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
Source: Source: 10.1200/JCO.22.00644 Journal of Clinical Oncology 40, no. 29 (October 10, 2022) 3377-3382.
Maem Hussein MD

Dr. Maem Hussein's Thoughts

Another use of genomic testing in prostate cancer, pts with high risk mutation may need systemic therapy  in addition to oligometastatic stereotactic radiotherapy, well informed patients with no high risk mutation signature may elect to go under surveillance to avoid side effects of androgen deprivation therapy,  this also emphasizes the importance of genomic testing in personalizing pt’s care.

ABSTRACT

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 5 .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, NJ; 2Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD; 3Department of Pathology and Human Structure and Repair, University of Ghent, Ghent, Belgium; 4Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; 5Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium; 6Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; 7Department of Urology, Ghent University Hospital, Ghent, Belgium; 8Department of Radiation Oncology, Mayo Clinic, Rochester, MN; 9Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD; 10Department of Radiology and Nuclear Medicine, Ghent University, and Department of Nuclear Medicine, AZ Maria-Middelares Ghent, Belgium; 11Department of Radiology, Ghent University Hospital, Ghent, Belgium; 12Department of Pathology, Ghent University Hospital, Ghent, Belgium; 13Department of Nuclear Medicine, Ghent University Hospital, Ghent, Belgium; 14Department of Urology, AZ Maria-Middelares Ghent, Ghent, Belgium; 15Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD; 16Departments of Medicine, Urology and Radiation Oncology, UCSF, San Francisco, CA; 17Department of Urologic Sciences, University of British Columbia, and Vancouver Prostate Centre, Vancouver, Canada; 18James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD; 19Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA; 20Department of Epidemiology & Public Health, University of Maryland School of Medicine, Baltimore, MD; 21Department of Urology, Catholic University Leuven, Leuven, Belgium; 22Department of Urology, AZ Nikolaas, Sint-Niklaas, Belgium; 23Department of Radiation Oncology, Catholic University Leuven, Leuven, Belgium; 24Department of Medicine, University of Minnesota School of Medicine, Minneapolis, MN; 25Department of Radiation Oncology, Princess Margaret Cancer Center, Toronto, Canada; 26Department of Radiation Oncology, Peter MacCallum Cancer Center, Melbourne Australia; 27Department of Radiation Oncology, Iridium Network, Antwerp, Belgium; 28Department of Human Structure and Repair, Ghent University, Ghent, Belgium

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