This is a prospective observational study. The study will proceed with the enrollment of 60 patients in 2 years. he aim of the present study is to evaluate effectiveness of ultra-hypofractionated (UH) CyberKnife Stereotactic Body Radiation Therapy treatment on the whole prostate gland plus Simultaneous integrated boost (SIB) to the dominant intraprostatic lesions (DIL(s) in intermediate-unfavourable to high-risk Prostate Cancer (PCa) patients.

The patient to be enrolled in the prospective observational phase will be screened at first visit; prescription of Prostate Specific Antigen (PSA) and testosterone analysis, uroflowmetry and multiparametric Magnetic Resonance Imaging (mpMRI) are mandatory if not already done.

Additional staging imaging (computed tomography (CT) and/or bone scan) will be required according to National Comprehensive Cancer Network (NCCN) category risk group.

Subsequently, for the eligible patient, the enrollment phase involves eco-guided transrectal insertion of 3-4 gold fiducials in the prostate gland.

CT with full bladder and empty rectum will be done after 7-10 days from fiducials insertion; CyberKnife-Stereotactic Body Radiation Therapy (SBRT) treatment will start after 5-7 days from the simulation CT. A total of 36.25 Gy to the prostate gland will be executed in 5 alternate days. For each treatment delivery, the patient is required to be prepared in roughly the same bladder and rectum filling condition of the simulation day. Finally, in the last treatment day QoL and both clinician- and patient-reported genitourinary (GU) and gastrointestinal (GI) acute toxicity assessment is required.

Inclusion Criteria:

• Age > 18 and < 80 years
• Histologically confirmed adenocarcinoma of the prostate
• Low, Intermediate and high-risk category according to NCCN version 02.2021
• Clinically node negative and no distant metastasis
• Eastern Cooperative Oncology Group (ECOG) Performance Status <2
• Good urinary flow (peak flow >10 mL/s) or IPSS < 15
• Prostate volume < 100 cc
• Available mpMRI of the prostate
• Less than 3 DILs at mpMRI (if >2 DILs, only DILs with higher Prostate Imaging - Reporting and Data System (PIRADS) will be included and only PI-RADS >2)
• Written informed consent for treatment and research purpose

Exclusion Criteria:

• platelets count < 75000
• urethral stricture
• Previous pelvic RT
• Concomitant inflammatory bowel disease or other serious systemic comorbidities
• Previous prostatectomy
• Presence of hip prosthesis