Perioperative mortality and morbidity after sublobar versus lobar resection for early-stage non-small-cell lung cancer: post-hoc analysis of an international, randomised, phase 3 trial (CALGB/Alliance 140503).

BACKGROUND: Increased detection of small-sized, peripheral, non-small-cell lung cancer has renewed interest in sublobar resection instead of lobectomy, the traditional standard of care for early-stage lung cancer. We aimed to assess morbidity and mortality associated with lobar and sublobar resection for early-stage lung cancer. METHODS: CALGB/Alliance 140503 is a multicentre, international, non-inferiority, phase 3 trial in patients with peripheral non-small-cell lung cancer clinically staged as T1aN0. Patients were recruited from 69 academic and community-based institutions in Australia, Canada, and the USA. Patients were randomly assigned intraoperatively to either lobar or sublobar resection. The random assignment was based on permuted block randomisation without concealment and was stratified according to radiographic tumour size, histology, and smoking status. The primary endpoint of the trial is disease-free survival; here, we report a post-hoc, exploratory, comparative analysis of perioperative mortality and morbidity associated with lobar and sublobar resection. Perioperative mortality was defined as death from any cause within 30 days and 90 days of surgical intervention and was calculated for all randomised patients. Morbidity was graded using Common Terminology Criteria for Adverse Events version 4.0. All analyses were done on an intention-to-treat basis for randomised patients with data available. This trial is registered with ClinicalTrials.gov, number NCT00499330. FINDINGS: Between June 15, 2007, and March 13, 2017, 697 patients were randomly allocated to either lobar resection (n=357) or sublobar resection (n=340; 59% wedge resection). Six (0·9%) patients died by 30 days, four (1·1%) after lobar resection and two (0·6%) after sublobar resection; by 90 days, ten (1·4%) patients had died, six (1·7%) after lobar resection and four (1·2%) after sublobar resection (difference at 30 days, 0·5%, 95% CI -1·1 to 2·3; difference at 90 days, 0·5%, 95% CI -1·5 to 2·6). An adverse event of any grade occurred in 193 (54%) of 355 patients after lobar resection and 172 (51%) of 337 patients after sublobar resection. Adverse events of grade 3 or worse occurred in 54 (15%) patients assigned lobar resection and in 48 (14%) patients assigned sublobar resection. No differences between surgical approaches were noted in cardiac or pulmonary complications. Grade 3 haemorrhage (requiring transfusion) occurred in six (2%) patients assigned lobar resection and eight (2%) patients assigned sublobar resection. Prolonged air leak occurred in nine (3%) patients after lobar resection and two (1%) patients after sublobar resection. INTERPRETATION: Our post-hoc analysis showed that perioperative mortality and morbidity did not seem to differ between lobar and sublobar resection in physically and functionally fit patients with clinical T1aN0 non-small-cell lung cancer. These data may affect the daily choices made by patients and their doctors in establishing the best treatment approach for stage I lung cancer. FUNDING: National Cancer Institute.

Biopsy first: Lessons learned from Cancer and Leukemia Group B (CALGB) 140503.

OBJECTIVE: Cancer and Leukemia Group B 140503 is an ongoing, multicenter randomized trial assessing whether sublobar resection is equivalent to lobectomy for the treatment of stage I A non-small cell lung cancer (NSCLC) ≤2 cm in diameter. The objective of this report is to determine the reasons precluding intraoperative randomization. METHODS: From June 15, 2007, to March 22, 2013, 637 patients were preregistered to the trial. Three hundred eighty-nine were randomized successfully (61%), and 248 patients were not randomized (39%). We analyzed the reasons for nonrandomization among a subset of the nonrandomized patients (208) for whom additional data were available. RESULTS: Of these 208 patients, undiagnosed benign nodules (n =104, 16% of all registered patients) and understaging of NSCLC (n =45, 7% of all registered patients) were the dominant reasons precluding randomization. Granulomas represent one-quarter of the benign nodules. The understaged patients had unsuspected nodal metastases (n =28) or other more advanced NSCLC. The rate of randomization was significantly greater in those patients who had a preoperative biopsy (P <.001). CONCLUSIONS: In a carefully monitored cohort of patients with suspected small NSCLC ≤2 cm, a substantial number are misdiagnosed (benign nodules) or understaged. These patients may not have benefited from a thoracic surgical procedure. Preoperative biopsy significantly increased the rate of correct diagnosis. Preoperative biopsy of small suspected NSCLC will reduce the number of nontherapeutic or unnecessary thoracic procedures. Accuracy in preoperative diagnosis is increasingly important as more such small nodules are discovered through lung cancer screening.

