In primary analysis, enzalutamide plus androgen deprivation therapy (ADT) improved radiographic progression-free survival (rPFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC); however, overall survival data were immature.
Long-Term Outcomes and Genetic Predictors of Response to Metastasis-Directed Therapy Versus Observation in Oligometastatic Prostate Cancer: Analysis of STOMP and ORIOLE Trials
The initial STOMP and ORIOLE trial reports suggested that metastasis-directed therapy (MDT) in oligometastatic castration-sensitive prostate cancer (omCSPC) was associated with improved treatment outcomes. Here, we present long-term outcomes of MDT in omCSPC by pooling STOMP and ORIOLE and assess the ability of a high-risk mutational signature to risk stratify outcomes after MDT. The primary end point was progression-free survival (PFS) calculated using the Kaplan-Meier method. High-risk mutations were defined as pathogenic somatic mutations within ATM, BRCA1/2, Rb1, or TP53. The median follow-up for the whole group was 52.5 months. Median PFS was prolonged with MDT compared with observation (pooled hazard ratio [HR], 0.44; 95% CI, 0.29 to 0.66; P value < .001), with the largest benefit of MDT in patients with a high-risk mutation (HR high-risk: 0.05; HR no high-risk: 0.42; P value for interaction: .12). Within the MDT cohort, the PFS was 13.4 months in those without a high-risk mutation, compared with 7.5 months in those with a high-risk mutation (HR, 0.53; 95% CI, 0.25 to 1.11; P = .09). Long-term outcomes from the only two randomized trials in omCSPC suggest a sustained clinical benefit to MDT over observation. A high-risk mutational signature may help risk stratify treatment outcomes after MDT.
Author Affiliations1Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ2Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD3Department of Pathology and Human Structure and Repair, University of Ghent, Ghent, Belgium4Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA5Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium6Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD7Department of Urology, Ghent University Hospital, Ghent, Belgium8Department of Radiation Oncology, Mayo Clinic, Rochester, MN9Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD10Department of Radiology and Nuclear Medicine, Ghent University, and Department of Nuclear Medicine, AZ Maria-Middelares Ghent, Belgium11Department of Radiology, Ghent University Hospital, Ghent, Belgium12Department of Pathology, Ghent University Hospital, Ghent, Belgium13Department of Nuclear Medicine, Ghent University Hospital, Ghent, Belgium14Department of Urology, AZ Maria-Middelares Ghent, Ghent, Belgium15Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD16Departments of Medicine, Urology and Radiation Oncology, UCSF, San Francisco, CA17Department of Urologic Sciences, University of British Columbia, and Vancouver Prostate Centre, Vancouver, Canada18James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD19Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA20Department of Epidemiology & Public Health, University of Maryland School of Medicine, Baltimore, MD21Department of Urology, Catholic University Leuven, Leuven, Belgium22Department of Urology, AZ Nikolaas, Sint-Niklaas, Belgium23Department of Radiation Oncology, Catholic University Leuven, Leuven, Belgium24Department of Medicine, University of Minnesota School of Medicine, Minneapolis, MN25Department of Radiation Oncology, Princess Margaret Cancer Center, Toronto, Canada26Department of Radiation Oncology, Peter MacCallum Cancer Center, Melbourne Australia27Department of Radiation Oncology, Iridium Network, Antwerp, Belgium28Department of Human Structure and Repair, Ghent University, Ghent, Belgium *M.P.D., K.V.d.E., P.O., and P.T.T. contributed equally to this work. P.O., and P.T.T. are co-senior authors.
The risk of major adverse cardiovascular events (MACE) following the initiation of androgen deprivation therapy (ADT) in men with prostate cancer is higher for older men compared with their younger counterparts. However, the overall MACE risk at 1 year in all age groups starting ADT is 1% or less, which is much lower than previously published reports. The findings, gleaned from analyses of U.S. electronic medical records, were presented during the virtual National Comprehensive Cancer Network 2022 Annual Meeting.
Darolutamide is a potent androgen-receptor inhibitor that has been associated with increased overall survival among patients with nonmetastatic, castration-resistant prostate cancer.
To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management.
Health-Related Quality of Life in Metastatic, Hormone-Sensitive Prostate Cancer: ENZAMET (ANZUP 1304), an International, Randomized Phase III Trial Led by ANZUP
We previously reported that enzalutamide improved overall survival when added to standard of care in metastatic, hormone-sensitive prostate cancer.