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      International guidelines on stage III N2 nonsmall cell lung cancer: surgery or radiotherapy?

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          Abstract

          Stage III N2 nonsmall cell lung cancer (NSCLC) is a complex disease with poor treatment outcomes. For patients in whom the disease is considered technically resectable, the main treatment options include surgery (with neoadjuvant or adjuvant chemotherapy/neoadjuvant chemoradiotherapy (CRT)) or CRT followed by adjuvant immunotherapy (dependent on programmed death ligand 1 status). As there is no clear evidence demonstrating a survival benefit between these options, patient preference plays an important role. A lack of a consensus definition of resectability of N2 disease adds to the complexity of the decision-making process. We compared 10 international guidelines on the treatment of NSCLC to investigate the recommendations on preoperatively diagnosed stage III N2 NSCLC. This comparison simplified the treatment paths to multimodal therapy based on surgery or radiotherapy (RT). We analysed factors relevant to decision-making within these guidelines. Overall, for nonbulky mediastinal lymph node involvement there was no clear preference between surgery and CRT. With increasing extent of mediastinal nodal disease, a tendency towards multimodal treatment based on RT was identified. In multiple scenarios, surgery or RT-based treatments are feasible and patient involvement in decision-making is critical.

          Abstract

          For many patients with stage III N2 NSCLC, radiotherapy or surgery are options and should be discussed with the patient http://bit.ly/2Z39MW5

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          Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial.

          Results from phase II studies in patients with stage IIIA non-small-cell lung cancer with ipsilateral mediastinal nodal metastases (N2) have shown the feasibility of resection after concurrent chemotherapy and radiotherapy with promising rates of survival. We therefore did this phase III trial to compare concurrent chemotherapy and radiotherapy followed by resection with standard concurrent chemotherapy and definitive radiotherapy without resection. Patients with stage T1-3pN2M0 non-small-cell lung cancer were randomly assigned in a 1:1 ratio to concurrent induction chemotherapy (two cycles of cisplatin [50 mg/m(2) on days 1, 8, 29, and 36] and etoposide [50 mg/m(2) on days 1-5 and 29-33]) plus radiotherapy (45 Gy) in multiple academic and community hospitals. If no progression, patients in group 1 underwent resection and those in group 2 continued radiotherapy uninterrupted up to 61 Gy. Two additional cycles of cisplatin and etoposide were given in both groups. The primary endpoint was overall survival (OS). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00002550. 202 patients (median age 59 years, range 31-77) were assigned to group 1 and 194 (61 years, 32-78) to group 2. Median OS was 23.6 months (IQR 9.0-not reached) in group 1 versus 22.2 months (9.4-52.7) in group 2 (hazard ratio [HR] 0.87 [0.70-1.10]; p=0.24). Number of patients alive at 5 years was 37 (point estimate 27%) in group 1 and 24 (point estimate 20%) in group 2 (odds ratio 0.63 [0.36-1.10]; p=0.10). With N0 status at thoracotomy, the median OS was 34.4 months (IQR 15.7-not reached; 19 [point estimate 41%] patients alive at 5 years). Progression-free survival (PFS) was better in group 1 than in group 2, median 12.8 months (5.3-42.2) vs 10.5 months (4.8-20.6), HR 0.77 [0.62-0.96]; p=0.017); the number of patients without disease progression at 5 years was 32 (point estimate 22%) versus 13 (point estimate 11%), respectively. Neutropenia and oesophagitis were the main grade 3 or 4 toxicities associated with chemotherapy plus radiotherapy in group 1 (77 [38%] and 20 [10%], respectively) and group 2 (80 [41%] and 44 [23%], respectively). In group 1, 16 (8%) deaths were treatment related versus four (2%) in group 2. In an exploratory analysis, OS was improved for patients who underwent lobectomy, but not pneumonectomy, versus chemotherapy plus radiotherapy. Chemotherapy plus radiotherapy with or without resection (preferably lobectomy) are options for patients with stage IIIA(N2) non-small-cell lung cancer. National Cancer Institute, Canadian Cancer Society, and National Cancer Institute of Canada.
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            NCCN Guidelines Insights: Non–Small Cell Lung Cancer, Version 5.2018

            The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the targeted therapy and immunotherapy sections in the NCCN Guidelines. For the 2018 update, a new section on biomarkers was added.
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              Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer.

              Induction chemotherapy before surgical resection increases survival compared with surgical resection alone in patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC). We hypothesized that, following a response to induction chemotherapy, surgical resection would be superior to thoracic radiotherapy as locoregional therapy. Selected patients with histologic or cytologic proven stage IIIA-N2 NSCLC were given three cycles of platinum-based induction chemotherapy. Responding patients were subsequently randomly assigned to surgical resection or radiotherapy. Survival curves were estimated using Kaplan-Meier analyses from time of randomization. Induction chemotherapy resulted in a response rate of 61% (95% confidence interval [CI] = 57% to 65%) among the 579 eligible patients. A total of 167 patients were allocated to resection and 165 to radiotherapy. Of the 154 (92%) patients who underwent surgery, 14% had an exploratory thoracotomy, 50% a radical resection, 42% a pathologic downstaging, and 5% a pathologic complete response; 4% died after surgery. Postoperative radiotherapy was administered to 62 (40%) of patients in the surgery arm. Among the 154 (93%) irradiated patients, overall compliance to the radiotherapy prescription was 55%, and grade 3/4 acute and late esophageal and pulmonary toxic effects occurred in 4% and 7%; one patient died of radiation pneumonitis. Median and 5-year overall survival for patients randomly assigned to resection versus radiotherapy were 16.4 versus 17.5 months and 15.7% versus 14%, respectively (hazard ratio = 1.06, 95% CI = 0.84 to 1.35). Rates of progression-free survival were also similar in both groups. In selected patients with pathologically proven stage IIIA-N2 NSCLC and a response to induction chemotherapy, surgical resection did not improve overall or progression-free survival compared with radiotherapy. In view of its low morbidity and mortality, radiotherapy should be considered the preferred locoregional treatment for these patients.
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                Author and article information

                Journal
                ERJ Open Res
                ERJ Open Res
                ERJOR
                erjor
                ERJ Open Research
                European Respiratory Society
                2312-0541
                January 2020
                17 February 2020
                : 6
                : 1
                : 00159-2019
                Affiliations
                [1 ]Dept of Radiation Oncology, Kantonsspital St Gallen, St Gallen, Switzerland
                [2 ]Dept of Radiation Oncology, University of Bern, Bern, Switzerland
                [3 ]Dept of Thoracic Surgery, Kantonsspital St Gallen, St Gallen, Switzerland
                [4 ]Dept of Radiotherapy, The Royal Marsden NHS Foundation Trust, London, UK
                [5 ]Dept of Thoracic Surgery, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
                [6 ]Manchester Thoracic Oncology Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK
                Author notes
                Pawel Leskow, Kantonsspital Sankt Gallen – Dept of Thoracic Surgery, Rorschacherstrasse 95, Sankt Gallen 9007, Switzerland. E-mail: leskowpj@ 123456yahoo.de
                Article
                00159-2019
                10.1183/23120541.00159-2019
                7024765
                32083114
                0760ed41-b387-4cd7-a0b3-703666d3719d
                Copyright ©ERS 2020

                This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

                History
                : 21 June 2019
                : 12 December 2019
                Categories
                Original Articles
                Lung Cancer
                6

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