(18)F-fluoride positron emission tomography/computed tomography and bone scintigraphy for diagnosis of bone metastases in newly diagnosed, high-risk prostate cancer patients: study protocol for a multicentre, diagnostic test accuracy study.
For decades, planar bone scintigraphy has been the standard practice for detection of bone metastases in prostate cancer and has been endorsed by recent oncology/urology guidelines. It is a sensitive method with modest specificity. (18)F-fluoride positron emission tomography/computed tomography has shown improved sensitivity and specificity over bone scintigraphy, but because of methodological issues such as retrospective design and verification bias, the existing level of evidence with (18)F-fluoride positron emission tomography/computed tomography is limited. The primary objective is to compare the diagnostic properties of (18)F-fluoride positron emission tomography/computed tomography versus bone scintigraphy on an individual patient basis.
One hundred forty consecutive, high-risk prostate cancer patients will be recruited from several hospitals in Denmark. Sample size was calculated using Hayen's method for diagnostic comparative studies. This study will be conducted in accordance with recommendations of standards for reporting diagnostic accuracy studies. Eligibility criteria comprise the following: 1) biopsy-proven prostate cancer, 2) PSA = 50 ng/ml (equals a prevalence of bone metastasis of ˜ 50% in the study population on bone scintigraphy), 3) patients must be eligible for androgen deprivation therapy, 4) no current or prior cancer (within the past 5 years), 5) ability to comply with imaging procedures, and 6) patients must not receive any investigational drugs. Planar bone scintigraphy and (18)F-fluoride positron emission tomography/computed tomography will be performed within a window of 14 days at baseline. All scans will be repeated after 26 weeks of androgen deprivation therapy, and response of individual lesions will be used for diagnostic classification of the lesions on baseline imaging among responding patients. A response is defined as PSA normalisation or = 80% reduction compared with baseline levels, testosterone below castration levels, no skeletal related events, and no clinical signs of progression. Images are read by blinded nuclear medicine physicians. The protocol is currently recruiting.
To the best of our knowledge, this is one of the largest prospective studies comparing (18)F-fluoride positron emission tomography/computed tomography and bone scintigraphy. It is conducted in full accordance with recommendations for diagnostic accuracy trials. It is intended to provide valid documentation for the use of (18)F-fluoride positron emission tomography/computed tomography for examination of bone metastasis in the staging of prostate cancer.
The results of 44 trephine (OD 1.4-4 mm) biopsies and 39 fine needle (0.7-0.9 mm) aspirations of skeletal, mainly vertebral, lesions performed under CT-guidance in 54 patients were evaluated. The fine needle sample was aspirated through the trephine as a complementary procedure in 29 patients and a fine needle aspiration only was performed in 10 patients. Trephine biopsy only was performed in 15 patients. Sufficient material for histologic and cytologic analyses was obtained in 93% (41/44) and 97% (38/39) and a correct benign or malignant diagnosis was obtained in 84% (37/44) and 90% (35/39), respectively. Among the combined examinations the fine needle aspiration alone was diagnostic in 2 cases while the trephine specimen alone provided diagnostic material in 2 cases. In 24 cases both the cytologic and histologic samples were adequate for diagnostic purposes. In one case both methods gave false-negative results. The combined use of cytologic and histologic samples in CT-guided bone biopsies increased diagnostic accuracy. The aorta was perforated once with a 1.4-mm needle but without sequelae. CT-guided bone biopsy was found to be a safe, reliable and cost-efficient method.