EA8191 – Phase III Study of Local or Systemic Therapy INtensification DIrected by PET in Prostate CAncer Patients with Post-ProstaTEctomy Biochemical Recurrence (INDICATE)

By Neha Vapiwala, MD

@NehaVapiwala

The INDICATE (EA8191) clinical trial for advanced prostate cancer is specifically for patients with post-prostatectomy biochemical recurrence (BCR). This condition involves a rise in blood prostate-specific antigen (PSA) levels after surgery, without any evidence of cancer on a physical exam or conventional imaging tests, such as CT scans or MRI. The trial uses PET imaging to guide the amount of treatment patients may need—and aims to answer important questions about which subgroups of patients may harbor microscopic traces of metastatic disease and may benefit from additional targeted treatment.

The current standard-of-care (SOC) treatment for BCR is radiation therapy (RT) to the prostate bed and pelvic nodes, plus a short-term course of androgen deprivation therapy (ADT). Even after this salvage therapy, some patients experience a second biochemical recurrence, indicating the need for improved strategies to deliver more tailored treatment.

INDICATE is designed to address two key questions:

1. For patients without PET evidence of extra-pelvic metastases (defined as outside of standard salvage RT fields or any osseous lesion): does the addition of enhanced systemic therapy (apalutamide) to SOC RT + short-term ADT improve progression-free survival (PFS)?
2. For patients with PET-only evidence of extra-pelvic metastases: does the addition of metastasis-directed RT to SOC RT + short-term ADT + apalutamide prolong PFS?

Eligible patients should have an initial baseline SOC PET scan to determine if they have extra-pelvic metastases. Those without metastases were randomized to either Arm A or B: SOC RT + short-term ADT +/- apalutamide, an androgen receptor pathway inhibitor. These arms completed enrollment in January 2025.

Patients with extra-pelvic metastases are randomized to either Arm C or D: SOC RT + short-term ADT + apalutamide +/- upfront metastasis-directed RT. These arms are still open and enrolling. Arms C and D are critical to help verify the utility of PET in the setting of negative or indeterminate conventional imaging and to evaluate the clinical benefit of metastasis-directed RT based on PET-only findings.

Patients are eligible for Arms C or D if their post-operative baseline PET has at least one suspected or positive lesion in any bone or nodes/soft tissue outside of the pelvis or in any visceral organ. Any detectable post-prostatectomy PSA level is allowed. All pathological stages and findings are allowed. Patients must be candidates for pelvic and prostate bed radiotherapy, plus six months of ADT.

Learn more about EA8191 at ecog-acrin.org.

Dr. Vapiwala (University of Pennsylvania/Abramson Cancer Center) is the study chair for this trial. The study co-chairs are Steve Cho, MD (University of Wisconsin/Carbone Cancer Center) for imaging, Christos Kyriakopoulos, MD (University of Wisconsin/Carbone Cancer Center) for medical oncology, and Alicia Morgans, MD (Dana-Farber/Harvard Cancer Center) for quality of life.

The NCTN group study champions are Rana McKay, MD (University of California San Diego/Moores Cancer Center) for Alliance, Bridget Koontz, MD (East Carolina University) for NRG Oncology, and Evan Yu, MD (University of Washington/Fred Hutchinson Cancer Research Center) for SWOG.