Evidence map›Paper›PMID 41124032›Full record

ArticleThe oncologist2025

Genomic alterations and associated outcomes in patients with PSMA-positive metastatic castration-resistant prostate cancer treated with 177Lu-PSMA-617.

Justine Panian, Nicholas C Henderson, Daniel Herchenhorn, Pedro C Barata, Mehmet Asim Bilen, Laura Graham, Elisabeth Heath, Clara Hwang, Avery Supernois, Deepak Kilari and 15 more

Abstract read
In one paragraph

Article in The oncologist, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Justine PanianUniversity of California San Diego, Department of Medicine, San Diego, CA 92037, United States.ORCID 0000-0002-6651-195X
Nicholas C HendersonUniversity of Michigan, Department of Medicine, Ann Arbor, MI 48109, United States.
Daniel HerchenhornUniversity of California San Diego, Department of Medicine, San Diego, CA 92037, United States.ORCID 0000-0001-5166-848X
Pedro C BarataUniversity Hospitals Seidman Cancer Center, Department of Medicine, Cleveland, OH 44106, United States.ORCID 0000-0002-8890-2951
Mehmet Asim BilenWinship Cancer Institute of Emory University, Department of Medicine, Atlanta, GA 30322, United States.
Laura GrahamUniversity of Colorado Anschutz Medical Campus, Department of Medicine, Aurora, CO 80045, United States.
Elisabeth HeathWayne State University, Department of Medicine, Detroit, MI 48201, United States.
Clara HwangHenry Ford Health System, Department of Medicine, Detroit, MI 49201, United States.
Avery SupernoisHenry Ford Health System, Department of Medicine, Detroit, MI 49201, United States.
Deepak KilariMedical College of Wisconsin, Department of Medicine, Milwaukee, WI 53226, United States.
Bicky ThapaDana-Farber Cancer Institute, Department of Medicine, Boston, MA 02215, United States.
Vadim S KoshkinUniversity of California San Francisco, Department of Medicine, San Francisco, CA 94143, United States.ORCID 0000-0003-2277-8668
Tanya JindalUniversity Hospitals Seidman Cancer Center, Department of Medicine, Cleveland, OH 44106, United States.
Jones T NauseefWeill Cornell Medicine, Department of Medicine, New York, NY 10065, United States.
Alexandra SokolovaOregon Health & Science University, Department of Medicine, Portland, OR 97239, United States.
Taylor AmeryOregon Health & Science University, Department of Medicine, Portland, OR 97239, United States.
Yousef ZakhariaUniversity of Iowa Holden Comprehensive Cancer Center, Department of Medicine, Iowa City IA, 52242, United States.
Michael T SchweizerUniversity of Washington/Fred Hutchinson Cancer Center, Department of Medicine, Seattle, WA 98109, United States.
Ruben RaychaudhuriUniversity of Washington/Fred Hutchinson Cancer Center, Department of Medicine, Seattle, WA 98109, United States.
Zachery R ReichertUniversity of Michigan, Department of Medicine, Ann Arbor, MI 48109, United States.
Tanya DorffCity of Hope Comprehensive Cancer Center, Department of Medicine, Duarte, CA 91010, United States.ORCID 0000-0001-5990-298X
Andrew J ArmstrongDuke Cancer Institute Center for Prostate and Urologic Cancer, Duke University, Department of Medicine, Durham, NC 27710, United States.ORCID 0000-0001-7012-1754
John WangDuke Cancer Institute Center for Prostate and Urologic Cancer, Duke University, Department of Medicine, Durham, NC 27710, United States.
Ajjai AlvaUniversity of Michigan, Department of Medicine, Ann Arbor, MI 48109, United States.
Rana R McKayUniversity of California San Diego, Department of Medicine, San Diego, CA 92037, United States.ORCID 0000-0002-0581-7963

Funding

Medical Scientist Training Program Training GrantT32GM145449 · NIGMS · DUKE UNIVERSITY · PI Christopher D Kontos · 2022 to 2026
$6.6M
NIGMS NIH HHS T32 GM145449
6 · The paper itself

Abstract

background177Lu-PSMA-617 is approved for patients with metastatic castration-resistant prostate cancer (mCRPC). Although treatment is associated with improved outcomes, not all patients benefit and response is heterogeneous. We aim to characterize genomic alterations associated with benefit to 177Lu-PSMA-617. MATERIALS AND

methodsThis study used the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) clinical-genomic database (n = 2445). The primary endpoint was ≥50% PSA decline (PSA50) from baseline with 177Lu-PSMA-617 in molecular subgroups. Secondary endpoints included 90% PSA decline (PSA90). Associations were assessed using Fisher's exact test and Cox regression in multivariable analysis.

resultsWe identified 183 mCRPC patients treated with 177Lu-PSMA-617. Median number of prior lines of mCRPC therapy was 3. Overall, PSA50 was 49%, median progression-free survival was 7.6 months, and median overall survival was 13.9 months. NF1 (n = 8) and FOXA1 alterations (n = 5) were associated with increased PSA50 (88% vs 47%, P = .03 for NF1; 100% vs 47%, P = .03 for FOXA1). Among CRPC sequenced tumors (n = 119), androgen receptor (AR) alterations (n = 58) were associated with lower PSA50 (38% vs 60%, P = .03). While any tumor suppressor genes (TSG) (PTEN, TP53, RB1) (n = 109) or TP53 (n = 83) alteration were associated with lower PSA90 (P = .02 for both), NF1 (n = 8), and FOXA1 alterations were associated with higher PSA90 (P = .03 and P = .003, respectively).

conclusionsThis analysis identifies potential genomic predictors of response to 177Lu-PSMA-617, with NF1 and FOXA1 alterations associated with favorable outcomes and AR and TSG alterations with diminished response. These hypothesis-generating findings suggest genomic profiling may inform selection for PSMA-targeted therapy and warrant prospective validation in larger cohorts.

Indexed as

DipeptidesGlutamate Carboxypeptidase IIHeterocyclic Compounds, 1-RingLutetiumProstatic Neoplasms, Castration-ResistantAgedAged, 80 and overGenomicsHumansMaleMiddle AgedNeoplasm MetastasisProstate-Specific AntigenRadioisotopesDipeptidesGlutamate Carboxypeptidase IIHeterocyclic Compounds, 1-RingLutetiumLutetium-177Prostate-Specific AntigenPSMA-617Radioisotopes177Lu-PSMA-617genomicsmetastaticprostate

Identifiers

PMID41124032
PMCPMC12622373

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.