18F-FDG PET/CT versus CT imaging in staging of primary Muscle Invasive Bladder Cancer

Accurate pre-operative and post-operative tumour staging in most cancers is of
essential importance for decision-making and prognostic classification. FDG
PET/CT has been demonstrated to have good sensitivity and specificity in the
detection of metastatic disease in malignancies and provide additional
diagnostic information that enhances clinical management more than CT or MRI
alone. Combined PET/CT is now widely used for tumour staging. In a number of
malignancies it has been shown that PET/CT staging with FDG is significantly
more accurate than PET alone, and side-by-side PET and CT.
Bladder cancer is the most frequent tumour of the urinary tract and the 9th
most common cancer diagnosis worldwide. Estimated incidence is more than
330,000 new cases per year and more than 130,000 deaths per year worldwide. In
bladder cancer, relatively few imaging studies have been performed with FDG PET
alone. In current practice, PET/CT is routinely used in many centers worldwide
either alone or in combination with high resolution, contrast enhanced CT as
diagnostic modality for the preoperative staging of muscle invasive bladder
cancer. The standard imaging work up in most Western European countries already
includes PET/CT although its superiority compared to CT alone has not
unequivocally been demonstrated. Within countries the approach may differ
between centers based on local criteria including availability of PET/CT.
In the present study combined 18F-FDG PET/CT scans will be performed in all of
the patients in order to assess the added value of PET/CT imaging. The results
of this large study will either result in evidence based level 1 evidence of
current practice of using PET/CT in preoperative staging of patients considered
for cystectomy (scientific assessment of level of evidence) or to omit PET/CT
in the current standard work up policy of many centers (efficiency outcome and
implications for health economics).

The purpose of this prospective study is to evaluate the value of 18F-FDG
PET/CT and CT for preoperative regional N staging of bladder cancer and to
verify the results by comparison with histopathological analysis, the gold
standard.

Prospective observational study among patients with a clinical diagnosis of
muscle invasive bladder cancer with active disease identified within the
bladder at the time of consent and imaging.

To elucidate the role of FDG PET/CT in the clinical management of
muscle-invasive bladder cancer and to assess a 10% difference in specific
and/or sensitivity of PET/CT over conventional work up with CT.

Procedure: CT scan, and FDG PET/CT scan. The surgeon will remain blinded for
the outcome of the PET/CT scan until after the operation. Patients will be
scheduled for surgery to remove their bladder and lymph nodes according to the
template LND as described in section 4.2 within 6 weeks after the CT and FDG
PET/CT imaging. Since conventional workup includes only a CT scan and since the
surgeons will operate and remove lymph nodes from different anatomical regions
according to a well-defined consensus template procedure, the patient will
receive optimal care according to current guidelines. Therefore, pre-operative
knowledge of the surgeon with regard to the outcome of PET/CT may result in a
bias and the statistically rigorous value of the outcome of the trial will be
jeopardized. It is thus fully justified that there will be no knowledge of the
PET/CT readings prior to surgery to avoid biased decision making which is not
in agreement with the design of the study.

To test differences in diagnostic performance between the 2 imaging procedures
for significance by the paired sample comparison with a significance level of
.05 and a power of 0.8 superiority of PET/CT over CT will be determined aiming
at an improvement of 10% in specificity and/or an improvement of 10% in
sensitivity (PET/CT being superior). Sensitivities, specificities, negative
predictive values, positive predictive values, and accuracies (with exact 95%
confidence intervals [CIs]) for both modalities will be determined for
detection of metastases to lymph nodes as well as for distant metastases.

The benefits for both participants and future patients certainly outweigh the
burden placed upon the participants by the extra FDG PET/CT that will be
performed in addition to standard care and the 2 extra blood samples that will
be collected at the time of routine blood collection for standard clinical
procedures.