RESUMEN
Improved risk stratification of patients suspected of prostate cancer prior to biopsy continues to be an unmet clinical need. ExoDx Prostate (IntelliScore) "EPI" is a non-invasive urine test utilizing RNA from exosomes to provide a risk score that correlates with the likelihood of finding high grade prostate cancer at biopsy. Here, we present the results from a prospective clinical validation study of EPI-CE, a CE-marked in-vitro diagnostic (IVD) assay, specifically developed for use in European clinical laboratories. The study (NCT04720599) enrolled patients with ≥ 50 years, PSA 2-10 ng/mL, prior to MRI, who were scheduled for initial biopsy. First catch urine samples were collected from participants without prior digital rectal examination or prostate massage. Exosomal RNA was isolated and expression levels of three biomarkers ERG, PCA3 and SPDEF were analyzed according to the EPI-CE Instructions For Use. In the study cohort of N = 109 patients, EPI-CE was validated to have a Negative Predictive Value of 89%, a Sensitivity of 92% and a superior performance to two commonly used multiparametric risk calculators (PCPT and ERSPC) in both Receiver Operating Characteristics with a higher Area Under the Curve for EPI-CE 0.67 (95% CI 0.56-0.77) versus PCPT 0.59 (95% CI 0.47-0.71) and ERSPC 0.60 (95% CI 0.49-0.72) and higher Net Benefits analysis across a wide range of risk acceptance levels. This is the first clinical study reporting on the performance of EPI-CE. We demonstrate that EPI-CE provides information beyond standard clinical parameters and provides a better risk assessment prior to MRI, of patients suspected of prostate cancer, than the commonly used multiparametric risk calculators.
Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata , Biopsia , Humanos , Masculino , Clasificación del Tumor , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , ARN , Medición de Riesgo/métodosRESUMEN
Purpose: Blood-based liquid biopsies offer easy access to genomic material for molecular diagnostics in cancer. Commonly used cell-free DNA (cfDNA) originates from dying cells. Exosomal nucleic acids (exoNAs) originate from living cells, which can better reflect underlying cancer biology.Experimental Design: Next-generation sequencing (NGS) was used to test exoNA, and droplet digital PCR (ddPCR) and BEAMing PCR were used to test cfDNA for BRAFV600, KRASG12/G13, and EGFRexon19del/L858R mutations in 43 patients with progressing advanced cancers. Results were compared with clinical testing of archival tumor tissue and clinical outcomes.Results: Forty-one patients had BRAF, KRAS, or EGFR mutations in tumor tissue. These mutations were detected by NGS in 95% of plasma exoNA samples, by ddPCR in 92% of cfDNA samples, and by BEAMing in 97% cfDNA samples. NGS of exoNA did not detect any mutations not present in tumor, whereas ddPCR and BEAMing detected one and two such mutations, respectively. Compared with patients with high exoNA mutation allelic frequency (MAF), patients with low MAF had longer median survival (11.8 vs. 5.9 months; P = 0.006) and time to treatment failure (7.4 vs. 2.3 months; P = 0.009). A low amount of exoNA was associated with partial response and stable disease ≥6 months (P = 0.006).Conclusions: NGS of plasma exoNA for common BRAF, KRAS, and EGFR mutations has high sensitivity compared with clinical testing of archival tumor and testing of plasma cfDNA. Low exoNA MAF is an independent prognostic factor for longer survival. Clin Cancer Res; 24(1); 181-8. ©2017 AACR.