New trial aims to improve both survival and quality of life for men with advanced prostate cancer

The Alliance for Clinical Trials in Oncology has launched a randomized phase III clinical trial called RECIPROCAL (Alliance A032304) to explore whether doctors can optimize the timing of targeted radiation therapy to minimize side effects while preserving efficacy in men with advanced prostate cancer.

Our goal in this trial is to strategically improve both survival and quality of life for men living with advanced prostate cancer. We hope to prove we can safely adjust the therapy based on an individual's cancer instead of sticking to a rigid schedule, thus maintaining the effectiveness of targeted radiation therapy while reducing side effects."

Thomas Hope, MD, Alliance study chair, nuclear medicine physician and Professor in Residence, University of California, San Francisco

The current standard of care for men with metastatic castration-resistant prostate cancer includes Lutetium-177 Prostate Specific Membrane Antigen (PSMA) targeted Radioligand Therapy (RLT), a targeted radiation therapy attached to a drug molecule and injected into the bloodstream. Once in the body, PSMA RLT binds to cancer cells, killing them cells while minimizing harm to healthy tissue.

While PSMA RLT improves survival, it can cause side effects, such dry mouth, fatigue and gastrointestinal issues. Serious side effects can include blood disorders, kidney damage or liver problems.

In the trial, clinicians will enroll about 1,500 participants. All participants will start by receiving two infusions of PSMA RLT every six weeks. During this time, if a patient's prostate specific antigen (PSA) level falls, they will be randomized into one of two groups:

Standard arm

• Participants receive up to four more PSMA RLT treatments every six weeks.

Adaptive arm

• Participants have their PSA levels checked every 3 weeks. They will receive additional treatments only if their PSA increases or doctors see evidence of disease progression. At that point, patients will receive up to four more doses of PSMA RLT.

Follow‑up schedule

• After completing treatment, patients will receive follow-up care every 12 weeks until disease progression, then every six months for up to five years after enrollment.

Our goal with RECIPROCAL is to show that treatment can be smarter, not just stronger. By tailoring therapy to each patient's PSA response, we aim to reduce unnecessary toxicity and diminish side effects while still delivering the same survival benefit. Ultimately, we want men with advanced prostate cancer to not only live longer, but to also feel better during their treatment."

Deaglan McHugh, MD, lead medical oncologist on the trial and Assistant Professor at Memorial Sloan Kettering Cancer Center