Long-Term Outcomes and Genetic Predictors of Response to Metastasis-Directed Therapy Versus Observation in Oligometastatic Prostate Cancer: Analysis of STOMP and ORIOLE Trials

Author(s): Matthew P. Deek, MD1,2;Kim Van der Eecken, MD, PhD3;Philip Sutera, MD2;Rebecca A. Deek, MS4;Valérie Fonteyne, MD, PhD5;Adrianna A. Mendes, MD6;Karel Decaestecker, MD, PhD7;Ana Ponce Kiess, MD, PhD2;Nicolaas Lumen, MD, PhD5;Ryan Phillips, MD, PhD8;Aurélie De Bruycker, MD7;Mark Mishra, MD9;Zaker Rana, MD9;Jason Molitoris, MD, PhD9;Bieke Lambert, MD10;Louke Delrue, MD11;Hailun Wang, PhD2;Kathryn Lowe, BS2;Sofie Verbeke, MD, PhD12;Jo Van Dorpe, MD, PhD12;Renée Bultijnck, PhD7;Geert Villeirs, MD10;Kathia De Man, MD13;Filip Ameye, MD14;Daniel Y. Song, MD2;Theodore DeWeese, MD2;Channing J. Paller, MD15;Felix Y. Feng, MD16;Alexander Wyatt, PhD17;Kenneth J. Pienta, MD15,18;Maximillian Diehn, MD, PhD19;Soren M. Bentzen, PhD, DMsc9,20;Steven Joniau, MD, PhD21;Friedl Vanhaverbeke, MD22;Gert De Meerleer, MD23;Emmanuel S. Antonarakis, MD24;Tamara L. Lotan, MD6;Alejandro Berlin, MD25;Shankar Siva, MD, PhD26;Piet Ost, MD, PhD27,28;and Phuoc T. Tran, MD, PhD2,9,15,18 *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.
Source: DOI: 10.1200/JCO.22.00644
Lucio Gordan MD

Fascinating report/study making salient points on the continued need to characterize patients’ neoplasm from a genomic standpoint and the impact of direct management of oligometastatic disease in patients with high-risk mutational signature.

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 ATMBRCA1/2Rb1, 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 Affiliations

1Department 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.

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