Title: Reply to Stefano Fanti, Bernd Krause, Wolfgang Weber, et al's Letter to the Editor re: Nicolas Mottet, Joaquim Bellmunt, Michel Bolla, et al. EAU Guidelines on Prostate Cancer. Part II: Treatment of Advanced, Relapsing, and Castration-Resistant Prostate Cancer. Eur Urol 2011;59:572-83
Other Titles: Letter to the Editor
Authors: Mottet, Nicolas ×
Bellmunt, Joaquim
Bolla, Michel
Joniau, Steven
Mason, Malcolm
Matveev, Vsevolod
Schmid, Hans-Peter
Van der Kwast, Theo
Wiegel, Thomas
Zattoni, Filiberto
Heidenreich, Axel #
Issue Date: Nov-2011
Publisher: Elsevier Science
Series Title: European Urology vol:60 issue:5 pages:E39-E41
Abstract: We appreciate the valuable comments of Fanti and
colleagues with regard to the statements of the current
European Association of Urology (EAU) guidelines on the
role of choline positron emission tomography (PET)/
computed tomography (CT) in the routine diagnostic
work-up of patients with prostate-specific antigen (PSA)
rise after local treatment with curative intent.
Unfortunately, considering most of the papers cited by
Fanti et al, the authors most probably did not realize that
the cited version of the EAU guidelines on prostate cancer
(PCa) published in European Urology [1] only reflects the
short version of the guidelines and that the role of choline
PET/CT is discussed in more detail in the long version of the
guidelines [2]. However, we would like to address the final
conclusions of some of the papers mentioned to delineate
the potential role of choline PET/CT in the detection and
localization of metastases due to PCa following radical
prostatectomy (RP). Furthermore, we have included the
results of the most recently published papers on the issue of
choline PET/CT in relapsing PCa.
Imaging studies of patients’ PSA progression following
RP are performed to guide the type of salvage therapy that is
local versus systemic treatment. Therefore, any imaging
study used in this clinical scenario should be valid enough
to detect and localize metastatic deposits, and it should
have an impact on the further management of the
individual patient.
The EAU guidelines state that 11C-choline PET/CT is of
limited importance if the PSA is <2.5 ng/ml but that 11Ccholine
PET/CT might be of importance in patients with PSA
levels >2.5 ng/ml [1]. This conclusion derives from the data
of a recently published study by Castellucci et al [3] on 190
men with PSA relapse after RP. 11C-Choline PET/CT showed
localized disease relapse in 74 of 190 patients (38.9%) and
was negative in 116 patients, despite mean and median PSA
values of 4.2 ng/ml and 2.1 ng/ml, respectively. Castellucci
et al [3] evaluated (1) the effect of total PSA at the time of
11C-choline PET/CT (trigger PSA), (2) PSA velocity (PSAV),
and (3) PSA doubling time (PSA DT) on the 11C-choline PET/
CT detection rate in 190 patients with PSA relapse following
RP (mean: 4.2 ng/ml; median: 2.1 ng/ml; range: 0.2–25.4
ng/ml). Trigger PSA values were statistically different
between PET-positive patients (median PSA: 4.0 ng/ml)
and PET-negative patients (median PSA: 1.4 ng/ml)
( p = 0.0001), with the optimal cut-off point for a trigger
PSA of 2.43 ng/ml.
Keeping thesedata inmind, in106 patients, the PSADTand
PET-positive ( p = 0.04) and PET-negative ( p = 0.03) scan
findings. The 11C-choline PET/CT detection rate was 12% in
patients with PSAV <1 ng/ml per year (33 patients), 34% in
patients with PSAV between 1 and 2 ng/ml per year (26
patients), 42% in patients with PSAV between 2 and 5 ng/ml
per year (19 patients), and 70% in patients with PSAV >5 ng/
ml per year (28 patients). The 11C-choline PET/CT detection
ratewas20%inpatients with PSADT>6mo (45patients), 40%
inpatientswithPSADTbetween4and6mo (20 patients),48%
inpatientswithPSADTbetween2 and 4mo(31patients), and
60% in patients with PSA DT <2 mo (10 patients).
The review cited most by the authors [4] was simply not
published at the time the EAU guidelines were updated and
published. The same holds true for the recent review paper
published by Picchio et al [5], with valuable contributions
from members of the EAU guidelines group on PCa, who
updatedversionoftheEAUguidelines tobepublishedin2012.
Rinnab et al [6] evaluated 40 patients with PSA rise
following RP. The mean PSA value in men with positive PET/
CT findings was 3.62 ng/ml, far above the trigger point of
0.5 ng/ml to identify patients who might be candidates for
local salvage radiation therapy with curative intent.
Therefore, choline PET/CT was not identified as a valid
imaging study to stratify candidates for local versus
systemic treatment.
The cited paper from Cimitan et al [7] reaches the same
conclusion as the EAU guidelines: ‘‘FCH [fluorocholine] PET/
CT is not likely to have a significant impact on the care of prostate cancer patients with biochemical recurrence until
PSA increases to above 4 ng/ml.’’
Even one of the latest publications of the group around
Professor Scattoni [8], comprising 109 patients with rising
PSA and negative conventional imaging studies, reached
the conclusion that choline PET/CT might be useful to
restage PCA but that it cannot be used to guide therapy. In
that study, only 12 of 109 patients (11%) had positive PET/
CT findings. Scans were positive in 5%, 15%, and 28% of
patients with PSA<1ng/ml, between1and2ng/ml, and>2
ng/ml, respectively ( p<0.05). Recommending choline PET/
CT in allmen with a rising PSA level >1 ng/ml would result
in 85% incidence of unnecessary examinations, significant
increase of medical costs, and no benefit for the individual
In another retrospective study of 37 patients scheduled
for salvage radiation therapy after RP, Savatzoglou et al [9]
reported that about 13% of the patients demonstrated
choline PET/CT–positive lymph nodes outside the prostatic
fossa, implicating an extension of the target volume.
However, none of the lesions was verified histologically,
and the mean PSA of choline-positive patients (1.1 ng/ml;
range: 0.5–1.8 ng/ml) was significantly higher than
in choline PET/CT–negative patients (0.4 ng/ml; range:
0.3–0.7 ng/ml).
The conclusions of themost recent review published by
Picchio et al [4] are that the routine use of choline PET/CT
cannot be recommended for PSA values <1 ng/ml. Its
accuracy is correlated to PSA value, PSA DT, and other
pathologic features. Choline PET/CT may be proposed as a
guide for individualized treatment of recurrence. The
same holds true for a recently published study published
by Castellucci et al [10]. Basically, there is not a significant
difference between the statements of the EAU guidelines
and the most recent review on this issue. However, the
indication to perform choline PET/CT has to be placed in
the context of the above-mentioned clinical parameters.
Based on the clinical studies, it is still doubtful that a
patient with elevated PSA, rapid PSA DT and a prostatectomy
Gleason score 8 will receive any therapy other than
androgen deprivation therapy based on the findings of
choline PET/CT.
In summary, the role and the diagnostic accuracy of
choline PET/CT in men with rising PSA following RP is
dependent on absolute PSA, PSA DT, and PSAV. The higher
the PSA and the faster PSA DT, the better the predictive
value of this imaging modality. However, even in patients
with PSA values >2 ng/ml and negative imaging studies,
choline PET/CT is positive in only 28%. Therefore, we
urgently need well-conducted and histologically controlled
trials to explore the potential role of choline PET/CT.
ISSN: 0302-2838
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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