Active surveillance (AS) is a standard management strategy for low-risk prostate cancer (PCa), but a significant proportion of patients ultimately experience disease progression. Metformin, a commonly prescribed antidiabetic agent, has demonstrated antitumor activity in preclinical studies and observational data, prompting investigation into its potential to delay PCa progression.
The Metformin Active Surveillance Trial (MAST) was a multicenter, randomized, double-blind, placebo-controlled phase III trial evaluating the efficacy of metformin in men with low-risk, localized PCa managed with AS. Eligible participants were randomly assigned 1:1 to receive either metformin (850 mg twice daily) or placebo and were followed for up to 36 months. The primary end point was time to progression, defined as therapeutic and/or pathologic progression. Progression-free survival (PFS) was assessed using Kaplan-Meier analysis and Cox proportional hazards models.
A total of 408 patients were randomly assigned (205 metformin, 203 placebo). After a median follow-up of 36 months, 144 participants experienced progression (70 metformin, 74 placebo), with no significant difference in PFS (hazard ratio [HR], 1.09 [95% CI, 0.79 to 1.52]; P = .59). Negative biopsy rates 36 months were 41.0% (metformin) versus 31.1% (placebo; P = .181). In prespecified subgroup analysis, metformin was associated with increased pathologic progression among obese patients (BMI ??? 30; HR, 2.36 [95% CI, 1.21 to 4.59]; P = .0092).
Metformin did not reduce progression in men with low-risk PCa on AS. The observed adverse effect in obese patients merits further investigation.
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.
A 13% reduction in mortality was observed in the screening group, with an improved harm-benefit ratio. For every 456 men screened, one prostate cancer death was prevented. It is an easy and inexpensive test, though concerns remain regarding unnecessary biopsies and overtreatment.
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.