Apalutamide for Intermediate-Risk Prostate Cancer: Phase II Trial Results and Molecular Correlates

What is it about?

The study aimed to determine if 6 months of preoperative apalutamide for intermediate-risk prostate cancer (IRPCa) reduces the risk of postoperative radiotherapy and evaluate associations of molecular perturbations with clinical outcomes in this cohort. Apalutamide 240 mg/day was given to eligible patients for 6 months before radical prostatectomy (RP). The primary endpoint was the presence of any adverse pathological feature at risk of pelvic radiation. Translational studies, including germline and somatic DNA alterations and RNA and protein expression, were performed on post-apalutamide RP specimens. The study found that preoperative apalutamide did not reduce the aggregate postoperative radiation risk to the pre-specified threshold in biomarker-unselected men with IRPCa. However, transcriptomic analysis identified key dysregulated pathways in tumours associated with adverse pathological outcomes and BCR, which warrant further investigation.

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Why is it important?

The study aims to determine whether 6 months of preoperative apalutamide for intermediate-risk prostate cancer (IRPCa) reduces the aggregate postoperative radiotherapy risk and to evaluate associations of molecular perturbations with clinical outcomes in this study cohort. This research is important because IRPCa is a unique disease state where a subset of patients with initially non-lethal cancer subsequently develop recurrent and potentially lethal PCa. Understanding the molecular perturbations and identifying the minority of patients at highest risk of lethal, androgen-indifferent PCa who may benefit from intensified, earlier escalation of systemic therapy is crucial for effective treatment and patient outcomes. Key Takeaways: 1. Preoperative apalutamide did not reduce the aggregate postoperative RT risk to the pre-specified threshold in biomarker-unselected men with IRPCa. 2. Transcriptomic analysis identified key, potentially targetable replication and DDR pathways upregulated in tumours with adverse pathology and/or BCR. 3. These pathways may serve as potential biomarkers and warrant further investigation to identify the minority of patients with localised disease at highest risk of lethal, androgen-indifferent PCa who may benefit from intensified, earlier escalation of systemic therapy.