Personalized Ultrahypofractionated Stereotactic Ablative Radiotherapy Guided by [68Ga] PSMA-11 PET/CT Response for the Treatment of High Risk Prostate Cancer, The PULSAR ProPhet Trial

Inclusion Criteria

• Pathologically confirmed adenocarcinoma of the prostate (within 180 days of registration) of high risk by national comprehensive cancer network (NCCN) criteria as determined by >=cT3a stage (American Joint Committee on Cancer [AJCC] 8th edition) OR prostate-specific antigen (PSA) > 20ng/mL OR International Society of Urological Pathology (ISUP) grade group 4-5 (gleason grade 8-10).
• Age ≥ 18 years.
• Planned for definitive intent stereotactic ablative radiotherapy (SabR) with integrated dose boost to intra-prostatic tumor and androgen deprivation therapy (ADT) with baseline American Urological Association (AUA) International Prostate Symptom Score (IPSS) =< 18 and prostate size =< 100cc.
• Staging 68Ga PMSA-11 PET -CT or –MRI performed within 90 days of registration and before initiation of anti-androgen or androgen deprivation therapy and demonstrating no evidence of distant metastases by (PMSA avid or non-avid nodes =< 1.5cm short axis allowed). Conventional imaging (CT, bone scan, MRI) may also be used in addition to PMSA-PET, and definitive findings of distant extra-pelvic metastases on these scans are not allowed for enrollment.
• Staging 68Ga PSMA-11 PET –CT or –MRI demonstrating a PSMA-avid primary intra-prostatic target lesion amenable at investigator discretion to dose boost.
• All men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of standard of care SabR and for a period of time of 6 months thereafter as per standard guidelines. Should a man’s partner become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria

• Prior curative intent local therapy (e.g. prostatectomy, radiotherapy, focal ablative therapy) for prostate cancer is not allowed, with following exceptions regarding androgen deprivation therapy (ADT)/anti-androgen therapy (AAT): * Prior androgen deprivation therapy (ADT) allowed if < 3 month total duration and stopped >= 3 months prior to registration with demonstration of non-castrate testosterone recovery (> 50ng/dL) and meeting all other inclusion criteria. * Ongoing androgen deprivation therapy (ADT) is allowed if =< 60 days total duration AND meeting following criteria: ** If gonadotropin releasing hormone (GnRH) agonist used (e.g. leuprolide), bicalutamide must have been used for at least 30 days +/-14 days from start of GnRH agonist. ** All other inclusion criteria.
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
• History of allergic reactions to PMSA-11 68Ga imaging agent.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Prior pelvic radiotherapy other than cutaneous/superficial treatments.