Toward a new era of cancer detection: patient-friendly solutions

SUMMARY High cancer mortality rates and the rising cancer burden worldwide prioritize the development of innovative methods that facilitate the early and accurate detection of cancer. Combining patient-friendly sampling methods with reliable biomarker testing offers a method that is convenient for patients and effective in detecting cancer at a curable stage, with improved patient outcomes as an ultimate goal. This thesis assessed the feasibility of DNA methylation testing in urine as a diagnostic tool for different cancer types, including endometrial, ovarian, and lung cancer. For endometrial and ovarian cancer, the value of DNA methylation testing in self-collected cervicovaginal samples and clinician-taken cervical scrapes was also investigated. Part 1: Endometrial and ovarian cancer detection in patient-friendly samples Part 1 describes the detection of endometrial and ovarian cancer in urine, cervicovaginal self-samples, and clinician-taken cervical scrapes. The outcomes of Part 1 revealed the value of methylation analysis in patient-friendly sample types for endometrial cancer detection of all stages. Convenient modes of sample collection offer the possibility of at-home collection with high patient acceptability. This approach is clinically useful to screen patient populations at risk for endometrial cancer and to streamline who needs to undergo invasive endometrial tissue sampling. Although promising, the clinical effectiveness of this approach requires further confirmation in additional cohorts, including individuals presenting with postmenopausal bleeding and asymptomatic women at risk for endometrial cancer. The presence of ovarian cancer-derived DNA in the urine provides the first steps toward urine-based diagnostics for ovarian cancer. Further research is needed to further explore and refine the use of urine biomarkers for ovarian cancer diagnostics. Part 2: Non-small cell lung cancer detection in urine In Part 2 of this thesis, the diagnostic potential of urine as a liquid biopsy for non-small cell lung cancer (NSCLC) detection was evaluated. The outcomes of Part 2 demonstrate the technical feasibility of detecting NSCLC in the urine using DNA methylation markers. Further research, including larger patient cohorts and controls with benign pulmonary nodules, is needed to validate the clinical usefulness of this approach. The considerable variability between urine samples highlights the need for a more thorough understanding of cfDNA dynamics and enhancements in test development to ensure reliability. Upon further refinement, this test has the potential to serve as a valuable complementary diagnostic tool to low-dose CT screening to guide clinical decisions in patients with pulmonary nodules.