Observer Agreement and Accuracy of 18F-Sodium Fluoride PET/CT in the Diagnosis of Bone Metastases in Prostate Cancer.

Our aim was to evaluate the interobserver agreement in 18F-sodium fluoride (NaF) PET/CT for the detection of bone metastases in patients with prostate cancer (PCa). Methods:18F-NaF PET/CT scans were retrieved from all patients who participated in 4 recent prospective trials. Two experienced observers independently evaluated the 18F-NaF PET/CT scans on a patient level using a 3-category scale (no bone metastases [M0], equivocal for bone metastases, and bone metastases present [M1]) and on a dichotomous scale (M0/M1). In patients with no more than 10 lesions, the location and number of lesions were recorded. On a patient level, the diagnostic performance was calculated using a sensitivity analysis, in which equivocal lesions were handled as M0 as well as M1. Results:18F-NaF PET/CT scans from 219 patients with PCa were included, of whom 129 patients were scanned for primary staging, 67 for biochemical recurrence, and 23 for metastatic castration-resistant PCa. Agreement between the observers was almost perfect on a patient level (3-category unweighted κ = 0.83 ± 0.05, linear weighted κ = 0.90 ± 0.06, and dichotomous κ = 0.91 ± 0.07). On a lesion level (dichotomous scale), the observers agreed on the number and location of bone metastases in 205 (93.6%) patients. In the remaining 14 patients, the readers disagreed on the number of lesions in 13 patients and the location of bone metastases in 1 patient. A final diagnosis of bone metastases was made for 211 of 219 patients. The sensitivity ranged from 0.86 to 0.92, specificity from 0.83 to 0.97, positive predictive value from 0.70 to 0.93, and negative predictive value from 0.94 to 0.96. Conclusion: The interobserver agreement on 18F-NaF PET/CT for the detection of bone metastases in patients with PCa was very high among trained observers, both on a patient level and on a lesion level. Moreover, the diagnostic performance of 18F-NaF PET/CT was satisfactory, rendering 18F-NaF PET/CT a robust tool in the diagnostic armamentarium.

No Added Value of 18F-Sodium Fluoride PET/CT for the Detection of Bone Metastases in Patients with Newly Diagnosed Prostate Cancer with Normal Bone Scintigraphy.

The aim of this study was to determine if additional 18F-sodium fluoride PET/CT (NaF PET/CT) improves the prognostic accuracy in the initial staging of prostate cancer patients with normal bone scintigraphy undergoing prostatectomy. Methods: A prospective cohort study examined NaF PET/CT in intermediate- or high-risk prostate cancer with negative bone scintigraphy who were scheduled for prostatectomy. Biochemical response: PSA levels < 0.2 ng/mL at 6 wk and 6 mo postoperatively, PSA level ≥ 0.2 ng/mL was biochemical failure. Results: Eighty-one patients were included in the study; 75 patients (93%) achieved biochemical responses, 6 patients had biochemical failure. NaF PET/CT indicated bone metastasis in 1 patient (1.2%), was equivocal in 7 patients (8.6%), without bone metastases in 73 patients (90.1%). Eight patients with bone metastases or equivocal results on NaF PET/CT exhibited biochemical responses. All patients with biochemical failure had negative NaF PET/CT and bone scintigraphy for bone metastases. Conclusion: NaF PET/CT has no added value for bone staging in intermediate- and high-risk prostate cancer patients with normal bone scintigraphy results undergoing prostatectomy.

Diagnostic test accuracy study of 18F-sodium fluoride PET/CT, 99mTc-labelled diphosphonate SPECT/CT, and planar bone scintigraphy for diagnosis of bone metastases in newly diagnosed, high-risk prostate cancer.

The aim of this study was to prospectively compare planar, bone scan (BS) versus SPECT/CT and NaF PET/CT in detecting bone metastases in prostate cancer. Thirty-seven consecutive, newly diagnosed, prostate cancer patients with prostate specific antigen (PSA) levels ≥ 50 ng/mL and who were considered eligible for androgen-deprivation therapy (ADT) were included in this study. BS, SPECT/CT, and NaF PET/CT, were performed prior to treatment and were repeated after six months of ADT. Baseline images from each index test were independently read by two experienced readers. The reference standard was based on a consensus decision made by a multidisciplinary team on the basis of baseline and follow-up images of the index tests, the findings of the baseline index tests by the experienced readers, and any available imaging, biochemical, and clinical data, including the response to ADT. Twenty-seven (73%) of the 37 patients had bone metastases according to the reference standard. The sensitivities for BS, SPECT/CT and NaF PET/CT were 78%, 89%, and 89%, respectively, and the specificities were 90%, 100%, and 90%, respectively. The positive predictive values of BS, SPECT/CT and NaF PET/CT were 96%, 100%, and 96%, respectively, and the negative predictive values were 60%, 77% and 75%, respectively. No statistically significant difference among the three imaging modalities was observed. All three imaging modalities showed high sensitivity and specificity. NaF PET/CT and SPECT/CT showed numerically improved, but not statistically superior, sensitivity compared with BS in this limited and selected patient cohort.

