Metformin Active Surveillance Trial in Low-Risk Prostate Cancer
Metformin did not significantly reduce the risk of disease progression compared with active surveillance in patients with low-risk prostate cancer.
The European Randomized Study of Screening for Prostate Cancer (ERSPC) was initiated in 1993 to assess the effect of prostate-specific antigen (PSA) testing on prostate cancer mortality. Because deaths from prostate cancer are expected to rise worldwide owing to increased life expectancy and population growth, a final analysis of the long-term outcomes of prostate cancer screening is essential to understanding the benefits and harms of PSA testing.
We updated the findings from ERSPC, a multicenter, randomized study conducted across eight European countries with a focus on a predefined core age group of 162,236 men who were 55 to 69 years of age the time of randomization. Participants were randomly assigned to the screening group and offered repeated PSA testing or to the control group and not invited for screening. The primary outcome was prostate cancer mortality. Research Summary European Study of Prostate Cancer Screening — 23-Year Follow-up
After a median follow-up of 23 years, prostate cancer mortality was 13% lower in the screening group (rate ratio, 0.87; 95% confidence interval [CI], 0.80 to 0.95), and the absolute risk reduction was 0.22% (95% CI, 0.10 to 0.34). The cumulative incidence of prostate cancer was higher in the screening group than in the control group (rate ratio, 1.30; 95% CI, 1.26 to 1.33). a median of 23 years of follow-up, one death from prostate cancer was prevented for every 456 men (95% CI, 306 to 943) who were invited for screening, and one death from prostate cancer was averted for every 12 men (95% CI, 8 to 26) in whom prostate cancer was diagnosed, as compared with one death from prostate cancer prevented for every 628 men (95% CI, 419 to 1481) and one death averted for every 18 men (95% CI, 12 to 45) 16 years of follow-up.
Long-term follow-up confirms a sustained reduction in deaths from prostate cancer with PSA testing, alongside an improved harm–benefit ratio. Future screening strategies should adopt risk-based approaches to minimize overdiagnosis while maintaining clinical benefits. (Funded by the Dutch Cancer Society and others; ERSPC ISRCTN registry number, ISRCTN49127736.)
Metformin did not significantly reduce the risk of disease progression compared with active surveillance in patients with low-risk prostate cancer.
For our radiation oncology colleagues, the addition of PSMA-directed therapy prior to stereotactic body radiation therapy (SBRT) improved progression-free survival (PFS) in patients with oligometastatic prostate cancer. Two cycles of PSMA-directed therapy were administered before SBRT.
A new MMAI-derived digital pathology biomarker was trained and prospectively validated across multiple NRG/RTOG phase III trials, including RTOG 9202 (N=1,192), to predict which high-risk/locally advanced PCa patients benefit from LT-ADT vs ST-ADT with RT. In the overall cohort, LT-ADT reduced DM (17% vs 26% at 15 years) and DDM (15% vs 23% at 15 years), but this benefit was limited to biomarker-positive patients (DM: 19% vs 33%; DDM: 19% vs 30%), with no advantage seen in biomarker-negative patients (DM: 11% vs 11%; DDM: 9% vs 10%). This tool could allow about a third of our "high-risk" patients to avoid two extra years of ADT without compromising metastasis outcomes, while ensuring we intensify for those most likely to benefit. In short, this is a practical step toward personalizing ADT duration and sparing toxicity for a significant subset of our patients.
Pasritamig was administered to patients who had received a median of four prior lines of systemic therapy. It was well tolerated, with manageable adverse events, making it suitable for outpatient administration. The treatment showed a median radiographic progression-free survival of 7.85 months, and 14 out of 33 participants achieved a ≥50% reduction in baseline PSA levels. So, stay tuned.
In patients with localized prostate cancer, predominantly low-risk and intermediate-risk disease, the long-term update reveals 13-year outcomes. Treatment failure occurred less frequently in men undergoing HIMRT (n = 13) compared with those undergoing CIMRT.