Chest
Volume 143, Issue 5, Supplement, May 2013, Pages e278S-e313S
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Treatment of Stage I and II Non-small Cell Lung Cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

https://doi.org/10.1378/chest.12-2359Get rights and content

Background

The treatment of stage I and II non-small cell lung cancer (NSCLC) in patients with good or low surgical risk is primarily surgical resection. However, this area is undergoing many changes. With a greater prevalence of CT imaging, many lung cancers are being found that are small or constitute primarily ground-glass opacities. Treatment such as sublobar resection and nonsurgical approaches such as stereotactic body radiotherapy (SBRT) are being explored. With the advent of minimally invasive resections, the criteria to classify a patient as too ill to undergo an anatomic lung resection are being redefined.

Methods

The writing panel selected topics for review based on clinical relevance to treatment of early-stage lung cancer and the amount and quality of data available for analysis and relative controversy on best approaches in stage I and II NSCLC: general surgical care vs specialist care; sublobar vs lobar surgical approaches to stage I lung cancer; video-assisted thoracic surgery vs open resection; mediastinal lymph node sampling vs lymphadenectomy at the time of surgical resection; the use of radiation therapy, with a focus on SBRT, for primary treatment of early-stage NSCLC in high-risk or medically inoperable patients as well as adjuvant radiation therapy in the sublobar and lobar resection settings; adjuvant chemotherapy for early-stage NSCLC; and the impact of ethnicity, geography, and socioeconomic status on lung cancer survival. Recommendations by the writing committee were based on an evidence-based review of the literature and in accordance with the approach described by the Guidelines Oversight Committee of the American College of Chest Physicians.

Results

Surgical resection remains the primary and preferred approach to the treatment of stage I and II NSCLC. Lobectomy or greater resection remains the preferred approach to T1b and larger tumors. The use of sublobar resection for T1a tumors and the application of adjuvant radiation therapy in this group are being actively studied in large clinical trials. Every patient should have systematic mediastinal lymph node sampling at the time of curative intent surgical resection, and mediastinal lymphadenectomy can be performed without increased morbidity. Perioperative morbidity and mortality are reduced and long-term survival is improved when surgical resection is performed by a board-certified thoracic surgeon. The use of adjuvant chemotherapy for stage II NSCLC is recommended and has shown benefit. The use of adjuvant radiation or chemotherapy for stage I NSCLC is of unproven benefit. Primary radiation therapy remains the primary curative intent approach for patients who refuse surgical resection or are determined by a multidisciplinary team to be inoperable. There is growing evidence that SBRT provides greater local control than standard radiation therapy for high-risk and medically inoperable patients with NSCLC. The role of ablative therapies in the treatment of high-risk patients with stage I NSCLC is evolving. Radiofrequency ablation, the most studied of the ablative modalities, has been used effectively in medically inoperable patients with small (< 3 cm) peripheral NSCLC that are clinical stage I.

Section snippets

General Approach

2.1.1. For patients with clinical stage I and II non-small cell lung cancer (NSCLC) and no medical contraindications to operative intervention, surgical resection is recommended (Grade 1B).

2.1.2. For patients with clinical stage I and II NSCLC, it is suggested that they be evaluated by a thoracic surgical oncologist or a multidisciplinary team even if the patients are considered for nonsurgical therapies such as percutaneous ablation or stereotactic body radiation therapy (Grade 2C).

Remark: At

Methods

A multidisciplinary writing committee composed of a pulmonologist, a methodologist, and four thoracic surgeons was assembled and approved according to the process for the ACCP Lung Cancer Guidelines as described by Lewis et al,1 “Methodology for Development of Guidelines for Lung Cancer,” in the ACCP Lung Cancer Guidelines.1 To update previous recommendations on the treatment of stages I and II NSCLC, a series of population, intervention, comparator, outcome (PICO) questions (Table S1) were

