PROSTATE cancer (PCa) remains the second most commonly diagnosed malignancy in men worldwide. In developing Asian countries, over 50% of newly diagnosed PCa cases present at an advanced stage, leading to poorer survival outcomes compared to early-stage diagnoses in Western nations. A multimodal treatment approach, incorporating local surgical intervention and neoadjuvant systemic therapy (NT), has been explored to improve survival in patients with locally advanced PCa and oligometastatic prostate cancer (OMPCa). However, an optimal NT regimen is yet to be established.
Neoadjuvant systemic therapy is administered before local surgery to reduce tumour burden and address micrometastases. While conventional androgen deprivation therapy (ADT) has been extensively studied, it has not demonstrated significant survival benefits. This limitation is attributed to the persistence of intratumoural and adrenal androgens that continue to activate the androgen receptor (AR). To overcome this, novel androgen receptor signalling inhibitors (ARSIs) such as abiraterone, enzalutamide, and apalutamide have been combined with ADT. However, this combination has only shown limited improvement in pathological complete response (pCR) rates. Research suggests that the presence of castration-resistant cells may be an early event in PCa progression, necessitating the inclusion of chemotherapy in NT strategies.
Next-generation sequencing (NGS) has identified actionable targets beyond the AR axis, highlighting PCa’s molecular complexity. Precision medicine, which tailors treatment based on individual tumour characteristics, is increasingly recognised as essential. Despite extensive studies, no universally accepted neoadjuvant therapy exists for locally advanced PCa and OMPCa. Trials investigating neoadjuvant chemo-hormonal therapy (NCHT) have shown modest improvements, with pCR rates remaining low. Studies have also explored ARSIs in monotherapy and combination regimens, but the impact on pathological response has been limited.
Recent research suggests that precision treatment may improve outcomes. In a study of patients with germline DNA damage repair gene alterations, 28.6% achieved pCR following docetaxel and cisplatin NCHT. Given PCa’s heterogeneity, further research is needed, particularly in Asian populations. A phase II umbrella trial in China aims to evaluate the effectiveness of genomic biomarker-guided NT. This study, which began recruitment on 1st April 2024, could provide critical evidence supporting precision medicine in the neoadjuvant setting for PCa treatment.
Katie Wright, EMJ
Reference
Huang H et al. Safety and efficacy of genomic biomarker-guided neoadjuvant therapy for locally advanced and oligometastatic prostate cancer (SEGNO): study protocol for an open-label prospective phase II umbrella clinical trial. BMC Cancer. 2025;25(1):432.
