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Perioperative treatment for muscle invasive bladder cancer in the era of immunotherapy

29 August 2026 at 18:00

Ther Adv Urol. 2026 Aug 27;18:17562872261481954. doi: 10.1177/17562872261481954. eCollection 2026 Jan-Dec.

ABSTRACT

Muscle-invasive bladder cancer (MIBC) remains associated with high recurrence and mortality despite radical cystectomy and cisplatin-based neoadjuvant chemotherapy (NAC). For decades, perioperative therapy was defined by platinum-based regimens, which improve survival but are limited to fewer than half of patients due to comorbidities. Recent advances in the past year have redefined this landscape. Multiple pivotal phase III trials have demonstrated the efficacy of immune checkpoint inhibitors (ICIs) in both neoadjuvant and adjuvant settings. The phase III trials, KEYNOTE-905/EV-303 and KEYNOTE-B15/EV-304 have established perioperative enfortumab vedotin plus pembrolizumab as a new standard of care for neoadjuvant therapy. Parallel translational research has identified biomarkers that may refine patient selection and optimize therapy. PD-L1 expression, DNA damage repair gene alterations, molecular subtyping, and circulating tumor DNA (ctDNA) have all emerged as predictive and prognostic tools. Liquid biopsy approaches may guide adjuvant therapy decisions and facilitate real-time monitoring of minimal residual disease. This review synthesizes the evolving role of perioperative therapies in MIBC, from the historical reliance on cisplatin-based chemotherapy to the transformative integration of immunotherapy, ADCs, and biomarker-guided approaches. Together, these advances represent a significant progress in perioperative bladder cancer care, heralding a shift toward individualized, biomarker-driven strategies that promise improved survival and broader treatment applicability.

PMID:42666617 | PMC:PMC13522676 | DOI:10.1177/17562872261481954

OSCAR: Orchestrated Self-verification and Cross-path Refinement

arXiv:2604.01624v1 Announce Type: new Abstract: Diffusion language models (DLMs) expose their denoising trajectories, offering a natural handle for inference-time control; accordingly, an ideal hallucination mitigation framework should intervene during generation using this model-native signal rather than relying on an externally trained hallucination classifier. Toward this, we formulate commitment uncertainty localization: given a denoising trajectory, identify token positions whose cross-chain entropy exceeds an unsupervised threshold before factually unreliable commitments propagate into self-consistent but incorrect outputs. We introduce a suite of trajectory-level assessments, including a cross-chain divergence-at-hallucination (CDH) metric, for principled comparison of localization methods. We also introduce OSCAR, a training-free inference-time framework operationalizing this formulation. OSCAR runs N parallel denoising chains with randomized reveal orders, computes cross-chain Shannon entropy to detect high-uncertainty positions, and then performs targeted remasking conditioned on retrieved evidence. Ablations confirm that localization and correction contribute complementary gains, robust across N in {4, 8, 16}. On TriviaQA, HotpotQA, RAGTruth, and CommonsenseQA using LLaDA-8B and Dream-7B, OSCAR enhances generation quality by significantly reducing hallucinated content and improving factual accuracy through uncertainty-guided remasking, which also facilitates more effective integration of retrieved evidence. Its native entropy-based uncertainty signal surpasses that of specialized trained detectors, highlighting an inherent capacity of diffusion language models to identify factual uncertainty that is not present in the sequential token commitment structure of autoregressive models. We are releasing the codebase1 to support future research on localization and uncertainty-aware generation in DLMs.
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