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.

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

Journal

European urology oncology
ISSN: 2588-9311
Titre abrégé: Eur Urol Oncol
Pays: Netherlands
ID NLM: 101724904

Informations de publication

Date de publication:
06 2022
Historique:
received: 07 02 2021
revised: 12 05 2021
accepted: 11 06 2021
pubmed: 29 6 2021
medline: 9 6 2022
entrez: 28 6 2021
Statut: ppublish

Résumé

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. To assess the definition and clinical implications of persistently elevated PSA after sLND for node-only recurrent PCa after radical prostatectomy. The study included 579 patients treated with sLND at 11 high-volume centers between 2000 and 2016. 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. 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%. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 34176768
pii: S2588-9311(21)00118-8
doi: 10.1016/j.euo.2021.06.003
pii:
doi:

Substances chimiques

Androgen Antagonists 0
Prostate-Specific Antigen EC 3.4.21.77

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

285-295

Informations de copyright

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

Auteurs

Carlo A Bravi (CA)

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy. Electronic address: bravi.carloandrea@hsr.it.

Matteo Droghetti (M)

Division of Urology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Nicola Fossati (N)

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Giorgio Gandaglia (G)

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Nazareno Suardi (N)

Department of Urology, Policlinico San Martino Hospital, University of Genova, Genova, Italy.

Elio Mazzone (E)

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Vito Cucchiara (V)

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Simone Scuderi (S)

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Francesco Barletta (F)

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Riccardo Schiavina (R)

Division of Urology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Daniar Osmonov (D)

Department of Urology and Pediatric Urology, University Hospital Schleswig Holstein, Campus Kiel, Kiel, Germany.

Klaus-Peter Juenemann (KP)

Department of Urology and Pediatric Urology, University Hospital Schleswig Holstein, Campus Kiel, Kiel, Germany.

Luca Boeri (L)

Department of Urology, Mayo Clinic, Rochester, MN, USA; Department of Urology, IRCCS Foundation Ca Granda, Maggiore Policlinico Hospital, University of Milan, Milan, Italy.

R Jeffrey Karnes (RJ)

Department of Urology, Mayo Clinic, Rochester, MN, USA.

Alexander Kretschmer (A)

Department of Urology, Ludwig-Maximilians University, Munich, Germany.

Alexander Buchner (A)

Department of Urology, Ludwig-Maximilians University, Munich, Germany.

Christian Stief (C)

Department of Urology, Ludwig-Maximilians University, Munich, Germany.

Andreas Hiester (A)

Department of Urology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.

Alessandro Nini (A)

Department of Urology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Klinik für Urologie und Kinderurologie, Universitätsklinikum des Saarlandes, Homburg, Germany.

Peter Albers (P)

Department of Urology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.

Gaëtan Devos (G)

Department of Urology, University Hospitals Leuven, Leuven, Belgium.

Steven Joniau (S)

Department of Urology, University Hospitals Leuven, Leuven, Belgium.

Hendrik Van Poppel (H)

Department of Urology, University Hospitals Leuven, Leuven, Belgium.

Bernhard Grubmüller (B)

Department of Urology, Medical University of Vienna, Vienna, Austria.

Shahrokh F Shariat (SF)

Department of Urology, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia.

Axel Heidenreich (A)

Department of Urology, University of Cologne, Cologne, Germany.

David Pfister (D)

Department of Urology, University of Cologne, Cologne, Germany.

Derya Tilki (D)

Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Markus Graefen (M)

Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

Inderbir S Gill (IS)

USC Institute of Urology, University of Southern California, Los Angeles, CA, USA.

Alexandre Mottrie (A)

Department of Urology, OLV Ziekenhuis Aalst, Aalst, Belgium; Orsi Academy, Melle, Belgium.

Pierre I Karakiewicz (PI)

Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada.

Francesco Montorsi (F)

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Alberto Briganti (A)

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

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