The expanded FDA approval allows Pluvicto to be used in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC) who have not yet undergone androgen receptor pathway inhibition or chemotherapy, according to Novartis officials. This approval covers metastatic castration-sensitive prostate cancer (mCSPC) and metastatic androgen pathway modulation–naive/sensitive (mAPMN/S) disease, broadening the therapy’s use beyond its prior authorization for metastatic castration-resistant prostate cancer (mCRPC). Novartis representatives said the new indication nearly doubles the number of patients eligible for Pluvicto in the United States, reflecting the larger population of hormone-sensitive metastatic patients compared with those in later-stage castration-resistant disease.

Pluvicto reduced the risk of disease progression or death by 28% in the primary analysis (hazard ratio [HR] 0.72; 95% confidence interval [CI], 0.58–0.90).

The FDA’s decision on July 31, 2026, was based on results from the Phase III PSMAddition trial, which evaluated Pluvicto combined with standard of care—an androgen receptor pathway inhibitor (ARPI) plus androgen deprivation therapy (ADT)—against standard of care alone. According to trial data presented by Novartis, An updated analysis showed an even greater risk reduction of 33% (HR 0.67; 95% CI, 0.55–0.82). Overall survival data indicated a positive trend favoring Pluvicto plus standard of care (HR 0.80; 95% CI, 0.63–1.01), though the final overall survival analysis is pending, Novartis officials said.

Pluvicto (lutetium Lu 177 vipivotide tetraxetan), also known as 177Lu-PSMA-617, is a targeted radioligand therapy that delivers beta-emitting lutetium-177 directly to prostate-specific membrane antigen (PSMA)–expressing prostate cancer cells. The therapy requires confirmation of PSMA-positive disease via FDA-approved PSMA PET imaging agents, such as Locametz (gallium Ga 68 gozetotide), consistent with prior labeling requirements. The recommended dosing for the mCRPC indication is 7.4 gigabecquerels (200 millicuries) administered intravenously every six weeks for six doses or until disease progression or unacceptable toxicity, according to FDA prescribing information.

Pluvicto was first approved by the FDA on March 23, 2022, for adults with PSMA-positive metastatic castration-resistant prostate cancer who had previously received both androgen receptor pathway inhibition and taxane-based chemotherapy. That approval was supported by the Phase III VISION trial, which demonstrated significant improvements in overall survival and radiographic progression-free survival. In VISION, Pluvicto plus best standard of care yielded a median overall survival of 15.3 months compared with 11.3 months in the control arm (HR 0.62; 95% CI, 0.52–0.74). Approximately 30% of patients treated with Pluvicto showed an overall response by RECIST 1.1 criteria, compared with 2% in the control group, records show.

On March 28, 2025, the FDA expanded Pluvicto’s indication to include adults with PSMA-positive mCRPC who had received ARPI therapy and were appropriate to delay taxane-based chemotherapy. This earlier use was supported by the Phase III PSMAfore trial, which showed that Pluvicto reduced the risk of radiographic progression or death by 59% compared with switching ARPI therapy (HR 0.41; 95% CI, 0.29–0.56; p<0.0001). Updated analyses from PSMAfore indicated that Pluvicto more than doubled median radiographic progression-free survival to 11.6 months compared with 5.6 months for ARPI change, according to trial investigators.

The 2026 approval for hormone-sensitive metastatic disease builds on these prior expansions by moving Pluvicto earlier in the metastatic prostate cancer continuum. Novartis officials described this as advancing a potential new standard of care across PSMA-positive metastatic prostate cancer. Industry sources and academic reviewers have noted that the shift allows for radioligand therapy to be integrated before chemotherapy in mCRPC and now in hormone-sensitive metastatic settings, potentially altering treatment sequences.

Patient selection for Pluvicto requires PSMA-positive metastatic disease confirmed by approved imaging. For the expanded mCRPC indication, patients must have prior ARPI exposure and be clinically appropriate to delay taxane chemotherapy. The therapy’s targeted mechanism offers precise tumor delivery with reduced systemic toxicity compared with conventional systemic treatments, according to peer-reviewed analyses cited by Novartis and academic experts.

