A recent study published in Euroepan Urology Oncologyexplores the potential of anti-PD-L1 immunotherapy for men with metastatic castration-resistant prostate cancer (mCRPC) who have DNA mismatch repair (MMR) deficiencies, a genetic feature found in about 5% of advanced cases.

Anti-PD-L1 drugs, such as atezolizumab or durvalimab, work by blocking the PD-L1 protein, which cancer cells use to hide from the immune system. In patients with MMR deficiencies, tumors often have microsatellite instability-high (MSI-H) status, meaning they carry many mutations that make them more visible to immune cells. This makes them candidates for immunotherapy, unlike most mCRPC cases, which typically resist immune-based treatments due to low immune activity in tumors.

The study looked at a small group of men (93) with MMR-deficient mCRPC who had progressed on standard treatments, including hormone therapies and often chemotherapy like docetaxel.

Results showed that some patients responded well.

Among treated patients, the objective response rate was 46%, meaning nearly half experienced measurable tumor shrinkage. Even more striking, 60% achieved a PSA-50 decline, indicating a ≥50% reduction in prostate-specific antigen levels, a strong marker of treatment response. The therapy delivered a median progression-free survival of 7.7 months, suggesting patients went over half a year without disease worsening, and a median overall survival of 27 months, far longer than typically expected in this advanced setting.

The study emphasizes the need for genetic testing to identify MMR deficiencies, as only a small fraction of mCRPC patients have this profile.

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