Real-world patient (pt) characteristics, treatment patterns, and overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC): Insights by <i>PTEN</i> status.
Bibliographic record
Abstract
5096 Background: The loss of function of the tumor suppressor gene PTEN is associated with an increased risk of recurrence and poor clinical outcomes in advanced prostate cancer (PC). Current understanding of PTEN prevalence and pt characteristics, treatment patterns, and survival outcomes by PTEN status in mHSPC is limited. Methods: This cohort study used retrospective longitudinal data from the US-based deidentified Flatiron Health-Foundation Medicine mPC clinicogenomic database. Male pts diagnosed (dx) with mHSPC between January 1, 2018, and March 31, 2024, who underwent comprehensive genomic profiling of a solid tumor specimen were included. Pts with PTEN alterations were classified as PTEN -homs del (homozygous deletion, defined as a copy number variant [CNV]=0) or PTEN -mut (CNV=1, pathological short variant alterations or rearrangements). Pts without PTEN alterations identified were classified as PTEN -nonaltered. Pt characteristics and treatment patterns were descriptively analyzed. Kaplan-Meier survival probabilities for real-world overall survival (rwOS; unadjusted) were estimated by PTEN status ( PTEN -homs del, PTEN -mut, and PTEN -nonaltered). Results: Of 1630 included pts, 39.8% had tumors with PTEN alterations ( PTEN -homs del, 23.2%; PTEN -mut, 16.6%). Overall, pts were predominantly non-Hispanic White with a mean (SD) age of 69 (9.1) years at mHSPC dx. At initial dx, 66.7% presented with a Gleason score of 8 to 10, and 68.1% had de novo metastatic disease. Median (IQR) prostate-specific antigen level (ng/mL) at metastatic diagnosis was lower in PTEN -homs del (47 [9-193]) and PTEN -mut (42 [11-157]) mHSPC relative to PTEN -nonaltered (68 [15-337]) mHSPC. BRCA mutations were less frequent in PTEN -homs del (6.1%) tumors relative to PTEN -mut (9.6%) and PTEN -nonaltered (10.3%) tumors. All other pt characteristics were generally similar across PTEN groups. The most common first-line treatments across all PTEN groups were ADT alone and ARPI ± ADT. Median (95% CI) rwOS (months) was 29.0 (24.1-33.6) in PTEN -homs del, 32.7 (27.8-37.9) in PTEN -mut, and 42.3 (38.7-46.0) in PTEN -nonaltered mHSPC groups. Pts with PTEN alterations tended to have lower landmark survival probabilities than pts without PTEN alterations (Table). Conclusions: Among pts with mHSPC, worse survival was observed in pts with tumors harboring PTEN alterations relative to pts without PTEN tumor alterations, despite similar pt characteristics and treatment patterns across PTEN groups. rwOS probability, % (95% CI) PTEN -homs del (n=378) PTEN -mut (n=271) PTEN -nonaltered (n=981) 12 month 81.6 (76.0-87.6) 83.9 (77.9-90.4) 90.7 (88.2-93.4) 24 month 56.8 (50.6-63.7) 64.4 (57.5-72.0) 73.8 (70.3-77.4)
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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) | 0.001 | 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".