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

Deek, MP; Van der Eecken, K; Sutera, P; Deek, RA; Fonteyne, V; Mendes, AA; Decaestecker, K; Kiess, AP; Lumen, N; Phillips, R; De Bruycker, A; Mishra, M; Rana, Z; Molitoris, J; Lambert, B; Delrue, L; Wang, H; Lowe, K; Verbeke, S; Van Dorpe, J; Bultijnck, R; Villeirs, G; De Man, K; Ameye, F; Song, DY; DeWeese, T; Paller, CJ; Feng, FY; Wyatt, A; Pienta, KJ; Diehn, M; Bentzen, SM; Joniau, S; Vanhaverbeke, F; De Meerleer, G; Antonarakis, ES; Lotan, TL; Berlin, A; Siva, S; Ost, P; Tran, PT

Author(s): Deek, MP; Van der Eecken, K; Sutera, P; Deek, RA; Fonteyne, V; Mendes, AA; Decaestecker, K; Kiess, AP; Lumen, N; Phillips, R; De Bruycker, A; Mishra, M; Rana, Z; Molitoris, J; Lambert, B; Delrue, L; Wang, H; Lowe, K; Verbeke, S; Van Dorpe, J; Bultijnck, R; Villeirs, G; De Man, K; Ameye, F; Song, DY; DeWeese, T; Paller, CJ; Feng, FY; Wyatt, A; Pienta, KJ; Diehn, M; Bentzen, SM; Joniau, S; Vanhaverbeke, F; De Meerleer, G; Antonarakis, ES; Lotan, TL; Berlin, A; Siva, S; Ost, P; Tran, PT;
Details: Publication Year 2022-10-10,Volume 40,Issue #29,Page 3377-3382
Journal Title: Journal of Clinical Oncology
Publication Type: Research article
Abstract: Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.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.
Keywords: Clinical Trials as Topic; Humans; Male; Progression-Free Survival; *Prostatic Neoplasms/drug therapy/genetics; Treatment Outcome
Department(s): Radiation Oncology
PubMed ID: 36001857
Publisher's Version: https://doi.org/10.1200/JCO.22.00644
Open Access at Publisher's Site: https://doi.org/10.1200/jco.22.00644
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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