• Lung Cancer Disease Site Group. Okawara G, Ung YC, Markman BR, Mackay JA, Evans WK. Postoperative adjuvant radiation therapy in stage II or IIIA completely resected non-small cell lung cancer. Toronto (ON): Cancer Care Ontario (CCO); 2005 Feb [online update]. 16 p. (Practice guideline report; no. 7-1-1). [18 references]

Stage II or IIIA non-small cell lung cancer (NSCLC)

Assessment of Therapeutic Effectiveness
Management
Treatment

Oncology
Pulmonary Medicine
Radiation Oncology

Physicians

• To evaluate the use of postoperative radiotherapy in improving survival in patients with completely resected pathologic stage II or IIIA non-small cell lung cancer
• To evaluate the use of postoperative radiotherapy in reducing the risk of local recurrence in patients with completely resected pathologic stage II or IIIA non-small cell lung cancer

Adults with completely resected pathologic stage II or IIIA non-small cell lung cancer (NSCLC)

Postoperative radiotherapy

• Survival
• Local tumor recurrence

Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases

One meta-analysis and one randomized controlled trial were reviewed.

Expert Consensus (Committee)

Not applicable

Review of Published Meta-Analyses
Systematic Review with Evidence Tables

The Lung Disease Site Group decided not to pool the results of trials of adjuvant radiotherapy compared with surgery alone in completely resected stage II or III non-small cell lung cancer because of the availability of a published meta-analysis of individual patient data that compared those two treatment approaches in patients with stages I, II, or III non-small cell lung cancer.

Expert Consensus

The original recommendation regarding the role of postoperative radiotherapy in stage II and III non-small cell lung cancer (NSCLC) supported the use of postoperative radiotherapy in completely resected stage II and III non-small cell lung cancer because of evidence that it reduced local recurrence. Since the publication of the original guideline recommendation, important evidence has been reported in several papers that justified the revision of the guideline, particularly in relation to the role of postoperative radiotherapy. The consensus of the Lung Disease Site Group (DSG) was to discuss postoperative radiotherapy and postoperative chemotherapy with or without radiotherapy in two related guidelines. There was consensus among Lung DSG members on the greater importance and urgency of revising and updating the original recommendation on postoperative radiation in light of newly published data.

As in the original practice guideline, the literature review did not allow a clear separation between stage IIIA and IIIB disease. Therefore, the recommendations remain restricted to completely resected stage IIIA disease and do not address other subsets of stage III disease. The Lung DSG found that the completeness of resection is uncertain or unreported in many studies and they suggest that this should be reported in future research studies.

Not applicable

A formal cost analysis was not performed and published cost analyses were not included.

External Peer Review
Internal Peer Review

Practitioner feedback was obtained through a mailed survey of 110 practitioners in Ontario (40 medical oncologists, 21 radiation oncologists, 22 surgeons, 26 respirologists, and 1 hematologist). The survey consisted of items evaluating the methods, results, and interpretive summary used to inform the draft recommendation and whether the draft recommendation should be approved as a practice guideline. Written comments were invited. Follow-up reminders were sent at two weeks (post card) and four weeks (complete package mailed again). The Lung Disease Site Group (DSG) reviewed the results of the survey.

Practice Guidelines Coordinating Committee Approval Process

The practice guideline report was circulated to members of the Practice Guidelines Coordinating Committee (PGCC) for review and approval. Ten of 11 members of the PGCC returned ballots. Six PGCC members approved the practice guideline report as written; one member approved the practice guideline as written and provided suggestions for consideration by the Lung DSG; and three members approved the practice guideline report conditional on the Lung DSG addressing specific concerns. The Lung DSG responded to the PGCC concerns and the guideline was subsequently approved.

• Postoperative radiation therapy is not recommended for use following complete resection of stage II non-small cell lung cancer.
• For stage IIIA disease, no definitive recommendation can be made for the use of postoperative radiotherapy, as a survival benefit has not been demonstrated and the data for improved local control is conflicting. The decision for postoperative radiotherapy must therefore be based on an individualized case assessment.

None provided

The recommendations are supported by randomized controlled trials and meta-analyses.

These guideline recommendations may aid physicians in making decisions concerning use of postoperative radiotherapy in the management of patients with stage II or IIIA completely resected non-small cell lung cancer.

• There is evidence from a meta-analysis of individual patient data from ten randomized controlled trials that postoperative thoracic irradiation in patients with completely resected non-small cell lung cancer significantly reduces overall survival (mortality hazard ratio, 1.18; 95% confidence interval, 1.07 to 1.31; p=0.002). Of the three relevant randomized controlled trials published after the meta-analysis, two of which also included data reported in the meta-analysis, one detected a survival advantage for patients treated with surgery alone compared with surgery followed by radiotherapy (p=0.002 log rank) and two detected no difference between the two treatments (p=0.56 and p>0.05).
• Subset analyses on data from the meta-analysis and one randomized controlled trial suggested that the detrimental effect associated with radiotherapy was greatest for patients with stage II disease. There was no clear evidence of an adverse effect or benefit for patients with stage III disease.
• Results from the meta-analysis detected a statistically significant difference in local recurrence-free survival (time to local recurrence or death) in favour of surgery alone (hazard ratio, 1.13; p=0.02). Three relevant randomized controlled trials published after the meta-analysis also examined local recurrence rate. One did not detect a difference between treatments (relative risk, 0.85; 95% confidence interval, 0.64 to 1.14, p=0.28 log rank) and two detected an advantage for postoperative radiotherapy (both p<0.01).

• Most reported trials involved radiation using cobalt-60 equipment which is no longer considered optimal for treatment in the majority of lung cancer patients. There is insufficient evidence to assess the effectiveness of postoperative radiotherapy with the use of newer equipment such as linear accelerators.
• Care has been taken in the preparation of the information contained in this document. Nonetheless, any person seeking to apply or consult these guidelines is expected to use independent medical judgement in the context of individual clinical circumstances or seek out the supervision of a qualified clinician. Cancer Care Ontario makes no representation or warranties of any kind whatsoever regarding their content or use or application and disclaims any responsibility for their application or use in any way.

An implementation strategy was not provided.

Living with Illness

Effectiveness

• Lung Cancer Disease Site Group. Okawara G, Ung YC, Markman BR, Mackay JA, Evans WK. Postoperative adjuvant radiation therapy in stage II or IIIA completely resected non-small cell lung cancer. Toronto (ON): Cancer Care Ontario (CCO); 2005 Feb [online update]. 16 p. (Practice guideline report; no. 7-1-1). [18 references]

Not applicable: The guideline was not adapted from another source.

1997 Sep 15 (revised 2005 Feb)

Program in Evidence-based Care - State/Local Government Agency [Non-U.S.]

The Practice Guidelines Initiative (PGI) is the main project of the Program in Evidence-based Care (PEBC), a Province of Ontario initiative sponsored by Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care.

Cancer Care Ontario, Ontario Ministry of Health and Long-Term Care

Provincial Lung Cancer Disease Site Group

Members of the Lung Cancer Disease Site Group disclosed potential conflict of interest information.

None available

This summary was completed by ECRI on January 5, 1999. The information was verified by the guideline developer as of February 22, 1999. This NGC summary was updated by ECRI on December 17, 2001, June 23, 2003, January 23, 2004, and most recently on February 28, 2005.