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Poster session 14

1791P - Molecular profiling and prognostic relevance of low PTEN expression in metastatic hormone-sensitive prostate cancer patients

Date

21 Oct 2023

Session

Poster session 14

Topics

Pathology/Molecular Biology;  Molecular Oncology

Tumour Site

Prostate Cancer

Presenters

Marta Garcia De Herreros

Citation

Annals of Oncology (2023) 34 (suppl_2): S954-S1000. 10.1016/S0923-7534(23)01946-4

Authors

M. Garcia De Herreros1, N. Jimenez Blasco2, O. Reig Torras1, V. Ruiz de Porras3, J.C. Pardo3, A. Font Pous3, C. Aversa1, L. Ferrer-Mileo1, M. Jorda3, L. Rodríguez-Carunchio4, I. Trias Puigsureda4, A. Sánchez-Font5, A. Rodriguez-Vida6, M. Domenech Santasusana7, M. Figols Gorina7, M.A. Climent Duran8, I. Chirivella Gonzalez9, D. Herrero Rivera10, E. Gonzalez Billalabeitia11, B. Mellado Gonzalez1

Author affiliations

  • 1 Medical Oncology Department, Hospital Clinic y Provincial de Barcelona, 08036 - Barcelona/ES
  • 2 Fundació De Recerca Clínic Barcelona - Institut D'investigacions Biomèdiques August Pi I Sunyer (frcb-idibaps),, Translational Genomics and Targeted Therapeutics in Solid Tumors Lab,, 08036 - Barcelona/ES
  • 3 Departamento De Oncologia, ICO - Institut Català d'Oncologia Badalona (Hospital Universitario Germans Trias i Pujol), 08916 - Badalona/ES
  • 4 Pathology Department, Hospital Clinic y Provincial de Barcelona, 08036 - Barcelona/ES
  • 5 Medical Oncology Department, Hospital del Mar - Parc de Salut Mar, 8003 - Barcelona/ES
  • 6 Medical Oncology Department, Hospital del Mar, 8003 - Barcelona/ES
  • 7 Dept. Oncology, Hospital de Sant Joan de Déu - Althaia, Xarxa Assistencial Universitària de Manresa, 08243 - Manresa/ES
  • 8 Medical Oncology, IVO - Fundación Instituto Valenciano de Oncología, 46009 - Valencia/ES
  • 9 Medical Oncology Department, Hospital Clinico Universitario de Valencia, 46010 - Valencia/ES
  • 10 Medical Oncology Department, HLA Moncloa Universitary Hospital, 28008 - Madrid/ES
  • 11 Medical Oncology Dept., Hospital Universitario 12 de Octubre, 28041 - Madrid/ES

Resources

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Abstract 1791P

Background

Alterations in PTEN are associated with aggressive behavior and treatment resistance in patients (pts) with castration-resistant prostate cancer (PC). The aim of this study is to characterize the molecular alterations related to PTEN low mRNA expression and its prognostic value in metastatic hormone-sensitive PC (mHSPC) pts.

Methods

This is a multicenter retrospective study enrolling mHSPC pts. Alterations in PTEN were assessed by mRNA expression by nCounter platform, targeted sequencing, and protein by IHC in FFPE tumor samples. RNA-seq analysis was performed to assess differences in gene expression between low vs. high/medium PTEN expression tumors. PTEN expression was correlated with castration resistance-free survival (CRPC-FS) and overall survival (OS) by Kaplan Meier and multivariate Cox analysis.

Results

218 pts were included: 125 treated with ADT + docetaxel (D) and 93 with ADT, with a median follow-up of 46 months (7-223). Median age was 66 years, 76% of pts presented de novo stage IV and 68% had high-volume disease. 54 pts were tested for PTEN expression and targeted sequencing. Pts with low PTEN expression (PTEN-low) had higher frequency of PTEN mutations (p<0.02) and lower IHC expression (p<0.01). RNAseq (n=66) differential expression analysis found 13 genes differentially expressed (padj<0.05) in PTEN-low vs the rest. In the functional analysis PTEN-low tumors had overexpression of several pathways including cell cycle, DNA repair, metabolism and immune reponse, and infraexpression of the androgen-response hallmark. In the whole cohort, PTEN-low (31%) was independently associated with lower CRPC-FS (13 vs. 20.5 m, HR 1.8 (95% CI, 1.3 – 2.5), p<0.001) and OS (40.1 vs 57.9 m, HR 1.7 (95% CI, 1.2 – 2.3) p=0.003). Moreover, PTEN-low pts treated with ADT+D or ADT presented similar CRPC-FS (12.1 and 14.6 m, respectively) or OS (38.8 and 41 m), while PTEN-high/mid treated with ADT+D had the largest CRPC-FS (21.9 m, p=0.01) and OS (60.1 m, p=0.032), suggesting that PTEN-low pts may not benefit from chemotherapy.

Conclusions

Lower expression of PTEN correlates with a distinct molecular profile and a more aggressive disease in pts with mHSPC, supporting the development of new therapeutic strategies for these pts.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Instituto de Salud Carlos III-Subdirección General de Evaluación y Fomento de la Investigación (PI18/714).

Disclosure

O. Reig Torras: Financial Interests, Personal, Invited Speaker: BMS, Ipsen, Pfizer. A. Font Pous: Financial Interests, Personal and Institutional, Research Funding: AstraZeneca; Financial Interests, Institutional, Research Funding: Astellas, Pierre Fabre; Financial Interests, Personal, Advisory Role: Janssen, Roche. L. Ferrer-Mileo: Financial Interests, Personal, Invited Speaker: BMS. A. Sánchez-Font: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Bayer; Financial Interests, Personal, Invited Speaker: Janssen. A. Rodriguez-Vida: Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Board: Bayer, BMS, MSD; Financial Interests, Personal, Speaker, Consultant, Advisor: Roche. M. Figols Gorina: Financial Interests, Personal, Speaker’s Bureau: Pfizer, Ipsen. M.A. Climent Duran: Financial Interests, Personal, Invited Speaker: BMS, Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Role: Roche, Novartis, Pfizer. E. Gonzalez Billalabeitia: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Astellas, Janssen, Bayer. B. Mellado Gonzalez: Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Invited Speaker: BMS, Pfizer; Financial Interests, Personal and Institutional, Research Funding: Janssen; Financial Interests, Institutional, Research Funding: Bayer, Pfizer. All other authors have declared no conflicts of interest.

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