Background
Phase 2 single-arm trial (SWOG 9416 / Intergroup 0160). 110 patients with T3-4N0-1 superior sulcus (Pancoast) NSCLC. Enrolled April 1995–November 1999 at SWOG/ECOG/RTOG/NCCTG institutions. Eligible if thoracotomy feasible and no N2-3 disease, distant metastases, or malignant pleural effusion.
Interventions and follow up
Arm A: Cisplatin 50 mg/m² days 1, 8, 29, 36 + etoposide 50 mg/m² days 1–5, 29–33 concurrent with RT 45 Gy (25 fractions) → thoracotomy (patients with stable or responding disease) → cisplatin/etoposide × 2 more cycle
Primary endpoint: Feasibility, complete resection rate, 5-year OS
mFollow up: Median 69.5 month
Primary endpoint: Feasibility, complete resection rate, 5-year OS
mFollow up: Median 69.5 month
Results
Induction completion rate: 95% (104/110)
Complete resection rate: 76% (83/110 all patients; 88/95 eligible underwent thoracotomy)
Pathologic CR or minimal residual disease: 56%
5-yr OS (all patients): 44%
5-yr OS (complete resection): 54%
T3 vs T4 5-yr OS: No significant difference (P=.68)
Pathologic CR vs residual disease OS: P=.02 (favoring pCR)
Complete resection rate: 76% (83/110 all patients; 88/95 eligible underwent thoracotomy)
Pathologic CR or minimal residual disease: 56%
5-yr OS (all patients): 44%
5-yr OS (complete resection): 54%
T3 vs T4 5-yr OS: No significant difference (P=.68)
Pathologic CR vs residual disease OS: P=.02 (favoring pCR)
Adverse events
Main adverse events: Postoperative mortality: 2 patients (1.8%). Grade ≥3 hematologic toxicity during induction: 49%. Esophagitis grade ≥3: 5%. No unexpected pulmonary or cardiac toxicities from trimodality approach.
Conclusions
Trimodality therapy (cisplatin/etoposide + 45 Gy → surgery) achieves high complete resection rates (76%) and 5-year OS of 44% for superior sulcus NSCLC — markedly superior to historical results with RT ± surgery (~30% 5-yr OS). T4 tumors did not have worse outcomes than T3, and pathologic complete response was strongly prognostic.
Key Limitations
Key Limitations: Single-arm phase 2 — no concurrent randomized comparator. Only N0-1 superior sulcus tumors enrolled; N2-3 disease (which carries worse prognosis) was excluded. Conducted exclusively at SWOG network institutions with high thoracic surgical expertise — outcomes may not replicate in lower-volume centers. Subclavian vessel or vertebral body involvement (T4) was permitted but details on resectability by anatomical extension were limited. Pre-PET staging era; some patients may have had occult distant disease.
Clinical Context
Established concurrent cisplatin/etoposide + 45 Gy → surgical resection as the standard trimodality approach for resectable superior sulcus NSCLC, replacing preoperative RT alone → surgery. The 54% 5-year OS for completely resected patients is the benchmark outcome data used in guidelines. Per NCCN: resectable superior sulcus NSCLC (T3-4N0-1) → concurrent chemoRT (45 Gy) → resection → adjuvant chemotherapy. Pathologic CR (56%) is substantially higher than other stage III NSCLC trimodality approaches, likely reflecting the favorable biology of N0-1 Pancoast tumors.
References