ES12.01 Defining Operability

Abstract

Stage III, so called loco-regionally or locally advanced» NSCLC comprises about one third of NSCLC patients and is very heterogeneous with varying outcome. Because of the heterogeneity (IIIA 36 %, IIIB 26% and IIIC 13% 5-years survival rate) a schematic management approach is very difficult, which is reflected in complex algorithms of existing guidelines. The current optimal staging and treatment decision for this patient group - usually a combination of local therapy (surgery or radiotherapy) and systemic therapy - requires multidisciplinary expert team effort.The definition of functional, technical, and oncological operability is depending on many factors and is not standardized to date. For adequate decision-making, several points need to be taken into consideration: Thorough preop-staging needs to be performed with caveat to differences between clinical and pathological staging. Recent analysis of Navani et al1. used individual participant data from randomized controlled trials (RCTs) and assessed agreement between clinical TNM (cTNM) stage at randomization and pathologic TNM (pTNM) stage. The results are based on 698 patients and demonstrated suboptimal agreement between clinical and pathologic staging. Discrepancies between clinical and pathologic T and N staging could have led to different treatment decisions in 10% and 38% of cases, respectively. Agreement between clinical N stage and pathologic N stage showed accordance between cN2 and pN2 is 67% (104/155) and if clinical staging overestimates the extent of nodal disease (114 patients [15%] in this meta-analysis), then this may mean patients are potentially denied from surgery. Eventually, further molecular and immunological staging of the tumors may help to move forwards to more personalized precision medicine.Functional assessment is equally important for the indication for tumor resection. Current guidelines include algorithms2; however, patients with limited lung function and emphysema should be assessed for a potential lung volume reduction effect where resection can even lead to improvement of lung function3-5. Extremely important is also the patient’s individual expectation for postoperative quality of life and fitness, and should be taken into account during decision-making (figure 1). Figure 1: Algorithm illustrating the approach to patients with reduced lung function and stage I lung cancer6 The most critical point of operability assessment is how to define resectability. Across guidelines, only limited agreement exists (table 1) and in here, solely the fact that bulky N2 (only NCCN guidelines give a clear recommendation what “bulky” means > 3cm) should be excluded from surgery is in alignment between the different existing recommendations, besides clear resection margins. With regard to the number or zones of lymph node involvement, the variety ranges from “single”, to “discrete”, to “low volume” which are not further refined. Table 1: Summary of UK, European and American guidelines on the management of potentially resectable N2 NSCLCTabled 1GuidelineDefinition of ‘resectable’RecommendationsNotesBTS and SCTS 20107Non-fixed lymph nodes Non-bulky lymph nodes Single-zone N2 disease Reasonable chance of: Complete resection Clear pathological marginsConsider surgery as part of multimodality treatment in non-fixed, nonbulky, single-zone N2 NSCLC Further research into the role of surgery in non-fixed, non-bulky, multi-zone N2 NSCLCSignificant weight placed on IASLC staging database outcomes despite lack of comparator group and lack of clinical N2 Guidelines consider evidence for adjuvant chemotherapy more robust than pre-operative chemotherapyACCP 20138Discrete lymph nodes Easily measurable and defined lymph nodes Free from major structures, such as the great vessels and tracheaDefinitive CRT or induction therapy (chemotherapy or CRT) followed by surgery Surgery followed by adjuvant chemotherapy not ecommendedDoes not support the concept that surgery can only be justified in patients with minimal N2 disease Pre-operative chemotherapy better than surgery alone in all NSCLC (small studies) and therefore surgery plus adjuvant chemotherapy is not recommendedESMO 20159Minimal, non-bulky N2 disease Single-station N2 diseaseDefinitive CRT, induction chemotherapy followed by surgery or induction CRT followed by surgeryParamount importance of an experienced and high-volume multi-disciplinary team (MDT) and treatment centres able to minimise risk and complications from multi-modality treatment highlightedNCCN 201810Low-volume lymph nodes Non-invasive lymph nodes Pathologically proven Measuring <3 cmDefinitive CRT or induction chemotherapy followed by surgery or induction CRT followed by surgery Maintenance durvalumab following cCRTBenefit from pre-operative chemotherapy is similar to that of post-operative chemotherapy and either approach is justifiedNICE 201911None providedConsider CRT followed by surgeryCRT followed by surgery improves PFS and might improve survival compared with CRT alone Open table in a new tab (created by Evison12 using guidance from indicated Guidelines) ACCP American College of Chest Physicians, BTS British Thoracic Society, CRT chemoradiotherapy, cCRT concurrent chemoradiotherapy, ESMO European Society of Medical Oncology, IASLC International Association for the Study of Lung Cancer, NICE National Institute for Health and Care Excellence, NCCN National Comprehensive Cancer Network, NSCLC non-small cell lung cancer, PFS progression-free survival, SCTS The Society for Cardiothoracic Surgery in Great Britain and Ireland. 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