The RECONCILE study protocol: Exploiting image-based risk stratification in early prostate cancer to discriminate progressors from non-progressors (RECONCILE).

Abstract

IntroductionRECONCILE (ClinicalTrials.gov:NCT04340245) will identify molecular and radiomic markers associated with clinical progression and radiological progression events in a cohort of localised, newly diagnosed Gleason 3 + 4 tumours. Molecular markers will be correlated against standard of care MRI-targeted histology and oncological outcomes.MethodsRECONCILE is an ethics approved (20/LO/0366) single centre, prospective, longitudinal, observational cohort study of recently diagnosed (within 12 months), organ-confined Gleason 3 + 4 cancers (MCCL ≤10mm) currently under active surveillance. 60 treatment-naïve participants with a concordant MRI lesion (Likert score 4 or 5) and PSA ≤ 15 ng/ml will be recruited. Blood, urine and targeted prostate tissue cores will be subject to next generation sequencing at baseline and one year in all participants. Semen will be collected from a specified sub-population. Baseline and interval MR images will be extracted from standard of care prostate MRI ahead of radiomic analysis. Data extracted from radiological and biological samples will be used to derive the association of molecular change and radiological progression, the primary outcome of the study. To compensate for spatial intratumoral heterogeneity and inherent sampling bias, a molecular index will be derived for each participant using the molecular profile of tumour tissue at both baseline (MolBL) and one year (MolFU). We will extract a ΔMolBL:MolFU score for each participant. Molecular progression will be defined as a MolBL:MolFU score >95% CI of the combined ΔMolBL scores. Radiological progression is defined as a PRECISE score of 4 or 5. The study is powered to detect an association with a statistical power of 80%.ResultsRecruitment began in July 2020 (n = 62). To date, 37 participants have donated tissue for analysis.ConclusionWe have designed and implemented a prospective, longitudinal study to evaluate the underlying molecular landscape of intermediate risk, MR-visible prostate tumours. Recruitment is ongoing.