Bone Scan Index Is an Independent Predictor of Time to Castration-resistant Prostate Cancer in Newly Diagnosed Prostate Cancer: A Prospective Study.

OBJECTIVE: To prospectively determine the prognostic value of the bone scan index (BSI) for time to development of castration-resistant prostate cancer (CRPC) in consecutive, hormone-naïve patients with newly diagnosed prostate cancer. PATIENTS AND METHODS: Eligible patients participated in a prospective, observational, multicenter study of the value of bone scintigraphy (BS) at staging. BSI was determined using the EXINI BoneBSI software in 208 consecutive patients undergoing androgen deprivation therapy. The presence or absence of bone metastases at staging was classified by BS with or without supplementary imaging. Follow-up was performed >5 years after including the last patient. RESULTS: During follow-up, 149 of the 208 patients (72%) were diagnosed with CRPC. Median time to CRPC was 20 months. Median follow-up time was 4.4 years in patients without CRPC. In univariate analyses, presence of bone metastases (M1) (hazard ratio [HR] 3.00, 95% confidence interval [CI] 2.10-4.30), Gleason grade (HR 1.53, 95% CI 1.31-1.79), and BSI (HR 1.17, 95% CI 1.12-1.23) but not PSA significantly predicted time to CRPC (all, P < .001). The predictive values of M1 (HR 2.06), Gleason grade (HR 1.47), and BSI (HR 1.10) were confirmed in multivariate analyses. Log-rank test for equality of time to CRPC showed the significant predictive value of BSI (BSI = 0 vs 0 < BSI ≤ 1 vs BSI > 1, P < .001). In addition to routine assessment of M1 vs M0 status, BSI contributed to the predictive power. CONCLUSIONS: BSI is an independent risk factor for the time from initiation of androgen deprivation therapy to CRPC in hormone-naïve patients. The significant prognostic factors, in rank order, were M1 status, Gleason grade, and BSI.

Prospective evaluation of computer-assisted analysis of skeletal lesions for the staging of prostate cancer.

BACKGROUND: The purpose of this study was to compare the agreement of the bone scan index (BSI) using EXINI BoneBSI versus experts' readings in the initial staging for bone metastasis in prostate cancer. In addition, the diagnostic outcome was assessed in a large subset of patients where a true reference for metastases could be determined based on clinical and biochemical follow-up and/or supplementary imaging. METHODS: A total of 342 patients had a bone scintigraphy as part of routine staging for prostate cancer. Supplementary imaging was obtained at the discretion of the referring urologist. After full recruitment, the BSI and the number of malignant lesions were calculated using EXINI BoneBSI, and three imaging experts independently classified bone status by a dichotomous outcome (M1 for bone metastasis, M0 for no bone metastasis). A true reference was available in a subset of the patients based on post-operative prostate-specific antigen responses after radical prostatectomy and/or supplementary imaging. RESULTS: Software analysis with a BSI > 0 as the cut-off for metastasis showed excellent agreement with expert classification for M1 disease (96% of the patients) but modest agreement for M0 disease (38%). With a BSI > 1, the agreement was 58% for M1 and 98% for M0. Software analyses based on individual European Association of Urology risk classification did not improve the diagnostic performance. Among patients with a true reference, the software showed metastasis in 64% of the M0 patients but correctly classified metastases in all M1 patients. The sensitivity was 100%, the specificity was 36%, the positive predictive value was 12.6% and the negative predictive value was 100% with a BSI >0 compared with 66.7%, 97.8%, 72.7%, and 97.0% with a BSI > 1. CONCLUSION: The diagnostic value of using EXINI Bone for the BSI in the staging of newly diagnosed prostate cancer is limited.

Unexplained Bone Pain Is an Independent Risk Factor for Bone Metastases in Newly Diagnosed Prostate Cancer: A Prospective Study.

