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    Combined longitudinal clinical and autopsy phenomic assessment in lethal metastatic prostate cancer: recommendations for advancing precision medicine

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    Authors
    Jasu, J.
    Tolonen, T.
    Antonarakis, E. S.
    Beltran, H.
    Halabi, S.
    Eisenberger, M. A.
    Carducci, M. A.
    Loriot, Y.
    Van der Eecken, K.
    Lolkema, M.
    Ryan, C. J.
    Taavitsainen, S.
    Gillessen, Silke
    Hognas, G.
    Talvitie, T.
    Taylor, R. J.
    Koskenalho, A.
    Ost, P.
    Murtola, T. J.
    Rinta-Kiikka, I.
    Tammela, T.
    Auvinen, A.
    Kujala, P.
    Smith, T. J.
    Kellokumpu-Lehtinen, P. L.
    Isaacs, W. B.
    Nykter, M.
    Kesseli, J
    Bova, G. S.
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    Affiliation
    Faculty of Medicine and Health Technology, Prostate Cancer Research Center, Tampere University and Tays Cancer Center, Tampere, FI-33014, Finland.
    Issue Date
    2021
    
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    Show full item record
    Abstract
    Background: Systematic identification of data essential for outcome prediction in metastatic prostate cancer (mPC) would accelerate development of precision oncology. Objective: To identify novel phenotypes and features associated with mPC outcome, and to identify biomarker and data requirements to be tested in future precision oncology trials. Design setting and participants: We analyzed deep longitudinal clinical, neuroendocrine expression, and autopsy data of 33 men who died from mPC between 1995 and 2004 (PELICAN33), and related findings to mPC biomarkers reported in the literature. Intervention: Thirty-three men prospectively consented to participate in an integrated clinical-molecular rapid autopsy study of mPC. Outcome measurements and statistical analysis: Data exploration with correction for multiple testing and survival analysis from the time of diagnosis to time to death and time to first occurrence of severe pain as outcomes were carried out. The effect of seven complications on the modeled probability of dying within 2 yr after presenting with the complication was evaluated using logistic regression. Results and limitations: Feature exploration revealed novel phenotypes related to mPC outcome. Four complications (pleural effusion, severe anemia, severe or controlled pain, and bone fracture) predict the likelihood of death within 2 yr. Men with Gleason grade group 5 cancers developed severe pain sooner than those with lower-grade tumors. Surprisingly, neuroendocrine (NE) differentiation was frequently observed in the setting of high serum prostate-specific antigen (PSA) levels (≥30 ng/ml). In 4/33 patients, no controlled (requiring analgesics) or severe pain was detected, and strikingly, 14/15 metastatic sites studied in these men did not express NE markers, suggesting an inverse relationship between NE differentiation and pain in mPC. Intracranial subdural metastasis is common (36%) and is usually clinically undetected. Categorization of "skeletal-related events" complications used in recent studies likely obscures the understanding of spinal cord compression and fracture. Early death from prostate cancer was identified in a subgroup of men with a low longitudinal PSA bandwidth. Cachexia is common (body mass index <0.89 in 24/31 patients) but limited to the last year of life. Biomarker review identified 30 categories of mPC biomarkers in need of winnowing in future trials. All findings require validation in larger cohorts, preferably alongside data from this study. Conclusions: The study identified novel outcome subgroups for future validation and provides "vision for mPC precision oncology 2020-2050" draft recommendations for future data collection and biomarker studies.
    Citation
    Jasu J, Tolonen T, Antonarakis ES, Beltran H, Halabi S, Eisenberger MA, et al. Combined Longitudinal Clinical and Autopsy Phenomic Assessment in Lethal Metastatic Prostate Cancer: Recommendations for Advancing Precision Medicine. European Urology Open Science. 2021 Aug;30:47–62.
    Journal
    European Urology Open Science
    URI
    http://hdl.handle.net/10541/624496
    DOI
    10.1016/j.euros.2021.05.011
    PubMed ID
    34337548
    Additional Links
    https://dx.doi.org/10.1016/j.euros.2021.05.011
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.euros.2021.05.011
    Scopus Count
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    All Paterson Institute for Cancer Research

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