Molecular Subtyping for Predicting Pathological Upstaging and Survival Outcomes in Clinically Organ-confined Bladder Cancer Patients Undergoing Radical Cystectomy
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
In patients with clinically organ-confined bladder cancer, luminal tumors show lower rates of pathological upstaging at radical cystectomy. Furthermore, patients with luminal bladder cancer have better overall survival after radical cystectomy without neoadjuvant therapy than patients harboring nonluminal bladder cancer. Many patients with bladder cancer are understaged. Previous work revealed that molecular subtyping using Decipher Bladder improves clinical staging. This multicenter validation study evaluated Decipher Bladder for upstaging in patients who underwent radical cystectomy (RC) without neoadjuvant therapy. The Decipher Bladder genomic subtyping classifier (GSC; Veracyte, San Diego, CA, USA) was performed on bladder tumor specimens from patients with high-grade, clinically organ-confined (cTa-T2N0M0) urothelial carcinoma who subsequently underwent RC without neoadjuvant chemotherapy. The primary endpoint was pathological upstaging to non–organ-confined (NOC) disease (pT3+ and/or N+) at RC. The secondary endpoints included overall survival (OS) and pathological upstaging to MIBC+ disease (pT2+ and/or N+) at RC within clinically non–muscle-invasive bladder cancer (cNMIBC) cases. A total of 226 patients (134 cNMIBC [cTa/Tis/T1] and 92 cT2) were analyzed from eight participating institutions. Upstaging to NOC disease was observed in 33% of patients (19% for cNMIBC and 53% for cT2). Molecular subtyping identified 138 luminal and 88 nonluminal tumors. Rates of upstaging to NOC were 41% in nonluminal and 28% in luminal tumors (univariable p = 0.04), which was not independently significant after adjusting for clinical variables. Upstaging to MIBC+ in cNMIBC patients was lower in luminal versus nonluminal tumors (32% vs 51%, multivariable p = 0.03). Patients with nonluminal tumors had worse OS on multivariable analyses ( p < 0.05). Limitations include retrospective design and sample size. Luminal tumors represent less aggressive disease, reflected by lower rates of pathological upstaging and favorable OS with RC compared with nonluminal tumors. Molecular subtyping suggests that in clinically non–muscle-invasive bladder cancer, luminal tumors harbor less aggressive disease, as reflected by lower rates of pathological upstaging to muscle-invasive disease and favorable outcomes with radical cystectomy, in comparison with nonluminal bladder cancer.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it