You may not be interested in lung nodules, but lung nodules are interested in you.
In May 2025, an Australian National Lung Cancer Screening Program (NLCSP) will commence and will uncover thousands of prevalent lung nodules in West Australian patients, each requiring consideration and appropriate management.
Up to 10 subsequent rounds of biennial screening with potential additional interval scans will generate further though smaller waves of incident nodules thereafter.
Lung nodules are very common on chest CT scans in smokers and non-smokers. Thirty-nine per cent of smokers screened for lung cancer at Royal Perth Hospital in 2009 had lung nodules, though in a high-risk population screened at Sir Charles Gairdner Hospital between 2010 and 2020 only 9% had nodules of sufficient concern to warrant further investigation (1.4% were cancer) – this data is consistent with the international experience that almost all lung nodules are benign.
A lung nodule is defined as a rounded or irregularly bordered discrete opacity on chest X-ray or CT less than 30mm in diameter (those larger than 30mm are designated “masses”).
One of the most mentioned lung nodules in the radiology report is, paradoxically, not a nodule. This is the erroneously termed peri-fissural nodule (PFN), sometimes known as a juxta-pleural nodule.
A PFN is not a nodule in that it is not round or irregular, it is instead faceted and polygonal when considered in three dimensions and appears pyramidal or lentiform in two dimensions. PFNs are normal pulmonary lymph tissue, and their characteristic shape is dictated by the tension of the surrounding interstitium as they are only firm enough to ‘peel’ the interstitium back and not bulge or invade it in the way a true lung lesion would.
Risk of malignancy – size density and growth
Lung nodules are analogous to calcifications on mammography, being very common with radiologists trained to recognise the difference between benign and malignant features. From a radiological perspective, the most prognostic features of lung nodules are their size, density and growth velocity.
The larger the nodule the more likely it is to be malignant.
The density characteristics on CT affects the probability of malignancy as the density pattern reflects the histological differences between lesions.
The least suspicious nodules overall are solid nodules – most often uniform soft tissue density (though may contain calcium and rarely fat) and completely replace normal lung. This is because almost all the benign lesions (including granulomas, PFNs and hamartomas) are histologically confluent which translates to their uninterrupted density on CT.
The most suspicious are part solid nodules, that is those that are part ground glass and part soft tissue density (with the ground glass portion evoking a pre-invasive component and the solid portion an invasive component). Less commonly, the non-soft tissue component is an air-cyst density with the air cysts due to destruction of basement membranes with secondary conglomeration of air sacs by the cicatrising effect of invasive malignancy.
Of intermediate suspicion are the non-solid nodules which are of a pure hazy or ‘ground glass’ density. These nodules are the most specific and are usually indicative of atypical adenomatous hyperplasia (a pre-cursor to early invasive adenocarcinoma) or focal interstitial fibrosis. Their hazy appearance is due to fine intermixing of dense (lesion) and non-dense (normal lung) components.
Nodule growth is expressed by volume doubling time (VDT). The VDT of a nodule is the number of days required for a nodule to double its volume. A longer VDT indicates a more benign lesion, whilst a short VDT suggests a higher histological grade.
According to most studies a volume doubling time less than 500 days represents a high likelihood of malignancy and the longer the VDT the less concerning the lesion.
The NLCSP will use a risk prediction model for the initial round of screening (the Pan-Canadian Early Detection of Lung Cancer (PanCan) risk model). This calculates the probability of lung cancer on a continuous scale.
PanCan incorporates patient characteristics (age, sex, presence of emphysema and family history of lung cancer) and nodule characteristics (size, type, location, number of nodules, and signs of spiculation). A nodule risk index of less than 1.5% is regarded as benign, 1.5% to 5% low risk, 6% to 30% moderate risk and greater than 30% high risk of malignancy.
The PanCan result will determine if a patient requires further testing immediately and guide the schedule for subsequent screening rounds.
For the subsequent rounds, Lung-RADS will be used as the reporting template. This was developed to standardise the reporting and management of lung nodules. Lung-RADS models cancer risk on three nodule characteristics – size, density and growth.
The Lung-RADS category 1 means negative (no nodule), 2 means benign, 3 means probably benign, 4A means suspicious (with 5% to 15% probability of clinically active cancer in the next year), 4B means very suspicious (with greater than 15% probability of cancer in the next year), and 4X means very suspicious (not otherwise specified).
For a deep dive into the rationale for the adoption of these lung nodule management models we refer you to Medicare Service Advisory Committees March-April 2022 Public Summary Document.
The Australian National Cancer Screening Register (NCSR) will support the NLCSP by:
- maintaining a national database of lung screening records
- reminding participants when they are due or overdue for lung screening and when they need to take action after a scan
- providing participant lung screening reports to
– assist radiologists in reporting LDCT scans
– support healthcare providers in recommending follow-up investigations - enabling participants to access their lung cancer screening information in the register, including updating their participation
- monitoring of the effectiveness, quality and safety of lung cancer screening to improve delivery of the NLCSP.
Minimising overdiagnosis is critical to the success of any screening program. The risk of overdiagnosis requires careful consideration before embarking on invasive investigations. The most common lung cancer is an early invasive adenocarcinoma, and these lesions are typically indolent, therefore elderly patients with multiple co-morbidities may not live long enough to suffer from these lesions.
Key messages
- Lung nodules are very common and the great majority are benign. Nodules larger than 6mm, with short doubling times or with part-solid density are of greatest concern
- The Australian National Lung Cancer Screening Program commences in 2025 and will uncover prevalent lung nodules in thousands of people. Doctors will be supported by the National Cancer Screening Registry and education from representative colleges.
- The risk of malignancy per nodule in the initial round will be determined by the PanCan model and in subsequent rounds Lung-RADS.
Author competing interests – nil