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Prognostic biomarkers and clinical outcomes in neuroendocrine prostate cancer (NEPC).

2023· article· en· W4324136600 on OpenAlexaff
Richard Gagnon, Ealia Khosh Kish, Sarah Cook, Kosuke Takemura, Brian Yu Chieh Cheng, Kamiko R. Bressler, Daniel Yick Chin Heng, Nimira Alimohamed, Joseph D. Ruether, Richard M. Lee‐Ying, Pinaki Bose, Michael Kolinsky, Catalina Vásquez, Divya Samuel, John D. Lewis, Rehan M. Faridi, Minal Borkar, Adrian Fairey, Tarek A. Bismar, Steven Yip

Bibliographic record

VenueJournal of Clinical Oncology · 2023
Typearticle
Languageen
FieldMedicine
TopicProstate Cancer Treatment and Research
Canadian institutionsUniversity of AlbertaUniversity of Calgary
Fundersnot available
KeywordsMedicineProstate cancerStage (stratigraphy)Internal medicineProportional hazards modelAndrogen deprivation therapyImmunohistochemistryCancerAdenocarcinomaOncologyBiopsyProstateLog-rank testPathologyGastroenterology

Abstract

fetched live from OpenAlex

209 Background: NEPC includes both pure small cell carcinoma and mixed tumors with varying degrees of adenocarcinoma and neuroendocrine histology. It arises de novo or is treatment associated (TA) post androgen deprivation therapy. Clinical outcome data and prognostic biomarkers are limited and were thus explored. Methods: Patients with high grade prostate cancer and morphologic and/or immunohistochemical (IHC) NEPC features were included in this retrospective multicentre study. Clinical stage, Gleason score, and serum biomarkers were recorded. Kaplan-Meier method and log-rank test calculated and compared overall survival (OS) from time of NEPC diagnosis.Cox proportional hazards regression assessed prognostic impact of serum biomarkers at diagnosis and de novo vs TA status, adjusting for clinical stage and castration resistance. Results: 135 NEPC cases were identified. 124 (92%) were mixed tumors. 56 (41%) arose de novo. 79 (59%) were TA. 77% of those with a Gleason score (N=85/110) were grade group 5. Median PSA pre-NEPC biopsy was 11.6 ng/mL. At NEPC diagnosis, 19 (14%) had localized disease (median OS 123.0 mo); 33 (24%) non-metastatic castrate-sensitive disease (median OS 42.3 mo); 6 (4%) non-metastatic castrate-resistant disease (median OS 14.3 mo); 35 (26%) metastatic castrate-sensitive disease (median OS 17.6 mo); and 42 (31%) metastatic castrate-resistant disease (median OS 9.6 mo). Median OS for those with visceral metastases was 8.6 mo (95% CI 6.0 – 14.6), compared to patients with non-visceral metastases (11.1 mo; 95% CI 13.7 – 21.5) and no metastases (42.3 mo; 95% CI 47 – 89). Anemia (adjusted HR 1.66; 95% CI 1.05 - 2.16, p = 0.031) and NLR >3 (adjusted HR 1.51; 95% CI 1.01 - 2.52, p = 0.045) were associated with increased risk of death. De novo disease, elevated LDH, serum PSA, and Gleason score were not prognostic. Conclusions: This study identifies NEPC clinical outcomes by stage, with survival poorer than expected in pure prostate adenocarcinoma. Anemia and elevated NLR >3 are prognostic biomarkers that may help risk stratify and guide treatment intensification, including platinum-based chemotherapy. Further biomarker characterization of NEPC through IHC-staining pattern and genomic analysis is currently underway by this group.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.181
GPT teacher head0.553
Teacher spread0.372 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations3
Published2023
Admission routes1
Has abstractyes

Explore more

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