Randomized trial of p53 targeted adjuvant therapy for patients (pts) with organ- confined node-negative urothelial bladder cancer (UBC)
Bibliographic record
Abstract
5017 Background: Retrospective studies suggest that p53 mutation and associated immunohistochemical (IHC) detectable expression are prognostic for recurrence in pts with organ confined UBC and may be predictive for benefit from MVAC adjuvant chemotherapy. Methods: Pts with pT1–2N0M0 UBC following radical cystectomy and bilateral pelvic lymph node dissection were eligible. IHC for p53 was centrally performed and pts with ≥10% nuclear reactivity were offered randomization to 3 cycles of adjuvant MVAC vs. observation. P53 negative and p53 positive pts who declined randomization were observed. Primary endpoint was recurrence-free survival (RFS) in the randomized population. Secondary endpoints were RFS in p53 negative versus p53 positive pts and overall survival in each of these groups. Using a one-sided log-rank test with α = 0.05 and β = 0.15, 190 p53 positive patients were planned to be randomized to detect an absolute improvement in RFS at 3 years (yrs) from 50% to 70% (corresponding hazards ratio of 0.51). Results: 521 pts were registered, 499 underwent successful p53 assessment (male: 80%, <65 yrs: 57%, Caucasian: 91%, pathologic stage P1/P2: 37%/63%, lymphovascular invasion: 20% yes/28% unknown), 272 (55%) were p53 positive and 114 were randomized (42%). Further accrual was halted based on data safety monitoring board review of futility analysis on the first 100 randomized pts. P53 positive tumors were higher grade (97% vs 93% grade 3/4, p = 0.04) and less likely to express p21 (59% vs 84%, p < 0.001). Overall 5-yr RFS was 80 ± 2% with no difference based on p53 status. P53 positive patients declining were older but otherwise similar to those accepting randomization. Only 67% of pts randomized to MVAC received all 3 cycles with 12 (21%) receiving none. There was no difference in RFS in the randomized population (overall 5 yr RFS 83 ± 4%, hazard ratio = 0.88, p = 0.78). Conclusions: The prognostic and predictive value of p53 IHC were not confirmed in this prospective study, but the lower than expected event rate and failures to receive assigned therapy severely compromised the study's power. The value of p53 mutations is being assessed. No significant financial relationships to disclose.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".