical efficacy of SABR and lobectomy in stage I NSCLC patients. METHODS:An online search identified eight eligible articles (including 2 trials and 7 cohort studies) for inclusion. The odds ratio (OR) was used as a summary statistic. Overall survival (OS), cause-specific survival (CSS), and recurrence-free survival (RFS) were selected to calculate ORs with 95% confidence intervals (CI). Fixed-effects or random-effects models were conducted according to study heterogeneity. RESULTS:There were no significant differences between SABR and lobectomy in terms of one-year OS or CSS. Significant benefits of surgery were observed in three-year OS (OR?2.11, 95% CI 1.55-2.86), three-year CSS (OR?1.94, 95% CI 1.05-3.57), three-year RFS (OR?1.63, 95% CI 1.12-2.36), and five-year OS (OR?2.40, 95% CI 1.71-3.36). In addition, lobectomy demonstrated a beneficial trend in one-year RFS, five-year RFS, and CSS. CONCLUSION:Meta-analyses of current evidence suggested that lobectomy provides better long-term survival outcomes for stage I NSCLC patients.
Project description:Recent data have suggested possible oncologic equivalence of sublobar resection with lobectomy for early-stage non-small-cell lung cancer (NSCLC). Our aim was to evaluate and compare short-term and long-term survival for these surgical approaches.This retrospective cohort study utilized the National Cancer Data Base. Patients undergoing lobectomy, segmentectomy, or wedge resection for preoperative clinical T1A N0 NSCLC from 2003 to 2011 were identified. Overall survival (OS) and 30-day mortality were analyzed using multivariable Cox proportional hazards models, logistic regression models, and propensity score matching. Further analysis of survival stratified by tumor size, facility type, number of lymph nodes (LNs) examined, and surgical margins was performed.A total of 13,606 patients were identified. After propensity score matching, 987 patients remained in each group. Both segmentectomy and wedge resection were associated with significantly worse OS when compared with lobectomy (hazard ratio: 1.70 and 1.45, respectively, both p < 0.001), with no difference in 30-day mortality. Median OS for lobectomy, segmentectomy, and wedge resection were 100, 74, and 68 months, respectively (p < 0.001). Finally, sublobar resection was associated with increased likelihood of positive surgical margins, lower likelihood of having more than three LNs examined, and significantly lower rates of nodal upstaging.In this large national-level, clinically diverse sample of clinical T1A NSCLC patients, wedge and segmental resections were shown to have significantly worse OS compared with lobectomy. Further patients undergoing sublobar resection were more likely to have inadequate lymphadenectomy and positive margins. Ongoing prospective study taking into account LN upstaging and margin status is still needed.