Circulating tumour DNA and extrachromosomal DNA in prostate and bladder cancer: biology, clinical applications and future perspectives.

PURPOSE: To critically appraise circulating tumour DNA (ctDNA) and extrachromosomal DNA (ecDNA) in prostate and bladder cancer, and to define what evidence links the two.

METHODS

Narrative review of search period July-September 2026, supplemented by reference-list and citation screening, covering ctDNA and ecDNA biology, detection and clinical application in prostate and urothelial cancer. The ctDNA-ecDNA interface was appraised using a five-tier evidentiary framework (copy-number gain; structural rearrangement; amplicon-graph reconstruction; phasing/optical mapping; orthogonal validation).

RESULTS

In bladder cancer, the phase 3 IMvigor011 trial validated ctDNA-guided adjuvant atezolizumab (disease-free survival [DFS] HR 0.64; overall survival [OS] HR 0.59), while persistently ctDNA-negative patients had 2-year DFS/OS of 88.4%/97.1% without adjuvant therapy. In prostate cancer, ctDNA positivity and androgen-receptor alterations are strongly prognostic (median OS 29.0 vs. 47.4 months; HR 2.0), but no prospective ctDNA-guided interventional trial exists. ecDNA is present in approximately 36% of urothelial carcinomas and drives oncogene amplification, heterogeneity, immune evasion and resistance. Evidence linking the two is indirect and asymmetric: prostate cancer offers stronger longitudinal ctDNA evidence via plasma AR-ecDNA proxy signatures, whereas bladder cancer shows stronger structural evidence from urinary sediment; no structurally validated blood ecDNA has been reported. This evidence derives predominantly from metastatic cohorts (mCRPC, post-cystectomy bladder cancer), with no established role in earlier-stage or minimal-residual-disease settings.

CONCLUSION

ctDNA is clinically actionable in bladder cancer and prognostic in advanced prostate cancer, whereas ecDNA remains an investigational driver. Structural confirmation of ecDNA in blood, assay standardisation and prospective biomarker-stratified trials are the priorities for the field.