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DNA-repair status should be assessed in treatment-emergent neuroendocrine prostate cancer before platinum-based therapy

The ProstateZhu S, Zhang Z, Zhang H, et al. | January 21, 2022

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In treatment-emergent neuroendocrine prostate cancer (t-NEPC), DNA-repair genes (DRGs) status is therapeutically meaningful. Next generation sequencing should be employed clinically in t-NEPC cases to detect DRGs aberrations, given the potential responses to platinum-based chemotherapy.

  • This study included 43 NEPC patients, of whom 13/43 (30%) carried homozygous deletions, deleterious mutations, or both in DRGs.

  • Effective response was evident in 11 patients (11/13, 85%) having DRGs aberrations, including 7 cases with BRCA1/2 defects and 2 with mismatch repair-deficient induced by MSH2 alterations.

  • In patients without DRGs aberrations, there were significantly fewer responders (30%) (odds ratio = 12.83).

  • For radiologic progression and death, the hazard ratio was estimated to be 0.42 and 0.65, respectively, in patients with DRGs defects vs those without genomic DRGs aberrations.

  • Anemia, the most common adverse event of Grade 3 or 4, developed in 7 patients (16%).

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