Hideki Furuya

Triple-negative breast cancer (TNBC) lacks a blood-based biomarker for predicting or monitoring distant recurrence. We profiled 39 serum samples from 38 women (10 healthy controls; 12 non-recurrent [NR]; eight diagnosis-timepoint samples from patients who later recurred [DR-DIG]; nine recurrence-timepoint samples [DR-REC]) using the SomaScan v5.0 aptamer platform). Public tumor-tissue transcriptomic cohorts were used for supportive and exploratory analyses. No protein reached a false discovery rate (FDR) < 0.05 for NR vs. DR-DIG; granzyme A (GZMA) and endoplasmic reticulum aminopeptidase 1 (ERAP1) showed the strongest nominal signals. For DR-DIG vs. DR-REC, 38 aptamers (37 proteins) reached FDR < 0.05, enriched for RNA-binding and nuclear-envelope proteins; this signature was retained in leave-one-out and storage-adjusted analyses. Higher GZMA mRNA was associated with longer recurrence-free survival in two independent cohorts (hazard ratio [HR] = 0.795, p = 0.018; HR = 0.186, p = 0.0057). Monitor genes showed near-chance concordance with metastatic tissue, and the source of the signature could not be resolved. An exploratory four-gene elastic-net panel reached a concordance index of 0.613 internally but 0.559 externally. GZMA is a candidate serum biomarker of TNBC recurrence risk, and the monitor signature is a preliminary observation. Both require protein-level validation in independent, prospectively collected serum cohorts.

Participating Sites and Patient Enrollment.

Characteristics of Urine Samples Used for Development and Validation.

Purpose:More than 50% of patients with non–muscle-invasive bladder cancer experience recurrence, requiring lifelong surveillance with repeated cystoscopy. Given the invasive nature and cost of cystoscopy, accurate noninvasive tools are needed to support risk-adapted monitoring. We evaluated the ability of Oncuria-Monitor, a multiplex urine biomarker assay, to detect recurrent bladder cancer during surveillance. Patients and Methods:Between February 2017 and August 2020, six medical centers in the United States and Japan prospectively enrolled 300 patients with a history of bladder cancer, generating 1,248 serial urine samples. Participants were divided into training and validation cohorts. At each surveillance visit over 2 years, urine samples were analyzed in a blinded manner using Oncuria-Monitor and BladderChek, alongside urine cytology. Test performance was compared with cystoscopy and histopathology-confirmed recurrence. Results:Recurrent bladder cancer was identified in 31% (93/300) of participants, with 143 total recurrences during follow-up, including 90 tumors in the validation cohort. In the validation cohort, Oncuria-Monitor achieved a sensitivity of 85.6% [95% confidence interval (CI), 78.1%–92.2%] and a negative predictive value (NPV) of 93% (95% CI, 89.2%–96.4%). In comparison, BladderChek demonstrated a sensitivity of 20.0% and an NPV of 88%, whereas urine cytology showed a sensitivity of 36.9% and an NPV of 91.6%. The number needed to evaluate to detect one recurrence was 3 for both cystoscopy and Oncuria-Monitor, compared with 15 for BladderChek and 8 for cytology. Conclusions:In this large prospective longitudinal study, Oncuria-Monitor demonstrated clinically actionable performance, enabling a rule-out strategy that could safely reduce cystoscopy in approximately 25% of surveillance visits. These findings support a paradigm shift toward biomarker-guided, risk-adapted surveillance in bladder cancer that reduces unnecessary invasive procedures while maintaining oncologic safety.

Representativeness of Study Participants.

Specificities of Oncuria-Monitor, BladderChekTM and Cytology in Benign Urological Conditions.

Exogenous l -glutamine has preclinical antitumor activity although formal clinical translation has not been attempted. We conducted a single-arm phase 1 trial to assess the safety and preliminary efficacy of clinical-grade, US Food and Drug Administration-approved l -glutamine therapy with gemcitabine and nab-paclitaxel (GA) in participants with treatment-naive, advanced pancreatic cancer ( n = 16). The primary endpoint was to determine the recommended phase 2 dose (RP2D) by adaptive Bayesian design across standard doses of GA and a dose range of 0.1–0.3 g kg ⁻¹ twice-daily oral l -glutamine. Secondary endpoints included safety and preliminary efficacy of the study combination. The primary endpoint was met with the RP2D reached at maximum doses of l -glutamine and GA. The grade ≥3 treatment-related adverse event rate was 66.7%, primarily from GA. Addition of l -glutamine to GA induced tumor shrinkage in 94% of subjects with a best overall response rate (ORR) of 44% (12.5% complete response). Median progression-free survival and overall survival (OS) were 8.5 months (95% confidence interval (CI) 6–not reached (NR)) and 22 months (95% CI 11–NR), respectively. l -Glutamine induced distinct metagenomic and metabolomic signatures on exploratory analyses in glutamine-treated subjects as a single agent, while the combination of l -glutamine and GA nearly doubled the ORR and tripled the OS compared to historical GA alone (ClinicalTrials.gov registration: NCT04634539 ).

Muscle-invasive bladder cancer (MIBC) is an aggressive and heterogeneous malignancy with limited biomarkers to guide patient stratification and response to

Purpose: More than 50% of patients with non–muscle-invasive bladder cancer experience recurrence, requiring lifelong surveillance with repeated cystoscopy. Given the invasive nature and cost of cystoscopy, accurate noninvasive tools are needed to support risk-adapted monitoring. We evaluated the ability of Oncuria-Monitor, a multiplex urine biomarker assay, to detect recurrent bladder cancer during surveillance. Patients and Methods: Between February 2017 and August 2020, six medical centers in the United States and Japan prospectively enrolled 300 patients with a history of bladder cancer, generating 1,248 serial urine samples. Participants were divided into training and validation cohorts. At each surveillance visit over 2 years, urine samples were analyzed in a blinded manner using Oncuria-Monitor and BladderChek, alongside urine cytology. Test performance was compared with cystoscopy and histopathology-confirmed recurrence. Results: Recurrent bladder cancer was identified in 31% (93/300) of participants, with 143 total recurrences during follow-up, including 90 tumors in the validation cohort. In the validation cohort, Oncuria-Monitor achieved a sensitivity of 85.6% [95% confidence interval (CI), 78.1%–92.2%] and a negative predictive value (NPV) of 93% (95% CI, 89.2%–96.4%). In comparison, BladderChek demonstrated a sensitivity of 20.0% and an NPV of 88%, whereas urine cytology showed a sensitivity of 36.9% and an NPV of 91.6%. The number needed to evaluate to detect one recurrence was 3 for both cystoscopy and Oncuria-Monitor, compared with 15 for BladderChek and 8 for cytology. Conclusions: In this large prospective longitudinal study, Oncuria-Monitor demonstrated clinically actionable performance, enabling a rule-out strategy that could safely reduce cystoscopy in approximately 25% of surveillance visits. These findings support a paradigm shift toward biomarker-guided, risk-adapted surveillance in bladder cancer that reduces unnecessary invasive procedures while maintaining oncologic safety.