211 Summary and general discussion reliable detection of cervical (pre)cancer (6-8) and is closer to clinical implementation as compared to other gynecological cancers. Urine sampling has the potential to increase participation rates of non-responders in the current cervical cancer screening program, particularly among women who experience difficulties with conventional methods that require the collection of cervical or vaginal cells (9). It is therefore likely that urine-based cervical cancer screening may be implemented in the future, paving the way for a single urine-based biomarker test for cervical, endometrial, and ovarian cancer detection. Lung cancer The value of urine-based biomarker testing for lung cancer detection is evaluated in Chapters 6 and 7. This approach could guide the management of low-dose computed tomography (LDCT) scans with suspicious lung nodules, helping to identify in which individuals further invasive diagnostic procedures are required. In the future, one could also consider performing urine testing before screening to preselect individuals who are most likely to benefit from low-dose CT screening. Restricting the number of screened individuals to those with a high risk of malignancy would be beneficial in terms of costeffectiveness and might minimize potential harmful effects of LDCT screening (e.g. development of radiation-induced cancers). The non-invasive nature of urine collection also allows for patient-friendly monitoring of treatment response and the timely detection of recurrences, as explored in Chapter 6. Although not examined in this thesis, urine biomarkers could also be useful to improve lung cancer management after diagnosis. For example, urine tests could guide the treatment selection of lung cancer and preselect patients who are most likely to respond to immunotherapy. It is, however, essential to note that molecular testing in blood has already entered the clinic to guide therapy selection in non-small cell lung cancer (NSCLC) patients. Blood-based liquid biopsies could therefore also easily be extended to the analysis of novel (epi)genetic biomarkers. Large multi-center lung cancer screening implementation trials, such as the 4-in-the-lung-run Lung Cancer Screening Trial, will provide more insight into the value of personalized screening strategies and the potential of liquid biopsy in lung cancer management (10). 8.1.2 The state of readiness of liquid biopsy tests in clinical practice The state of readiness for the integration of liquid biopsy tests into clinical practice can be assessed using five navigators in the translational research phase, adapted from previously described criteria (11). The current evidence of urine tests described in this thesis is marked in the context of blood-based tests, including an FDA-approved cancer-specific test and multi-cancer early detection tests (Figure 1). 8
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