Clin Chim Acta. 2026 Mar 31;588:120992. doi: 10.1016/j.cca.2026.120992. Online ahead of print.

ABSTRACT

Bladder cancer diagnosis and surveillance remain anchored in cystoscopy and urine cytology, despite their invasiveness, operator dependence, and limited sensitivity for low-grade or flat lesions. These constraints have accelerated interest in liquid biopsy approaches that provide noninvasive, real-time molecular insights into tumor biology. This narrative review examines emerging evidence on three key classes of circulating biomarkers, namely, circulating tumor DNA (ctDNA), exosomes, and circulating tumor cells (CTCs), and their expanding roles in diagnosis, prognosis, and treatment guidance. ctDNA reflects tumor-specific genomic alterations and shows particular strength in detecting minimal residual disease, identifying early molecular relapse, and monitoring therapeutic response, although its diagnostic sensitivity remains moderate. Urinary exosomes demonstrate some of the highest diagnostic accuracies among liquid biopsy platforms, with multimarker RNA panels achieving sensitivities and specificities above 90%, while their diverse cargo of miRNAs, mRNAs, and lncRNAs provides robust prognostic information linked to recurrence and survival. CTCs, although technically challenging to isolate owing to their phenotypic heterogeneity, offer valuable insights into tumor aggressiveness, metastatic potential, and treatment responsiveness, especially in muscle-invasive disease. Advances in ultrasensitive sequencing, microfluidic CTC capture, and multi-omics integration are accelerating clinical translation. Collectively, circulating biomarkers are poised to complement and, in selected contexts, transform bladder cancer management by enabling earlier detection, individualized risk stratification, and more precise therapeutic decision-making.

PMID:41933678 | DOI:10.1016/j.cca.2026.120992

Eur J Cancer. 2026 Mar 19;239:116676. doi: 10.1016/j.ejca.2026.116676. Online ahead of print.

ABSTRACT

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker in melanoma, with higher sensitivity for tumor burden detection than conventional diagnostics. While well established in research, clinical routine implementation remains pending. Key global questions concern optimal clinical applications and barriers to adoption.

METHODS: A web-based survey of 116 members of the Melanoma World Society Study Group assessed international expert opinions on ctDNA utility across predefined clinical scenarios. The questionnaire included 18 general questions on ctDNA use and 5 clinical vignettes with de-identified patient data and retrospectively obtained ctDNA results.

RESULTS: ctDNA was rated most valuable for detecting minimal residual disease (mean score 3.63), surveillance of recurrent disease (3.85), and stage IV melanoma (3.82), with limited utility in early stages. Experts considered ctDNA superior to S100 and LDH for early relapse detection and identifying progressive disease. Most participants (80%) agreed that ctDNA correlates with radiographic response, and 82% favored its integration into routine follow-ups. In urgent high-tumor-burden settings, 82.8% would initiate BRAFi/MEKi therapy based on ctDNA if tissue analysis was pending, and 93.9% if unavailable. For central nervous system lesions, 62% did not support blood ctDNA, while 66% considered cerebrospinal fluid valuable. Pragmatic approaches with small to mid-size targeted panels and short turnaround times were preferred. Major barriers included the need for prospective trials (85%), standardized guidelines (83%), and reimbursement policies (82%).

CONCLUSION: Key opinion leaders regarded ctDNA as a valuable adjunct selected melanoma scenarios. Validation through prospective studies, guideline development, and reimbursement frameworks are essential for broader clinical implementation.

PMID:41932032 | DOI:10.1016/j.ejca.2026.116676