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    European urology oncology. 2021 Jun 24. pii: S2588-9311(21)00118-8. doi: 10.1016/j.euo.2021.06.003
    Definition and Impact on Oncologic Outcomes of Persistently Elevated Prostate-specific Antigen After Salvage Lymph Node Dissection for Node-only Recurrent Prostate Cancer After Radical Prostatectomy: Clinical Implications for Multimodal Therapy.
    Bravi CA1,  Droghetti M2,  Fossati N3,  Gandaglia G4,  Suardi N5,  Mazzone E6,  Cucchiara V7,  Scuderi S8,  Barletta F9,  Schiavina R10,  Osmonov D11,  Juenemann KP12,  Boeri L13,  Karnes RJ14,  Kretschmer A15,  Buchner A16,  Stief C17,  Hiester A18,  Nini A19,  Albers P20,  Devos G21,  Joniau S22,  Van Poppel H23,  Grubmüller B24,  Shariat SF25,  Heidenreich A26,  Pfister D27,  Tilki D28,  Graefen M29,  Gill IS30,  Mottrie A31,  Karakiewicz PI32,  Montorsi F33,  Briganti A34
    Author information
    1Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy. Electronic address: bravi.carloandrea@hsr.it.
    2Division of Urology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
    3Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
    4Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
    5Department of Urology, Policlinico San Martino Hospital, University of Genova, Genova, Italy.
    6Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
    7Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
    8Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
    9Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
    10Division of Urology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
    11Department of Urology and Pediatric Urology, University Hospital Schleswig Holstein, Campus Kiel, Kiel, Germany.
    12Department of Urology and Pediatric Urology, University Hospital Schleswig Holstein, Campus Kiel, Kiel, Germany.
    13Department of Urology, Mayo Clinic, Rochester, MN, USA; Department of Urology, IRCCS Foundation Ca Granda, Maggiore Policlinico Hospital, University of Milan, Milan, Italy.
    14Department of Urology, Mayo Clinic, Rochester, MN, USA.
    15Department of Urology, Ludwig-Maximilians University, Munich, Germany.
    16Department of Urology, Ludwig-Maximilians University, Munich, Germany.
    17Department of Urology, Ludwig-Maximilians University, Munich, Germany.
    18Department of Urology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
    19Department of Urology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Klinik für Urologie und Kinderurologie, Universitätsklinikum des Saarlandes, Homburg, Germany.
    20Department of Urology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
    21Department of Urology, University Hospitals Leuven, Leuven, Belgium.
    22Department of Urology, University Hospitals Leuven, Leuven, Belgium.
    23Department of Urology, University Hospitals Leuven, Leuven, Belgium.
    24Department of Urology, Medical University of Vienna, Vienna, Austria.
    25Department of Urology, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia.
    26Department of Urology, University of Cologne, Cologne, Germany.
    27Department of Urology, University of Cologne, Cologne, Germany.
    28Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
    29Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
    30USC Institute of Urology, University of Southern California, Los Angeles, CA, USA.
    31Department of Urology, OLV Ziekenhuis Aalst, Aalst, Belgium; Orsi Academy, Melle, Belgium.
    32Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada.
    33Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
    34Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
    Abstract

    BACKGROUND: The optimal definition and prognostic significance of persistently elevated prostate-specific antigen (PSA) after salvage lymph node dissection (sLND) for node-only recurrent prostate cancer (PCa) remain unknown.

    OBJECTIVE: To assess the definition and clinical implications of persistently elevated PSA after sLND for node-only recurrent PCa after radical prostatectomy.

    DESIGN, SETTING, AND PARTICIPANTS: The study included 579 patients treated with sLND at 11 high-volume centers between 2000 and 2016.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the linear relationship between the first PSA after sLND and death from PCa. Different definitions of PSA persistence were included in a multivariable model predicting cancer-specific mortality (CSM) after surgery to identify the best cutoff value. We investigated the association between PSA persistence and oncologic outcomes using multivariable regression models. Moreover, the effect of early androgen deprivation therapy (ADT) after sLND was tested according to PSA persistence status and estimated risk of CSM.

    RESULTS AND LIMITATIONS: We found an inverse relationship between the first PSA after sLND and the probability of cancer-specific survival. PSA persistence defined as first postoperative PSA ≥0.3 ng/ml provided the best discrimination accuracy (C index 0.757). According to this cutoff, 331 patients (57%) experienced PSA persistence. The median follow-up for survivors was 48 mo (interquartile range 27-74). After adjusting for confounders, men with persistently elevated PSA had higher risk of clinical recurrence (hazard ratio [HR] 1.61), overall mortality (HR 2.20), and CSM (HR 2.59; all p < 0.001) after sLND. Early ADT administration after sLND improved survival only for patients with PSA persistence after surgery (HR 0.49; p = 0.024). Similarly, when PSA persistence status was included in multivariable models accounting for pathologic features, early ADT use after sLND was beneficial only for patients with a predicted risk of CSM at 5 yr of >10%.

    CONCLUSIONS: PSA persistence after sLND independently predicts adverse prognosis, with the best discrimination accuracy for CSM provided by a definition of PSA ≥ 0.3 ng/ml. We showed that when stratifying patients by final pathology results and PSA persistence status, early ADT use after sLND was beneficial only for patients with PSA persistence or with a calculated 5-yr risk of CSM of >10%, which could be useful as we await results from ongoing prospective trials.

    PATIENT SUMMARY: We found that for patients with prostate cancer who had lymph nodes removed after their cancer recurred, persistently elevated prostate-specific antigen (PSA) levels predict poorer prognosis. We showed that a PSA level of ≥0.3 ng/ml provides the best accuracy in identifying patients with worse prognosis. This may help to improve risk stratification after lymph node removal and allow physicians to optimize treatment strategies after surgery.


    Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.

    KEYWORDS: Androgen deprivation therapy, Metastasis-directed therapy, Positron emission tomography, Prostate cancer, Prostate-specific antigen persistence, Salvage lymph node dissection

    Publikations ID: 34176768
    Quelle: öffnen
     
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