Phase III study of concurrent chemotherapy and radiotherapy (CT/RT) vs CT/RT followed by surgical resection for stage IIIA(pN2) non-small cell lung cancer (NSCLC): Outcomes update of North American Intergroup 0139 (RTOG 9309)

Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study

“…Results from a phase III trial comparing chemotherapy and radiotherapy with preoperative chemotherapy and surgical resection in patients with stage IIIA pN2 NSCLC found no survival differences between treatment arms (Johnstone et al, 2002). In contrast, the final results from a study conducted by the North American Intergroup, in which patients with stage IIIA NSCLC were randomised to postinduction resection or further chemotherapy and radiotherapy following induction with chemoradiotherapy, showed improved progression-free survival in the surgery arm (Albain et al, 2003(Albain et al, , 2005. The European Organisation for Research and Treatment of Cancer (EORTC) study (INT 08941) randomised patients with nonresectable locally advanced stage IIIA disease to cisplatin-based induction chemotherapy followed either by surgery or radiotherapy.…”

How to evaluate the risk/benefit of trimodality therapy in locally advanced non-small-cell lung cancer

“…In fact, the local relapse rate appeared to have decreased, especially in R0-surgery cases. In an intention-to-treat analysis, 'local relapse only' accounted for 10% of the cases showing disease progression in the trimodality arm of INT0139 (Albain et al, 2005), whereas it accounted for 22% of the cases showing disease progression in the chemoradiotherapy arm (P ¼ 0.002). However, these figures might have been biased by competitive risks; as the trimodality approach was associated with a larger number of treatment-related deaths, and as it is plausible that cases at a higher risk of postoperative morbidity/mortality were more likely suffer from uncontrollable local tumours, the local control rate with the trimodality approach could have been exaggerated by the exclusion of these high-risk patients.…”

“…However, the compliance rate for this strategy was reported to be poor (Pisters et al, 2000;Rusch et al, 2001). In addition, some deaths related to drug toxicity have also been reported during the consolidation phase (Albain et al, 2005), prompting further questioning of its benefits. The role of consolidation therapy after surgery, therefore, still remains to be established.…”

“…In fact, surgery may not be indicated at all for clinically suspected and pathologically confirmed (via mediastinoscopy) N2 disease, even when the disease is technically 'resectable' (Albain et al, 2005).…”

“…A large-scale US trial, INT0139, compared surgical resection and boost radiotherapy, in patients with N2 NSCLC receiving induction chemoradiotherapy (Albain et al, 2005). Although the progressionfree survival (PFS) rate favoured the surgery (trimodality) arm, the overall survival rate was not statistically significantly different between the two arms, with only a marginally larger number of long-term survivors in the surgery arm.…”