PMID- 35465985
OWN - NLM
STAT- MEDLINE
DCOM- 20220614
LR  - 20221130
IS  - 1873-7560 (Electronic)
IS  - 0302-2838 (Linking)
VI  - 82
IP  - 1
DP  - 2022 Jul
TI  - Intensification of Systemic Therapy in Addition to Definitive Local Treatment in 
      Nonmetastatic Unfavourable Prostate Cancer: A Systematic Review and 
      Meta-analysis.
PG  - 82-96
LID - S0302-2838(22)01802-4 [pii]
LID - 10.1016/j.eururo.2022.03.031 [doi]
AB  - CONTEXT: Several recent randomised trials have evaluated the role of combination 
      systemic treatment using androgen deprivation therapy (ADT) plus chemotherapy or 
      an androgen receptor signaling inhibitor (ARSI) in patients with high-risk and/or 
      unfavourable nonmetastatic prostate cancer (nmPC). OBJECTIVE: To assess the 
      outcomes associated with adding combination systemic treatment to primary 
      definitive local therapy in patients with high-risk and/or unfavourable nmPC. 
      EVIDENCE ACQUISITION: We queried the PubMed, Web of Science, and Scopus databases 
      and conference abstracts to identify prospective randomised trials examining the 
      value of adding chemotherapy or an ARSI to ADT and primary local therapy with 
      curative intent for nmPC. The primary endpoints were overall survival (OS), 
      cancer-specific survival (CSS), metastasis-free survival (MFS), and failure-free 
      survival (FFS). Secondary endpoints included adverse events (AEs) and pathologic 
      outcomes. EVIDENCE SYNTHESIS: We identified 15 randomised studies, of which nine 
      evaluated chemohormonal and six investigated ARSI-based treatment strategies. In 
      both radical prostatectomy (RP) and radiation therapy (RT) settings, addition of 
      docetaxel to ADT was associated with significantly better CSS (pooled hazard 
      ratio [HR] 0.68, 95% confidence interval [CI] 0.49-0.95; p = 0.025), MFS (pooled 
      HR 0.82, 95% CI 0.71-0.95; p = 0.008), and FFS (pooled HR 0.70, 95% CI 0.62-0.79; 
      p < 0.001); the difference did not meet the conventional level of statistical 
      significance for OS (pooled HR 0.86, 95% CI 0.73-1.01; p = 0.072). For patients 
      treated with RT alone, docetaxel-based combination treatment did not meet the 
      significance threshold set for OS (p = 0.3), CSS (p = 0.072), or MFS (p = 0.079), 
      but the difference for FFS was statistically significant (pooled HR 0.72, 95% CI 
      0.63-0.84; p < 0.001). On network meta-analyses including RT studies, ARSI + ADT 
      outperformed docetaxel + ADT for survival endpoints and had a more favourable AE 
      profile. CONCLUSIONS: Intensification of systemic therapy with docetaxel or an 
      ARSI in addition to ADT improves oncologic endpoints in high-risk and/or 
      unfavourable nmPC treated with local definitive therapy. The highest efficacy was 
      achieved with ARSI + ADT, specifically in patients treated with RT. PATIENT 
      SUMMARY: Our findings highlight that selected patients with high-risk 
      nonmetastatic prostate cancer benefit from intensification of systemic therapy 
      beyond hormonal treatment.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Rajwa, Pawel
AU  - Rajwa P
AD  - Department of Urology, Medical University of Vienna, Vienna, Austria; Department 
      of Urology, Medical University of Silesia, Zabrze, Poland.
FAU - Pradere, Benjamin
AU  - Pradere B
AD  - Department of Urology, Medical University of Vienna, Vienna, Austria.
FAU - Gandaglia, Giorgio
AU  - Gandaglia G
AD  - Unit of Urology/Division of Oncology, IRCCS San Raffaele, San Raffaele Hospital, 
      Milan, Italy.
FAU - van den Bergh, Roderick C N
AU  - van den Bergh RCN
AD  - Department of Urology, St. Antonius Hospital, Nieuwegein, the Netherlands.
FAU - Tsaur, Igor
AU  - Tsaur I
AD  - Department of Urology and Pediatric Urology, University Medical Center, Johannes 
      Gutenberg University, Mainz, Germany.
FAU - Shim, Sung Ryul
AU  - Shim SR
AD  - Department of Health and Medical Informatics, Kyungnam University College of 
      Health Sciences, Changwon, Republic of Korea.
FAU - Yanagisawa, Takafumi
AU  - Yanagisawa T
AD  - Department of Urology, Medical University of Vienna, Vienna, Austria; Department 
      of Urology, The Jikei University School of Medicine, Tokyo, Japan.
FAU - Laukhtina, Ekaterina
AU  - Laukhtina E
AD  - Department of Urology, Medical University of Vienna, Vienna, Austria; Institute 
      for Urology and Reproductive Health, Sechenov University, Moscow, Russia.
FAU - Mori, Keiichiro
AU  - Mori K
AD  - Department of Urology, Medical University of Vienna, Vienna, Austria; Department 
      of Urology, The Jikei University School of Medicine, Tokyo, Japan.
