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They have linked AR-V7 status to progression-free and overall

survival in 36 patients with castration-resistant prostate

cancer undergoing treatment with abiraterone or enzaluta-

mide. They report that median progression-free and

overall survival in AR-V7–negative patients exceeded that

in AR-V7–positive patients by more than 1 yr. They conclude

that the presence of AR-V7 may predict resistance to

hormonal therapy.

Expert’s comments:

Biomarker-guided selection of the most suitable treatment

has become an important trend in oncology in general



in urology


. A role for AR-V7 in responsiveness to antihor-

monal therapy has been proposed before


. The main value

of the study by del Re et al is establishing a method for AR-V7

quantification based on mRNA circulating in plasma. This is

apparently more sensitive than assessing circulating tumor

cells, as it has fewer false negatives. Moreover, in contrast to

tumor biopsies, it allows serial measurements to account for

possible shifts in tumor genotype and phenotype over time.

Del Re et al claim that their plasma-based test predicts

survival, but what they have shown is association rather

than predictivity. Convincing proof of predictive value

(compared to association) requires prospective studies,

preferentially in two independent cohorts. While primarily

developed for commercial drug development, guidance by

the US Food and Drug Administration on the development

of biomarkers in oncology may also benefit academic



. For optimal treatment results, the quality

of biomarker validation should not differ between academic

and commercial investigators.

Demonstrating that AR-V7 status is associated with

length of survival at the group level does not necessarily

help the treatment decision for an individual patient. Future

prospective studies are required to determine whether AR-

V7–guided treatment has better outcomes than treatment

allocation without biomarkers. It has been argued that such

studies are sparse because they are very expensive


. The

method developed by del Re et al may make it easier and

less costly to perform such trials. Therefore, the ultimate

value may reside in developing a technology that allows

prospective outcome trials with limited patient numbers

and budget.

Conflicts of interest:

The author has been a consultant for Boehringer

Ingelheim, Dr. Wilmar Schwabe, Sanofi, and Velicept Therapeutics, is a

shareholder in Velicept Therapeutics, and was an employee of

Boehringer Ingelheim (2011–2016).



Antonarakis ES, Lu C, Wang H, et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 2014;371:1028–38



Kelloff GJ, Sigman CC. Cancer biomarkers: selecting the right drug for the right patient. Nat Rev Drug Discov 2012;11:201–14.


Barbieri CE, Chinnaiyan AM, Lerner SP, Swanton C, Rubin MA. The emergence of precision urologic oncology: a collaborative review on biomarker-driven therapies. Eur Urol 2017;71:237–46



Pal SK, Karam JA, Chennamsetty A, Jones JO. Biomarkers in genito- urinary cancers: blazing the path forward. Eur Urol 2017;71:247–8


Martin C. Michel


Pharmacology Department, Johannes Gutenberg University, Mainz,


*Pharmacology Department, Johannes Gutenberg University, Obere

Zahlbacher Strasse 67, Mainz 55131, Germany.

E-mail address: .


2017 European Association of Urology.

Published by Elsevier B.V. All rights reserved.

Re: Adjuvant Sunitinib in High-risk Renal-cell

Carcinoma after Nephrectomy

Ravaud A, Motzer RJ, Pandha HS, et al

N Engl J Med 2016;375:2246–54

Expert’s summary:

In this phase 3 trial (S-TRAC, NCT00375674), 1 yr of adjuvant

sunitinib was compared with placebo in patients who under-

went full surgical resection of high-risk clear cell renal-cell

carcinoma (RCC). Sunitinib was administered orally at a dose

of 50 mg/d in the classic 4-wk on/2-wk off schedule. The

primary endpoint was disease-free survival, which was sig-

nificantly prolonged in the sunitinib arm (hazard ratio: 0.76,

95% confidence interval: 0.59–0.98,


= 0.03). There were no

differences in overall survival (hazard ratio: 1.01, 95% confi-

dence interval: 0.72–1.44,


= 0.94). The incidence of Grade

3 and 4 adverse events was 48% in the sunitinib arm and 12%

in the placebo arm. Forty-six percent of patients in the suni-

tinib arm had dose reductions, of which


90% were due to

adverse events



Expert’s comments:

More than 50% of patients with high-risk RCC will recur

following complete surgical resection


, which is likely due

to growth of microscopic metastases that are present at the

time of diagnosis or which develop during the perioperative

period. The aim of an adjuvant therapy is to eradicate these

microscopic metastases, and ultimately improve disease-free

and overall survival. Several adjuvant trials have been initiated

to eradicate these possible microscopic tumour deposits, in-

cluding trials with sunitinib, sorafenib, pazopanib, and axitinib.

These therapies have been the standard of care in the palliative

setting for about a decade; however, complete tumour eradi-

cation of visible metastases has rarely been reported.

The present study showed that the risk for disease

recurrence is reduced by 24% with adjuvant sunitinib, with a

5-yr disease-free survival rate of 59% in the sunitinib arm,

and 51% in the placebo arm. This difference in disease-free

survival developed within the 1st yr and remained relatively

stable thereafter. Thus, it appears that sunitinib discontinu-

ation after 1 yr does not lead to rebound growth of

microscopic metastases due to revascularisation. Patients

E U R O P E A N U R O L O G Y 7 1 ( 2 0 1 7 ) 8 3 1 – 8 3 6