Clinical variables associated with immune checkpoint inhibitor outcomes in patients with metastatic urothelial carcinoma
Bibliographic record
Abstract
Abstract Background Anti-PD-1/L1 immune checkpoint inhibitors (ICI) are indicated for metastatic urothelial cancer (mUC), however, only a minority of patients will derive therapeutic benefit. Strong predictive and prognostic factors are lacking. We investigated if clinical variables were associated with ICI outcomes in mUC. Methods We performed a multi-center retrospective cohort study of patients with mUC who received anti-PD-1/L1 ICI for metastatic disease between 2016-2021 at 3 Canadian cancer centres. Clinical characteristics, including demographics, BMI, metastatic sites, neutrophil-to-lymphocyte ratio (NLR), objective response, and survival were abstracted from chart review. ICI treatment response was determined by investigator assessment of clinical and radiologic parameters. Fisher’s exact test was used to assess differences in response rates between groups. Log rank and Cox regression models were used to assess overall survival (OS). Results We identified 135 patients with mUC who received anti-PD1/L1 ICI. A BMI ≥ 25 was significantly correlated to a higher overall response rate (ORR) to ICI (45.4% vs 16.3%, P = 0.020). After a median follow-up of 14.5 months, patients with BMI ≥ 30 experienced significant longer median OS 24.8 months vs. 14.4 months for 25 ≤ BMI < 30 and 8.5 months for BMI < 25 (P = 0.012). The ORR was significantly less in the presence of bone metastasis 16% vs 41% P = 0.006, and liver metastasis 16% vs 39% P = 0.013. Conversely, the presence of metastatic lymph nodes was significantly correlated with higher ORR 40% vs 20% P = 0.032. The median OS for patients with bone metastasis was 7.3 months vs 18 months in the absence of bone metastasis (P < 0.001). Patients with liver metastasis had a median OS of 8.6 months compared to 15 months for those without liver metastasis (P = 0.006). For lung metastasis, median OS was 8.7 months compared to 17.3 months (P = 0.004). No statistical difference was shown in OS for lymph nodes metastasis, with a median of 13.5 months vs 12.7 months (P = 0.175). Patients with NLR ≥ 4 had a significant worse OS (8.2 months vs 17.7 months P = 0.0001). In multivariate analysis, BMI ≥ 30, bone metastasis and NLR ≥ 4 were independent prognosis factor for OS. Conclusions Our data identified BMI and bone metastasis as novel, independent, clinical biomarkers that were strongly and independently associated with ICI response and survival in mUC. External validation of these data in a larger study and investigations into the mechanisms behind these findings are warranted.
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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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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".