Clinical implications of germline and somatic genetic testing in ovarian carcinoma: BRCA and beyond. The PERSONA-Ovary trial.

OBJECTIVE

The PERSONA-Ovary study evaluated germline pathogenic/likely-pathogenic variant prevalence, feasibility of unselected multigene testing integration in routine clinical care, and germline-somatic BRCA concordance in ovarian cancer patients.

METHODS

We conducted a prospective observational study of consecutive ovarian carcinoma patients treated at a tertiary-cancer care center, between July 2018 and September 2021. Germline multigene panel testing was performed using next-generation sequencing. Feasibility was assessed by informative rate and turnaround time. Germline-somatic concordance was assessed in patients with paired tumor BRCA results.

RESULTS

Among 320 patients, pathogenic/likely-pathogenic variants were identified in 95 (29.7%, 95% CI 24.7-35.0); 81 (85.3%, 95% CI 76.5-91.7) carried mutations in ovarian cancer susceptibility genes, including 60 with BRCA alterations (63.2%, BRCA1 n=43, BRCA2 n=17). Germline testing was informative in all patients (100%). Median turnaround time was 221days (IQR 173-284), improving significantly across study periods (p<0.001). Tumor BRCA testing was available in 298 patients (93.1%), with germline-somatic concordance of 94.0% (κ=0.82, 95% CI 0.72-0.90). A germline-first strategy with reflex tumor testing achieved complete detection with fewer assays than parallel testing; a tumor-first strategy required the fewest assays (366 vs 596) but missed two germline BRCA carriers (detection rate of 96.3%).

CONCLUSION

Unselected germline multigene panel testing was technically feasible and clinically informative in routine ovarian cancer care. Pathogenic/likely-pathogenic variants were identified in 29.7% of patients, supporting germline testing integration into contemporary ovarian cancer management. Although germline-first strategies maximize hereditary cancer detection, dedicated molecular workflows remain necessary to ensure clinically actionable turnaround times.