Liquid biopsies for earlier detection of recurrent endometrial tumours

Endometrial cancer affects many thousands of women across the globe. The early detection of recurrent endometrial cancer is crucial as it can directly impact patient outcomes, ensuring timely intervention and improved chances of successful treatment. Liquid biopsies, an exciting frontier in oncology, have emerged as a promising tool for early detection of recurrent endometrial cancer. These non-invasive diagnostic techniques provide a window into the body’s molecular landscape, offering valuable insights into tumour dynamics and genetic mutations.

In this final article in our ‘Communicating complexity with clarity’ series, nspm Medical Writer Diviya Gorsia summarises her important research into the use of liquid biopsies in detecting and monitoring endometrial cancer.

Endometrial cancer is the most common gynecological cancer, affecting over 400,000 people worldwide¹. Most patients have a good prognosis due to early detection through abnormal bleeding. However, treatment options are limited for patients with recurring endometrial cancer and their prognosis is poor, with only 17% of patients surviving for 5 years^2,3. Currently, endometrial cancer recurrence is primarily monitored and identified through uncomfortable physical examinations and imaging.

A genetic condition called microsatellite instability (MSI), where there are frequent errors in repeating sections of DNA called microsatellites, is common in a subgroup of endometrial cancers. As cancers with high MSI can respond positively to immunotherapy, detecting MSI earlier, particularly in recurrent endometrial cancer cases, is notable given that potentially effective therapy could be started more promptly.

As there is currently no reliable way to monitor these patients and detect cancer recurrence earlier, this study explored the use of liquid biopsies to detect circulating tumour DNA (ctDNA) – that is, DNA from cancerous cells found in the bloodstream – and MSI, to monitor disease prognosis. The authors used a DNA sequencing technique called targeted next-generation sequencing (tNGS) to find significant DNA mutations driving cancer growth in endometrial cancer patients. They also examined tumour DNA in blood samples to identify cancer-specific mutations. Patients with regular blood samples had their levels of ctDNA analysed and researchers monitored their response to chemotherapy, to detect signs of recurrence, before the need for radiological imaging.

For a small group of patients who showed no mutations with the tNGS approach, the team used a more extensive test called whole exome sequencing (WES). They compared mutations found in tumour tissue but absent in normal tissue, to identify potential markers linked with driving cancer development and growth. Combining these markers with the MSI markers, the researchers created a custom set of diagnostic tests to study tumour and normal tissue, as well as plasma samples.

ctDNA was detected in all patients with recurrent endometrial cancer, whether they were diagnosed with early-stage recurrent disease or late-stage and progressive disease. This highlights the potential of using liquid biopsies to track tumour DNA and MSI in blood samples, potentially detecting disease progression much earlier compared to standard imaging and clinical monitoring.

To read the full paper, visit the PubMed website