The Prostate Cancer Foundation has highlighted the significance of earlier Pluvicto use, noting that about half of mCRPC patients do not survive long enough to receive second-line therapies, underscoring the need for effective treatments earlier in the disease course. The foundation described the 2025 expanded approval as allowing use before chemotherapy to slow disease progression and maintain quality of life.

FDA communications and Novartis statements confirm that Pluvicto’s expanded indication now covers adults with PSMA-positive metastatic prostate cancer across both hormone-sensitive and castration-resistant stages. The therapy’s availability throughout the metastatic disease spectrum marks a shift from end-stage treatment to earlier intervention. The final overall survival data from the PSMAddition trial are anticipated to provide further clarity on long-term benefits in the hormone-sensitive setting.

The review reported a modest mortality benefit of about two fewer prostate cancer deaths per 1,000 men screened, based on moderate-certainty evidence, according to the Cochrane evidence summary. This represents a change from the group’s 2013 update, which concluded that PSA screening did not significantly reduce prostate cancer mortality.

The updated Cochrane review, published in May 2026, analyzed data from six trials conducted across Europe and North America, involving nearly 800,000 men, and found that prostate-specific antigen (PSA) blood testing likely reduces the risk of dying from prostate cancer.

One major trial contributing to the updated analysis followed 162,241 men for 23 years, providing longer-term follow-up data than previous reviews, according to Cochrane records and reporting by STAT. Juan Franco, the review’s first author and a researcher at Heinrich Heine University Düsseldorf, told STAT that the group now has “moderate certainty” that PSA screening reduces disease-specific deaths. Cochrane officials said the mortality benefit emerges only with longer-term follow-up, emphasizing the importance of extended observation periods in evaluating screening outcomes.

The review also indicates that PSA screening may reduce the risk of dying from any cause, though this evidence is less certain. Cochrane noted that approximately 500 men would need to be invited to screening to prevent one prostate cancer death. The overall effect is described as modest, with Cochrane officials cautioning that the reduction in deaths is small in absolute terms.

In addition to mortality benefits, the review found that PSA screening increases the number of prostate cancers detected. Cochrane reported that screening likely results in 36 more men diagnosed with any prostate cancer per 1,000 screened and 34 more men diagnosed with localized prostate cancer per 1,000 screened. The Imaging Wire cited the review’s findings of a roughly 30% increase in prostate cancer diagnoses overall, mostly at an early stage. The review also suggested that PSA screening may reduce the number of metastatic prostate cancers by about five fewer cases per 1,000 men screened.

Cochrane officials acknowledged that the screening benefit comes with a substantial risk of overdiagnosis. The review found that for every one to two prostate cancer deaths prevented, there are about 36 additional cancers diagnosed. This tradeoff was similarly noted by The Imaging Wire. The review also stated that PSA screening may make little to no difference in deaths related to biopsy procedures or prostate cancer treatment. Evidence on quality of life showed little to no difference in the limited data available, according to Cochrane.

Experts from the Science Media Centre commented that the review draws on high-quality primary research and described the conclusion as robust. They also highlighted that the mortality benefit became apparent only with longer-term follow-up. Cochrane’s announcement framed the updated findings as a shift from its previous conclusions, reflecting the impact of extended data collection.

Clinically, Cochrane said PSA screening likely reduces prostate cancer deaths primarily in men with sufficient life expectancy. The review noted that newer approaches combining PSA with additional blood markers and prostate imaging might detect more cancers, but their effect on mortality remains unclear. The updated evidence supports a role for PSA screening in practice while underscoring the need to balance benefits with the risk of overdiagnosis and to use screening carefully.

The broader evidence base still leaves open questions about the optimal screening strategy, particularly regarding how to balance the modest mortality benefit against harms from overdiagnosis and overtreatment. Cochrane’s 2026 update builds on previous reviews by incorporating longer-term follow-up and larger sample sizes, contributing to ongoing discussions about prostate cancer screening policies in Europe and North America.

