Definitions for the strength of evidence and recommendation grades (1A-2C) follow the recommendations.
The patients with non-small cell lung cancer (NSCLC) with stage IIIA (N2) tumors present substantial heterogeneity in clinical presentation, treatment, and prognosis. Therefore, for the purposes of generating rational treatment guidelines, the guideline developers have chosen to classify N2 tumors into four subsets (see Table below).
Table: Subsets of Stage IIIA(N2)*
Subset |
Description |
IIIA1 |
Incidental nodal metastases found on final pathology examination of the resection specimen |
IIIA2 |
Nodal (single station) metastases recognized intraoperatively |
IIIA3 |
Nodal metastases (single or multiple station) recognized by prethoracotomy staging (mediastinoscopy, other nodal biopsy, or positron emission tomography [PET] scan) |
IIIA4 |
Bulky or fixed multistation N2 disease |
*Adapted from Ruckdeschel JC. Combined modality therapy of non-small cell lung cancer. Semin Oncol 1997; 24:429-439.
- Surgical Considerations: In patients with non-small cell lung cancer (NSCLC) who have incidental (occult) N2 disease (IIIA2) found at surgical resection and in whom complete resection of the lymph nodes and primary tumor is technically possible, completion of the planned lung resection and mediastinal lymphadenectomy is recommended. Grade of recommendation, 2C
- Surgical Considerations: In patients with NSCLC undergoing surgical resection, systematic mediastinal lymph node sampling or complete mediastinal lymph node dissection is recommended. Grade of recommendation, 1B
- Adjuvant Chemotherapy: In patients with resected NSCLC who were found to have incidental (occult) N2 disease (IIIA1-2) and who have good performance status, adjuvant platinum-based chemotherapy is recommended. Grade of recommendation, 1A
- Adjuvant Radiotherapy: In patients with resected NSCLC who were found to have incidental (occult) N2 disease (IIIA1-2), adjuvant postoperative radiotherapy should be considered after adjuvant chemotherapy to reduce local recurrence. Grade of recommendation, 2C
- Adjuvant Chemoradiotherapy: In patients with resected NSCLC who were found to have incidental (occult) N2 disease (IIIA1-2), combined postoperative concurrent chemotherapy and radiotherapy is not recommended except as part of a clinical trial. Grade of recommendation, 1B
- In NSCLC patients with N2 disease identified preoperatively (IIIA3), referral for multidisciplinary evaluation (which includes a thoracic surgeon) is recommended before embarking on definitive treatment. Grade of recommendation, 1C
- In NSCLC patients with N2 disease identified preoperatively (IIIA3), induction therapy followed by surgery is not recommended except as part of a clinical trial. Grade of recommendation, 1C
- In NSCLC patients with N2 disease identified preoperatively (IIIA3) who do receive induction chemoradiotherapy as part of a clinical trial, pneumonectomy is not recommended. The subsequent surgical resection in this setting should be limited to a lobectomy. If after induction chemoradiotherapy it appears that a pneumonectomy will be needed, it is recommended that pneumonectomy not be performed and treatment should be continued with full-dose radiotherapy. Grade of recommendation, 1B
- In NSCLC patients with N2 disease identified preoperatively (IIIA3), primary surgical resection followed by adjuvant therapy is not recommended except as part of a clinical trial. Grade of recommendation, 1C
- In NSCLC patients with N2 disease identified preoperatively (IIIA3), surgery alone is not recommended. Grade of recommendation, 1A
- In NSCLC patients with N2 disease identified preoperatively (IIIA3), platinum-based combination chemoradiotherapy is recommended as primary treatment. Grade of recommendation, 1B
- Surgical Considerations: In NSCLC patients with N2 disease identified preoperatively (IIIA3), surgical debulking procedures are not recommended. Grade of recommendation, 1A
- Surgical Considerations: In NSCLC patients with N2 disease identified preoperatively (IIIA3) who have incomplete resections, postoperative platinum-based chemoradiotherapy is recommended. Grade of recommendation, 1C
- In patients with NSCLC who have bulky N2 disease (IIIA4) and good performance status, radiotherapy alone is not recommended. Grade of recommendation, 1A
- In patients with NSCLC who have bulky N2 disease (IIIA4) and good performance status, combination platinum-based chemotherapy and radiotherapy are recommended. Grade of recommendation, 1A
- In patients with NSCLC who have bulky N2 disease (IIIA4), good performance status, and minimal weight loss, concurrent chemoradiotherapy is recommended over sequential chemo radiotherapy. Grade of recommendation, 1A
Definitions:
Quality of Evidence Scale
High - Randomized controlled trials (RCTs) without important limitations or overwhelming evidence from observational studies*
Moderate - RCTs with important limitations (inconsistent results, methodologic flaws, indirect, or imprecise) or exceptionally strong evidence from observational studies*
Low or very low - Observational studies or case series
*Although the determination of magnitude of the effect based on observational studies is often a matter of judgment, the guideline developers offer the following suggested rule to assist this decision: a large effect would be a relative risk > 2 (risk ratio < 0.5) [which would justify moving from weak to moderate], and a very large effect is a relative risk > 5 (risk ratio < 0.2) [which would justify moving from weak to strong]. There is some theoretical justification in the statistical literature for these thresholds (the magnitude of effect that is unlikely or very unlikely to be due to residual confounding after adjusted analysis). However, once the decision is made, authors should be explicit in justifying their decisions.
Grade of Recommendations Scale
Grade |
Recommendation |
1A |
Strong |
1B |
Strong |
1C |
Strong |
2A |
Weak |
2B |
Weak |
2C |
Weak |
Relationship of Strength of the Supporting Evidence to the Balance of Benefits to Risks and Burdens
Balance of Benefits to Risks and Burdens |
Quality of Evidence |
Benefits Outweigh Risks/Burdens |
Risks/Burdens Outweigh Benefits |
Evenly Balanced |
Uncertain |
High |
1A |
1A |
2A |
|
Moderate |
1B |
1B |
2B |
|
Low or very low |
1C |
1C |
2C |
2C |