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

Abstract

OBJECTIVE CALGB 140503 is an ongoing multi-center randomized trial assessing whether sub-lobar resection is equivalent to lobectomy for the treatment of stage IA non-small cell lung cancer (NSCLC) ≤ 2 cm in diameter. The objective of this report is to determine the reasons precluding intra-operative randomization. METHODS From June 15, 2007 to March 22, 2013, 637 patients were preregistered to the trial. Three hundred eighty-nine were successfully randomized (61%) and 248 patients were not randomized (39%). We analyzed the reasons for non-randomization among a subset of the non-randomized patients (208) for which 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 higher in those patients who had a preoperative biopsy (p<0.001) 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 non-therapeutic or unnecessary thoracic procedures. Accuracy in preoperative diagnosis is increasingly important as more such small nodules are discovered through lung cancer screening.

Surgery versus stereotactic body radiation therapy for stage I non–small cell lung cancer: A comprehensive review

“…A preliminary analysis demonstrated that 16% of all registered patients had benign pathology. In addition, nodal upstaging occurred in 6.4% of the patients; this rate was lower than the rates in other published studies, perhaps because of improved staging procedures and patient selection …”

“…Lobectomy has been the gold standard for the resection of early‐stage NSCLC since the Lung Cancer Study Group trial results were published in 1995 . Although there were no differences in perioperative morbidity or mortality between the groups, patients with limited resection (either wedge resection or segmentectomy) experienced a significantly higher incidence of disease recurrence, perhaps because of occult nodal metastases, which may be present in 4% to 20% of patients undergoing resection of clinical stage I lung cancer . Wedge resection is a nonanatomic resection in which interlobar and parenchymal (N1) lymph nodes are not typically obtained for pathologic analysis.…”

Surgical treatment for early stage non-small cell lung cancer

“…The Japan Clinical Oncology Group and West Japan Oncology Group trial, JCOG0802/WJOG4607L, randomizes patients with invasive adenocarcinomas smaller than two centimeters to segmentectomy or lobectomy (76). The Alliance for Clinical Trials in Oncology study, CALGB 140503, assigns patients with small (<2 cm) peripheral tumors to either sublobar resection (wedge resection or segmentectomy) or lobar resection via VATS or thoracotomy (77,78). A phase II trial, JCOG0804/WJOG4507L, compares wide wedge resections to segmentectomies in small adenocarcinomas (79).…”

T1a lung carcinoma: the place of segmentectomy in the treatment array

“…Both trials just completed enrollment and they are similar in design in that they randomized patients to either lobectomy or sub-lobar resection for peripheral cancer less than 2 cm in diameter (11). The Japanese trial (JCOG0802/ WJOG4607L) included 1,100 patients accrued from 71 institutions within 3 years (10).…”

“…However, the role of parenchymal-sparing operations such as segmentectomy in the treatment of T1a lung carcinoma, is still of much debate, in part because of the retrospective nature of existing published studies (7)(8)(9). Two randomized control trials however, both of which have currently finished enrollment, will hopefully shed further light on this topic (10,11). Understanding the nuances of segmentectomy is essential to minimize patient morbidity and improve overall oncologic efficiency, and a crucial skill for today's thoracic surgeon.…”