A targeted radioactive drug has moved closer to the front line of metastatic prostate cancer treatment, after a large international phase 3 trial found that using it early can delay disease progression. The PSMAddition study, led by investigators from Weill Cornell Medicine, NewYork-Presbyterian, Memorial Sloan Kettering Cancer Center and partner institutions worldwide, showed that adding lutetium-177 PSMA-617 to standard hormone-based treatment reduced the risk of radiographic progression or death by 28% in men with prostate-specific membrane antigen (PSMA)-positive metastatic disease.
Published in The Lancet on Aug. 6, the findings could reshape treatment for patients whose cancer has recently spread and has received little or no prior systemic therapy. The results supported the U.S. Food and Drug Administration’s approval in late July of lutetium Lu-177 vipivotide tetraxetan, also known as ^177Lu-PSMA-617, for earlier use alongside an androgen receptor pathway inhibitor and androgen deprivation therapy.
Metastatic prostate cancer is commonly driven by male sex hormones, particularly testosterone and related androgens. For that reason, the standard treatment backbone has typically combined androgen deprivation therapy, which suppresses the body’s production of testosterone, with an androgen receptor pathway inhibitor, which blocks cancer cells from responding to residual hormonal signals. Although this approach can control disease for a time, resistance eventually develops in many patients. The PSMAddition trial tested whether introducing a targeted radiopharmaceutical before resistance emerges could extend that period of control.
The study enrolled more than 1,100 men with PSMA-positive metastatic prostate cancer at 169 sites in 20 countries. Approximately half received intravenous ^177Lu-PSMA-617 every six weeks in addition to androgen deprivation therapy and an androgen receptor pathway inhibitor. The other participants received the hormonal treatment combination alone, representing the previous standard of care. Patients in the control group were permitted to cross over to the three-drug regimen if their disease progressed, a design that allowed them access to the investigational treatment while preserving the trial’s ability to compare initial treatment strategies.
The radiopharmaceutical works through a molecular targeting system. PSMA is a protein found at high levels on the surface of most prostate cancer cells; according to the investigators, roughly nine in ten patients with metastatic prostate cancer have PSMA-positive tumors. ^177Lu-PSMA-617 consists of a PSMA-binding molecule chemically linked to lutetium-177, a radioactive isotope. After the drug binds to PSMA, it is taken toward or into the tumor cell, where the isotope emits beta radiation. This radiation damages nearby cellular DNA, helping destroy malignant cells while limiting exposure to tissues that carry little or no PSMA.
The trial’s primary result was radiographic progression-free survival, which measures how long patients live without visible growth or spread of cancer on imaging or death from any cause. Early addition of ^177Lu-PSMA-617 extended this interval compared with hormonal treatment alone. The investigators also reported that the drug delayed the development of castration-resistant disease, the stage at which prostate cancer continues progressing despite testosterone suppression. In addition, patients receiving the targeted radiotherapy experienced a longer interval before cancer-related symptoms involving the skeleton appeared.
Bone complications are a major concern in advanced prostate cancer because the disease frequently spreads to the skeleton. Tumors in bone can cause pain, fractures, spinal cord compression and other disabling problems. By delaying skeletal symptoms, the treatment may preserve quality of life as well as postpone the need for subsequent therapies. However, the researchers emphasized that longer follow-up is still needed to determine whether the early progression benefit will translate into a statistically confirmed improvement in overall survival.
The added treatment also brought additional side effects, as expected from a three-drug regimen that combines hormonal therapy with systemic radiation. Dry mouth was the most frequently reported adverse event, affecting 46% of patients who received ^177Lu-PSMA-617. The symptom occurs because salivary glands can express PSMA and may absorb some of the radiopharmaceutical. Fatigue was also common, reflecting the effects of both radiation and hormonal treatment. Physicians must weigh these risks against the potential benefit and monitor patients over time for less common or delayed complications.
The therapy is not suitable for every person with metastatic prostate cancer. Patients must first undergo specialized molecular imaging to confirm that their tumors contain sufficient PSMA for targeting. Administration requires nuclear medicine physicians or radiation oncologists, as well as facilities equipped to handle radioactive medicines. Treatment centers must also provide guidance on radiation safety, including precautions designed to reduce exposure to family members and others in the household. These requirements may make access more difficult for patients who live far from academic medical centers or specialized oncology programs.
The early success of ^177Lu-PSMA-617 follows earlier studies showing activity in patients whose metastatic prostate cancer had already become resistant to hormonal treatment. Its use at diagnosis represents a shift in strategy: rather than reserving targeted radiotherapy for advanced, treatment-resistant disease, clinicians may now deploy it while tumors remain more vulnerable to combined treatment. The PSMAddition investigators are continuing to analyze long-term survival and safety data. As additional molecular imaging agents and biomarker-driven therapies enter clinical practice, treatment selection is likely to become increasingly individualized, with the biology of each tumor helping determine which targeted drug is introduced, and when.
Subject of Research: Early use of targeted radionuclide therapy with ^177Lu-PSMA-617 in PSMA-positive metastatic prostate cancer.
News Publication Date: 6-Aug-2026
Web References: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lutetium-lu-177-vipivotide-tetraxetan-androgen-receptor-pathway-inhibitor-therapy; https://news.weill.cornell.edu/news/2017/05/first-clinical-trial-of-new-targeted-molecular-therapy-in-us-takes-aim-at-incurable
References: The Lancet; PSMAddition phase 3 clinical trial.
Keywords: Prostate cancer, metastatic prostate cancer, PSMA, ^177Lu-PSMA-617, lutetium vipivotide tetraxetan, targeted radionuclide therapy, radiopharmaceuticals, androgen deprivation therapy, androgen receptor pathway inhibitors, cancer treatment
