TOPLINE:

In patients with muscle-invasive bladder cancer, circulating tumor DNA (ctDNA)-guided adjuvant atezolizumab after radical cystectomy produced a greater clinical benefit and was cost-effective than standard stage-based care. Over 5 years, the ctDNA-guided strategy led to cost savings of more than $50,000 per patient.

METHODOLOGY:

• Although trials of adjuvant immunotherapy for muscle-invasive bladder cancer have yielded inconsistent results, postoperative ctDNA positivity has emerged as a prognostic biomarker that may help identify patients who benefit from this immunotherapy. The IMvigor011 trial showed improved outcomes with postoperative ctDNA-guided adjuvant atezolizumab, but the economic implications of this biomarker-driven approach remain unclear.
• Researchers constructed a three-state Markov model (including the health states of disease-free, recurrence, and death) to compare the cost-effectiveness of ctDNA-guided adjuvant atezolizumab with standard of care in patients with muscle-invasive bladder cancer who underwent radical cystectomy from the perspective of a US healthcare payer over a period of 5 years. The model adopted a 1-month cycle length with half-cycle correction, and transition probabilities were estimated on the basis of data obtained from the IMvigor011 trial, the CheckMate274 trial, and a large retrospective study.
• In the ctDNA-guided strategy, patients with a positive ctDNA status received adjuvant atezolizumab (an intravenous dose of 1680 mg given once every 4 weeks for up to 1 year). Those with a persistently negative ctDNA status remained under observation. In the standard-of-care strategy, patients with high-risk pathologic features (ypT2-4/pT3-4 or N+) received adjuvant nivolumab (intravenous dose of 240 mg given once every 2 weeks for up to 1 year), whereas those with pT2N0 disease were kept under observation.
• The outcomes included total costs, incremental net monetary benefit, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs), with cost-effectiveness assessed against willingness-to-pay thresholds ranging from $50,000 to $150,000 per QALY.
• Researchers performed deterministic and probabilistic sensitivity analyses to assess model robustness and scenario analyses to explore alternative assumptions.

TAKEAWAY:

• The ctDNA-guided strategy yielded 3.05 QALYs at a total cost of $78,796 vs 2.92 QALYs at $131,601 with standard of care, which led to an incremental cost of -$52,805 and an ICER of -$397,163 per QALY gained, indicating higher effectiveness at a lower cost.
• Across the willingness-to-pay thresholds of $50,000-$150,000 per QALY, the incremental net monetary benefit remained positive, supporting consistent cost-effectiveness of the ctDNA-guided approach.
• One-way sensitivity analyses demonstrated that ctDNA positivity had the greatest effect on economic outcomes; a higher prevalence of ctDNA was associated with increased incremental cost and reduced incremental QALYs. Nivolumab uptake in the standard-of-care arm was the second most influential parameter — a higher uptake was associated with slightly reduced QALYs and thus a modest reduction in the relative benefit of the ctDNA-guided strategy.
• Probabilistic sensitivity analyses showed that the ctDNA-guided strategy dominated in over 98% of simulations across all willingness-to-pay thresholds; cost-effectiveness probabilities were 99.2%, 98.9%, and 98.5% at willingness-to-pay levels of $50,000, $100,000, and $150,000 per QALY, respectively.
• Regarding scenario analyses, ctDNA-guided strategy remained dominant when the prevalence of ctDNA positivity was 40% or less. At higher prevalence levels exceeding 60%, it transitioned toward a trade-off scenario in which it was less effective but less costly overall.

IN PRACTICE:

The study is “the first comprehensive cost-effectiveness evaluation of the ctDNA-guided adjuvant strategy for MIBC [muscle-invasive bladder cancer]. Our findings indicate that ctDNA-guided atezolizumab achieves greater oncologic benefit with superior cost-effectiveness compared with standard adjuvant care,” the authors of the study wrote. “By targeting immunotherapy to patients most likely to benefit and safely sparing individuals with negative ctDNA results, this approach optimizes resource utilization and reduces overtreatment.”

SOURCE:

The study, led by Zihan Xue, MD, Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China, was published online in JCO Oncology Practice.

LIMITATIONS:

The study adopted a 5-year time horizon and may have therefore underestimated the long-term benefits or costs of ctDNA-guided strategies. Real-world variability in neoadjuvant therapy use and adjuvant treatment patterns was not fully captured. Transition probabilities were reconstructed using extended survival curves rather than patient-level raw data, which may have introduced bias. Additionally, the analysis excluded indirect costs such as lost productivity and caregiver burden, which may have underestimated the overall economic benefit of ctDNA-guided strategies.

DISCLOSURES:

The study received support from the National Key R&D Program of China, the Noncommunicable Chronic Diseases-National Science and Technology Major Project, the Joint Funds of the Natural Science Foundation of Tianjin, and several other organizations. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.