Long-term outcomes of postoperative radiotherapy for patients with pIIIA-N2 non-small-cell lung cancer after complete resection and adjuvant chemotherapy (PORT-C): a single-centre, randomized, phase 3 trial
Mené sur 394 patients atteints d’un cancer du poumon non à petites cellules de stade pIIIA-N2 traité par résection complète et chimiothérapie adjuvante (durée médiane de suivi : 87,9 mois), cet essai randomisé de phase III évalue l'efficacité à long terme, du point de vue de la survie sans maladie, d'une radiothérapie tridimensionnelle ou d'une radiothérapie avec modulation d'intensité
Background: The PORT-C trial was the first published phase III randomized clinical trial (RCT) to evaluate the role of postoperative radiotherapy (PORT) using intensity-modulated radiation therapy (IMRT)/three-dimensional conformal radiation therapy (3D-CRT) in patients with resected pIIIA-N2 non-small-cell lung cancer (NSCLC). We aimed to assess the long-term outcomes of this RCT.
Methods: Patients with pIIIA-N2 NSCLC treated with complete resection followed by four cycles of platinum-based chemotherapy between January 1, 2009 and December 31, 2017 were randomly assigned in a 1:1 ratio to PORT or observation. Radiotherapy was delivered using a 6 MV-X ray linear accelerator via 3D-CRT or IMRT, with 2 Gy per fraction up to 50 Gy over 5 weeks. The primary endpoint was disease-free survival (DFS), analyzed using modified intent-to-treat (mITT). Secondary endpoints included overall survival (OS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and toxic effects. DFS, OS, LRFS, and DMFS rates were estimated using Kaplan–Meier method, compared using log-rank test, and modeled using Cox proportional hazards method. The patterns of first failures were analyzed using competing risk analyses. This trial is registered with ClinicalTrials.gov, NCT00880971.
Findings: Overall, 394 patients were randomly allocated to the PORT (n = 184) or observation (n = 180) arms. The median follow-up time was 87.9 months (interquartile range [IQR] 72.2–113.8). In the mITT analyses, DFS showed no significant difference between the PORT and observation arms (hazards ratio [HR], 0.90; 95% CI, 0.70–1.12; p = 0.39). The 5-year DFS rates in the PORT and observation arms were 36% (95% confidence interval [CI], 28.9%–43.1%) and 31.5% (95% CI, 24.6%–38.4%), respectively; the 5-year OS rates were 64.7% (95% CI, 57.6%–71.8%) and 70.4% (95% CI, 63.5%–77.3%), respectively (p = 0.20). In the per-protocol analyses, 140 and 170 patients were included in the PORT and observation arms, respectively. PORT did not significantly improve DFS (HR, 0.80; 95% CI, 0.61–1.05; p = 0.11) or OS (HR, 1.09; 95% CI, 0.77–1.53; p = 0.63). Most patients died of cancer. However, more deaths due to cardiopulmonary disease were observed in the PORT arm than in the observation arm (6/184, 3.3% vs. 2/180, 1.1%). The first failure of locoregional recurrence (LR)-only was significantly lower in the PORT arm than in the observation arm (10.9%, 95% CI, 6.8%–15.9% vs. 18.9%, 95% CI, 14.0%–26.2%, p = 0.031). Only 1 patient (0.5%) in the PORT arm had grade 3 radiation pneumonitis. No radiotherapy-related grade 4 or 5 AEs were observed.
Interpretation: The long-term results of the PORT-C trial indicated no DFS benefit from receiving PORT for patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy.
eClinicalMedicine , article en libre accès, 2025