Analysis of prostate-specific antigen decline as a surrogate for overall survival in metastatic hormone-refractory prostate cancer (HRPC)
Bibliographic record
Abstract
5009 Background: A 30% PSA decline following initiation of cytotoxic chemotherapy has been identified as a potential surrogate for overall survival in metastatic HRPC. We sought to examine whether various levels of PSA decline were surrogates for overall survival in TAX327, a randomized trial of q3w docetaxel and prednisone (DP), q1w DP, and q3w mitoxantrone and prednisone (MP). Methods: In this trial of 1006 men with HRPC, 943 men had sufficient data on 3-month post-treatment PSA decline for analysis, and 646 had sufficient data for analysis for a change in PSA kinetics with therapy. Surrogacy was examined for a range of PSA decline from 0% to 90% and PSA normalization, and for post-treatment changes in PSA kinetics. We investigated the Prentice Criteria for surrogacy using Cox proportional hazards models and calculated the proportion of treatment effect explained (PTE) by each surrogate marker. Results: In this analysis, a 30% or greater PSA decline with therapy was identified as the optimal cutoff that correlated with overall survival, based on the highest PTE point estimate (0.66, 95% CI 0.23–1.0), with 1.0 being a perfect surrogate. A 30% decline in PSA in the first 3 months after treatment occurred in 65% of subjects receiving q3w DP, 67% q1w DP, and 44% q3w MP, despite the significant survival benefits seen only with q3w DP. A 30% PSA decline was associated with a hazard ratio (HR) of 0.43 (95% CI 0.36–0.51) for overall survival after adjusting for treatment effect, while treatment effect itself lost significance, indicating surrogacy. Additionally, PSA normalization, changes in PSA kinetics, and pain response were significant prognostic variables, yet were only modest surrogates for the survival benefit seen with q3w DP therapy. Conclusions: In this trial of two schedules of DP as compared to MP for HRPC, a PSA decline of 30% in the first three months following initiation of cytotoxic chemotherapy was found to have the highest degree of surrogacy for overall survival, thus confirming data from the SWOG 9916 trial. However, given that the confidence interval for the estimate of this surrogate effect is wide, overall survival should remain the preferred endpoint for phase III trials of cytotoxic agents in HRPC. 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 | 0.017 | 0.017 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| 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".