ESTRO 2025 - Abstract Book

S126

Invited Speaker

ESTRO 2025

will discuss the pros and cons of both strategies and will try to identify patients that are best suited for one or the other strategy. Objective: To evaluate the role and efficacy of MDT, with or without systemic therapy (ADT ± Androgen Receptor Pathway Inhibitors [ARPI] or Radioligand Therapy [RLT]), in managing oligo-recurrent HSPC, focusing on nodal and distant metastatic patterns. Methods: This review synthesizes findings from key prospective trials investigating MDT in or-HSPC. Major trials reviewed include PEACE V-STORM (nodal recurrence), STOMP, ORIOLE (MDT alone vs. observation), EXTEND, RADIOSA (MDT vs. ADT, MDT ± ADT), trials exploring RLT (BULLSEYE, RAVENS). Endpoints considered include progression-free survival (PFS), biochemical PFS (bPFS), ADT-free survival (ADT-FS), toxicity, and quality of life (QoL). Results: • Nodal Oligo-Recurrence: Radiotherapy options include SBRT to involved nodes or ENRT to the whole pelvis with boost. While early studies debated efficacy versus toxicity, the Phase II PEACE V-STORM trial randomized patients with a biochemical recurrence to SBRT vs. ENRT, both with 6 months ADT. ENRT did not significantly increase acute grade 2+ GU/GI toxicity compared to SBRT (GU: 13% vs 8%; GI: 4.3% vs 3%) and maintained QoL. Preliminary efficacy data favors ENRT, showing significantly improved biochemical and loco-regional relapse-free survival compared to SBRT. The results on metastasis-free survival will be presented at ESTRO25 on the 5th of May in the Late Breaking session. • Distant Oligo-Recurrence (MDT Alone): The Phase II STOMP and ORIOLE trials demonstrated that MDT (SBRT or surgery) for limited distant metastases (≤3) significantly delayed ADT initiation and prolonged PFS compared to observation, without compromising QoL. Pooled analysis confirmed a doubling of median PFS with MDT (11.9 vs 5.9 months). Complete consolidation of all PET-avid lesions appeared critical for better outcomes. • Distant Oligo-Recurrence (Systemically Augmented MDT): Combining MDT with short-term systemic therapy shows promise. The Phase II EXTEND trial found that adding MDT (SBRT) to 6 months of intermittent ADT significantly improved bPFS versus ADT alone (median NR vs 15.8 months). Similarly, the Phase II RADIOSA trial showed adding 6 months of ADT to SBRT significantly improved bPFS compared to SBRT alone (median 26.8 vs 12.6 months). Both trials reported preserved QoL and testosterone recovery. Trials exploring intensification with ADT plus ARPIs (e.g., Persian) or ADT-sparing approaches using RLT combined with MDT (e.g., RAVENS) are dissapointing so far. • Patient Selection: Selection is moving beyond lesion count. Biochemical (e.g., PSA doubling time), metabolic (PSMA-PET findings), and genomic factors (e.g., high-risk mutations like TP53, ATM, BRCA) are emerging as key determinants for tailoring MDT approaches, identifying candidates for MDT alone versus those requiring systemic augmentation. Conclusion: MDT is a valuable strategy for selected patients with or-HSPC, capable of delaying systemic therapy initiation and progression. For nodal recurrence, ENRT combined with short-term ADT appears superior to SBRT+ADT based on current evidence, without excessive toxicity. For distant recurrence, MDT alone offers a meaningful delay in ADT, while augmenting MDT with short-term ADT significantly enhances disease control. Optimal patient selection incorporating clinical, imaging, and genomic markers is crucial. Ongoing Phase III trials will further refine the role of MDT and optimal systemic therapy combinations in this setting.

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Speaker Abstracts Controversial role of radiotherapy for small-cell lung cancer in the evolving IO landscape Antonin Levy 1 , Angela Botticella 1 , Cécile Le Péchoux 2 1 Radiation Oncology, Gustave Roussy, Villejuif, France. 2 Radiation Oncology, Gustave Roussy, France, France