Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer: not ready for prime time

Purpose Patients with oligometastatic prostate cancer (PC) may benefit from metastasis-directed therapy (MDT), delaying disease progression and the start of palliative systemic treatment. However, a significant proportion of oligometastatic PC patients progress to polymetastatic PC within a year following MDT, suggesting an underestimation of the metastatic load by current staging modalities. Molecular markers could help to identify true oligometastatic patients eligible for MDT. Methods Patients with asymptomatic biochemical recurrence following primary PC treatment were classified as oligo- or polymetastatic based on 18 F -choline PET/CT imaging. Oligometastatic patients had up to three metastases at baseline and did not progress to more than three lesions following MDT or surveillance within 1 year of diagnosis of metastases. Polymetastatic patients had > 3 metastases at baseline or developed > 3 metastases within 1 year following imaging. A model aiming to prospectively distinguish oligo- and polymetastatic PC patients was trained using clinicopathological parameters and serum-derived microRNA expression profiles from a discovery cohort of 20 oligometastatic and 20 polymetastatic PC patients. To confirm the models predictive performance, it was applied on biomarker data obtained from an independent validation cohort of 44 patients with oligometastatic and 39 patients with polymetastatic disease. Results Oligometastatic PC patients had a more favorable prognosis compared to polymetastatic ones, as defined by a significantly longer median CRPC-free survival (not reached versus 38 months; 95% confidence interval 31–45 months with P