Stage IIIA NSCLC Treatment
Adjuvant chemoradiation therapy
Combination chemotherapy and radiation administered before or following surgery should be viewed as investigational and requiring evaluation in future clinical trials.
- Five randomized trials have assessed the value of postoperative combination chemoradiation therapy versus radiation following surgical resection.[3,5,14,15,16][Level of evidence: 1iiA]
- Only one trial reported improved disease-free survival (DFS) and no trial reported improved OS.
- Three trials have evaluated platinum-based combination chemotherapy followed by surgery versus combined platinum-based combination chemoradiation therapy (60 Gy-69.6 Gy) alone to determine which local treatment modality (surgery or radiation therapy) was most efficacious.[16,17,18] Although studies were small, enrolling 73, 107, and 333 patients with stage IIIA-N2 disease, respectively, no trial reported a difference in local control or survival.[16,17,18][Level of evidence: 1iiA]
- In the largest series (EORTC-08941), 579 patients with histologic- or cytologic-proven stage IIIA-N2 NSCLC were given three cycles of platinum-based induction chemotherapy. The 333 responding patients were subsequently randomly assigned to surgical resection or radiation therapy. Of the 154 patients (92%) who underwent surgery, 50% had a radical resection, 42% had a pathologic downstaging, and 5% had a pathologic complete response; 4% died after surgery. Postoperative (adjuvant) radiation therapy (PORT) was administered to 62 patients (40%) in the surgery arm. Among the 154 patients (93%) who received radiation therapy, overall compliance to the radiation therapy prescription was 55%, and grade 3-4 acute and late esophageal and pulmonary toxic effects occurred in 4% and 7% of patients; one patient died of radiation pneumonitis.
- Median and 5-year OS for patients randomly assigned to resection versus radiation therapy were 16.4 versus 17.5 months and 15.7% versus 14%, respectively (HR = 1.06; 95% CI, 0.84-1.35).
- Rates of progression-free survival were also similar in both groups. In view of its low morbidity and mortality, it was concluded that radiation therapy should be considered the preferred locoregional treatment for these patients.
Adjuvant radiation therapy
The value of PORT has been assessed. Although some studies suggest that PORT can improve local control for node-positive patients whose tumors were resected, it remains controversial whether it can improve survival. The optimal dose of thoracic PORT is not known at this time. The majority of studies cited used doses ranging from 30 Gy to 60 Gy, typically provided in 2 Gy to 2.5 Gy fractions.
As referred to in the National Cancer Institute of Canada and Intergroup Study JBR.10 study (NCT00002583), PORT may be considered in selected patients to reduce the risk of local recurrence, if any of the following are present:
- Involvement of multiple nodal stations.
- Extracapsular tumor spread.
- Close or microscopically positive resection margins.