Liquid biopsy plays a growing role in early-stage lung cancer

Despite the recent improvements in the management of lung cancer, the vast majority of patients still experience poor clinical outcomes mainly due to challenges in early detection, the high risk of metastasis, and the development of resistance to multiple therapies. However, great strides have been made with the introduction of liquid biopsy in the diagnostic algorithm for this population (J Thorac Oncol. 2021;16:1647–1662; Lung Cancer. 2022;172:53–64).

In advanced disease, liquid biopsy has been established as a valid tool useful for substantially increasing the number of patients who could benefit from a targeted treatment, thus helping clinicians to avoid any patient being left behind (J Mol Pathol. 2021;2:255–273). Following the approval of effective targeted treatments in the adjuvant setting, with some promise also in the neo-adjuvant setting, researchers’ efforts have moved to the adoption of liquid biopsy in the early stages of disease (Cancers (Basel). 2023;15:2702). Liquid biopsy has demonstrated its suitability for monitoring minimal residual disease, predicting the efficacy of neo-adjuvant and adjuvant treatments, and predicting the risk of disease relapse and recurrence sooner than conventional radiological approaches (JAMA Oncol. 2022;8:1830–1839). However, a deeper understanding of its role in supporting therapy administration and predicting clinical outcomes in patients with resectable lung cancer is essential to improve the survival rate and prognosis.

Data from some abstracts presented at the ESMO Congress 2024 (Barcelona, 13–17 September) add to our knowledge of the role of liquid biopsy, and in particular of circulating tumour (ct) DNA, in early-stage disease.

In their poster, van den Heuvel et al. highlighted that sensitive tumor-informed detection of ctDNA is possible even in cases of suboptimal quantity ‘real-world’ samples (Abstract 1226P). They reported a prognostic value in samples collected before and soon after surgical treatment, thus suggesting that the predictive value of ctDNA may be useful to guide (neo)adjuvant treatments.

In a second poster presentation, Wakelee et al. analysed disease-free survival (DFS) and overall survival by ctDNA and PD-L1 status after surgery in ctDNA-evaluable patients with stage II–IIIA non-small cell lung cancer (NSCLC) from the IMpower010 trial (Abstract 1211P). They reported that post-operative and post-chemotherapy ctDNA positivity was a negative prognostic factor for DFS after 5 years of follow-up, thus supporting the concept that ctDNA evaluation – regardless of the presence of specific driver mutations – may be helpful as a prognostic marker in early-stage disease. Finally, the value of ctDNA from an epidemiological perspective was described in a third poster. In the ctDNA-Lung-Detect study assessing ctDNA detection and its association with recurrence-free survival in patients with early stage, resected NSCLC, Khan et al. prospectively profiled a population with non-shedding ctDNA tumours, showing that these patients were less likely to be male, current smokers, have tumours with high expression of PD-L1, and were more likely to have an identifiable driver mutation (Abstract 1236P).

Taken together, data presented at the Congress contribute to consolidate the role of liquid biopsy in lung cancer. However, prospective clinical trials in this field are strongly welcomed.