Speaker's Highlight

• Don Sin University of British Columbia, St. Paul Hospital (Canada)
  Kenneth R. Chapman Toronto General Hospital Research Institute (Canada)
• Parameswaran Nair McMaster University (Canada)
  Carolyn Calfee UCSF (U.S.A.)
• Gregory P. Downey University of Colorado School of Medicine (U.S.A.)
  David A. Schwartz University of Colorado School of Medicine (U.S.A.)
• Neil Schluger Tuberculosis Control Branch, California Department of Public Health (U.S.A.)
  Nick Kim Critical Care & Sleep Medicine, University of California San Diego (U.S.A.)
• Nicola Hananiah Baylor College of Medicine (U.S.A.)
  Jae-Joon Yim Seoul National University College of Medicine (Republic of Korea)
• Koichiro Asano Tokai University School of Medicine (Japan)
  Diahn-Warng Perng Taipei Veterans General Hospital (Taiwan)
• Konstantinos Kostikas University of Ioannina (Greece)
  Karin Klooster University Medical Center Groningen (Kingdom of the Netherlands)

• Novel biomarkers for early detection of lung cancer

  Lung cancer remains a major health concern in Australia, where many patients are diagnosed after symptoms have progressed. Earlier identification could widen treatment options, improve survival and reduce the need for intensive therapy. Biomarkers are attracting attention because they may reveal malignant changes before a tumour is large enough to cause persistent symptoms or obvious radiological signs.

  The field includes blood-based tests, breath analysis, sputum studies, molecular imaging and artificial intelligence-assisted scans. These approaches are not replacements for clinical assessment or diagnostic imaging yet. Their value lies in helping clinicians identify people who need further investigation, particularly those whose risk is missed by symptom-based care.

  Why earlier detection matters

  A persistent cough, unexplained weight loss, chest pain or coughing blood can prompt investigation, but early lung cancer may produce none of these signs. A biomarker could identify biological changes while a person still feels well, creating an opportunity for low-dose computed tomography and specialist review.

  Australia also faces uneven access to respiratory services. People in Western Sydney, regional Queensland or remote parts of the Northern Territory may encounter longer travel times than patients near major tertiary hospitals in Melbourne or Brisbane. A reliable blood or breath test could support risk assessment in general practice before referral.

  Blood-based signals and molecular clues

  Circulating tumour DNA is released into the bloodstream by cancer cells and may carry mutations, copy-number changes or abnormal methylation patterns. Methylation signatures are particularly promising because they can reflect the abnormal switching on and off of genes associated with tumour development. A single sample could potentially capture several cancer-related signals at once.

  Other candidates include circulating tumour cells, microRNAs, proteins and lipid metabolites. These markers may be useful in combination rather than isolation. A panel that integrates age, smoking history, occupational exposure and molecular results is more likely to perform consistently than a single universal threshold.

  Respiratory biology is relevant too. Research into airway remodelling mechanisms illustrates how chronic inflammation and structural airway change can influence the lung environment. Such background disease must be considered when distinguishing cancer-associated signals from changes caused by asthma, bronchiectasis or chronic obstructive pulmonary disease.

  Breath, sputum and non-invasive testing

  Exhaled breath contains volatile organic compounds produced by normal metabolism and altered by malignant tissue. Electronic noses and laboratory-based chemical analysis are being studied to identify patterns associated with lung cancer. Breath testing is appealing because collection is painless, repeatable and potentially suitable for community clinics.

  Sputum can also contain abnormal cells, DNA fragments and molecular markers shed from the airways. It may be especially relevant for centrally located tumours or for people who cannot easily attend repeated imaging appointments. However, mucus production varies widely, and infection, smoking and chronic airway inflammation can affect results.

  Neither method is ready to function as a stand-alone diagnosis. A positive result should lead to a carefully governed pathway, while a negative test must not dismiss worrying symptoms. Test performance needs to be measured in real-world Australian populations rather than only in highly selected research groups.

