Optimal approach for upfront resectable non-small-cell lung cancer

Abstract

Approximately one third of patients with non-small-cell lung cancer (NSCLC) present with resectable disease, defined as clinical stages I and II and some borderline stage III extensions (e.g. T3N0–1). Although radical resection is the cornerstone of treatment in adequately staged patients, its outcome is not always curative, as some patients might be functionally inoperable, refuse surgery, have an unexpected non-radical resection or stage upgrading, or relapse locally or with distant metastases. The following reviews address the current state of the art in the peri- and intra-operative management of patients with resectable NSCLC. As disease extent is an important predictor of prognosis and determines treatment choices, accurate staging is of prime importance. The 10 modifications and the mediastinal lymph-node map – adopted by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (IUCC) in their respective seventh revision of the tumour-node-metastasis (TNM) system – are considered a quality indicator for disease extent, initial treatment allocation and the reporting of treatment results. Difficulties arise in accurate prognosis owing to the role of stage migration and the increasing number of biological factors interfering with disease extent. There are many tumour-related pathological factors, but only one is actually routinely used in clinical practice. Most factors probably lack potential clinical usefulness. Surgical resection remains the standard of care for functionally operable early-stage NSCLC and resectable stage IIIA disease. The role of invasive staging and restaging techniques is currently under debate, but they provide large biopsy specimens which allow for precise mediastinal staging. Different operative procedures are currently available to the thoracic surgeon, and some can be performed by video-assisted thoracic surgery (VATS) with oncological results equal to those of open thoracotomy. The new multidisciplinary adenocarcinoma classification has profound surgical implications. The role of limited or sublobar resection comprising anatomical segmentectomy and wide wedge resection are considered for early-stage lesions which are more frequently encountered with the recently introduced screening programmes. Large databases are currently collecting many surgical parameters, allowing more precise calculation of mortality and morbidity according to predefined risk factors. Centralisation of care has been shown to improve results. Quality-of-life evaluation is becoming increasingly important and should be considered when deciding on a specific treatment, especially in a multimodality setting. In the situation of totally resected NSCLC patients, the role of post-operative chemotherapy is now established for stages II and IIIA and remains debatable in stage IB. Various attempts to identify prognostic biomarkers for selecting patients for adjuvant chemotherapy have failed so far. Patient selection for adjuvant therapy should be based upon more discriminatory pathological data than a crude assessment such as stage, but only if supported by evidence. The present recommendations for resected NSCLC from the European Society for Medical Oncology (ESMO) are to deliver a cisplatin-based chemotherapy for stages II and III. The role of post-operative radiation therapy (PORT) in this group of patients remains controversial. In a meta-analysis, the conclusions were that PORT was detrimental to patients with early-stage completely resected NSCLC, but the role of PORT in the treatment of tumours with N2 involvement was unclear, and further research was warranted. Recent retrospective and non-randomised studies – as well as subgroup analyses of randomised trials evaluating adjuvant chemotherapy – provide evidence of possible benefit of PORT in patients with mediastinal nodal involvement. In summary, these are exciting times for the treatment of early-stage lung cancer as prevalence, classification, staging and treatment have changed, although proof of better outcome has still to be delivered.