The study found that metformin consistently raised levels of N-lactoyl-phenylalanine (Lac-Phe), a molecule linked to exercise, in prostate cancer patients regardless of disease stage, according to research published April 6, 2026, in EMBO Molecular Medicine.

In a clinical trial subgroup, patients treated with metformin showed significant increases in Lac-Phe, reaching concentrations comparable to those observed in healthy individuals after intense physical activity, the report said.

Lac-Phe is an exercise-induced metabolite associated with weight loss and appetite suppression, researchers said. It has been identified in healthy people and athletes, including ultramarathon runners, and is released during physical activity to mimic some metabolic benefits of exercise. Previous observations noted elevated Lac-Phe levels in diabetes patients treated with metformin, but this study is among the first to demonstrate similar effects in prostate cancer patients who may be unable to exercise due to treatment-related limitations.

The exploratory study included prostate cancer patients across various stages who were treated with metformin. Researchers compared Lac-Phe levels in patients taking the drug to those not receiving metformin, finding consistent increases regardless of cancer stage or body weight. The clinical trial subgroup showed statistically significant rises in Lac-Phe following metformin administration, and these effects persisted regardless of other treatments the patients were undergoing, according to lead author Gigen Mammoser. The findings were fact-checked by Jill Seladi-Schulman, Ph.D., and reported on April 10, 2026.

Metformin’s ability to elevate Lac-Phe to levels comparable to strenuous exercise suggests it may mimic one key metabolic effect of physical activity, officials said. This could help manage treatment-related weight gain and support metabolic health in prostate cancer patients who are unable to participate in regular exercise. While metformin does not replace all the benefits of physical activity, the drug’s impact on Lac-Phe production may contribute to improved appetite control and weight management during cancer treatment, sources confirmed.

Beyond its effects on Lac-Phe, metformin has several mechanisms of action relevant to prostate cancer, according to prior research cited in the study. It inhibits the mTOR pathway, which reduces protein synthesis and tumor cell growth by targeting proteins such as 4E-BP1 and p70S6K1. Metformin also affects the Krebs cycle, altering lipid synthesis and beta-oxidation, processes that are important in prostate cancer metabolism. Additionally, the drug inhibits fatty acid synthase, an enzyme upregulated in cancer cells to promote fatty acid production.

Metformin activates AMP-activated protein kinase (AMPK) through AICAR-like effects, inducing metabolic stress in cancer cells, and targets the PI3K pathway, a major driver of prostate cancer growth alongside the androgen receptor. These mechanisms contribute to metformin’s ability to inhibit cancer cell proliferation and affect epithelial-mesenchymal transition (EMT) markers, which influence tumor invasion and metastasis, according to the study.

Clinical trials have demonstrated broader metabolic benefits of metformin in prostate cancer patients. One randomized trial showed that combining metformin with a low glycemic index diet and exercise led to reductions in abdominal girth, weight, body mass index, and systolic blood pressure in patients undergoing androgen deprivation therapy (ADT). However, that trial did not find differences in biochemical markers of insulin resistance. The drug’s influence on EMT expression via AMPK activation has also been observed in various cancers, including prostate cancer.

The study’s authors noted that metformin, a commonly prescribed diabetes medication, offers potential advantages for prostate cancer patients who cannot engage in physical activity due to treatment side effects or other limitations. By increasing Lac-Phe levels, metformin may help regulate appetite and control weight during cancer therapy, findings that build on previous observations in diabetes and exercise research.

The research was conducted with prostate cancer patients from multiple stages and treatment backgrounds, ensuring that the findings on Lac-Phe elevation were consistent across a diverse population. This consistency supports the potential use of metformin as part of metabolic management in prostate cancer care, according to the April 6, 2026, publication in EMBO Molecular Medicine.

Future studies may further explore the clinical implications of metformin-induced Lac-Phe increases and whether these metabolic effects translate into improved patient outcomes, including cancer progression and quality of life. The current findings provide a foundation for investigating metformin’s role in mimicking exercise benefits in populations unable to engage in physical activity.