Clinical trial NCT00520546: Clinical Value of FEC-PET Combined With Endorectal MRI for Pre-therapeutic Staging of Prostate Cancer
Official title: Clinical Value of [18]Fluoroethylcholine Positron-Emission-Tomography Combined With Endorectal Magnetic Resonance Imaging by Software Fusion for Pre-therapeutic Staging of Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: PET
MRI
Choline
FEC
prostate cancer
Lead sponsor: German Federal Armed Forces
Sponsor class: OTHER
First posted: 2007-08-24
Enrollment: 44
Sex: MALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: To investigate the sensitivity of the \[18F\]fluoroethylcholine (FEC) Positron-Emission-Tomography/ Magnetic Resonance Imaging (PET/MRI) method in tumour detection and location (side assignment, encapsulation, invasion of the seminal vesicle) and detection of affected lymph nodes, and to compare these with presently used detection procedures (needle biopsy, digital rectal examination, transrectal ultrasound, and pre-therapeutic assessment), with a view to finding out whether the \[18F\]fluoroethylcholine PET/MRI method is comparable to, or superior to, the established method. Postoperative histology served as the standard of reference.

Detailed description: 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. \[1985\]. This was followed by two detailed reports from a Japanese group: Hara et al. \[1997\] 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. \[2003\] 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. \[2003\] 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 \[FDA, 2011\].

Eligibility criteria: Inclusion Criteria:

* Histologically diagnosed prostate cancer (needle biopsy)
* Radical prostatectomy as primary treatment
* No nutrition within 12 hours before Positron-Emission-Tomography (PET)
* No food containing choline within 24 hous before PET
* Age \> 50 years

Exclusion Criteria:

* Total endo-prothesis of the hip region
* Clinical or chemical detection of an acute infection
* Missing patient agreement
* Secondary cancer
* Surgical treatment within 3 month before PET
* Claustrophobia
* Medical drugs with choline
* Severe liver damage
* Cardiac infarction
* Bradycardia (pulse rate \< 55/min)
* Allergic reaction against Neurotropan
* Bronchial asthma
* Cardiac pacemaker
* Small metal implants (e.g., clips, cochlea-implants, etc.)

Primary outcomes:
measure: Number of Participants With Positive or Negative Results in PET, MRI or PET/MRI for Prostate Cancer Compared to Histological Findings
timeFrame: within < 2 weeks after PET/MRI
Secondary outcomes:
measure: Lesion Based Analysis of FEC-PET, Endorectal MRI and Combined FEC-PET/eMRI in All Patients
timeFrame: within < 2 weeks after PET/MRI
measure: Lesion Based Analysis of FEC-PET, Endorectal MRI and Combined FEC-PET/eMRI in Patients With Gleason Score >6 (3+3)
timeFrame: within < 2 weeks after PET/MRI
measure: Lesion Based Analysis of FEC-PET, Endorectal MRI and Combined FEC-PET/eMRI in Patients With Malignant Lesions >5mm (n=98)
timeFrame: within < 2 weeks after PET/MRI
Other outcomes:
Locations:
city: Ulm
country: Germany
facility: German Federal Armed Forces Hospital
state: Baden-Württemberg
Study officials:
affiliation: German Federal Armed Forces Hospital, Ulm, Dep. of Nuclear Medicine
name: Markus Hartenbach, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: German Federal Armed Forces Hospital Ulm, Dep. of Urology
name: Christoph Sparwasser, Prof. Dr.
role: STUDY_DIRECTOR
References:
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