Abstract:
This update concerns the prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) and key controversies in managing nodal and distant metastases in prostate cancer. PSMA PET is increasingly favored over conventional imaging techniques, yet treatment decisions for positive findings remain debated, particularly regarding (1) therapeutic strategies, (2) disease progression monitoring, and (3) intensification approaches for metastatic castration-resistant prostate cancer (mCRPC).
For nodal metastases, both metastasis-directed and systemic treatments have been explored. Total androgen blockade with gonadotropin-releasing hormone (GnRH) agonists or antagonists, combined with anti-androgens, is recommended. GnRH antagonists offer faster, more effective responses with fewer complications. Patients with nodal or distant metastases should generally avoid Intermittent androgen deprivation therapy. Prostatectomy remains investigational for oligometastatic cases.
Upon progression to castration-resistant prostate cancer, intensification strategies may include radiotherapy (e.g., radium-223, lutetium-177 PSMA-targeted therapy), chemotherapy, and immunotherapy. Lutetium-177 PSMA therapy is FDA-approved only for mCRPC patients who have failed androgen receptor pathway inhibitors (ARPI). Triplet therapy or early radiopharmaceutical administration may benefit younger, fit patients. Pembrolizumab and poly (ADP-ribose) polymerase (PARP) inhibitors have become standard-of-care for patients with germline or somatic BRCA or ATM mutations in mCRPC. However, controversy persists regarding the prognostic role of tumor suppressor genes.
In conclusion, various approaches exist for managing nodal or distant site positivity detected via PSMA PET. This review highlights ongoing debates in radiotherapy (including PSMA radioligand therapy), systemic therapies, and immunotherapy to improve treatment outcomes for prostate cancer patients.
