1077 - A Dynamic Treatment Strategy for Oligometastatic CSPC: Integrating Molecular Imaging and SBRT to Personalize Systemic Therapy Intensification and De-Intensification

Purpose/Objective(s): Recent advances in CSPC management, particularly PET-PSMA imaging and evolving therapeutic strategies, have improved patient outcomes. Oligometastatic CSPC (OM-CSPC) treatment includes therapeutic intensification (TI) and de-intensification (TD) strategies. TI consists of continuous ADT (cADT) ± ARPI ± docetaxel ± RT to the primary tumor, while TD incorporates intermittent ADT (iADT) and SBRT, aiming to delay systemic therapy, reduce toxicity, and preserve quality of life (QoL). Traditionally, TI and TD have been applied separately until disease progression to CRPC, limiting adaptive strategies. This study evaluates whether a dynamic therapeutic approach integrating TI and TD optimizes safety, efficacy, and cost-efficiency in OM-CSPC, aiming to maximize tumor control while minimizing toxicity and preserving QoL.

Materials/Methods: Patients with non-visceral OM-CSPC (=5 lesions, PET-PSMA staged) were included. A dynamic strategy combining TD and TI was applied based on individual response.

• TD Phase: All patients initially received iADT with induction ADT for 3–9 months. Treatment was paused (switch-off) upon achieving PSA nadir =0.2 ng/mL and restarted (switch-on) if PSA exceeded 8 ng/mL. SBRT targeted PET-positive lesions, including untreated primary tumors. New PET-positive lesions detected during switch-off were considered for treatment at physician’s discretion.
• TI Phase: Patients escalated to TI if PSA nadir =0.2 ng/mL was not reached during TD switch-on, PSADT <6 months, or radiological progression (>5 lesions or visceral metastases) occurred during switch-off. TI included ADT + ARPI ± docetaxel. Patients underwent PSA testing, imaging, and clinical assessments to monitor progression and response.

Results: Over a median follow-up of 25 months, 33 patients with OM-CSPC were analyzed. The dynamic strategy achieved 97% OS and a 97% CRPC-free survival rate. Disease control was maintained without escalation to TI in 81% of patients, avoiding cADT, ARPI, or chemotherapy. SBRT played a key role in delaying systemic therapy, contributing to a median time off-ADT of 30 months. Toxicity was minimal, with no grade =3 events and only 3% experiencing grade 2 toxicity from ADT. SBRT was well-tolerated, with no grade =2 complications. Cost analysis showed a 40% reduction in healthcare expenses compared to a hypothetical cohort receiving continuous TI, primarily due to reduced systemic therapy use and extended switch-off intervals.

Conclusion: Integrating TI and TD provides a feasible, effective approach for OM-CSPC. This strategy balances tumor control and QoL preservation while adapting to disease progression and individual needs. Molecular imaging enables personalized treatment selection, while SBRT plays a pivotal role in extending TD duration and delaying systemic therapy escalation, optimizing interventions and resource use. This model improves clinical outcomes and cost efficiency, offering a transformative approach to metastatic CSPC management.