Utility of ctDNA in predicting outcome and pathological complete response in patients with bladder cancer as a guide for selective bladder preservation strategies
| Autor: | Lars Dyrskjøt, George Laliotis MD, PhD, Iver Nordentoft, Karin Birkenkamp-Demtröder, Sia Viborg Lindskrog, Philippe Lamy, Elshaddai White, Natalia Pajak, Tine Ginnerup Andreasen, Punashi Dutta, Shruti Sharma, Mark Calhoun, Adam ElNaggar, Minetta C. Liu, Mads Agerbaek, Jørgen Bjerggaard Jensen |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 41:563-563 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 563 Background: Muscle-invasive bladder cancer (MIBC) accounts for ~25–30% of all bladder cancer diagnoses. With neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) as standard-of-care, the 5-year survival rate ranges from 40%–60%. Bladder-sparing protocols (BSP) have emerged as a feasible alternative to RC for MIBC treatment, however better tools are needed. In this study, we evaluated the prognostic value of circulating tumor DNA (ctDNA) in predicting recurrence in patients who achieved pathological complete response (pCR). Methods: We analyzed a previously described cohort of 68 patients (656 plasma samples; Christensen et al., JCO 2019) with MIBC who received NAC prior to cystectomy. Patients had an updated median follow-up of 58.94 months (range: 7.19-81.77) post-cystectomy. ctDNA was analyzed at baseline (before NAC; N=64), and prior to cystectomy (N=65) using a commercially available assay (Signatera, Natera, Inc.). Additionally, exploratory RNA-Seq was performed on tumors from 59 patients (samples with >5M total counts were utilized). Pathway analysis was used to compare ctDNA-positive and ctDNA-negative patients who failed to achieve pCR. Results: Of the 64 patients with ctDNA results available at baseline, 59.4% (38/64) tested ctDNA-negative, and of these 84.2% (32/38) achieved pCR. Furthermore, 40.6% (26/64) tested ctDNA-positive, and only 34.6% (9/26) achieved pCR. Likewise, prior to cystectomy, 83.9% (52/62) of patients were ctDNA-negative, and 80.7% (42/52) achieved pCR, while none of the ctDNA-positive patients achieved pCR (positive predictive value 100%; negative predictive value 80.8%). Based on both ctDNA timepoints, the probability of ctDNA-negative patients to achieve pCR was significantly higher than ctDNA-positive patients ( p |
| Databáze: | OpenAIRE |
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