Clinical and Genomic Characterization of Low–Prostate-specific Antigen, High-grade Prostate Cancer
Bibliographic record
Abstract
The consequences of low prostate-specific antigen (PSA) in high-grade (Gleason 8–10) prostate cancer are unknown. To evaluate the clinical implications and genomic features of low-PSA, high-grade disease. This was a retrospective study of clinical data for 494 793 patients from the National Cancer Data Base and 136 113 patients from the Surveillance, Epidemiology, and End Results program with cT1–4N0M0 prostate cancer (median follow-up 48.9 and 25.0 mo, respectively), and genomic data for 4960 patients from the Decipher Genomic Resource Information Database. Data were collected for 2004–2017. Multivariable Fine-Gray and Cox regressions were used to analyze prostate cancer–specific mortality (PCSM) and all-cause mortality, respectively. For Gleason 8–10 disease, using PSA 4.1–10.0 ng/ml (n = 38 719) as referent, the distribution of PCSM by PSA was U-shaped, with an adjusted hazard ratio (AHR) of 2.70 for PSA ≤2.5 ng/ml (n = 3862, p < 0.001) versus 1.97, 1.36, and 2.56 for PSA of 2.6–4.0 (n = 4199), 10.1–20.0 (n = 17 372), and >20.0 ng/ml (n = 16 114), respectively. By contrast, the distribution of PCSM by PSA was linear for Gleason ≤7 (using PSA 4.1–10.0 ng/ml as the referent, n = 359 898), with an AHR of 0.41 (p = 0.13) for PSA ≤2.5 ng/ml (n = 37 812) versus 1.38, 2.28, and 4.61 for PSA of 2.6–4.0 (n = 54 152), 10.1–20.0 (n = 63 319), and >20.0 ng/ml (n = 35 459), respectively (pinteraction < 0.001). Gleason 8–10, PSA ≤2.5 ng/ml disease had a significantly higher PCSM than standard high-risk/very high-risk disease with PSA >2.5 ng/ml (AHR 2.15, p = 0.002; 47-mo PCSM 14% vs 4.9%). Among Gleason 8–10 patients treated with radiotherapy, androgen deprivation therapy was associated with a survival benefit for PSA >2.5 ng/ml (AHR 0.87; p < 0.001) but not ≤2.5 ng/ml (AHR 1.36; p = 0.084; pinteraction = 0.021). For Gleason 8–10 tumors, PSA ≤2.5 ng/ml was associated with higher expression of neuroendocrine/small-cell markers compared to >2.5 ng/ml (p = 0.046), with no such relationship for Gleason ≤7 disease. Low-PSA, high-grade prostate cancer has very high risk for PCSM, potentially responds poorly to androgen deprivation therapy, and is associated with neuroendocrine genomic features. In this study, we found that low–prostate-specific antigen, high-grade prostate cancer has a very high risk for prostate cancer death, may not respond well to androgen deprivation therapy, and is associated with neuroendocrine genomic features. These findings suggest that current nomograms and treatment paradigms may need modification.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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".