Metastasis-Directed Radiotherapy for the Treatment of Men with Oligometastatic Prostate Cancer, METANOVA Trial

Inclusion Criteria

• Patient must be ≥ 18 years of age
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Histologic confirmation of prostate adenocarcinoma of the prostate gland, with evidence of metastasis on imaging by conventional imaging (MRI, CT, or 99mTc bone scan) or PSMA PET/CT. Biopsy of sites of metastasis is strongly encouraged, but not required. * There must be at least 10-15 unstained slides from 2 cores of the highest tumor cellularity available
• Newly diagnosed disease with no prior treatment (surgery, radiation or systemic treatment, ie hormone therapy or chemotherapy) to the primary disease. * Patients may have started luteinising hormone-releasing factor (LHRH) agonist or antagonist therapy, and/or androgen receptor signaling inhibitor (ARSI) as long as it was not started more than 30 days before the patient is enrolled on this study
• In patients who undergo only conventional imaging, oligometastatic disease is defined as 1-5 discrete metastatic sites in the bone and/or extra-pelvic lymph node (LN) stations. * Extra-pelvic LN stations are superior to the regional/pelvic LN stations. Pelvic LN stations commence at the bifurcation of the aorta and bifurcation of the proximal inferior vena cava to the common iliac veins. ** Radiographic criteria for a LN to be considered a metastatic focus is defined as short-axis diameter in the axial plane of ≥ 1.0 cm, with irregular border and/or heterogeneous morphology
• In patients who undergo PSMA PET/CT (in the presence or absence of conventional imaging), oligometastatic disease is defined as 1-10 PSMA avid bone lesions and/or extra-pelvic LN stations. The molecular imaging reporting and data system (MI-RADS) reporting system will be followed to guide PSMA PET interpretation * In patients extra-pelvic nodal (M1a) disease only by PSMA PET/CT and M0 by conventional imaging (i.e. extra-pelvic LN did not meet size criteria by CT), patient must meet 2 of 3 following criteria in order to be eligible: ** Prostate specific antigen (PSA) ≥ 40 ** Evidence of cN1 disease (pelvic LN) ** Decipher score ≥ 0.89
• Adequate organ and marrow function to receive treatment per treating physician
• Medically fit for treatment and agreeable to follow-up
• Ability to understand and the willingness to sign a written informed consent
• Note: Metastatic sites are defined as any bony metastasis or extra-pelvic nodal station. > 1 lymph node in the same nodal station will be considered 1 metastatic site. Extra-pelvic nodal stations include popliteal, inguinal/femoral, para-aortic, mesenteric, splenic, gastric, hilar, mediastinal, supraclavicular, infraclavicular, axillary, and cervical. Nodal stations are divided at the midplane of the body into left and right stations, and are each counted separately as metastatic sites

Exclusion Criteria

• Castration resistant prostate cancer (CRPC)
• Evidence of visceral or intracranial metastases
• Patient receiving any other investigational agents for cancer
• Patient is participating in a concurrent treatment protocol for cancer
• Unable to lie flat during or tolerate PET/MRI, PET/CT or stereotactic body radiation therapy (SBRT)
• Prior definitive treatment to the primary prostate cancer or pelvis
• Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled diabetes (glycosylated hemoglobin [HgA1c] > 10), active pituitary or adrenal dysfunction, or psychiatric illness/social situations that would limit compliance with study requirements
• History of another active malignancy within the previous 2 years, except for non-melanoma skin cancer, non-muscle invasive bladder cancer, or a malignancy that is considered cured with minimal risk of recurrence
• Active Crohn’s disease or ulcerative colitis despite medical management
• Refusal to sign informed consent
• Any condition that in the opinion of the investigator would preclude participation in this study