Clinical testing of transcriptome-wide expression profiles in high-risk localized and metastatic prostate cancer starting androgen deprivation therapy: an ancillary study of the STAMPEDE abiraterone Phase 3 trial

Gerhardt Attard; Marina Parry; Emily Grist; Larissa Mendes; Peter Dutey-Magni; Ashwin Sachdeva; Christopher Brawley; Laura Murphy; James Proudfoot; Sharanpreet Lall; Yang Liu; Stefanie Friedrich; Mazlina Ismail; Alex Hoyle; Adnan Ali; Aine Haran; Anna Wingate; Leila Zakka; Daniel Wetterskog; Claire Amos; Nafisah B. Atako; Victoria Wang; Hannah Rush; Robert Jones; Hing Y. Leung; William Cross; silke gillessen; Chris Parker; Simon Chowdhury; Tamara Lotan; Teresa Marafioti; Alfonso Urbanucci; Edward Schaeffer; Daniel E  Spratt; David J. J. Waugh; Thomas Powles; Daniel Berney; Matthew Sydes; Mahesh Parmar; Anis Hamid; Felix Feng; Christopher Sweeney; Elai Davicioni; Noel Clarke; Nicholas D James; Louise Brown

doi:10.21203/rs.3.rs-2488586/v1

Clinical testing of transcriptome-wide expression profiles in high-risk localized and metastatic prostate cancer starting androgen deprivation therapy: an ancillary study of the STAMPEDE abiraterone Phase 3 trial

Gerhardt Attard, Marina Parry, Emily Grist, Larissa Mendes, Peter Dutey-Magni, Ashwin Sachdeva, Christopher Brawley, Laura Murphy, James Proudfoot, Sharanpreet Lall, Yang Liu, Stefanie Friedrich, Mazlina Ismail, Alex Hoyle, Adnan Ali, Aine Haran, Anna Wingate, Leila Zakka, Daniel Wetterskog, Claire AmosNafisah B. Atako, Victoria Wang, Hannah Rush, Robert Jones, Hing Y. Leung, William Cross, silke gillessen, Chris Parker, Simon Chowdhury, Tamara Lotan, Teresa Marafioti, Alfonso Urbanucci, Edward Schaeffer, Daniel E Spratt, David J. J. Waugh, Thomas Powles, Daniel Berney, Matthew Sydes, Mahesh Parmar, Anis Hamid, Felix Feng, Christopher Sweeney, Elai Davicioni, Noel Clarke, Nicholas D James, Louise Brown

Research output: Other contribution

Abstract

Metastatic and high-risk localized prostate cancer respond to hormone therapy but outcomes vary. Following a pre-specified statistical plan, we used Cox models adjusted for clinical variables to test associations with survival of multi-gene expression-based classifiers from 781 patients randomized to androgen deprivation with or without abiraterone in the STAMPEDE trial. Decipher score was strongly prognostic (p<2x10 -5 ) and identified clinically-relevant differences in absolute benefit, especially for localized cancers. In metastatic disease, classifiers of proliferation, PTEN or TP53 loss and treatment-persistent cells were prognostic. In localized disease, androgen receptor activity was protective whilst interferon signaling (that strongly associated with tumor lymphocyte infiltration) was detrimental. Post-Operative Radiation-Therapy Outcomes Score was prognostic in localized but not metastatic disease (interaction p=0.0001) suggesting the impact of tumor biology on clinical outcome is context-dependent on metastatic state. Transcriptome-wide testing has clinical utility for advanced prostate cancer and identified worse outcomes for localized cancers with tumor-promoting inflammation.

