Curative-intent Metastasis-directed Therapies for Molecularly-defined Oligorecurrent Prostate Cancer: A Prospective Phase II Trial Testing the Oligometastasis Hypothesis.

Humans Male Middle Aged Neoplasm Micrometastasis / diagnosis Neoplasm Recurrence, Local / blood Prospective Studies Prostate-Specific Antigen / blood Prostatectomy Prostatic Neoplasms / blood Radiotherapy, Adjuvant
Metastasis directed treatment Oligometastasis PSMA PET Prostate cancer SABR

Journal

European urology
ISSN: 1873-7560
Titre abrégé: Eur Urol
Pays: Switzerland
ID NLM: 7512719

Informations de publication

Date de publication:
09 2021
Historique:
received: 24 10 2020
accepted: 17 02 2021
pubmed: 10 3 2021
medline: 15 3 2022
entrez: 9 3 2021
Statut: ppublish

Résumé

The hypothesis of a curable oligometastatic prostate cancer (PCa) state remains to be clinically-proven. Conventional imaging often fails to localize early recurrences, hampering the potential for radical approaches. We hypothesize that prostate-specific membrane antigen (PSMA)-targeted PET-MR/CT allows for earlier detection and localization of oligorecurrent-PCa, unveiling a molecularly-defined state amenable to curative-intent metastasis-directed treatment (MDT). Single-institution single-arm phase-two study. Patients with rising PSA (0.4-3.0 ng/mL) after maximal local therapy (radical prostatectomy and post-operative radiotherapy), negative conventional staging, and no prior salvage hormonal therapy (HT) were eligible. All patients underwent [ Primary endpoint was biochemical response (complete, i.e. biochemical 'no evidence of disease' [bNED], or partial response [100% or ≥50% PSA decline from baseline, respectively]) after MDT. Simon's two-stage design was employed (null and alternate hypotheses <5% and >20% response rate, respectively), with α and β of 0.1. Seventy-two patients were enrolled (May/2017-July/2019). Thirty-eight (53%) had PSMA-detected oligorecurrent-PCa amenable for MDT. Thirty-seven (51%) agreed to MDT: 10 and 27 underwent surgery and SABR, respectively. Median follow-up was 15.9 months (IQR 9.8-19.1). Of patients receiving MDT, the overall response rate was 60%, including 22% rendered bNED. One (2.7%) grade 3 toxicity (intra-operative ureteric injury) was observed. PSMA-defined oligorecurrent-PCa can be rendered bNED, a necessary step towards cure, in 1 of 5 patients receiving MDT alone. Randomized trials are justified to determine if MDT +/- systemic agents can expand the curative therapeutic armamentarium for PCa. We studied men treated for prostate cancer with rising PSA. We found PSMA imaging detected recurrent cancer in three-quarters of patients, and targeted treatment to these areas significantly decreased PSA in half of patients.

Sections du résumé

BACKGROUND
The hypothesis of a curable oligometastatic prostate cancer (PCa) state remains to be clinically-proven. Conventional imaging often fails to localize early recurrences, hampering the potential for radical approaches.
OBJECTIVE
We hypothesize that prostate-specific membrane antigen (PSMA)-targeted PET-MR/CT allows for earlier detection and localization of oligorecurrent-PCa, unveiling a molecularly-defined state amenable to curative-intent metastasis-directed treatment (MDT).
DESIGN/SETTING/PARTICIPANTS
Single-institution single-arm phase-two study. Patients with rising PSA (0.4-3.0 ng/mL) after maximal local therapy (radical prostatectomy and post-operative radiotherapy), negative conventional staging, and no prior salvage hormonal therapy (HT) were eligible.
INTERVENTIONS
All patients underwent [
OUTCOME MEASUREMENTS/STATISTICAL ANALYSIS
Primary endpoint was biochemical response (complete, i.e. biochemical 'no evidence of disease' [bNED], or partial response [100% or ≥50% PSA decline from baseline, respectively]) after MDT. Simon's two-stage design was employed (null and alternate hypotheses <5% and >20% response rate, respectively), with α and β of 0.1.
RESULTS
Seventy-two patients were enrolled (May/2017-July/2019). Thirty-eight (53%) had PSMA-detected oligorecurrent-PCa amenable for MDT. Thirty-seven (51%) agreed to MDT: 10 and 27 underwent surgery and SABR, respectively. Median follow-up was 15.9 months (IQR 9.8-19.1). Of patients receiving MDT, the overall response rate was 60%, including 22% rendered bNED. One (2.7%) grade 3 toxicity (intra-operative ureteric injury) was observed.
CONCLUSIONS
PSMA-defined oligorecurrent-PCa can be rendered bNED, a necessary step towards cure, in 1 of 5 patients receiving MDT alone. Randomized trials are justified to determine if MDT +/- systemic agents can expand the curative therapeutic armamentarium for PCa.
PATIENT SUMMARY
We studied men treated for prostate cancer with rising PSA. We found PSMA imaging detected recurrent cancer in three-quarters of patients, and targeted treatment to these areas significantly decreased PSA in half of patients.

