Retrospective analysis of outcomes of patients with bladder cancer when neoadjuvant chemotherapy is delayed.
Bibliographic record
Abstract
e16588 Background: Bladder (urothelial) cancer is the sixth most common form of cancer in the United States of America and results in significant morbidity and mortality. American Urological Association (AUA) guidelines recommend that muscle-invasive bladder cancer (MIBC) is treated with a course of cisplatin-based multi-agent neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC). The optimal timing of NAC is not well studied. Therefore, we aimed to evaluate the impact of timing NAC treatment to compare clinical outcomes among patients at the Saskatchewan Cancer Agency (SCA). Methods: We conducted a retrospective cohort study of the SCA electronic registry, reviewing the clinical and pathological data of 42 patients diagnosed with MIBC and treated with platinum-based NAC from January 2000 to December 2018. Patients with non-MIBC, metastatic bladder cancer, non-urothelial carcinoma histology, and charts with insufficient data were excluded. Survival analysis using Kaplan-Meier methods and log rank tests were utilized to compare overall survival (OS), disease recurrence, and post-RC surgical pathological staging of patients with respect to pre-specified time intervals between diagnosis, NAC and RC. Results: Patients who received NAC later than 8 weeks after diagnosis were more likely to have reduced OS (HR 1.25, 95% Confidence Interval (CI): 1.09-1.35, p=0.02). They also were more likely to have lymph node involvement (HR 1.63, 95% CI: 1.03-1.77, p=0.006). Patients who received RC more than 6 weeks after NAC completion were more likely to have more advanced primary tumour staging on pathology (HR 1.95, 95% CI: 1.3-2.09, p=0.01), but did not have significantly decreased OS (HR 1.88, 95% CI: 0.48-1.95, p=0.08). Delayed NAC (HR 2.77, 95% CI: 1.44-4.57, p<0.001) and RC (HR 1.50, 95% CI: 1.08-3.10, p<0.001) were associated with increased recurrence. Age, sex, body mass index, NAC regimen, and prior intravesical treatment were not statistically associated with OS upon analysis with univariate cox proportional hazard regression analysis. Conclusions: This review suggests an OS benefit by reducing the time from diagnosis to NAC in MIBC patients. This finding contrasts other studies that do not demonstrate any impact of delayed NAC on OS. These findings align with other works that do not show a survival detriment of delaying RC beyond 6 weeks after NAC completion. However, delaying surgery is associated with more advanced pathologic tumour staging. This study identifies the possibility of an association between delays in treatment delivery and worse clinical outcomes in some cohorts. Accordingly, further investigation of interval timing can better inform treatment planning and resource allocation in the management of patients with MIBC.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".