Clinical Value of Fluoroethylcholine Positron-Emission-Tomography Combined With Endorectal Magnetic Resonance Imaging by Software Fusion for Pre-therapeutic Staging of Prostate Cancer
Prostate carcinoma is today in Germany the most frequently diagnosed cancer disease of men
and is - after bronchial carcinoma - their second most frequent cause of cancer-related
death. Around 22% of all new cancer diagnoses among males are prostate-related. This
corresponds to an age-adjusted incidence rate of nearly 100 per 100,000 males in the
population, and to well above 40,000 new diagnoses of prostate cancer per year
[Robert-Koch-Institut, 2010]. The dramatic increase in recent decades is attributable more
to improved diagnostic methods and a generally increased life expectancy than to an actual
increase in the incidence of disease [Robert-Koch-Institut, 2010].
The total annual mortality rate is around 11,000 [Statistisches Bundesamt, 1994]. Prostate
carcinoma is virtually unknown among men under 40 years of age. The annual prevalence rises
with increasing age - between the 40th and 80th years of life by a factor of more than 1000.
Autopsies have shown that among men over 70 up to 80% have a latent prostate carcinoma,
without it being fatal [Breslow 1977; Börgemann, 2006]. The patients' average age at
diagnosis is 71 years.
The five-year prostate-cancer-specific survival rate after diagnosis is about 80-99% for
tumours that are restricted to the gland itself [Porter, 2006]. For disseminated tumours
this figure is considerably smaller, not more than 35% [von Eschenbach, 1996]. A prospect of
complete regression exists only for non-metastasing carcinomas, but there it is quite good:
under aggressive treatment, 90% of cancers restricted to the prostate itself can be
completely cured, as can 50% of those that have crossed the gland's capsule [Deutsche
Gesellschaft für Urologie, 2009].
At present, there is a lack of adequate pre-therapeutic staging methods. This in turn often
prevents the reliable choice of a stage-adapted therapeutic regimen, which could possibly
offer a better prognosis even for carcinomas extending into neighbouring organs. A
consequence of this uncertainty is that in individual cases the therapy is not ideally
suited to the stage of disease, and the success of radiation treatment, hormonal therapy and
chemotherapy can only approximately be matched with the stage of dissemination. Until now,
the only reliable method for lymph-node diagnosis is operative staging by lymphadenectomy.
No reliable diagnostic method is available by which the degree of spreading of the tumour
within the prostate can be established.
In this context, Positron-Emission-Tomography (PET) examination with radioactively labelled
choline appears to offer a promising primary imaging-diagnostic staging method, as indicated
by the studies reviewed below. This diagnostic method as applied to humans was first
described by Gauthier et al. . This was followed by two detailed reports from a
Japanese group: Hara et al.  first investigated the potential of [11C]choline in brain
tumours and found a clear enrichment of this marker in the tumours of 24 patients, while
normal brain tissue was not enriched with it. In a subsequent study by the same group [Hara,
1998], the enrichment of fluorodeoxyglucose was compared with the choline uptake in the
lesions of ten prostate-cancer patients. Thus, the choline enrichment (SUV, standardised
uptake value) was 3.48 ± 1.31 in 43 lesions, while in the normal environment of the lesser
pelvis the corresponding value was below 1.0. De Jong et al.  investigated 67
patients, of whom 15 had histologically confirmed lymph-node metastases: the [11C]choline
test gave a 'true positive' result in 12 of 15 patients and a 'false negative' in 3
patients, thus indicating that [11C]choline PET is sufficiently sensitive and specific for
the pre-operative staging of lymph-node metastases of prostate carcinoma. In a pre-operative
staging using Magnetic Resonance Imaging (MRI) with a combined endorectal and
body-phased-array coil, Pegios et al.  investigated 42 patients with strong clinical
suspicion, or with needle-biopsy confirmation, of prostate cancer and were able to
differentiate between stages of extracapsular growth and seminal-vesicle infiltration (tumor
stage T2 versus T3 [T2=tumor restricted to the gland itself; T3a=extracapsule growing of the
tumor; T3b= tumor infiltration into the seminal-vesicles]) with an accuracy of 94-97%
(sensitivity 100%, specificity between 87% and 93% for observers 1 and 2). The exact, local
tumour stage was identified with an accuracy of 75%. However, for lymph-node infiltration a
sensitivity of only 25% was achieved: one of four lymph-node-positive patients was correctly
identified. In a more recent study, a Japanese group [Yamaguchi, 2005] investigated the
application of nuclear magnetic resonance (NMR) spectroscopy, magnetic resonance imaging
(MRI) and choline-PET in 20 patients with needle-biopsy-confirmed prostate cancer. The PET
imaging achieved a sensitivity of 100%, NMR (quotient [(creatine + choline) / citrate]) 65%
and unsupported MRI 60%. For 16 patients radical prostatectomy was performed; results
correlated with those of pre-operative local staging with PET by 81%, and with MRI by 50%.
The site of choline uptakes in PET was visualised by MRI using the distance of the prostate
from the femoral head and the pubic symphysis.At present, no data relevant for the present
study indication are available on the software-fused imaging by combined PET/MRI. The
combination of high-resolution endorectal MRI with functional PET imaging could come to
offer a decisive advantage in the staging of prostate carcinoma. The present study was
designed to test this in an appropriate patient population.
A system combining PET and MRI was recently granted approval in the U.S.A. by the U.S. Food
and Drug Administration [FDA, 2011].
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Number of Participants With Positive or Negative Results in PET, MRI or PET/MRI for Prostate Cancer Compared to Histological Findings
PET positive lesions were measured on its own and evaluated as malignant just as hypointense lesions on MRI. In PET/MRI analysis, MRI suspect lesions without FEC uptake were considered not to be malignant. PET positive lesions in central periurethral zone with inhomogenous signal intensity and sharp edges on MRI images were also considered to be benign. PET positive lesions in the peripheral zone without a hypointense correlate on MRI were considered to be malignant. At least 1 histological confirmed cancer lesion has to be detected by each of the 3 methods to be patient based true positive.
within < 2 weeks after PET/MRI
Markus Hartenbach, Dr.
German Federal Armed Forces Hospital, Ulm, Dep. of Nuclear Medicine
Germany: Federal Institute for Drugs and Medical Devices