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Platinum Priority – Editorial

Referring to the article published on pp. 766–773 of this issue

Local Therapy for Gleason 9–10 Prostate Cancer: Looking to the


Wesley W. Ludwig, Ashley E. Ross, Philip M. Pierorazio


The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

The ideal management of very high-risk and locally

advanced prostate cancer continues to be a source of

debate within the medical community. Initial approaches to

treatment have traditionally entailed the use of external

beam radiation therapy (EBRT) with concurrent androgen

deprivation with or without brachytherapy (BT), or radical

prostatectomy with lymph node dissection. Recently,

clinical trials have suggested that oncologic outcomes in

such patients may be improved by the addition of docetaxel

to radiation regimens


. In addition, reports from

ASCENDE-RT, a randomized prospective trial exploring

the combined use of EBRT and BT, suggest that addition of

BT improves oncologic control, albeit at the expense of more

local morbidity

[3] .

What remains clear is that many

patients will require multimodal therapy to achieve cure or

a durable response

[4] .

While the number of options is

robust, evidence of clinical superiority for a particular

modality is lacking. There are no reported randomized

prospective trials comparing surgery and radiation-based

approaches in this setting. In the absence of such a trial,

scientific advances such as genomic and predictive bio-

markers, as well as novel imaging modalities for improved

diagnostic staging, may augment individualized decision-

making for patients with very high-risk disease



The article by Kishan et al


in this issue of



explores the outcomes for men with Gleason 9–10

prostate cancer treated with EBRT, extremely dose-escalat-

ed radiotherapy (EBRT + BT), or radical prostatectomy (RP).

The comparative effectiveness of the relative treatments is

hypothesis-generating at best and is limited by the

retrospective study design, lack of propensity matching,

and lack of uniform treatment. However, important points

can be gleaned and are highlighted by the authors. First, the

results support the findings of the ASCENDE-RT trial, with

the best cancer-specific outcomes observed among men

who had BT combined with EBRT


. This supports a

discussion of BT boost for men with high-grade disease, as

this may be a superior choice for men with limited baseline

urinary symptoms and favorable anatomy. Second, men

electing to undergo primary surgical therapy should be

counseled that the majority will require multimodal

therapy for local control. It is important to recognize the

evolution of surgery and adjuvant or salvage treatments, as

this evolution is not specifically addressed in the manu-

script. An improved understanding of the importance of

lymphadenectomy suggests that extended lymph-node

dissections be performed in patients with very high risk

[8] .

This practice will hopefully be facilitated by the

increasing aptitude of high-volume robotic surgeons.

Given the aggressive nature of Gleason 9–10 prostate

cancer, close follow-up is mandatory and there should be a

very low threshold for adjuvant and salvage RT after

surgery. When RT is applied in this setting, it should be done

so with the recognition that the disease may be local-

regional. In this regard, adjuvant or salvage RT should be

applied to the pelvis and not the prostate bed alone, as

shown in RTOG 9601, and should be applied concurrent

with hormonal deprivation

[9] .

Finally, while neoadjuvant

hormonal therapy has not shown oncologic benefit before

surgery in previous trials, it has not been thoroughly

investigated. The high-risk population is more likely to have

micrometastatic disease, and this issue has only begun to be

explored with the use of newer androgen-axis inhibitors

[10] . E U R O P E A N U R O L O G Y 7 1 ( 2 0 1 7 ) 7 7 4 – 7 7 5

available at


journal homepage:

DOI of original article:


* Corresponding author. The James Buchanan Brady Urological Institute, 600 North Wolfe Street, Baltimore, MD 21287, USA. Tel. +1 410 5025984;

Fax: +1 410 5027711.

E-mail address:

(P.M. Pierorazio).



2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.