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.
Between May 2018 and February 2020, eligible patients with IRPCa (Gleason 3 + 4 or 4 + 3 and clinical T2b-c or prostate-specific antigen level of 10-20 ng/mL) were treated with apalutamide 240 mg/day for 6 months followed by radical prostatectomy (RP) in this single-arm, phase II trial. The primary endpoint was presence of any adverse pathological feature at risk of pelvic radiation (pathological T stage after neoadjuvant therapy [yp]T3 or ypN1 or positive surgical margins). Translational studies, including germline and somatic DNA alterations and RNA and protein expression, were performed on post-apalutamide RP specimens, and assessed for associations with clinical outcomes.
A total of 40 patients underwent a RP, and only one patient discontinued apalutamide prior to 6 months. In all, 40% had adverse pathological features at time of RP, and the 3-year biochemical recurrence (BCR) rate was 15%, with 27.5% being not evaluable. Genomic alterations frequently seen in metastatic PCas, such as androgen receptor (AR), tumour protein p53 (TP53), phosphatase and tensin homologue (PTEN), or BReast CAncer associated gene (BRCA1/2) were underrepresented in this localised cohort. Adverse pathological features and BCR at 3-years were associated with increased expression of select cell cycle (e.g., E2F targets: adjusted P value [Padj] < 0.001, normalised enrichment score [NES] 2.47) and oxidative phosphorylation (Padj < 0.001, NES 1.62) pathways.
Preoperative apalutamide did not reduce the aggregate postoperative radiation risk to the pre-specified threshold in unselected men with IRPCa. However, transcriptomic analysis identified key dysregulated pathways in tumours associated with adverse pathological outcomes and BCR, which warrant future study. Further investigation of preoperative therapy is underway for men with high-risk PCa.
BJU international. 2024 Jun 04 [Epub ahead of print]
Andrew W Hahn, Ganiraju C Manyam, Brian F Chapin, Miao Zhang, Yao Yu, Curtis A Pettaway, Lisly Chery, Louis L Pisters, John F Ward, Justin R Gregg, John Papadopoulos, Ashish M Kamat, Marisa Lozano, Anh Hoang, Bradley Broom, Xuemei Wang, Chad D Huff, Christopher J Logothetis, Patricia Troncoso, Patrick G Pilié, John W Davis
Division of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Division of Basic Sciences, Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Division of Surgery, Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Division of Pathology and Laboratory Medicine, Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.