Original language	English
DOIs	https://doi.org/10.21203/rs.3.rs-2488586/v1
Publication status	Published - 8 Feb 2023

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Manchester Cancer Research Centre

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Attard, G., Parry, M., Grist, E., Mendes, L., Dutey-Magni, P., Sachdeva, A., Brawley, C., Murphy, L., Proudfoot, J., Lall, S., Liu, Y., Friedrich, S., Ismail, M., Hoyle, A., Ali, A., Haran, A., Wingate, A., Zakka, L., Wetterskog, D., ... Brown, L. (2023, Feb 8). Clinical testing of transcriptome-wide expression profiles in high-risk localized and metastatic prostate cancer starting androgen deprivation therapy: an ancillary study of the STAMPEDE abiraterone Phase 3 trial. https://doi.org/10.21203/rs.3.rs-2488586/v1

@misc{a0f9311efc614c53b852d11be0247de1,

title = "Clinical testing of transcriptome-wide expression profiles in high-risk localized and metastatic prostate cancer starting androgen deprivation therapy: an ancillary study of the STAMPEDE abiraterone Phase 3 trial",

abstract = "Metastatic and high-risk localized prostate cancer respond to hormone therapy but outcomes vary. Following a pre-specified statistical plan, we used Cox models adjusted for clinical variables to test associations with survival of multi-gene expression-based classifiers from 781 patients randomized to androgen deprivation with or without abiraterone in the STAMPEDE trial. Decipher score was strongly prognostic (p<2x10 -5 ) and identified clinically-relevant differences in absolute benefit, especially for localized cancers. In metastatic disease, classifiers of proliferation, PTEN or TP53 loss and treatment-persistent cells were prognostic. In localized disease, androgen receptor activity was protective whilst interferon signaling (that strongly associated with tumor lymphocyte infiltration) was detrimental. Post-Operative Radiation-Therapy Outcomes Score was prognostic in localized but not metastatic disease (interaction p=0.0001) suggesting the impact of tumor biology on clinical outcome is context-dependent on metastatic state. Transcriptome-wide testing has clinical utility for advanced prostate cancer and identified worse outcomes for localized cancers with tumor-promoting inflammation. ",

author = "Gerhardt Attard and Marina Parry and Emily Grist and Larissa Mendes and Peter Dutey-Magni and Ashwin Sachdeva and Christopher Brawley and Laura Murphy and James Proudfoot and Sharanpreet Lall and Yang Liu and Stefanie Friedrich and Mazlina Ismail and Alex Hoyle and Adnan Ali and Aine Haran and Anna Wingate and Leila Zakka and Daniel Wetterskog and Claire Amos and Atako, {Nafisah B.} and Victoria Wang and Hannah Rush and Robert Jones and Leung, {Hing Y.} and William Cross and silke gillessen and Chris Parker and Simon Chowdhury and Tamara Lotan and Teresa Marafioti and Alfonso Urbanucci and Edward Schaeffer and Spratt, {Daniel E} and Waugh, {David J. J.} and Thomas Powles and Daniel Berney and Matthew Sydes and Mahesh Parmar and Anis Hamid and Felix Feng and Christopher Sweeney and Elai Davicioni and Noel Clarke and James, {Nicholas D} and Louise Brown",

year = "2023",

month = feb,

day = "8",

doi = "10.21203/rs.3.rs-2488586/v1",

language = "English",

series = "Research square",

type = "Other",

}

Attard, G, Parry, M, Grist, E, Mendes, L, Dutey-Magni, P, Sachdeva, A, Brawley, C, Murphy, L, Proudfoot, J, Lall, S, Liu, Y, Friedrich, S, Ismail, M, Hoyle, A, Ali, A, Haran, A, Wingate, A, Zakka, L, Wetterskog, D, Amos, C, Atako, NB, Wang, V, Rush, H, Jones, R, Leung, HY, Cross, W, gillessen, S, Parker, C, Chowdhury, S, Lotan, T, Marafioti, T, Urbanucci, A, Schaeffer, E, Spratt, DE, Waugh, DJJ, Powles, T, Berney, D, Sydes, M, Parmar, M, Hamid, A, Feng, F, Sweeney, C, Davicioni, E, Clarke, N, James, ND & Brown, L 2023, Clinical testing of transcriptome-wide expression profiles in high-risk localized and metastatic prostate cancer starting androgen deprivation therapy: an ancillary study of the STAMPEDE abiraterone Phase 3 trial.. https://doi.org/10.21203/rs.3.rs-2488586/v1

TY - GEN

T1 - Clinical testing of transcriptome-wide expression profiles in high-risk localized and metastatic prostate cancer starting androgen deprivation therapy: an ancillary study of the STAMPEDE abiraterone Phase 3 trial

