Predictive and prognostic biomarkers in the perioperative treatment of muscle-invasive bladder cancer (MIBC) are an unmet need. Circulating tumor DNA (ctDNA) holds promise as a biomarker in this setting.
To review the evidence of ctDNA as a prognostic and predictive biomarker in the perioperative treatment of MIBC.
We systematically reviewed the literature using PubMed, MEDLINE, and Embase databases according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. We included prospective studies investigating neoadjuvant and/or adjuvant chemotherapy and/or immunotherapy for MIBC (T2-T4a, any N, and M0) treated with radical cystectomy. We reported ctDNA results to monitor and/or predict disease status, relapse, and progression. The research retrieved 223 records. Six papers were considered for this review based on prespecified inclusion criteria.
Our review confirms the prognostic role of ctDNA after cystectomy and shows a potential predictive benefit in using neoadjuvant chemotherapy and preoperative immunotherapy. Circulating tumor DNA was used to monitor recurrence, and changes in ctDNA status anticipated radiological progression with a median difference of time from 101 to 932 d. A subgroup analysis of the phase 3 Imvigor010 trial showed that only ctDNA-positive patients treated with atezolizumab had an improvement in disease-free survival (DFS; hazard ratio [HR] = 3.36, 95% confidence interval [CI]: 2.44-4.62). Clearance of ctDNA after two cycles of adjuvant atezolizumab was associated with improved outcomes (DFS HR = 0.26, 95% CI: 0.12-0.56, p = 0.0014; overall survival HR = 0.14, 95% CI: 0.03-0.59).
Circulating tumor DNA is a prognostic factor after cystectomy and may be used to monitor recurrence. In the adjuvant immunotherapy setting, ctDNA might select patients who benefit the most from this strategy.
In the perioperative treatment of muscle-invasive bladder cancer, circulating tumor DNA (ctDNA) positivity correlates with the outcomes after cystectomy and might select patients who may benefit from neoadjuvant chemotherapy and/or immunotherapy. Changes in ctDNA status anticipated radiological progression.
European urology oncology. 2023 Jun 15 [Epub ahead of print]
Emanuele Crupi, Tiago Costa de Padua, Laura Marandino, Daniele Raggi, Lars Dyrskjøt, Philippe E Spiess, Guru P Sonpavde, Ashish M Kamat, Andrea Necchi
Department of Medical Oncology, IRCCS San Raffaele Hospital, Milano, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: ., Department of Medical Oncology, IRCCS San Raffaele Hospital, Milano, Italy., Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USA., Genitourinary Oncology and Phase I Clinical Research Unit, AdventHealth Cancer Institute and the University of Central Florida, Orlando, FL, USA., Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Medical Oncology, IRCCS San Raffaele Hospital, Milano, Italy; Vita-Salute San Raffaele University, Milan, Italy.