  Comparing biomarker approaches

  Approach	Sample or input	Potential advantage	Main limitation
  Circulating tumour DNA	Blood	Detects genetic and epigenetic tumour signals	Low concentrations in early disease
  MicroRNA and protein panels	Blood	Relatively accessible and suitable for combined scoring	Results can vary with inflammation and other illnesses
  Exhaled volatile compounds	Breath	Non-invasive and repeatable	Equipment, calibration and standardisation remain difficult
  Sputum biomarkers	Airway secretions	Direct contact with respiratory tissue	Collection quality is inconsistent
  Radiomics with low-dose CT	Medical imaging	Adds quantitative features to established scans	Requires imaging access, software validation and expert oversight
  Multi-marker models	Several data types	May improve sensitivity and risk stratification	Greater cost, complexity and regulatory burden

  The strongest future pathway may combine a modestly priced blood test with clinical history and low-dose CT. This could help prioritise scans for people at higher risk, while limiting unnecessary follow-up for those with a low predicted probability. Any model must be tested for false positives, false negatives and performance across different age and cultural groups.

  Reaching diverse Australian communities

  Smoking remains an important risk factor, but lung cancer also occurs in former smokers, never-smokers and people exposed to asbestos, silica, diesel exhaust or other workplace hazards. Mining and construction workers in Western Australia, Queensland and New South Wales may have exposure histories that need careful documentation. Vaping and changing tobacco use patterns add further uncertainty to long-term risk assessment.

  Aboriginal and Torres Strait Islander communities may experience a higher burden of respiratory disease alongside barriers linked to distance, cost, trust and continuity of care. Biomarker programs should involve Aboriginal Community Controlled Health Services and local health workers from the design stage. A test that is technically accurate but difficult to access or poorly explained will not deliver earlier diagnosis.

  Validation, equity and clinical safety

  A biomarker must demonstrate clinical utility, not simply show a statistical association with cancer. Researchers need prospective studies that enrol people before diagnosis, include benign lung conditions and follow participants through imaging, biopsy and treatment. The important question is whether testing reduces late-stage disease and improves outcomes without causing excessive invasive procedures.

  Australian validation should include patients from metropolitan hospitals, regional centres and remote services, with representation across states and territories. Medicare funding, pathology logistics and referral capacity also matter. If a test identifies more suspicious cases than the health system can investigate promptly, delays may shift from screening to diagnosis.

  Privacy deserves attention when genomic data and longitudinal health records are combined. Clear consent, secure storage and understandable explanations are essential. Patients should know whether a result indicates a measurable risk, a possible tumour signal or a confirmed diagnosis; these categories carry very different clinical meanings.

  From research finding to routine care

  The next stage is likely to involve integrated risk models rather than one “magic” biomarker. A general practitioner might combine symptoms, smoking history, family history, occupational exposure and a blood-based score before deciding whether low-dose CT or respiratory referral is appropriate. Artificial intelligence could then help radiologists detect subtle nodules and compare changes over time.

  Implementation will require training for GPs, nurses, pathologists, radiologists and Aboriginal health practitioners. It will also require clear rules for repeat testing, incidental findings and communication of uncertain results. In Australia, pathways must work for someone attending a suburban practice in Adelaide as well as someone travelling hours from the Kimberley to reach specialist care.

  For now, established assessment remains central: investigate persistent symptoms, document exposure history, support smoking cessation and refer promptly when risk is significant. The practical takeaway is to treat emerging biomarkers as tools for earlier risk stratification alongside clinical judgement and appropriate imaging, not as a substitute for a complete diagnostic pathway.

  Richard Russell Nuffield Department of Clinical Medicine, University of Oxford (United Kingdom)
• Mona Bafadhel King’s College London (United Kingdom)
  David Jackson Guy’s and St Thomas’ Hospital, King’s College London (United Kingdom)
• James Chalmers University of Dundee (United Kingdom)
  David Price University of Aberdeen (United Kingdom)