Retrospective cohort analysis of real-world clinical outcomes in nonmetastatic (M0) castration-resistant prostate cancer (CRPC) treated with novel androgen receptor pathway inhibitors (ARPI).
Bibliographic record
Abstract
51 Background: The landscape of M0 CRPC has changed with the recent demonstration of metastasis-free survival (MFS) and overall survival (OS) improvements with the use of ARPIs in clinical trial settings. However, the extrapolation of this data to clinical practice is limited by strict exclusion criteria in these trials, including prior or concurrent malignancy, cardiovascular disease, or hypertension. The purpose of this study was to assess real-world outcomes in patients with M0 CRPC treated with ARPIs compared to historical controls. Methods: We designed a retrospective cohort study with the inclusion of patients in Alberta, Canada diagnosed with M0 CRPC between 2001-2020. Via chart review, we identified baseline characteristics, potential confounders, treatment details, and clinical outcomes. The primary outcome of interest was MFS. Secondary outcomes included: second progression-free survival (PFS2) and OS. Median survival times were measured using the Kaplan-Meier method and the log-rank test was used for comparison of outcomes based on ARPI exposure. Cox proportional hazard regression models were used to calculate hazard ratios (HR) accounting for impact of PSA doubling time (PSADT), use of osteoclast inhibiting agents, and presence of pelvic lymphadenopathy. Results: We identified 211 patients across multiple centres in Alberta with M0 CRPC, with 54 having received apalutamide (40/54), enzalutamide (7/54), or darolutamide (7/54). Median age at M0 CRPC diagnosis was 74 years; median PSADT was 4.4 months; and 19% of patients (40/211) had pelvic lymphadenopathy at diagnosis. Median MFS in patients treated with ARPIs was 47.5 months compared to 20.6 months in those not treated with ARPIs (HR, 0.23; 95% confidence interval [CI], 0.11-0.49; p < 0.001). Median PFS2 in ARPI treated patients was 66.3 months compared with 35.6 months (HR, 0.40; 95% CI, 0.18-0.87; p = 0.022). Median OS for patients treated with ARPI was not reached. Conclusions: Given the older age of men with advanced prostate cancer, real-world outcomes that include patients with comorbidities are important adjuncts to the interpretation of clinical trials exploring the benefit of novel therapeutics. Here, we demonstrate that in a real-world, unselected population of men with M0 CRPC, apalutamide, enzalutamide, and darolutamide seem to confer similar MFS and PFS2 benefits to those demonstrated in the SPARTAN, PROSPER, and ARAMIS studies. Real-world OS data remain immature and will be an important addition to these findings.
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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 | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| 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".