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Prostate cancer

Metastasis-Directed Therapy for Prostate Cancer Found Beneficial Long-Term

Metastasis-directed therapy (MDT) for oligometastatic castration-sensitive prostate cancer (omCSPC) offers a long-term benefit in terms of progression-free survival (PFS), according to a recent study. This benefit was most pronounced among patients with tumors harboring high-risk genetic mutations.

In an analysis of pooled data from the prospective STOMP (ClinicalTrials.gov Identifier: NCT01558427) and ORIOLE (ClinicalTrials.gov Identifier: NCT02680587) trials, a team led by Phuoc T. Tran, MD, PhD, of the University of Maryland School of Medicine in Baltimore, found that MDT was associated with a 56% reduction in the risk of disease progression compared with observation after a median follow-up of 52 months. The median PFS — the study’s primary endpoint — was 11.9 months with MDT compared with 5.9 months with observation, Dr Tran and colleagues reported in the Journal of Clinical Oncology.

Among patients with high-risk mutations, MDT was associated with a 95% lower risk for disease progression, according to the investigators. The median PFS was 7.5 months among MDT recipients compared with 2.8 months among those who underwent observation.


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In the MDT cohort, patients without high-risk mutations had a significantly longer median PFS survival compared with those who had these mutations (13.4 vs 7.5 months).

“Although more follow-up is needed, the encouraging PFS report here suggests that in appropriately selected patients, MDT without systemic therapy might be a reasonable option upfront in well-informed patients wishing to avoid side effects of androgen deprivation,” Dr Tran and colleagues wrote.

The STOMP and ORIOLE trials compared MDT (stereotactic ablative radiation) and observation in patients with omCSPC. Investigators defined omCSPC as the presence of 3 or fewer sites of metastases. These studies previously demonstrated that MDT prolonged androgen deprivation-free survival and PFS.

For their analysis, Dr Tran’s team included 116 patients (62 from STOMP and 54 from ORIOLE). They defined high-risk mutations as pathogenic somatic mutations within the ATM, BRCA1/2, Rb1, or TP53 genes.

The authors said it is notable that the PFS beyond 4 years was 15% to 20% with MDT regardless of mutation status, “and thus, a sizable proportion of patients will experience duration response to therapy.”

Reference

Deek MP, van der Eecken K, Sutera P, et al. Long-term outcomes and genetic predictors of response to metastasis-directed therapy versus observation in oligometastatic prostate cancer: Analysis of STOMP and ORIOLE trials. J Clin Oncol. Published online August 24, 2022. doi:10.1200/JCO.22.00644