Metastatic castration-sensitive prostate cancer (mCSPC) is commonly partitioned into high- and low-volume subgroups which have demonstrated differential biology, prognosis, and response to therapy. Timing of metastasis has similarly demonstrated differences in clinical outcomes; however, less is known about any underlying biologic differences between these disease states.
Herein, we aim to compare transcriptomic differences between synchronous and metachronous mCSPC and identify any differential responses to therapy.
We performed an international multi-institutional retrospective review of men with mCSPC who completed RNA expression profiling evaluation of their primary tumor. Patients were stratified according to disease timing (synchronous vs metachronous). The primary endpoint was to identify differences in transcriptomic profiles between disease time. Median transcriptomic scores between groups were compared with Mann-Whitney U test. Secondary analyses included determining clinical and transcriptomic variables associated with overall survival (OS) from time of metastasis. Survival analysis was performed with the Kaplan-Meier Method and Multivariable Cox regression.
252 patients were included with a median follow-up of 39.6 months. Patients with synchronous disease experienced worse 5-yr OS (39% vs 79%, p<0.01) and demonstrated lower median Androgen Receptor Activity (AR-A) (11.78 vs 12.64, p<0.01) and Hallmark Androgen Response (HAR) (3.15 vs 3.32; p<0.01). Multivariable cox-regression identified only high-volume disease (HR=4.97, 95%CI 2.71-9.10; p<0.01) and HAR score (HR=0.51, 95%CI 0.28-0.88; p=0.02) significantly associated with OS. Finally, patients with synchronous (HR=0.47, 95%CI 0.30-0.72; <0.01) but not metachronous (HR=1.37, 95%CI 0.50-3.92; p=0.56) disease were found to have better OS with AR + non-AR combination therapy as compared to monotherapy (p value for interaction = 0.05).
We have demonstrated a potential biologic difference between metastatic timing of mCSPC. Specifically, for patients with low volume disease, those with metachronous low volume disease have a more hormone dependent transcriptional profile and exhibit a better prognosis than synchronous low volume disease.
Annals of oncology : official journal of the European Society for Medical Oncology. 2023 May 08 [Epub ahead of print]
P A Sutera, A C Shetty, A Hakansson, K Van der Eecken, Y Song, Y Liu, J Chang, V Fonteyne, A A Mendes, N Lumen, L Delrue, S Verbeke, K De Man, Z Rana, T Hodges, A Hamid, N Roberts, D Y Song, K Pienta, A E Ross, F Feng, S Joniau, D Spratt, S Gillessen, G Attard, N D James, T Lotan, E Davicioni, C Sweeney, P T Tran, M P Deek, P Ost
Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD., Veracyte, San Diego, California, USA., Department of Pathology, Ghent University, Ghent, Belgium., Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD., Department of Radiation Oncology, Ghent University Hospital, Belgium., Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD., Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium., Department of Radiology, Ghent University Hospital, Ghent, Belgium., Department of Pathology, Ghent University Hospital, Ghent, Belgium., Department of Nuclear Medicine, Ghent University Hospital, Ghent, Belgium., Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA., Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA., Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD; James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, Maryland., Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD; James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, Maryland., Department of Urology, Northwestern University, Chicago, IL, USA., Departments of Medicine, Urology and Radiation Oncology, UCSF, San Francisco, CA., Department of Urology, Catholic University Leuven, Leuven, Belgium., Department of Radiation Oncology, University Hospitals, Cleveland, Ohio, USA., Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland., Division of Molecular Pathology, The Institute of Cancer Research, London, UK., The Royal Marsden Hospital NHS Foundation Trust and The Institute of Cancer Research, London, UK., South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide Australia., Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD., Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA. Electronic address: ., Department of Radiation Oncology, Iridium Network, Antwerp, Belgium; Department of Human Structure and Repair, Ghent University, Ghent, Belgium. Electronic address: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/37164128