AU - Attard, Gerhardt

AU - Parry, Marina

AU - Grist, Emily

AU - Mendes, Larissa

AU - Dutey-Magni, Peter

AU - Sachdeva, Ashwin

AU - Brawley, Christopher

AU - Murphy, Laura

AU - Proudfoot, James

AU - Lall, Sharanpreet

AU - Liu, Yang

AU - Friedrich, Stefanie

AU - Ismail, Mazlina

AU - Hoyle, Alex

AU - Ali, Adnan

AU - Haran, Aine

AU - Wingate, Anna

AU - Zakka, Leila

AU - Wetterskog, Daniel

AU - Amos, Claire

AU - Atako, Nafisah B.

AU - Wang, Victoria

AU - Rush, Hannah

AU - Jones, Robert

AU - Leung, Hing Y.

AU - Cross, William

AU - gillessen, silke

AU - Parker, Chris

AU - Chowdhury, Simon

AU - Lotan, Tamara

AU - Marafioti, Teresa

AU - Urbanucci, Alfonso

AU - Schaeffer, Edward

AU - Spratt, Daniel E

AU - Waugh, David J. J.

AU - Powles, Thomas

AU - Berney, Daniel

AU - Sydes, Matthew

AU - Parmar, Mahesh

AU - Hamid, Anis

AU - Feng, Felix

AU - Sweeney, Christopher

AU - Davicioni, Elai

AU - Clarke, Noel

AU - James, Nicholas D

AU - Brown, Louise

PY - 2023/2/8

Y1 - 2023/2/8

N2 - Metastatic and high-risk localized prostate cancer respond to hormone therapy but outcomes vary. Following a pre-specified statistical plan, we used Cox models adjusted for clinical variables to test associations with survival of multi-gene expression-based classifiers from 781 patients randomized to androgen deprivation with or without abiraterone in the STAMPEDE trial. Decipher score was strongly prognostic (p<2x10 -5 ) and identified clinically-relevant differences in absolute benefit, especially for localized cancers. In metastatic disease, classifiers of proliferation, PTEN or TP53 loss and treatment-persistent cells were prognostic. In localized disease, androgen receptor activity was protective whilst interferon signaling (that strongly associated with tumor lymphocyte infiltration) was detrimental. Post-Operative Radiation-Therapy Outcomes Score was prognostic in localized but not metastatic disease (interaction p=0.0001) suggesting the impact of tumor biology on clinical outcome is context-dependent on metastatic state. Transcriptome-wide testing has clinical utility for advanced prostate cancer and identified worse outcomes for localized cancers with tumor-promoting inflammation.

AB - Metastatic and high-risk localized prostate cancer respond to hormone therapy but outcomes vary. Following a pre-specified statistical plan, we used Cox models adjusted for clinical variables to test associations with survival of multi-gene expression-based classifiers from 781 patients randomized to androgen deprivation with or without abiraterone in the STAMPEDE trial. Decipher score was strongly prognostic (p<2x10 -5 ) and identified clinically-relevant differences in absolute benefit, especially for localized cancers. In metastatic disease, classifiers of proliferation, PTEN or TP53 loss and treatment-persistent cells were prognostic. In localized disease, androgen receptor activity was protective whilst interferon signaling (that strongly associated with tumor lymphocyte infiltration) was detrimental. Post-Operative Radiation-Therapy Outcomes Score was prognostic in localized but not metastatic disease (interaction p=0.0001) suggesting the impact of tumor biology on clinical outcome is context-dependent on metastatic state. Transcriptome-wide testing has clinical utility for advanced prostate cancer and identified worse outcomes for localized cancers with tumor-promoting inflammation.

UR - https://doi.org/10.21203/rs.3.rs-2488586/v1

U2 - 10.21203/rs.3.rs-2488586/v1

DO - 10.21203/rs.3.rs-2488586/v1

M3 - Other contribution

C2 - 36798177

T3 - Research square

ER -

Clinical testing of transcriptome-wide expression profiles in high-risk localized and metastatic prostate cancer starting androgen deprivation therapy: an ancillary study of the STAMPEDE abiraterone Phase 3 trial

Abstract

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Research Beacons, Institutes and Platforms

UN SDGs

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