Transcriptomic Analysis of Localized High-risk Prostate Cancer Improves Prognostication and Identifies Benefit from Adding Docetaxel to Definitive Radiotherapy with Androgen Suppression in the NRG Oncology/RTOG 0521 Phase 3 Trial
Bibliographic record
Abstract
BACKGROUND AND OBJECTIVE: NRG/RTOG 0521 randomized men with high-risk localized prostate cancer (PC) to androgen suppression (AS) and definitive radiotherapy (RT) ± docetaxel-based chemotherapy (CT). The overall survival (OS) benefit with CT initially reported was lost on longer follow-up. The Decipher genomic classifier (GC) measures multiple transcripts relevant to docetaxel action. Basal/luminal differentiation portends differential response to AS and CT for high-risk localized and metastatic hormone-sensitive PC. We validated the Decipher GC in pretreatment biopsy samples for risk stratification and examined basal-luminal subtyping to predict docetaxel response. METHODS: Decipher GC scores and basal-luminal cellular subtypes were generated for specimens from NRG/RTOG 0521. The primary objective was to validate the independent prognostic ability of GC for metastasis-free survival (MFS). Treatment effects in luminal proliferating (LP) and non-LP cell subtypes were examined in relation to MFS, OS, and distant metastasis (DM). KEY FINDINGS AND LIMITATIONS: Samples were obtained from 283 patients and yielded 183 GC scores. Over median follow-up of 9.9 yr, 67 metastasis events were observed, including 34 DM events. Multivariable analysis revealed that GC was independently associated with DM (subdistribution hazard ratio 1.45) and MFS (hazard ratio 1.20). No biomarker-by-treatment interaction with GC and docetaxel was detected. The 10-yr restricted mean survival time difference in OS with CT was 13.7 mo for LP (p = 0.053) and 2.5 mo for non-LP (p = 0.63) tumors. CONCLUSIONS AND CLINICAL IMPLICATIONS: The Decipher GC score was independently associated with DM and MFS, and LP tumors may benefit from addition of CT. Validation of these findings may allow more effective use of CT in men with localized PC. The original NRG/RTOG 0521 trial is registered on ClinicalTrials.gov as NCT00288080.
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How this classification was reachedexpand
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| 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 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".