Clinical Outcomes in Locally Advanced Prostate Cancer Between Radical Prostatectomy and Radiotherapy With Androgen Deprivation Therapy: A Propensity Score-matched Analysis

To compare clinical outcomes between the use of robotic-assisted laparoscopic radical prostatectomy (RP) and radiotherapy (RT) with long-term androgen deprivation therapy (ADT) in locally advanced prostate cancer (PC), we enrolled 315 patients with locally advanced PC (clinical T-stage 3/4). Propensity score-matching at a 1:1 ratio was performed. The median follow-up period was 59.2 months (IQR: 39.8-87.4). There were 117 (37.1%) patients in the RP group and 198 (62.9%) patients in the RT group. RT patients were older and had higher PSA at diagnosis, higher Gleason score grade group and more advanced T-stage (all p<0.001). After propensity score-matching, there were 68 patients in each group. Among locally advanced PC patients, treatment with RP had a higher risk of biochemical recurrence compared to the RT group. In multivariate Cox regression analysis, treatment with RT plus ADT significantly decreased the risk of biochemical failure (HR: 0.162, p<0.001), but there was no significant difference in local recurrence, distant metastasis and overall survival (p=0.470, p=0.268 and p=0.509, respectively). This information may provide insight for clinicians and patients for decision-making regarding their preference for either treatment strategy.

Biomarkers of Response to Neoadjuvant Androgen Deprivation in Localised Prostate Cancer

Prostate cancer (PCa) is a hormone driven cancer, characterised by defects in androgen receptor signalling which drive the disease process. As such, androgen targeted therapies have been the mainstay for PCa treatment for over 70 years. High-risk PCa presents unique therapeutic challenges, namely in minimising the primary tumour, and eliminating any undetected micro metastases. Trials of neoadjuvant androgen deprivation therapy aim to address these challenges. Patients typically respond well to neoadjuvant treatment, showing regression of the primary tumour and negative surgical margins at the time of resection, however the majority of patients relapse and progress to metastatic disease. The mechanisms affording this resistance are largely unknown. This commentary attempts to explore theories of resistance more broadly, namely, clonal evolution, cancer stem cells, cell persistence, and drug tolerance. Moreover, it aims to explore the application of these theories in the PCa setting. This commentary also highlights the distinction between castration resistant PCa, and neoadjuvant resistant disease, and identifies the markers and characteristics of neoadjuvant resistant disease presented by current literature.