Identifiants

DOI: 10.1016/j.eururo.2021.02.031 PMID: 33685838
pubmed: 33685838
pii: S0302-2838(21)00151-2
doi: 10.1016/j.eururo.2021.02.031
pii:
doi:

Substances chimiques

Prostate-Specific Antigen EC 3.4.21.77

Types de publication

Clinical Trial, Phase II Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

374-382

Commentaires et corrections

Type : CommentIn
Type : CommentIn
Type : CommentIn

Informations de copyright

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

Auteurs

Rachel M Glicksman (RM)

University of Toronto, Department of Radiation Oncology, 149 College Street, Unit 504, Toronto, Ontario, M5T 1P5, Canada.

Ur Metser (U)

Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital and Women's College Hospital, University of Toronto, 263 McCaul Street, 4th floor, Toronto, Ontario, M5T 1W7, Canada.

Douglass Vines (D)

University of Toronto, Department of Radiation Oncology, 149 College Street, Unit 504, Toronto, Ontario, M5T 1P5, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 700 University Avenue, 7th floor, Toronto, Ontario, M5G 1Z5, Canada.

John Valliant (J)

Centre for Probe Development and Commercialization, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4L8, Canada.

Zhihui Liu (Z)

Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, M5T 3M7, Canada.

Peter W Chung (PW)

University of Toronto, Department of Radiation Oncology, 149 College Street, Unit 504, Toronto, Ontario, M5T 1P5, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 700 University Avenue, 7th floor, Toronto, Ontario, M5G 1Z5, Canada.

Robert G Bristow (RG)

Manchester Cancer Research Centre, University of Manchester, 555 Wilmslow Road, Manchester, M20 4GJ, United Kingdom.

Antonio Finelli (A)

Department of Surgical Oncology, Division of Urology, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada.

Robert Hamilton (R)

Department of Surgical Oncology, Division of Urology, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada.

Neil E Fleshner (NE)

Department of Surgical Oncology, Division of Urology, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada.

Nathan Perlis (N)

Department of Surgical Oncology, Division of Urology, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada.

Alexandre R Zlotta (AR)

Department of Surgical Oncology, Division of Urology, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada.

David Green (D)

University of Toronto, Department of Radiation Oncology, 149 College Street, Unit 504, Toronto, Ontario, M5T 1P5, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 700 University Avenue, 7th floor, Toronto, Ontario, M5G 1Z5, Canada; TECHNA Institute, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada.

Andrew Bayley (A)

University of Toronto, Department of Radiation Oncology, 149 College Street, Unit 504, Toronto, Ontario, M5T 1P5, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 700 University Avenue, 7th floor, Toronto, Ontario, M5G 1Z5, Canada.

Joelle Helou (J)

University of Toronto, Department of Radiation Oncology, 149 College Street, Unit 504, Toronto, Ontario, M5T 1P5, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 700 University Avenue, 7th floor, Toronto, Ontario, M5G 1Z5, Canada.

Srinivas Raman (S)

University of Toronto, Department of Radiation Oncology, 149 College Street, Unit 504, Toronto, Ontario, M5T 1P5, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 700 University Avenue, 7th floor, Toronto, Ontario, M5G 1Z5, Canada.

Girish Kulkarni (G)

Department of Surgical Oncology, Division of Urology, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada.

Charles Catton (C)

University of Toronto, Department of Radiation Oncology, 149 College Street, Unit 504, Toronto, Ontario, M5T 1P5, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 700 University Avenue, 7th floor, Toronto, Ontario, M5G 1Z5, Canada.

Tony Lam (T)

Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 700 University Avenue, 7th floor, Toronto, Ontario, M5G 1Z5, Canada.

Rosanna Chan (R)

Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital and Women's College Hospital, University of Toronto, 263 McCaul Street, 4th floor, Toronto, Ontario, M5T 1W7, Canada.

Padraig Warde (P)

University of Toronto, Department of Radiation Oncology, 149 College Street, Unit 504, Toronto, Ontario, M5T 1P5, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 700 University Avenue, 7th floor, Toronto, Ontario, M5G 1Z5, Canada.

Mary Gospodarowicz (M)

University of Toronto, Department of Radiation Oncology, 149 College Street, Unit 504, Toronto, Ontario, M5T 1P5, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 700 University Avenue, 7th floor, Toronto, Ontario, M5G 1Z5, Canada.

David A Jaffray (DA)

TECHNA Institute, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada; Divisions of Radiation Oncology and Diagnostic Radiology, MD Anderson Cancer Centre, 1515 Holcombe Boulevard, Houston, Texas, 77030, United States.

Alejandro Berlin (A)

University of Toronto, Department of Radiation Oncology, 149 College Street, Unit 504, Toronto, Ontario, M5T 1P5, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, 700 University Avenue, 7th floor, Toronto, Ontario, M5G 1Z5, Canada; TECHNA Institute, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada. Electronic address: alejandro.berlin@rmp.uhn.ca.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Curative-intent Metastasis-directed Therapies...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Curative-intent Metastasis-directed Therapies...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Métastase tumorale › Micrométastase tumorale › Curative-intent Metastasis-directed Therapies...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Récidive tumorale locale › Curative-intent Metastasis-directed Therapies...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Curative-intent Metastasis-directed Therapies...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Antigène spécifique de la prostate › Curative-intent Metastasis-directed Therapies...
questionsmedicales.fr › Procédures de chirurgie opératoire › Procédures de chirurgie urogénitale › Procédures de chirurgie urologique › Procédures de chirurgie urologique masculine › Prostatectomie › Curative-intent Metastasis-directed Therapies...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › Curative-intent Metastasis-directed Therapies...
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