VATS lobectomy has better perioperative outcomes than open lobectomy: CALGB 31001, an ancillary analysis of CALGB 140202 (Alliance).

BACKGROUND: The short-term superiority of video-assisted thoracoscopic surgery lobectomy compared with open lobectomy for early-stage lung cancer has been suggested by single-institution studies. Lack of equipoise limits the feasibility of a randomized study to confirm this. The hypothesis of this study (CALGB 31001) was that VATS lobectomy results in shorter length of hospital stay and fewer complications compared with open lobectomy in stages I and II non-small cell lung cancer in a multi-institutional setting. METHODS: Five hundred nineteen patients whose tumors had been collected as part of CALGB 140202 (lung cancer tissue bank) were eligible. Propensity-scoring using age, race, sex, performance status, comorbidities, histology, tumor stage, and size as independent variables was used to create a 1:1 matched group of 175 pairs of patients. McNemar's test for binary variables and Wilcoxon signed-rank test for continuous variables were used to assess differences in length of hospital stay, complications, and discharge dispositions between the groups. Comparison of disease-free and overall survival between the two approaches was done using the log-rank test. Probability values of less than 0.05 were considered significant. RESULTS: The matched data on length of hospital stay, complications, and discharge dispositions significantly favored the video-assisted thoracoscopic surgery group. There was no statistically significant difference in survival between the two approaches. CONCLUSIONS: This multi-institutional study supports the assertion that thoracoscopic lobectomy results in shorter hospital length of stay, fewer perioperative complications, and greater likelihood of independent home discharge compared with open lobectomy for early-stage lung cancer. Survival was comparable between the two groups.

Optimal management of malignant pleural effusions (results of CALGB 30102).

The optimal strategy to achieve palliation of malignant pleural effusions (MPEs) is unknown. This multi-institutional, prospective, randomized trial compares 2 established methods for controlling symptomatic unilateral MPEs. Patients with unilateral MPEs were randomized to either daily tunneled catheter drainage (TCD) or bedside talc pleurodesis (TP). This trial is patterned after a previous randomized trial that showed that bedside TP was equivalent to thoracoscopic TP (CALGB 9334). The primary end point of the current study was combined success: consistent/reliable drainage/pleurodesis, lung expansion, and 30-day survival. A secondary end point, survival with effusion control, was added retrospectively. This trial randomized 57 patients who were similar in terms of age (62 years), active chemotherapy (28%), and histologic diagnosis (lung, 63%; breast, 12%; other/unknown cancers, 25%) to either bedside TP or TCD. Combined success was higher with TCD (62%) than with TP (46%; odds ratio, 5.0; P = .064). Multivariate regression analysis revealed that patients treated with TCD had better 30-day activity without dyspnea scores (8.7 vs. 5.9; P = .036), especially in the subgroup with impaired expansion (9.1 vs. 4.6; P = .042). Patients who underwent TCD had better survival with effusion control at 30 days compared with those who underwent TP (82% vs. 52%, respectively; P = .024). In this prospective randomized trial, TCD achieved superior palliation of unilateral MPEs than TP, particularly in patients with trapped lungs.