OBJECTIVE: To determine the relationship between bone pain and bone metastases in newly diagnosed prostate cancer. PATIENTS AND METHODS: This prospective study of bone scintigraphy enrolled 567 consecutive patients with newly diagnosed prostate cancer. The presence of all-cause bone pain, known benign bone disease, and unexplained bone pain (ie, not related to known benign bone disease) was derived from a patient questionnaire. Univariate logistic regression models (LRMs) were used to assess the relationship between individual clinical variables (all-cause bone pain, unexplained bone pain, prostate-specific antigen, Gleason grade, T stage, and age) and bone metastases. A multivariate LRM was used to assess the relationship between bone metastases and all factors in combination. Agreement between the LRMs and bone metastases was estimated by accuracy and by Cohen's κ. RESULTS: All-cause bone pain predicted bone metastasis in univariate but not multivariate analysis. Unexplained bone pain remained an independent predictor of bone metastases in multivariate analysis (odds ratio: 4.5; P < .001). Prostate-specific antigen was the single most important predictor of bone metastases (P < .001). CONCLUSION: Unexplained bone pain was a strong independent risk factor for bone metastasis. Guidelines should recommend staging bone scintigraphy in patients with unexplained bone pain, regardless of other risk factors.

Validation of contemporary guidelines for bone scintigraphy in prostate cancer staging: A prospective study in patients undergoing radical prostatectomy.

OBJECTIVE: The aim of this study was to evaluate, using international urology and oncology guidelines, the criteria for performing bone scintigraphy (BS) in patients with newly diagnosed prostate cancer in a prospective setting with 2 years of follow-up after prostatectomy. MATERIALS AND METHODS: In a prospective setting, criteria from European and US urology and oncology guidelines were evaluated in 220 unselected patients with BS performed as a routine investigation before radical prostatectomy. A prostate-specific antigen level of 0.1 ng/ml or lower after surgery was considered successful and was used as a measure of true-negative BS. RESULTS: Overall, 200 out of 220 patients (91%) experienced successful radical prostatectomy at 6 months, with a 2 year success rate of 83%. The proportion of redundant BS ranged from 56% to 89% among the guidelines, whereas the outcome after radical prostatectomy was 93% within 6 months after surgery and 86-89% after 2 years of follow-up, without significant differences among guideline recommendations. CONCLUSION: The guidelines from the American Urological Association and the criteria recently published by the present group proposed the largest proportion of redundant BS without compromising patient-related outcome.

Computer-assisted interpretation of planar whole-body bone scintigraphy in patients with newly diagnosed prostate cancer.

PURPOSE: The aim of this study was to compare the diagnostic properties of EXINI Bone(BSI) in newly diagnosed prostate cancer in comparison with expert reading. MATERIALS AND METHODS: Bone scintigraphy was performed in consecutive patients referred for staging at three clinics (342 patients with DICOM file format, 272 with Interfile format). Images were reported by three independent readers on a four-point scale (class 1-4) and by using a dichotomous outcome (M1 or M0). The software analyzed data in balanced mode, as well as using 'patient-specific' settings (based on tumor characteristics), and classified outcome as normal (N), probably normal (pN), probably abnormal (pA), and abnormal (A). RESULTS: Classification of bone metastasis using the software (pA+A) versus experts (class 3+4) showed a sensitivity of 93.3%, specificity of 89.3%, positive predictive value of 57.5%, and negative predictive value of 98.9% with DICOM files. The diagnostic properties of the software were notably different with Interfile format. For example, expert M1 versus software A showed a sensitivity of 90.0%, specificity of 98.9%, positive predictive value of 88.2%, and negative predictive value of 98.3% with DICOM files, versus 69.2, 88.2, 38.3, and 96.4% with Interfile format, respectively. Generally, patient-specific settings did not influence the diagnostic characteristics of the software versus balanced setting with expert reading as reference. CONCLUSION: EXINI Bone(BSI) showed high sensitivity and specificity for bone metastasis in patients with newly diagnosed prostate cancer. The software ruled out metastasis with confidence, whereas the positive predictive value was modest. The diagnostic properties were different for DICOM and Interfile file formats.

Observer agreement and accuracy in the evaluation of bone scans in newly diagnosed prostate cancer.