General Approach to Stage I and II NSCLC

Surgical resection is widely accepted as the optimal treatment of stage I and II NSCLC over no treatment. There are no RCTs comparing surgery alone to radiotherapy alone, chemotherapy alone, or ablative therapies in otherwise healthy patients with stage I and II NSCLC. The argument for surgery comes primarily from consistent data from retrospective surgical series and databases and registries showing higher survival rates after surgery than after other treatment modalities. Based on such

Minimally Invasive vs Open Surgical Resection

Several recent single-institution retrospective series have demonstrated that VATS lobectomy is associated with fewer complications,41, 42, 43, 44, 45, 46, 47 lower estimated blood loss or transfusion rate,42,48 and shorter hospital LOS,41,44, 45, 46, 47, 48 even for older patients (Figs 5A, 5B).41,42,47,49, 50, 51 Two meta-analyses50,52 (quality assessed as fair and good) and two systematic reviews53,54 (both poor quality) of VATS vs open lobectomy have been reported. These studies all found

Factors to Consider in Interpreting the Data

The standard extent of resection for lung cancer has been lobectomy with systematic lymph node sampling or mediastinal node dissection. Most series reporting the results of sublobar resection (wedge resection or segmentectomy) have no comparison group with lobectomy. Those that had a comparison lobectomy group as identified by our search are summarized in Figure 6.95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110 The table has three sections that group the studies by the

SBRT vs Surgical Resection for Stage 1 NSCLC

Refinements in radiation targeting and delivery have resulted in the development of several different platforms that deliver SBRT for local tumor control. The lung is the most common organ treated with SBRT.139 SBRT differs from standard radiation therapy by delivering shorter, more convenient regimens that involve smaller fields and higher delivered doses to the field. Because SBRT is well tolerated, does not require general anesthesia, and results in minimal damage to surrounding lung, it has

Adjuvant Chemotherapy for Resected Stage I/II NSCLC

6.1.1 Background: A significant number of patients with NSCLC undergoing “curative resection” ultimately die of systemic recurrence, providing continued impetus for development of adjuvant therapies.174,175 To this end, early randomized trials of adjuvant chemotherapy hinted at a beneficial effect of platinum-based therapy, although overall, they did not provide sufficient evidence to support use of adjuvant chemotherapy.176 These trials clearly demonstrated that all chemotherapeutic regimens

Definitions

Determining whether survival for stage I,II NSCLC is meaningfully impacted by ethnicity, geography, and socioeconomic status (SES) is difficult. There are numerous very large registry studies; however, these data are complicated by inherent biases of reporting and lack of sufficient detail. Studies are clearly confounded by the complex interaction of ethnicity, geography, and SES and, given the global nature of the disease, it is impossible to account for all racial and geographic and SES

Conclusion

The treatment of stage I and II NSCLC in good-risk patients is primarily surgical resection. In the seventh edition staging system with size cutoffs for T1a tumors ≤ 2 cm, the application of sublobar resection and nonsurgical therapy is being actively investigated. The role of minimally invasive VATS in the treatment of stage I and II NSCLC has increased since the last edition of guidelines. The best approach to high-risk patients with early-stage lung cancer remains controversial. For patients

Acknowledgments

Author contributions: Dr Howington had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Howington: contributed as the topic editor and oversaw the development of this guideline and contributed to the methodology, staging system, RFA in stage I and II, and thoracic surgeon vs general surgeon sections.

Dr Blum: contributed to the sublobar vs lobar resection and SBRT in stage I and II sections.

Dr Chang:

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    Funding/Sponsors: The overall process for the development of these guidelines, including matters pertaining to funding and conflicts of interest, are described in the methodology article.1 The development of this guideline was supported primarily by the American College of Chest Physicians. The lung cancer guidelines conference was supported in part by a grant from the Lung Cancer Research Foundation. The publication and dissemination of the guidelines was supported in part by a 2009 independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc.

    COI Grids reflecting the conflicts of interest that were current as of the date of the conference and voting are posted in the online supplementary materials.

    Disclaimer: American College of Chest Physician guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and physician advice, which always should be sought for any medical condition. The complete disclaimer for this guideline can be accessed at http://dx.doi.org/10.1378/chest.1435S1.

    © 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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