ES10.06 Putting It Together: Current Best Practices in the Evaluation and Follow-Up of the Indeterminate Pulmonary Nodule

Abstract

In a sense, all pulmonary nodules are indeterminate until there has been a definitive diagnosis or long-term follow-up. Which nodules are included in the “indeterminate” category is determined by the definition applied, and this can differ between established guidelines. For the purposes of this talk, which relates specifically to the context of LDCT screening for lung cancer, the recommendations from five key guidelines on the management of pulmonary nodules have been reviewed1 - 5. A further key guideline, the Fleischner Society 2017 update refers only to nodules detected incidentally, rather than in a screening setting so is not included in the comparisons6. Most comparisons of recommendations concentrate on the approach to nodules according to size categories because this is one of the major determinants of the probability that a nodule is both malignant and harmful. This is a useful approach but can produce some complicated tables. This talk approaches the subject from a slightly different and patient-centred angle. For participants in screening, it is important to think of the impact of management strategies and there are 3 key outcomes after either a prevalence or incident screen: return to the screening programme for the next scheduled screen; have additional low dose CT(s) before the next screen is due; and be referred to the hospital for further clinical work-up. The chance of harming the participant, both physically and psychologically, increases as we progress through these categories. It is thus important to avoid both additional LDCT and clinical work-up, unless beneficial. Guidelines aim to do this by managing the vast majority of nodules with minimal chance of harm whilst promptly investigating those nodules likely to be both malignant and harmful. It is important to appreciate that nodules that are malignant are not always harmful because they may be very slow growing and treating them may cause more harm. This can be the case for sub-solid nodules. Comparisons are made for four situations: baseline (prevalence) detection, new nodules (incidence screen), subsolid nodules and growing nodules. The table shows an example of a comparison for baseline detection. The Lung RADS 1.1 and NCCN guidelines essentially make the same recommendations. Guidelines generally agree on the threshold for returning to the screening programme but specify an annual screen (1 year interval) except for the British Thoracic Society (BTS), where the interval can be longer. Guidelines differ somewhat on the management of the nodules that require a shorter interval. It can be seen that there is the potential for a stage shift from T1a (≤10mm) for some of the recommendations although caveats are added such as the option for PET-CT or very short interval CT for larger nodules. Another potentially important difference is the use of semi-automated volumetry, which is the preferred method to measure nodules and their growth in both the BTS guideline and the European Position Statement (EUPS). Both of these documents make a case for the better accuracy of volumetry as compared with manual diameter measurements. This also has implications for some of the other recommendations for growing nodules where management is recommended on the basis of volume doubling time (VDT). For example, both BTS and the EUPS recommend work-up on the basis of specific VDTs, with less invasive options for participants who have nodules with a VDT of 400-600 days. I-ELCAP defines growth sufficient to prompt work-up as a VDT of 180 days, in contrast to BTS and EUPS where it is 400 days. BTS is the only guideline that firmly recommends the use of multivariable models in the management of people with nodules. The Brock / PanCan model is recommended at baseline to assist in deciding who should undergo PET-CT. This avoids this high-radiation dose scan in people who have low risk nodules. The Herder model is then used to classify nodules further. The use of PET-CT is generally recommended in the further assessment of nodules and the cut-off size is broadly >8-10mm diameter, reflecting the limitations of PET in nodules smaller than this. Guidelines are cautious with the management of sub-solid nodules, reflecting their often indolent nature and therefore the potential to harm participants by over-zealous treatment. The is particularly the case for pure ground glass / non-solid nodules; most guidelines only recommend an invasive approach if there is a solid component. Much progress has been made on the management of pulmonary nodules, and this is reflected in the much lower frequency of complications and invasive approaches in participants who do not have cancer. It will be important that screening centres adhere to guidelines to ensure participants experience the maximum benefit with least arm. 1. Callister ME, Baldwin DR, Akram AR, Barnard S, Cane P, Draffan J, et al. British Thoracic Society guidelines for the investigation and management of pulmonary nodules. Thorax. 2015;70 Suppl 2:ii1-ii54 2. Matthijs Oudkerk AD, Rozemarijn Vliegenthart, Thomas Henzler, Helmut Prosch, Claus P Heussel, Gorka Bastarrika, Nicola Sverzellati, Mario Mascalchi SD, David R Baldwin, Matthew E Callister, Nikolaus Becker, Marjolein A Heuvelmans, Witold Rzyman, Maurizio V Infante UP, Jesper H Pedersen, Eugenio Paci, Stephen W Duffy, Harry de Koning, John K Field. European position statement on lung cancer screening. Lancet Oncology. 2017;18(12): e754–e66. 3. American College Radiology. Lung RADS v 1.1 2019 [Available from: https://www.acr.org/-/media/ACR/Files/RADS/Lung-RADS/LungRADSAssessmentCategoriesv1-1.pdf?la=en. 4. National Comprehensive Cancer Network. NCCN Lung Cancer Screening Version 1 2021 [Available from: https://www.nccn.org/professionals/physician_gls/pdf/lung_screening.pdf. 5. International Early Lung Cancer Action Program Investigators Group. Protocol Documents 2016 [Available from: https://www.ielcap.org/sites/default/files/I-ELCAP-protocol-summary.pdf. 6. MacMahon H, Naidich DP, Goo JM, Lee KS, Leung ANC, Mayo JR, et al. Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Images: From the Fleischner Society 2017. Radiology. 2017;284(1):228-43.