Oligometastatic Prostate Cancer Treated with Metastasis-Directed Therapy Guided by Positron Emission Tomography: Does the Tracer Matter?

Simple Summary Metastatic disease is the leading cause of morbidity and mortality in prostate cancer. Current therapeutic strategies mostly target cancer cells with important systemic effects injuring normal cells and healthy tissues. In prostate cancer patients with less than five metastases (called "oligometastatic"), this could be circumvented by implementing metastases-directed therapies (e.g., stereotactic radiotherapy), potentially avoiding systemic toxicity. In this setting, more accurate disease staging will likely result in more patients receiving the appropriate treatment, with expected better oncological results. On this basis, we verified the impact of two different radiotracers for Positron Emission Tomography/Computed Tomography imaging used as the guide for metastases-directed therapy on the oncological outcome in a retrospective sample of prostate cancer patients having less than five distant metastases. Obtained data showed that using next-generation imaging with [68Ga]Ga-prostate-specific membrane antigen-11 Positron Emission Tomography/Computed Tomography might favourably impact the oncological outcome of oligometastatic prostate cancer patients treated with metastases-directed therapy. The superior diagnostic accuracy of [68Ga]Ga-prostate-specific membrane antigen-11 (PSMA) ([68Ga]Ga-PSMA-11) compared to [18F]F-Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT) in Prostate Cancer (PCa) is established. However, it is currently unclear if the added diagnostic accuracy actually translates into improved clinical outcomes in oligometastatic PCa patients treated with [68Ga]Ga-PSMA-11 PET-guided metastasis-directed therapy (MDT). The present study aimed to assess the impact of these two imaging techniques on Progression-Free Survival (PFS) in a real-world sample of oligometastatic PCa patients submitted to PET-guided MDT. Thirty-seven oligometastatic PCa patients treated with PET-guided MDT were retrospectively enrolled. MDT was guided by [18F]F-Fluorocholine PET/CT in eleven patients and by [68Ga]Ga-PSMA-11 PET/CT in twenty-six. Progression was defined as biochemical recurrence (BR), radiological progression at subsequent PET/CT imaging, clinical progression, androgen deprivation therapy initiation, or death. Clinical and imaging parameters were assessed as predictors of PFS. [18F]F-Fluorocholine PET-guided MDT was associated with significantly lower PFS compared to the [68Ga]Ga-PSMA-11 group (median PFS, mPFS 15.47 months, 95% CI: 4.13-38.00 vs. 40.93 months, 95% CI: 40.93-40.93, respectively; p < 0.05). Coherently, the radiotracer used for PET-guided MDT resulted in predictive PFS at the univariate analysis, as well as the castration-resistant status at the time of MDT and the PSA nadir after MDT. However, in the multivariate analysis, castration resistance and PSA nadir after MDT remained the sole independent predictors of PFS. In conclusion, in the present proof-of-concept study, [68Ga]Ga-PSMA-11 provided higher PFS rates than [18F]F-Fluorocholine imaging in oligometastatic PCa patients receiving PET-guided MDT. Although preliminary, this finding suggests that enlarging the "tip of the iceberg", by detecting a major proportion of the submerged disease thanks to next-generation imaging may favourably impact the oncological outcome of oligometastatic PCa treated with MDT.