In this issue of JAMA Oncology, Phillips et al1 report outcomes of the phase 2 ORIOLE (Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer) clinical trial in patients with hormone-sensitive oligometastatic prostate cancer randomized to receive stereotactic ablative radiotherapy (SABR) vs observation alone. Data on baseline prostate-specific membrane antigen (PSMA)–targeted positron emission tomography (PET) were blinded by protocol during SABR treatment planning, and 45% of patients treated with SABR were eventually found to harbor PSMA-avid lesions undetected by the treatment planning computed tomography (CT), which were left untreated. Progression-free and distant metastasis–free survival indicated adverse outcomes in these patients compared with the 55% of patients in whom all detectable lesions were ablated. Notwithstanding, the SABR-treated cohort had a significant 3-fold decrease in disease progression at 6 months compared with patients randomized to observation alone. One interpretation of these observations posits that macroscopic lesion consolidation by SABR alters the natural history of prostate oligometastatic disease by removing or greatly affecting signals that promote further development of micrometastatic disease.1 This hypothesis is consistent with the oligometastatic paradigm, which postulates that the oligometastatic state is a transient phase of metastatogenic equilibrium with delayed clonal expansion, potentially providing a window of opportunity for cancer cure if equilibrium-phase lesions are ablated before polymetastatic escape occurs.2
Greco C, Fuks Z. Forging New Strategies in the Cure of Human Oligometastatic Cancer. JAMA Oncol. 2020;6(5):659–660. doi:10.1001/jamaoncol.2020.0195
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