In 2020, nearly 600 000 individuals worldwide were diagnosed with bladder cancer, making it the tenth most common cancer globally [1], with approximately 25% of cases diagnosed as muscle-invasive bladder cancer (MIBC). For MIBC patients, trimodal therapy is a bladder-sparing treatment option involving concurrent chemoradiotherapy following local treatment. However, the risk of metastatic recurrence in MIBC after treatment remains high, so an efficient noninvasive approach to monitor these patients for early prediction of tumor recurrence is needed.
de Jong et al. [2] recently reported on a highly promising minimally invasive diagnostic tool for detecting genomic mutations and methylation status in urinary circulating tumor DNA (ctDNA). In a prospective study the authors evaluated the performance of this tool in predicting disease recurrence in patients with nonmetastatic MIBC undergoing bladder-sparing treatment with (chemo)radiotherapy. The analysis demonstrated sensitivity of 78% (95% confidence interval 52–94%), specificity of 77% (95% confidence interval 73–81%), and a negative predictive value of 99%. Importantly, the test accurately detected all three recurrences of upper tract urothelial carcinoma, which are undetectable via cystoscopy. In particular, therapy de-escalation is of interest for elderly patients, and having a urine-based monitoring tool can rationalize decisions on chemotherapy and radiation therapy. In comparison to cystoscopy, this method offers a less invasive and more convenient alternative to current diagnostic approaches.
Analysis of ctDNA in urine shows promising results in detecting minimal residual disease (MRD) and metastatic recurrence of bladder cancer. In a prospective study, ctDNA measurement detected clinical recurrence on average 3 month earlier than computed tomography scans. For patients who have undergone curative surgery, postoperative ctDNA status has strong prognostic value, along with high sensitivity and specificity, and patients with detectable ctDNA in urine have a higher risk of recurrence [3], [4]. Moreover, ctDNA outperforms pathological response status in predicting outcomes after neoadjuvant chemotherapy and the survival benefits of adjuvant immunotherapy for ctDNA-positive patients [5].
Overall, these results are promising, particularly for detecting residual disease and guiding adjuvant therapy. We believe that the tool developed by de Jong and colleagues is also applicable for detecting MRD in MIBC and predicting pathological complete response after neoadjuvant immunotherapy. Instead of focusing solely on genomic mutation information using next-generation sequencing methods as in most studies, de Jong et al. used a more widely available quantitative polymerase chain reaction(QPCR) method to detect mutations in FGFR3, TERT, and HRAS genes, along with the methylation status of OTX1, ONECUT2, and TWIST1 genes, thereby increasing sensitivity. However, it is worth noting that false-negative results for the test may also occur because of limitations in detection sensitivity, and the FGFR3 and HRAS mutations selected are not common in MIBC, which may also affect the detection sensitivity.
In conclusion, with appropriate adjustments to the genes tested and validation of the clinical utility in larger cohorts, this innovative approach may be of great value in the bladder-sparing setting for patients with MIBC.
Conflicts of interest: The author has nothing to disclose.
Use of generative AI and AI-assisted technologies: During preparation of this manuscript, the author used ChatGPT to improve the spelling and grammar. After using this tool, the author reviewed and edited the manuscript as needed and takes full responsibility for the content.
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