Oligometastatic Prostate Cancer: Clues from an N-of-1

Background/Objectives: Metastatic Prostate Cancer (mPCa) is generally treated with systemic therapy. Many of these treatments, particularly androgen ablation, are not curative and cause substantial morbidity. Oligometastasis is defined as a limited number of metastatic deposits, whose disease does not seem to progress to a widespread distribution of cancer. There have been some reports of trials of localized treatment of PCa oligometastatic disease with curative intent. We herein report a case of oligometastatic prostate cancer treated primarily with surgical removal of metastases, which has no evidence of active disease twenty years post-operatively. Methods: Extensive retrospective chart review, immunohistochemical staining, growth rate calculations, and imaging studies were performed to trace the progression of this patient’s disease course. Results: A detailed investigation of biochemical markers of recurrence revealed normal-low prostate specific antigen (PSA) despite advanced disease, early rather than metachronous dissemination of metastases to distant sites, and hypoxia-conditioned phenotypic plasticity and memory in disseminated tumor cells (DTCs). Conclusions: This rare outlier case of oligometastatic prostate adenocarcinoma challenges traditional linear models of metastatic progression and clinical reliance on PSA as a marker for PCa detection and treatment in advanced cases. By investigating key questions regarding the identity, timing, and trajectory of DTCs, we propose a biologically informed narrative of this patient’s disease progression and a reconsideration of metastases directed therapy (MDT) of oligometastases as primary therapy in select patients.