Ductal Prostate Cancers Demonstrate Poor Outcomes with Conventional Therapies.

Androgen deprivation therapy Ductal prostate cancer Localized Neoadjuvant Outcomes Radical prostatectomy Radiotherapy

Journal

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

Informations de publication

Date de publication:
02 2021
Historique:
received: 02 06 2020
accepted: 10 11 2020
pubmed: 7 12 2020
medline: 18 9 2021
entrez: 6 12 2020
Statut: ppublish

Résumé

Ductal prostate adenocarcinoma (DAC) is a rare, aggressive, histologic variant of prostate cancer that is treated with conventional therapies, similar to high-risk prostate adenocarcinoma (PAC). To assess the outcomes of men undergoing definitive therapy for DAC or high-risk PAC and to explore the effects of androgen deprivation therapy (ADT) in improving the outcomes of DAC. A single-center retrospective review of all patients with cT1-4/N0-1 DAC from 2005 to 2018 was performed. Those undergoing radical prostatectomy (RP) or radiotherapy (RTx) for DAC were compared with cohorts of high-risk PAC patients. Metastasis-free survival (MFS) and overall survival (OS) rates were analyzed using Kaplan-Meier and Cox regression models. A total of 228 men with DAC were identified; 163 underwent RP, 34 underwent RTx, and 31 had neoadjuvant therapy prior to RP. In this study, 163 DAC patients and 155 PAC patients undergoing RP were compared. Similarly, 34 DAC patients and 74 PAC patients undergoing RTx were compared. DAC patients undergoing RP or RTx had worse 5-yr MFS (75% vs 95% and 62% vs 93%, respectively, p < 0.001) and 5-yr OS (88% vs 97% and 82% vs 100%, respectively, p < 0.05) compared with PAC patients. In the 76 men who received adjuvant/salvage ADT after RP, DAC also had worse MFS and OS than PAC (p < 0.01). A genomic analysis revealed that 10/11 (91%) DACs treated with ADT had intrinsic upregulation of androgen-resistant pathways. Further, none of the DAC patients (0/15) who received only neoadjuvant ADT prior to RP had any pathologic downgrading. The retrospective nature was a limitation. Men undergoing RP or RTx for DAC had worse outcomes than PAC patients, regardless of the treatment modality. Upregulation of several intrinsic resistance pathways in DAC rendered ADT less effective. Further evaluation of the underlying biology of DAC with clinical trials is needed. This study demonstrated worse outcomes among patients with ductal adenocarcinoma of the prostate than among high-grade prostate adenocarcinoma patients, regardless of the treatment modality.

Sections du résumé

BACKGROUND
Ductal prostate adenocarcinoma (DAC) is a rare, aggressive, histologic variant of prostate cancer that is treated with conventional therapies, similar to high-risk prostate adenocarcinoma (PAC).
OBJECTIVE
To assess the outcomes of men undergoing definitive therapy for DAC or high-risk PAC and to explore the effects of androgen deprivation therapy (ADT) in improving the outcomes of DAC.
DESIGN, SETTING, AND PARTICIPANTS
A single-center retrospective review of all patients with cT1-4/N0-1 DAC from 2005 to 2018 was performed. Those undergoing radical prostatectomy (RP) or radiotherapy (RTx) for DAC were compared with cohorts of high-risk PAC patients.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Metastasis-free survival (MFS) and overall survival (OS) rates were analyzed using Kaplan-Meier and Cox regression models.
RESULTS AND LIMITATIONS
A total of 228 men with DAC were identified; 163 underwent RP, 34 underwent RTx, and 31 had neoadjuvant therapy prior to RP. In this study, 163 DAC patients and 155 PAC patients undergoing RP were compared. Similarly, 34 DAC patients and 74 PAC patients undergoing RTx were compared. DAC patients undergoing RP or RTx had worse 5-yr MFS (75% vs 95% and 62% vs 93%, respectively, p < 0.001) and 5-yr OS (88% vs 97% and 82% vs 100%, respectively, p < 0.05) compared with PAC patients. In the 76 men who received adjuvant/salvage ADT after RP, DAC also had worse MFS and OS than PAC (p < 0.01). A genomic analysis revealed that 10/11 (91%) DACs treated with ADT had intrinsic upregulation of androgen-resistant pathways. Further, none of the DAC patients (0/15) who received only neoadjuvant ADT prior to RP had any pathologic downgrading. The retrospective nature was a limitation.
CONCLUSIONS
Men undergoing RP or RTx for DAC had worse outcomes than PAC patients, regardless of the treatment modality. Upregulation of several intrinsic resistance pathways in DAC rendered ADT less effective. Further evaluation of the underlying biology of DAC with clinical trials is needed.
PATIENT SUMMARY
This study demonstrated worse outcomes among patients with ductal adenocarcinoma of the prostate than among high-grade prostate adenocarcinoma patients, regardless of the treatment modality.

Identifiants

pubmed: 33279304
pii: S0302-2838(20)30879-4
doi: 10.1016/j.eururo.2020.11.015
pii:
doi:

Types de publication

Comparative Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

298-306

Informations de copyright

Copyright © 2020. Published by Elsevier B.V.

Auteurs

Weranja Ranasinghe (W)

The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Daniel D Shapiro (DD)

The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Hyunsoo Hwang (H)

The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Xuemei Wang (X)

The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Chad A Reichard (CA)

Urology of Indiana, Indianapolis, IN, USA.

Mohamed Elsheshtawi (M)

The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Mary F Achim (MF)

The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Tharakeswara Bathala (T)

The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Chad Tang (C)

The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Ana Aparicio (A)

The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Shi-Ming Tu (SM)

The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Nora Navone (N)

The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Timothy C Thompson (TC)

The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Louis Pisters (L)

The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Patricia Troncoso (P)

The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

John W Davis (JW)

The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

Brian F Chapin (BF)

The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. Electronic address: BFChapin@mdanderson.org.

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Classifications MeSH