FAU - Mostafaei, Hadi
AU  - Mostafaei H
AD  - Department of Urology, Medical University of Vienna, Vienna, Austria; Research 
      Center for Evidence Based Medicine, Tabriz University of Medical Sciences, 
      Tabriz, Iran.
FAU - Quhal, Fahad
AU  - Quhal F
AD  - Department of Urology, Medical University of Vienna, Vienna, Austria; Department 
      of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia.
FAU - Bryniarski, Piotr
AU  - Bryniarski P
AD  - Department of Urology, Medical University of Silesia, Zabrze, Poland.
FAU - Comperat, Eva
AU  - Comperat E
AD  - Department of Pathology, Hopital Tenon, Sorbonne University Paris VI, Paris, 
      France.
FAU - Roubaud, Guilhem
AU  - Roubaud G
AD  - Department of Medical Oncology, Institut Bergonie, Bordeaux, France.
FAU - Massard, Christophe
AU  - Massard C
AD  - Departement des Innovations Therapeutiques et Essais Precoces, Gustave Roussy, 
      Universite Paris-Saclay, Villejuif, France.
FAU - Merseburger, Axel S
AU  - Merseburger AS
AD  - Department of Urology, University Hospital Schleswig-Holstein, Lubeck, Germany.
FAU - Leapman, Michael S
AU  - Leapman MS
AD  - Department of Urology, Yale School of Medicine, New Haven, CT, USA.
FAU - Spratt, Daniel E
AU  - Spratt DE
AD  - Department of Radiation Oncology, University Hospitals Seidman Cancer Center, 
      Case Western Reserve University, Cleveland, OH, USA.
FAU - Saad, Fred
AU  - Saad F
AD  - Division of Urology and Urologic Oncology, Centre Hospitalier de Universite de 
      Montreal, University of Montreal, Montreal, QC, Canada.
FAU - Joniau, Steven
AU  - Joniau S
AD  - Department of Urology, University Hospitals Leuven, Leuven, Belgium.
FAU - D'Amico, Anthony V
AU  - D'Amico AV
AD  - Department of Radiation Oncology, Brigham and Women's Hospital and Dana Farber 
      Cancer Institute, Boston, MA, USA.
FAU - Briganti, Alberto
AU  - Briganti A
AD  - Unit of Urology/Division of Oncology, IRCCS San Raffaele, San Raffaele Hospital, 
      Milan, Italy.
FAU - Shariat, Shahrokh F
AU  - Shariat SF
AD  - Department of Urology, Medical University of Vienna, Vienna, Austria; Institute 
      for Urology and Reproductive Health, Sechenov University, Moscow, Russia; Karl 
      Landsteiner Institute of Urology and Andrology, Vienna, Austria; Department of 
      Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; 
      Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, 
      Amman, Jordan; Department of Urology, Weill Cornell Medical College, New York, 
      NY, USA; Department of Urology, University of Texas Southwestern, Dallas, TX, 
      USA. Electronic address: shahrokh.shariat@meduniwien.ac.at.
FAU - Ploussard, Guillaume
AU  - Ploussard G
AD  - Department of Urology, La Croix du Sud Hospital, Quint Fonsegrives, France.
CN  - European Association of Urology Young Academic Urologists Prostate Cancer Working 
      Party
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PT  - Systematic Review
DEP - 20220422
PL  - Switzerland
TA  - Eur Urol
JT  - European urology
JID - 7512719
RN  - 0 (Androgen Antagonists)
RN  - 0 (Antineoplastic Agents)
RN  - 15H5577CQD (Docetaxel)
SB  - IM
CIN - Eur Urol. 2022 Oct;82(4):e105-e106. PMID: 35907662
MH  - Androgen Antagonists/adverse effects
MH  - *Antineoplastic Agents/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Docetaxel/therapeutic use
MH  - Humans
MH  - Male
MH  - Prospective Studies
MH  - *Prostatic Neoplasms/drug therapy/pathology
OTO - NOTNLM
OT  - Abiraterone
OT  - Chemotherapy
OT  - Docetaxel
OT  - Enzalutamide
OT  - Prostate cancer
OT  - Radiation therapy
OT  - Radical prostatectomy
EDAT- 2022/04/26 06:00
MHDA- 2022/06/15 06:00
CRDT- 2022/04/25 05:57
PHST- 2021/11/23 00:00 [received]
PHST- 2022/02/22 00:00 [revised]
PHST- 2022/03/24 00:00 [accepted]
PHST- 2022/04/26 06:00 [pubmed]
PHST- 2022/06/15 06:00 [medline]
PHST- 2022/04/25 05:57 [entrez]
AID - S0302-2838(22)01802-4 [pii]
AID - 10.1016/j.eururo.2022.03.031 [doi]
PST - ppublish
SO  - Eur Urol. 2022 Jul;82(1):82-96. doi: 10.1016/j.eururo.2022.03.031. Epub 2022 Apr 
      22.