Radiotherapy fails to extend DFS after complete resection in NSCLC
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Radiotherapy after complete resection and neoadjuvant chemotherapy failed to significantly improve 3-year DFS among certain patients with non-small cell lung cancer, according to study results presented during ESMO Virtual Congress 2020.
Researchers observed the lack of significant DFS benefit among patients with stage II to stage III NSCLC and mediastinal nodal involvement.
“This population of patients with nodal involvement is at higher risk for metastatic and locoregional failure and requires multidisciplinary treatment,” Cécile Le Pechoux, MD, radiation oncologist at Institut Gustav Roussy in Villejuif, France, said during a press conference. “Neoadjuvant chemotherapy has been the standard of care for these patients for more than a decade, but the question remains open for postoperative radiotherapy, taking into consideration that the risk for locoregional recurrence is about 30% to 60% for these patients.”
Le Pechoux and colleagues conducted the randomized, controlled LungART trial to assess the use of postoperative radiotherapy among 501 patients (median age, 61 years; range, 36-85; 66% men) with completely resected NSCLC and histologically/cytologically proven nodal involvement.
Researchers randomly assigned 252 patients to postoperative radiotherapy for 5 weeks and 249 patients to no radiotherapy.
DFS served as the primary endpoint. Secondary endpoints included OS, local control, recurrence patterns and toxicity.
Results showed median DFS of 30.5 months (95% CI, 24-49) in the radiotherapy group vs. 22.8 months (95% CI, 17-37) in the control group and 3-year DFS rates of 47.1% vs. 43.8% (HR = 0.85; 95% CI, 0.67-1.07).
Three-year OS rates favored the no-radiotherapy group (68.5% vs. 66.5%).
Researchers reported a significant reduction in mediastinal relapse among patients assigned radiotherapy. They observed 36 first events (25%) with radiotherapy compared with 70 first events (46.1%) among the control group. However, more deaths occurred in the radiotherapy group (21 vs. 8).
In addition, more grade 3 to grade 4 toxicities occurred with radiotherapy. The most common were cardiopulmonary toxicities (11% vs. 5%).
“LungART is the first European randomized study evaluating modern postoperative radiotherapy after complete resection in select patients who received neoadjuvant chemotherapy,” Le Pechoux said. “Conformal postoperative radiotherapy cannot be recommended as standard of care for all patients with completely resected stage IIIAN2 NSCLC. Further analyses are planned to assess patterns of failure, predictive factors of efficacy and toxicity, quality of radiotherapy and quality of surgery.”
Perspective
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Rafal Dziadziuszko, MD, PhD
Le Pechoux and colleagues have to be congratulated for providing us with an answer for perhaps the longest ongoing debate in thoracic oncology.
For more than 20 years, we have debated whether or not to radiate patients with mediastinal lymph node involvement after surgery. Currently, we provide patients with neoadjuvant chemotherapy and we stage these patients better. Before these results, physicians around the world hesitated on the question of providing postoperative radiotherapy to these patients. We now have a study that is a true academic effort from Institut Gustav Roussy and the French investigators, plus our colleagues from the U.K., Germany and Switzerland, that provides us with an answer.
Indeed, we can decrease the risk for local relapse; however, many of these patients will also have distant relapse, and the impact of the treatment on DFS is moderate at best and not significant. Radiotherapy also comes with increased toxicity, which probably has an impact on the death rate, as seen in this study. This is a clear message that routine postoperative radiotherapy should not be used for our patients with mediastinal involvement at time of surgery. We look forward to more systemic therapies that will also increase the likelihood that our patients survive.
Le Pechoux and colleagues should be congratulated for these results, which showed half of patients with mediastinal lymph node involvement at were alive at 5 years — a great result made possible with modern staging of patients and modern surgery.
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Le Pechoux C, et al. Abstract LBA3_PR. Presented at: European Society for Medical Oncology Virtual Congress 2020; Sept. 19-21, 2020.
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