Prognostic impact of PSA nadir (n) ≥0.1 ng/mL within 6 months (m) after completion of radiotherapy (RT) for localized prostate cancer (PCa): An individual patient-data (IPD) analysis of randomized trials from the ICECAP collaborative.
Bibliographic record
Abstract
5002 Background: RT + androgen deprivation therapy (ADT) is a standard of care in treatment of intermediate- and high-risk localized PCa. Identification of early surrogate measures for long-term outcome measures such as PCa-specific survival (PCSS), metastasis-free survival (MFS) and overall survival (OS) could expedite development of new systemic therapies added to RT/ADT while potentially identifying patients (pts) for therapy (de)escalation. Methods: IPD from the RT+/-ADT trials in the ICECAP repository with evaluable PSA follow-up were eligible for inclusion. Pts were grouped based on their trial-allocated treatment: RT alone, RT+stADT (short-term ADT: 3-6m), RT+ltADT (long-term ADT: 18-36m). PSAn was defined as the lowest PSA recorded within 6m after RT completion. A 12m landmark analysis for PCSS, MFS and OS was performed to account for guarantee-time bias. Multivariable Cox proportional hazards regression was used to estimate associations of PSAn < or ≥0.1ng/mL with MFS and OS, and a multivariable Fine and Gray distribution used for PCSS to account for competing risk of non-PCa deaths. Models were adjusted for age, ECOG performance status, clinical T stage, Gleason score and PSA at randomization. Results: 10,415 pts from 16 RCTs were included: 2629 (25%) allocated to RT, 6033 (58%) to RT+stADT, and 1753 (17%) to RT+ltADT. Median follow-up was 10.1years (yrs). 2339 (98%), 4756 (84%) and 1258 (77%) of patients allocated to RT, RT+stADT and RT+ltADT respectively achieved a PSAn ≥0.1ng/mL within 6m after RT completion. After adjustment, PSAn ≥0.1ng/mL was associated with poorer PCSS, MFS and OS in pts allocated to RT+stADT (PCSS hazard ratio [HR] = 1.97 [95% CI 1.52-2.92], MFS HR = 1.27 [1.12-1.44], OS HR = 1.26 [1.11-1.44]) and RT+ltADT (PCSS HR = 1.97 [1.11-3.49], MFS HR = 1.58 [1.27-1.96], OS HR = 1.59 [1.27-1.99]). A weaker association was noted in pts allocated to RT (PCSS HR = 1.82 [0.51-6.49], MFS HR = 2.23 [1.20-4.14], OS HR = 1.72 [0.97-3.05]). Table shows 5-yr MFS, 10-yr PCSS and 10-yr OS based on PSAn within 6m after RT completion. Conclusions: PSAn ≥0.1ng/mL within 6 mths after RT completion was strongly prognostic for PCSS, MFS and OS in pts receiving RT+ADT for localized PCa in this IPD analysis of > 10,000 patients. This could be used as an early signal-seeking endpoint in trials evaluating novel systemic therapies with RT + ADT and to help identify pts for therapy (de)escalation trials. [Table: see text]
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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 | 0.026 | 0.031 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.007 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".