Stratification of Oligometastatic Prostate Cancer Patients by Liquid Biopsy: Clinical Insights from a Pilot Study
Antonella Colosini,
Simona Bernardi,
Chiara Foroni,
Nadia Pasinetti,
Andrea Emanuele Guerini,
Domenico Russo,
Roberto Bresciani,
Cesare Tomasi,
Stefano Maria Magrini,
Lilia Bardoscia,
Luca Triggiani
Affiliations
Antonella Colosini
Department of Radiation Oncology, University and Spedali Civili Hospital, 25123 Brescia, Italy
Simona Bernardi
CREA Laboratory (Centro di Ricerca Emato-Oncologica AIL), ASST Spedali Civili of Brescia, 25123 Brescia, Italy
Chiara Foroni
CREA Laboratory (Centro di Ricerca Emato-Oncologica AIL), ASST Spedali Civili of Brescia, 25123 Brescia, Italy
Nadia Pasinetti
Department of Radiation Oncology, University and Spedali Civili Hospital, 25123 Brescia, Italy
Andrea Emanuele Guerini
Department of Radiation Oncology, University and Spedali Civili Hospital, 25123 Brescia, Italy
Domenico Russo
Unit of Blood Diseases and Bone Marrow Transplantation, Cell Therapies and Hematology Research Program, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123 Brescia, Italy
Roberto Bresciani
Division of Biotechnology, Department of Molecular and Translational Medicine (DMTM), University of Brescia, 25121 Brescia, Italy
Cesare Tomasi
Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Section of Public Health and Human Sciences, University of Brescia, 25121 Brescia, Italy
Stefano Maria Magrini
Department of Radiation Oncology, University and Spedali Civili Hospital, 25123 Brescia, Italy
Lilia Bardoscia
Department of Radiation Oncology, University and Spedali Civili Hospital, 25123 Brescia, Italy
Luca Triggiani
Department of Radiation Oncology, University and Spedali Civili Hospital, 25123 Brescia, Italy
We propose a pilot, prospective, translational study with the aim of identifying possible molecular markers underlying metastatic prostate cancer (PC) evolution with the use of liquid biopsy. Twenty-eight castrate sensitive, oligometastatic PC patients undergoing bone and/or nodal stereotactic body radiotherapy (SBRT) were recruited. Peripheral blood samples were collected before the commencement of SBRT, then they were processed for circulating cell free DNA (cfDNA) extraction. Deep targeted sequencing was performed using a custom gene panel. The primary endpoint was to identify differences in the molecular contribution between the oligometastatic and polymetastatic evolution of PC to same-first oligo-recurrent disease presentation. Seventy-seven mutations were detected in 25/28 cfDNA samples: ATM in 14 (50%) cases, BRCA2 11 (39%), BRCA1 6 (21%), AR 13 (46%), ETV4, and ETV6 2 (7%). SBRT failure was associated with an increased risk of harboring the BRCA1 mutation (OR 10.5) (p = 0.043). The median cfDNA concentration was 24.02 ng/mL for ATM mutation carriers vs. 40.04 ng/mL for non-carriers (p = 0.039). Real-time molecular characterization of oligometastatic PC may allow for the identification of a true oligometastatic phenotype, with a stable disease over a long time being more likely to benefit from local, curative treatments or the achievement of long-term disease control. A prospective validation of our promising findings is desirable for a better understanding of the real impact of liquid biopsy in detecting tumor aggressiveness and clonal evolution.
