Limited resection as a cure for early lung cancer: Time to challenge the gold standard?

Lung cancer remains the leading cause of cancer-related death in the U.S. With increased use of diagnostic and screening computed tomography (CT) scans, many lung cancers are discovered when they are small (≤ 2 cm). Do these small cancers require a standard lobectomy, or can a more limited resection, such as wedge resection or segmentectomy along with identical lymph node dissection, provide a similar oncologic outcome?

An active North American Phase III trial, Cancer and Leukemia Group B (CALGB) 140503, is expected to help determine whether small cancers require a standard lobectomy. The clinical trial is designed to reveal whether a limited resection (wedge resection or segmentectomy) provides equivalent survival to a lobectomy for treatment of early-stage non-small cell lung cancer (NSCLC). The current “gold standard” of lobectomy for NSCLC was established by the 1995 Lung Cancer Study Group (LCSG) trial that randomized patients with peripheral stage 1 (up to 3 cm) NSCLC to lobectomy versus limited resection in 267 patients. Survival results were not statistically different between the two groups, but lobectomy was favored because of fewer loco-regional recurrences.1

Ongoing advances

It has been 20 years since the results of the LCSG trial were published in the Annals of Thoracic Surgery.1 Over the course of these two decades, significant advances have occurred in screening, staging, and treatment of early-stage lung cancer. CT scanning, which can detect much smaller nodules, is now universally used for both diagnosis and screening. New generation CT and positron emission tomography scans provide more accurate noninvasive assessment and staging, including the ability to distinguish between solid, part-solid, and slow-growing non-solid lesions, which have a more indolent course.

Japanese oncologists were the first to identify a group of patients who could achieve high survival rates with limited resection.2-4 Many surgeons now have experience with segmentectomy, both open and video-assisted, making sublobar resection feasible and applicable for more of these patients. In addition, single institution studies have shown that limited lung resection provides similar local control and survival to lobectomy in well-selected patients.5-7 The timing is right to challenge the gold standard of lobectomy for early-stage NSCLC in a multicenter trial.

CALGB 140503

CALGB 140503

CALGB 140503

CALGB 140503 is a Phase III randomized trial of lobectomy versus sublobar resection for small (≤ 2 cm) peripheral NSCLC. Since 2007, 533 patients have been randomized, making this the largest multicenter trial evaluating this question. Target accrual is 692, more than twice the LCSG accrual.

Eligible patients include those who are older than 18 years of age with a peripheral lung nodule measuring ≤ 2 cm on a CT scan and suspected or proven lung cancer. The nodule must be peripherally located (defined as in the outer one-third of the lung) and the patient physiologically suited for either lobectomy or limited resection. Patients must not have had a previous malignancy within three years (with the exception of non-melanoma skin cancer, superficial bladder cancer, or cervical carcinoma in situ). Excluded from this trial are patients who have previously undergone chemotherapy and/or radiotherapy, as well as patients with locally advanced or metastatic disease. Patients are registered before surgery. During surgery, the cancer diagnosis is confirmed, if not previously determined by preoperative biopsy, and the required regional nodes are determined to be negative by frozen section (levels 4, 7, and 10 on the right; levels 5 or 6, 7, and 10 on the left) (see figure, this page). The patient is then intraoperatively randomized to either limited resection or lobectomy. Patients are followed for five years to determine disease-free and overall survival rate.

The results of CALGB 140503 are vital for evaluating the surgical management of patients with early stage lung cancer (T1aN0), a population that is under-represented in clinical trials. The implementation of CT screening for lung cancer, now approved by the Centers for Medicare & Medicaid Services, will result in the diagnosis of even more small peripheral lung cancers for which surgical treatment will be indicated.8 Many of these patients have poor lung function related to prior smoking behavior. Preservation of lung function by limited resection, if equal to lobectomy in cancer control, will result in a better quality of life for these individuals and maximize options for treatment of future second primaries.

Surgeons are urged to contribute to these research efforts by recommending this trial for their eligible patients to help determine the optimal extent of surgical resection for oncologic control of early-stage lung cancer, and decide whether it’s time to change the gold standard of lobectomy for early-stage NSCLC.


References

  1. Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg. 1995;60(3):615-622.
  2. Koike T, Yamato Y, Yoshiya K, Shimoyama T, Suzuki R. Intentional limited pulmonary resection for peripheral T1 N0 M0 small-sized lung cancer. J Thorac Cardiovasc Surg. 2003;125(4):924-928.
  3. Okada M, Nishio W, Sakamoto T, et al. Effect of tumor size on prognosis in patients with non-small cell lung cancer: The role of segmentectomy as a type of lesser resection. J Thorac Cardiovasc Surg. 2005;129(1):87-93.
  4. Okada M, Yoshikawa K, Hatta T, Tsubota N. Is segmentectomy with lymph node assessment an alternative to lobectomy for non-small cell lung cancer of 2 cm or smaller? Ann Thorac Surg. 2001;71(3):950-960.
  5. Landreneau RJ, Sugarbaker DJ, Mack MJ, et al. Wedge resection versus lobectomy for stage I (T1 N0 M0) non-small-cell lung cancer. J Thorac Cardiovasc Surg. 1997;113(4):691-698.
  6. Read RC, Yoder G, Schaeffer RC. Survival after conservative resection for T1 N0 M0 non-small cell lung cancer. Ann Thorac Surg. 1990;49(3):391-398.
  7. Keenan RJ, Landreneau RJ, Maley RH Jr, et al. Segmental resection spares pulmonary function in patients with stage I lung cancer. Ann Thorac Surg. 2004;78(1):228-233.
  8. Centers for Medicare & Medicaid Services. Decision Memo for Screening for Lung Cancer with Low Dose Computed Tomography (LDCT) (CAG-00439N). February 5, 2015. Available at: www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=274. Accessed March 1, 2015.

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