Immunogenomic landscape of neuroendocrine small cell prostate cancer.
Bibliographic record
Abstract
217 Background: Neuroendocrine small cell prostate cancer (NEPC) is a lethal variant of prostate cancer (PCa) unresponsive to hormone therapy and associated with poor prognosis. Cisplatin induces short-lived responses and therefore alternative novel therapeutic options are urgently needed. Methods: Prostate specimens from radical prostatectomy or transurethral resection (benign prostate specimens n = 4, primary untreated or neoadjuvant hormone-treated adenocarcinoma n = 30, castrate-resistant prostate cancer-CRPC n = 38 and NEPC n = 16) were evaluated for PD-L1 (SpringBio, M4420), AR, chromogranin A, synaptophysin, NSE and CD56 expression by immunohistochemistry (IHC). Archival tissue from liver, lymph nodes and prostate from 30 additional patients with de novo and treatment emergent NEPC were analyzed for PD-L1 expression by IHC. The intensity was assessed as percentage of positive cells / mm2 of tissue. Targeted and whole exome sequencing of the high-density tumor areas were performed and correlated to the PD-L1 status (PD-L1+ve: > 1% of positive cells). OS was calculated from the date of diagnosis of NEPC to death. We set out to define PD-L1 expression and immunogenomic characteristics of NEPC. Results: PD-L1 was expressed in 0%, 5%, 10% and 41% of benign, adenocarcinoma, CRPC and NEPC specimens, respectively. The PD-L1 expression intensity was significantly higher in patients with NEPC (mean: 40%, range: 5-100%) compared to benign, adenocarcinoma and CRPC samples (mean: 0%, 2% and 8%, respectively, P < 0.0001). There was a higher prevalence of biallelic DNA Repair Defects (DRD) in the PD-L1+ve vs PD-L1-ve patients (65% vs 0%, P = 0.005). The median OS of the NEPC patients was 8.5 months vs 10.5 months in PD-L1+ve vs PD-L1-ve tumors (HR 1.24, 95% CI: 0.59-2.75, p = 0.55). Conclusions: NEPC have greater PD-L1 expression than adenoCa and CRPC. Biallelic DRD was exclusively observed in PD-L1+ve patients. Since PD-L1 expression and DRD have been associated to response to PARP and PD1/PD-L1 inhibitors in prostate and other cancers, further studies evaluating the activity of those agents in NEPC patients are warranted.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| 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) | 0.001 | 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".