Integration of the blood test into the low-dose computed tomography lung cancer screening: reliable discrimination between malignant and non-malignant radiographic findings

Transl Lung Cancer Res 2021;10(10):4035-4038 | https://dx.doi. org/10.21037/tlcr-21-680 Lung cancer (LC) is the most common oncological disease worldwide. Its incidence currently exceeds 2 million cases per year, with 1.8 million subjects dying from this malignancy. LC accounts for 11.6% of total cancer diagnoses and 18.4% cancer-related deaths (1). Early-stage LC usually does not cause specific symptoms; consequently, more than 70% LCs are diagnosed at advanced stages (2,3). Recent breakthroughs in targeted and immune therapy resulted in dramatic improvement of LC outcomes (4,5). Nevertheless, LC is a direct cause of death in the majority of patients with this diagnosis (1). LC is often characterized in the scientific literature as a highly aggressive disease; nevertheless, patients diagnosed at stage IA have approximately 80% probability of being cured (6). Furthermore, 5-year overall survival rate for stage IA lung cancer may be close to 90%. In contrast, stage IV LC is associated with dismal prognosis, with 5-year overall survival rate falling below 20% (7). These data suggest that early diagnosis of LC is a key for reducing mortality from this disease. LC screening studies largely support this hypothesis: for example, it was shown that lowdose computed tomography (LDCT) reduces LC mortality by at least 20% in persons at-risk (i.e., in smokers) (8-10). The major problem of LDCT screening i s an unacceptably high rate of false-positive findings. Indeed, many healthy people, particularly elderly subjects and smokers, present with so-called lung “nodules”, i.e., some lumps detected by X-rays. These lumps reflect topical increase of the density of lung tissue due to alterations in its structure. The most ominous cause of these nodules is the LC. However, many benign processes, e.g., inflammatory infiltrates caused by smoking-related irritation of bronchi, infections, autoimmune processes etc., manifest with lumps which are largely indistinguishable from LC by imaging. Great efforts have been invested to improve radiographic procedures and their interpretation in order to discriminate between LC and non-LC nodules. Besides careful visual analysis of appearance of these nodules, to be performed by highly-trained specialists with the support of various electronic tools, it is suggested to consider some probability factors, e.g., age of the patient and his/her smoking history. This «clinical» approach, although being wise and intuitively attractive, has a high risk of missing malignant disease at a curable stage. Consequently, many subjects with LDCT-detected nodules end up with invasive procedures aimed to obtain a piece of suspected nodule and to subject it to a morphological analysis. Collection of tissue samples from thoracic cavity is obviously associated with suffering of examined subjects and often results in serious complications, particularly bleeding. Unfortunately, even this invasive intervention cannot guarantee right diagnosis: there are many instances of LC, where tissue biopsy produces false-negative results die to actual failure to obtain tumor sample (11-14). Liang et al. (15) recently presented a test called PulmoSeek, which is based on the detection of LCspecific methylation signatures in circulating tumor DNA Editorial Commentary