Presentation (CTI)

OBJECTIVES: The EU JCA requires early, transparent, and evidence-based definition of Population-Intervention-Comparator-Outcome (PICO) frameworks. Defining appropriate comparators can be particularly challenging when emerging therapies are being developed in settings where treatment standards are not yet established. In early-stage PC, neoadjuvant androgen receptor pathway inhibitor (ARPI) strategies prior to radical prostatectomy (RP) are under active investigation, while no guideline-recommended neoadjuvant standard currently exists. This study evaluated how a REAL-SLR approach enables evidence-based comparator identification and PICO development for future JCA planning.
METHODS: A PRISMA-compliant continuously updated REAL-SLR was conducted using protocol-driven searches for early-stage PC. Evidence from interventional trials, regulatory sources, clinical guidelines, and technology assessments was systematically identified and structured. Studies were mapped by study design, population, intervention, comparator, endpoints, and reported subgroup analyses. This continuously updated evidence-base REAL-SLR was used to refine JCA-relevant PICO scenarios without repeating literature searches.
RESULTS: As of June 16, 2026, the REAL-SLR identified 335 studies in early-stage PC, including 95 phase 2 or 3 randomized-controlled trials. In the absence of guideline-recommended neoadjuvant therapies for patients undergoing RP, evidence mapping identified multiple comparator options including surgery alone and treatment strategies established in definitive radiotherapy settings, such as androgen deprivation therapy (ADT) alone or ADT plus abiraterone. PICO refinement further identified clinically relevant populations based on disease risk stratification, treatment modality (RP versus radiotherapy), endpoint availability and alignment with existing guideline recommendations.
CONCLUSIONS: The REAL-SLR database enabled transparent, evidence-based comparator selection and PICO development in an evolving treatment setting lacking an established standard of care. Living evidence approaches may improve comparator justification, reduce evidence-generation uncertainty, and strengthen JCA preparedness for emerging oncology therapies. In settings where treatment paradigms are evolving faster than guideline development, continuously updated evidence mapping may support earlier alignment of clinical development, comparator selection, and HTA evidence requirements.