Age and Treatment Intensification in Metastatic Hormone-Sensitive Prostate Cancer
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
BACKGROUND: Older men with metastatic hormone-sensitive prostate cancer (mHSPC) are more likely to have comorbid medical conditions and die from causes other than prostate cancer. We aimed to determine if age impacts the overall survival (OS) benefit from systemic treatment intensification (TI) with androgen receptor pathway inhibitors (ARPIs) and/or chemotherapy in mHSPC. METHODS: A systematic literature search in MEDLINE, Embase, and conference proceedings was conducted to identify randomized phase 3 trials in mHSPC evaluating the role of TI between January 1, 2010, and January 1, 2024. Age was dichotomized as 70 years or older in all trials, except as 75 years or older in one trial. Meta-analyses were performed with random-effects modeling. Meta-regression was performed using Hartung-Knapp methods. Individual patient data (IPD) from three trials (TITAN, ARASENS, and LATITUDE) were used to validate the aggregate meta-analysis. RESULTS: Eleven randomized comparisons (n=13,648 patients; 8324 younger men and 5162 older men) were included in the aggregate meta-analysis. Overall, TI was associated with improved OS (hazard ratio, 0.73; 95% confidence interval [CI], 0.68 to 0.78). There was an interaction between age and TI on OS (P-interaction <0.001; younger men: hazard ratio, 0.63; 95% CI, 0.56 to 0.70; older men: hazard ratio, 0.82; 95% CI, 0.74 to 0.90). TI was not associated with improvement in OS in older men treated in trials utilizing predominantly triplet therapy (hazard ratio, 0.94; 95% CI, 0.77 to 1.14). These results were similar in the IPD analysis. In the IPD analysis, ARPI addition was associated with improved OS in men 70 years or older with high-volume synchronous disease (hazard ratio, 0.83; 95% CI, 0.70 to 0.99), but not in low-volume synchronous disease (hazard ratio, 0.89; 95% CI, 0.61 to 1.30). CONCLUSIONS: We observed an interaction between age and systemic TI on OS for men with mHSPC. Our data provide information on potential treatment strategies for men 70 years or older, especially in low-volume synchronous disease, where radiotherapy to the primary site is the standard of care. (Funded by the National Institutes of Health and others.).
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.000 | 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