HIGH-RISK localised prostate cancer (HRLPC) presents significant challenges, with aggressive characteristics such as Gleason scores ≥8, PSA levels ≥20 ng/mL, or clinical stage cT3N0-1. Radical prostatectomy (RP) remains the cornerstone of treatment, yet recurrence and disease progression necessitate multimodal approaches. Among these, neoadjuvant androgen deprivation therapy (nADT) is gaining traction as a promising adjunct to surgery.
Traditional androgen deprivation therapies (ADT) initially showed limited impact on long-term outcomes despite reducing prostate size and surgical margins. However, the emergence of next-generation androgen signalling inhibitors has reinvigorated interest in nADT, offering new hope for improved oncological outcomes in HRLPC.
A recent exploratory study delved into the pathological outcomes of nADT in HRLPC. Findings highlighted a 22.5% pathological response rate and a 27.4% downstage migration rate, consistent with other prospective studies. Crucially, baseline cancer burden emerged as a major predictor of response. Patients with low PSA levels and smaller tumour volumes showed better pathological outcomes, emphasising the importance of early detection and intervention.
Biomarkers such as PTEN and ERG also played pivotal roles in predicting treatment efficacy. Alterations in these biomarkers were strongly associated with poor response, underlining their potential as tools for patient stratification in future clinical trials. Interestingly, these genetic alterations were predominantly observed in Caucasian men, suggesting potential racial disparities in treatment responses.
Despite promising short-term results, the study acknowledges limitations. The absence of long-term survival data and reliance on immunohistochemistry for biomarker analysis underscore the need for further research. Moreover, the lack of standardised tumour regression criteria limits the generalisability of findings.
Nevertheless, the study supports the potential of nADT as an adjunctive therapy in HRLPC, particularly for select subgroups with favourable biomarkers and low baseline cancer burden. If long-term benefits are confirmed, nADT could redefine treatment paradigms, offering improved outcomes for patients with this challenging disease. Future trials will be crucial in validating these findings and addressing unanswered questions regarding its role in prostate cancer management.
Katie Wright, EMJ
Reference
Cardili L et al. Tumor regression after neoadjuvant hormonal therapy in high risk prostate cancer: pathological outcomes from a randomized phase II trial. World J Urol. 2024;42(1):618.
