This is a single-center prospective interventional study involving patients with histologically confirmed low-risk, high-risk and locally advanced PCa.

A cancer genome profiling with FPG 500 will be performed within these cohorts. Samples will be available from surgery for high-risk and locally advanced PCa, from prostate biopsy for low risk patients.

A cancer genome profiling with FPG500 will be performed on samples available from surgery or biopsy. Specimen are reviewed to assess tumor cell fraction. All H&E slides are digitized before nucleic acid extraction. Semi-automated process is used for DNA/RNA extraction, DNA fragmentation, quantification, library preparation, and sequencing. Profiling is done with the TruSight Oncology 500 assay, analyzing 523 genes for single nucleotide variants, insertions/deletions, copy number variations, and fusions/splicing variants in 55 genes. It also evaluates genomic signatures like microsatellite instability and tumor mutational burden. Sequencing data are processed using Illumina software and a custom pipeline. Post-sequencing quality control is performed. Variants are classified according to the Human Genome Variation Society and clinical actionability guidelines. Genomic report is reviewed by an institutional Molecular Tumor Board.

A raise in the PSA level is the first sign of disease progression for the whole non-metastatic PCa setting. After radical prostatectomy in high-risk patients, biochemical relapse anticipates radiographic progression and is a crucial point invoking re-staging and treatment decision making. A PSA doubling time below 8-10 months is significantly related to metastatic development and prostate cancer specific death (Smith MR, J Clin Oncol 2013;31:3800-3806).

The primary endpoint is to identify actionable mutations related to BCR (or persisting PSA) after surgery for high-risk and locally advanced PCa.

The primary endpoint is to identify actionable mutations related to progression of low-risk PCa. From the study from Hamdy et al, the occurrence of clinical progression requiring active treatment is as high as 25% at 15 years.

PCa cases with diagnosis of low-risk will be considered for FPG 500 genomic profiling from prostate biopsy to define mutations related to:

- Upstage and/or upgrade of cancer during surveillance protocol

Radiographic progression of cancers may relate with the development of symptoms and with an increased burden of cure to control clinical progression. FPG500 mutations relevant to this endpoint may suggest treatment anticipation /intensification after surgery or may be actionable of target treatment