JAMA Oncol
Effect of Postoperative Radiotherapy for Patients With pIIIA-N2 Non-Small Cell Lung Cancer After Complete Resection and Adjuvant Chemotherapy: The Phase 3 PORT-C Randomized Clinical Trial.
Abstract
Importance
The role of postoperative radiotherapy (PORT) has not been well defined in resected pIIIA-N2 non-small cell lung cancer (NSCLC).
Objective
To evaluate the effect of PORT using modern techniques on survival and safety in patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy.
Design, setting, and participants
The PORT-C randomized clinical trial was conducted in 394 patients with pIIIA-N2 NSCLC treated with complete resection and 4 cycles of platinum-based chemotherapy between January 2009 and December 2017. Data were analyzed between March 2019 and December 2020.
Interventions
Patients were randomized equally into the PORT arm (n = 202) or the observation arm (n = 192). The total dose of PORT was 50 Gy.
Main outcomes and measures
The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival, and toxic effects.
Results
In total, 394 patients were enrolled and 364 were eligible, with a median (range) age of 55 (25-70) years. There were 202 (55.5%) male and 162 (44.5%) female patients. The median follow-up was 46.0 (95% CI, 41.9-51.4) months, and 230 DFS events were reported. There were 184 patients in the PORT arm and 180 patients in the observation arm. The 3-year DFS rates were 40.5% with PORT vs 32.7% with observation (median, 22.1 vs 18.6 months), and the difference in DFS was not statistically significant without adjustment (hazard ratio [HR], 0.84; 95% CI, 0.65-1.09; P = .20), though it was significant with preplanned yet exploratory analysis (stratified analysis by the number of detected lymph nodes and positive lymph nodes, HR, 0.75; log-rank P = .04). The 3-year OS rates were 78.3% vs 82.8% (HR, 1.02; P = .93), and LRFS was 66.5% vs 59.7% (HR, 0.71; 95% CI, 0.51-0.97; P = .03), respectively. For 310 per-protocol patients (140 with PORT and 170 with observation), PORT significantly improved DFS (42.8% vs 30.6%; HR, 0.75; 95% CI, 0.57-1.00; P = .05) but not OS (HR, 0.83; 95% CI, 0.53-1.30; P = .41). The 3-year local recurrence only rates were 9.5% and 18.3% in the 2 arms, respectively (Fine-Gray HR, 0.55; Gray test P = .04). No radiotherapy-related grade 4 or 5 adverse event was observed.
Conclusions and relevance
In this phase 3 randomized clinical trial of patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy, PORT did not improve DFS. Further studies exploring patients who might best benefit from PORT are needed.
Trial registration
ClinicalTrials.gov Identifier: NCT00880971.
Related Questions
In resected N2 NSCLC, what nodal pathologic characteristics prompt you to recommend PORT?
Increasingly difficult question to answer with the evolution of neoadjuvant and adjuvant treatment paradigms. We know from both Lung ART and PORT-C that the addition of PORT in completely resected patients with N2 disease improves locoregional control across the cohort as a whole; however, this did ...
Would you offer postoperative radiation for a patient who initially had biopsy-proven multistation N2 NSCLC but had a nodal pCR upon surgical resection+ LND after neoadjuvant chemo-immunotherapy?
I would not routinely offer PORT for completely resected N2 disease based on lack of survival benefit from LungART (have my qualms about ~90% 3DCRT and the probable impact on cardiothoracic toxicity), particularly in a patient who appears to have had a fantastic response to neoadjuvant therapy. I th...
How do you approach adjuvant therapy for resected lung adenocarcinoma that was found unexpectedly postop to be N2?
Preliminary results of the phase 3 randomized LungART trial (NCT00410683) were recently presented at a virtual ESMO conference. 501 patients with pathologically confirmed N2 NSCLC s/p complete resection were randomized to postoperative RT (54 Gy) or observation. Almost all patients received chemothe...
How do you approach PORT for T3N0 NSCLC, which had chest wall invasion, now status post lobectomy with a microscopically positive margin?
PORT should still be offered/considered for R1 resection such as this T3N0 patient. It sounds as if this person, or someone in a similar scenario, would have been served well to have undergone NACT to help achieve R0 prior to surgery. But nonetheless, I would take the following approach (assuming ap...