Routine application of next-generation sequencing testing in uro-oncology-Are we ready for the next step of...

Next-generation sequencing (NGS) might represent a valuable diagnostic tool to identify somatic alterations and enable personalised medicine in uro-oncology. We aim to determine feasibility and impact of routine NGS in clinical practice.

Tumours from patients with genitourinary cancers were subjected to NGS. Results were discussed in a dedicated molecular tumour board. Statistical analyses included chi-square test and Mann-Whitney U test.

Between 2017 and 2020, 65 patients with advanced genitourinary cancers were consecutively enrolled. Number of tests increased (28 tests in 2020) and diagnostic turnaround time for generating output decreased (17.5 days [range 13-35]). Median patient's age was 62 years (range 33-84), and most NGS assays were performed upon start of systemic treatment (range 0-6 of treatment lines). 62/66 sequenced samples generated a report. Fifty samples (80.6%) showed at least one molecular alteration. Most prevalent alterations were TP53 (32.3%), PIK3CA (14.5%) and TMPRSS2-ERG (9.7%). Sequencing revealed potentially druggable targets in 29 samples (46.8%). Based on NGS results, six patients underwent therapy change, whereas for three patients, coverage of recommended off-label therapy was denied by health insurances.

NGS is increasingly feasible in clinical routine for patients with genitourinary cancers. Number of performed analyses is constantly growing, and turnaround time to therapy recommendation is decreasing. While the majority of tumours harbour clinically relevant mutations, alterations related to urologic cancers are underrepresented, thus treatment changes occurred only in a minority of patients. Further, access to target agents remains a considerable obstacle in the consequent implementation of precision uro-oncology.