Prediction models for progression to castration-resistant prostate cancer after androgen deprivation therapy: a narrative review (2021–2026)

Background Prostate cancer is one of the most common male malignancies. Androgen deprivation therapy (ADT) is the backbone of treatment for locally advanced and metastatic disease, yet many patients progress to castration-resistant prostate cancer (CRPC), historically within about 2 years of ADT monotherapy, and validated, widely generalisable tools to identify high-risk patients early remain limited. Methods PubMed and OpenAlex were searched from January 2021 to August 2026 and supplemented by citation tracking; peer-reviewed studies reporting prediction models for progression to CRPC after ADT were included and synthesised narratively, with a PROBAST+AI-style appraisal of representative models. Results Of 65 unique records screened, 53 met the eligibility criteria (12 excluded as outside the scope or superseded); 17 references were added during revision, so 70 references are cited. CRPC arises through androgen receptor pathway activation, AR-V7, and neuroendocrine differentiation. Gleason score, PSA nadir, bone metastasis, inflammatory blood indices (neutrophil-to-lymphocyte ratio, systemic immune-inflammation index), circulating tumor cells, circulating tumor DNA, and genetic signatures are established risk factors. Individual studies report higher discrimination for machine-learning models than for traditional nomograms, but the comparisons are within-study and at high risk of bias and optimism, and external validation was reported for only two of eight core models. Super Learner, an ensemble framework, has proved stable across clinical outcome predictions; its use for CRPC prediction is only beginning. Conclusion A multi-parameter Super Learner model could improve CRPC risk stratification after ADT, provided it is validated prospectively in multicenter cohorts and reported transparently.