Title
Metastasis-Directed Radiotherapy (MDRT) for Men With De-novo Oligometastatic Prostate Cancer Treated With Long-Term Androgen Deprivation Therapy in the Stampede Trial (METANOVA)

Description
Prostate cancer (PCa) is the most common cancer in men worldwide, with 10% diagnosed with metastatic disease at the time of presentation. The metastatic capacity of cancers behaves along a spectrum of disease progression, such that some solid tumors have spread widely before clinical detectability and others never metastasize. While metastatic disease has historically been treated with palliative intent, an oligometastatic state where metastases are limited in number and location has emerged in which participants with oligometastatic disease may benefit from effective local therapy in addition to systemic therapy. Systemic standard-of-care therapies often include androgen deprivation therapy (ADT) and Androgen receptor signaling inhibitor (ARSI). Studies have shown that administering local radiotherapy (RT) to the prostate in addition to standard of care may improve radiographic profession-free survival. It may be even more efficacious to add metastasis-directed radiotherapy (MDRT) to the treatment of oligometastatic prostate cancer cases. More research is necessary to investigate the application of MDRT to improve disease control.

Objective
Primary Objective:
FFS: Time from randomization to first evidence of at least one of: biochemical failure; progression either locally in lymph nodes, or in distant metastases (according to PCWG3 and RECIST 1.1); any salvage intervention (local or systemic) required after 12m of planned SOC therapy; or death from prostate cancer. PSA nadir is defined as the lowest level of PSA within 24 weeks after randomization. Biochemical failure is defined as at least one of:
(1) patients with the lowest recorded PSA in the 24 weeks following randomization that is > 50% of the pre-treatment PSA, will be considered biochemical failure at time zero;
(2) post-RT:
a. serum PSA 50% above nadir and at least 4 ng/mL if PSA nadir is less than 4 ng/mL, requiring confirmation ? 4 weeks later
b. PSA 50% above nadir if PSA nadir is at least 50% lower than the last pre-treatment PSA but remaining greater than 4 ng/mL, , requiring confirmation ? 4 weeks later
(3) post-RP: serum PSA nadir + 0.4 ng/mL, requiring confirmation ? 4 weeks later.

Secondary Objectives (2):
To compare additional measures of efficacy, including overall survival (OS), rPFS, time-to-next-intervention (TTNI), time-to-castration-resistant prostate cancer, and prostate-specific cancer mortality (PCSM).

To describe the toxicity and effects on patient-reported quality of life by collecting sexual domain (EPIC-26), hormone domain (EPIC-26), urinary domain (EPIC-26), bowel domain (EPIC-26), and skeletal-related events (SRE).

Treatment Participants will also have prostate RT. Up to 50 participants will have surgery to remove the prostate instead of having prostate RT. A portion of the participants will be randomized to receive MDRT to areas where the cancer has spread. For participants who have surgery to remove their prostate, they will be asked to allow tissue samples collected during the surgery to be sent to an outside lab for research tests and extra blood samples drawn for research tests before starting the study, and at the time the cancer becomes worse if applicable. Participation in the study will last approximately 12 months, and will be followed by their doctor for up to five years per standard of care.

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Prostate

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital