Prostate-specific Membrane Antigen Positron Emission Tomography-detected Oligorecurrent Prostate Cancer Treated with Metastases-directed Radiotherapy: Role of Addition and Duration of Androgen Deprivation.

Antiandrogen therapy Concurrent Oligometastases Prostate cancer Prostate-specific membrane antigen Radiotherapy Recurrence Stereotactic

Journal

European urology focus
ISSN: 2405-4569
Titre abrégé: Eur Urol Focus
Pays: Netherlands
ID NLM: 101665661

Informations de publication

Date de publication:
03 2021
Historique:
received: 27 03 2019
revised: 01 08 2019
accepted: 20 08 2019
pubmed: 10 9 2019
medline: 1 4 2022
entrez: 10 9 2019
Statut: ppublish

Résumé

Approximately 40-70% of biochemically recurrent prostate cancer (PCa) is oligorecurrent after prostate-specific membrane antigen (PSMA) positron emission tomography (PET) staging. Metastasis-directed radiotherapy (MDT) of PSMA-positive oligorecurrence is now frequently used, but the role of concurrent androgen deprivation therapy (ADT) remains unclear. To determine the effect of concurrent ADT with PSMA PET-directed MDT on biochemical progression-free survival (bRFS). This was a retrospective multicenter study of 305 patients with biochemical recurrence and PSMA PET-positive oligorecurrence following initial curative treatment between April 2013 and January 2018. MDT with fractionated or stereotactic body radiotherapy for all PSMA-positive metastatic sites; 37.8% received concurrent ADT. The primary outcome was bRFS, which was measured using Kaplan-Meier curves and log-rank testing. Secondary outcomes were ADT-free survival, overall survival (OS), and toxicity was analyzed using the Common Terminology Criteria for Adverse Events v4.03. Univariate and multivariate analyses were performed to determine independent clinicopathological factors. The median follow-up was 16 mo (interquartile range 9-27). Some 96% of the patients initially had high-risk PCa. A median of one (range 0-19) nodal metastases and one (range 0-5) distant metastases were treated. MDT+ADT significantly improved bRFS and remained an independent factor (hazard ratio 0.28, 95% confidence interval 0.16-0.51; p<0.0001). bRFS was not significantly different between MDT+≤6 mo of ADT and MDT alone (p=0.121). Patients receiving MDT had 1- and 2-yr ADT-free survival of 93% and 83%, respectively. New therapies, most frequently MDT (23%), were required more frequently after MDT (85% vs 29%; p<0.001). Grade ≥3 acute toxicity was observed in 0.9% of patients and late toxicity in 2.3%. In this cohort of patients with oligorecurrent PCa, concurrent ADT with MDT improved bRFS significantly, but a large number of patients treated with MDT were spared from ADT for 2yr, although a greater need for other salvage therapies was observed. The role of concurrent androgen deprivation therapy (ADT) with radiotherapy for prostate cancer oligorecurrence identified on prostate-specific membrane antigen positron emission tomography was studied. We concluded that radiotherapy alone could prolong the time to start of ADT. However, the risk of disease progression and consequently the need for further treatments is higher after local radiotherapy alone without immediate ADT.

Sections du résumé

BACKGROUND
Approximately 40-70% of biochemically recurrent prostate cancer (PCa) is oligorecurrent after prostate-specific membrane antigen (PSMA) positron emission tomography (PET) staging. Metastasis-directed radiotherapy (MDT) of PSMA-positive oligorecurrence is now frequently used, but the role of concurrent androgen deprivation therapy (ADT) remains unclear.
OBJECTIVE
To determine the effect of concurrent ADT with PSMA PET-directed MDT on biochemical progression-free survival (bRFS).
DESIGN, SETTING, AND PARTICIPANTS
This was a retrospective multicenter study of 305 patients with biochemical recurrence and PSMA PET-positive oligorecurrence following initial curative treatment between April 2013 and January 2018.
INTERVENTION
MDT with fractionated or stereotactic body radiotherapy for all PSMA-positive metastatic sites; 37.8% received concurrent ADT.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
The primary outcome was bRFS, which was measured using Kaplan-Meier curves and log-rank testing. Secondary outcomes were ADT-free survival, overall survival (OS), and toxicity was analyzed using the Common Terminology Criteria for Adverse Events v4.03. Univariate and multivariate analyses were performed to determine independent clinicopathological factors.
RESULTS AND LIMITATIONS
The median follow-up was 16 mo (interquartile range 9-27). Some 96% of the patients initially had high-risk PCa. A median of one (range 0-19) nodal metastases and one (range 0-5) distant metastases were treated. MDT+ADT significantly improved bRFS and remained an independent factor (hazard ratio 0.28, 95% confidence interval 0.16-0.51; p<0.0001). bRFS was not significantly different between MDT+≤6 mo of ADT and MDT alone (p=0.121). Patients receiving MDT had 1- and 2-yr ADT-free survival of 93% and 83%, respectively. New therapies, most frequently MDT (23%), were required more frequently after MDT (85% vs 29%; p<0.001). Grade ≥3 acute toxicity was observed in 0.9% of patients and late toxicity in 2.3%.
CONCLUSIONS
In this cohort of patients with oligorecurrent PCa, concurrent ADT with MDT improved bRFS significantly, but a large number of patients treated with MDT were spared from ADT for 2yr, although a greater need for other salvage therapies was observed.
PATIENT SUMMARY
The role of concurrent androgen deprivation therapy (ADT) with radiotherapy for prostate cancer oligorecurrence identified on prostate-specific membrane antigen positron emission tomography was studied. We concluded that radiotherapy alone could prolong the time to start of ADT. However, the risk of disease progression and consequently the need for further treatments is higher after local radiotherapy alone without immediate ADT.

Identifiants

pubmed: 31495759
pii: S2405-4569(19)30270-6
doi: 10.1016/j.euf.2019.08.012
pii:
doi:

Substances chimiques

Androgen Antagonists 0
Androgens 0

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

309-316

Informations de copyright

Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Auteurs

Stephanie G C Kroeze (SGC)

Department of Radiation Oncology, University Hospital Zürich, Zurich, Switzerland. Electronic address: stephanie.kroeze@usz.ch.

Christoph Henkenberens (C)

Department of Radiotherapy and Special Oncology, Hannover Medical School, Hannover, Germany.

Nina Sophie Schmidt-Hegemann (NS)

Department of Radiation Oncology, University Hospital LMU Munich, Munich, Germany.

Marco M E Vogel (MME)

Department of Radiation Oncology, Technical University Munich, Munich, Germany.

Simon Kirste (S)

Department of Radiation Oncology, University of Freiburg, Freiburg, Germany; German Cancer Consortium Partner Site Freiburg, German Cancer Research Center, Heidelberg, Germany.

Jessica Becker (J)

Department of Radiation Oncology, University Hospital Tübingen, Tübingen, Germany.

Irene A Burger (IA)

Department of Nuclear Medicine, University Hospital Zürich, Zurich, Switzerland.

Thorsten Derlin (T)

Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.

Peter Bartenstein (P)

Department of Nuclear Medicine, University Hospital LMU Munich, Munich, Germany.

Matthias Eiber (M)

Department of Nuclear Medicine, Technical University Munich, Munich, Germany.

Michael Mix (M)

Department of Nuclear Medicine, University of Freiburg, Freiburg, Germany.

Christian la Fougère (C)

Department of Nuclear Medicine, University Hospital Tübingen, Tübingen, Germany.

Hans Christiansen (H)

Department of Radiotherapy and Special Oncology, Hannover Medical School, Hannover, Germany.

Claus Belka (C)

Department of Radiation Oncology, University Hospital LMU Munich, Munich, Germany; German Cancer Consortium Partner Site Munich, German Cancer Research Center, Heidelberg, Germany.

Stephanie E Combs (SE)

Department of Radiation Oncology, Technical University Munich, Munich, Germany; Institute of Innovative Radiotherapy, Oberschleissheim, Germany.

Anca L Grosu (AL)

Department of Radiation Oncology, University of Freiburg, Freiburg, Germany; German Cancer Consortium Partner Site Freiburg, German Cancer Research Center, Heidelberg, Germany.

Arndt Christian Müller (AC)

Department of Radiation Oncology, University Hospital Tübingen, Tübingen, Germany.

Matthias Guckenberger (M)

Department of Radiation Oncology, University Hospital Zürich, Zurich, Switzerland.

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