OBJECTIVE: The aim of the study was to assess the agreement in the interpretation of bone scintigraphy (BS) in a newly diagnosed prostate cancer. MATERIALS AND METHODS: A total of 635 consecutive patients had their planar whole-body BS independently reviewed by three nuclear medicine physicians and classified by two grading systems: (a) a four-category scale (1: benign; 2: equivocal; 3: most likely malignant; and 4: multiple metastases) and (b) a dichotomous scale (bone metastasis present or absent). RESULTS: Agreement in the same category, or with one or two categories of differences, was found in 66, 34, and 1.3% of the readings, respectively. Average κ-values were 0.59, 0.72, and 0.83 for unweighted, linear, and quadratic weighted variants, respectively. Very high agreement was observed (96% of the readings) with the dichotomous scale (average κ=0.87); a comparison with a final imaging diagnosis with additional CT or MRI showed a sensitivity of 83% and a specificity of 98%. BS categories 1, 3, and 4 were consistent with the final imaging diagnosis in 96-99% of cases. The prevalence of metastasis was 10% in category 2. To optimize the diagnostic characteristics, category 2 should be regarded as a separate option. CONCLUSION: Close agreement was found among trained observers for the evaluation of BS in prostate cancer. The high level of agreement with a dichotomous scale was hampered by diagnostic misclassification. A scale with equivocal findings on planar BS is considered important to allow for additional imaging and correct staging at the bone level of BS in a population with newly diagnosed prostate cancer.

Enhanced external counterpulsation - effect on angina pectoris, QoL and exercise capacity after 1 year.

UNLABELLED: Enhanced external counterpulsation (EECP) is a new therapy offered to patients with refractory angina pectoris (AP). PURPOSE: To assess the effect of EECP on AP, quality of life (QoL) and exercise capacity in a design starting with a control period to avoid the influence of regression-towards-the-mean. METHODS: Patients were examined two months before EECP, just before, just after, and three and 12 months after EECP. EECP was given for 1 h 5 days a week in 7 weeks. Three sets of pneumatic cuffs were mounted on the lower extremities and inflated sequentially in diastole to 260 mm Hg. RESULTS: 50 patients were included (male 72%, mean age: 62.5 years). Mean daily AP attacks were reduced during EECP from 2.7 to 0.9 (p < 0.005) and the Canadian Cardiovascular Society classification was reduced by at least 1 class in 82% just after EECP, 79% 3 months and 76% 12 months after EECP (p < 0.0002). Generic (SF36) and disease-specific QoL (Seattle AP questionnaire) improved just after, 3 and 12 months after compared with that before EECP. There was a significant improvement in exercise capacity and exercise-induced chest pain just after, three and 12 months after EECP (p < 0.02). No change was detected during the control period. CONCLUSIONS: EECP improves generic and disease-specific QoL, angina intensity and exercise capacity in at least 12 months.

Prospective multicenter study of bone scintigraphy in consecutive patients with newly diagnosed prostate cancer.

BACKGROUND: International guidelines uniformly suggest no routine staging of bone metastasis in patients with bone scintigraphy (BS) in low-risk prostate cancer (PCa). These recommendations are based on retrospective investigations only. In addition, BS has most often been reported as a definitive investigation with no room for equivocal cases. OBJECTIVE: The objective of this study was to determine the diagnostic value of BS in a large cohort of consecutive patients with newly diagnosed PCa. DESIGN, SETTING, AND PARTICIPANTS: Over a period of 1.5 years in 2008 to 2009, consecutive patients with newly diagnosed PCa were enrolled in a noninterventional, multicenter, observational study. All patients had a whole-body, planar BS. Clinical history and clinical, pathological, and biochemical data were obtained from electronic patient files and questionnaires. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Bone scintigraphy was classified into 4 categories as nonmalignant, equivocal, likely malignant, or multiple metastasis. The primary end point was final imaging, which was a composite end point of BS and additional CT and MRI investigations. RESULTS AND LIMITATIONS: A total of 635 eligible patients were recruited. Their median prostate-specific antigen (PSA) was 15 ng/mL, median Gleason was 7, and 80% of patients had local disease (T1 or T2). The proportion of nonmalignant BS was 61%, equivocal scans 26%, and likely or definitive metastasis 13%. A total of 154 patients had additional CT or MRI investigations. The final imaging diagnosis showed a prevalence of bone metastases in 87 (13.7%) of 635 patients. No bone metastases were observed in (1) patients with PSA of less than 10 ng/mL, independently of the clinical Tstage and Gleason score (n = 212) and (2) PSA of less than 20 ng/mL if Tstage is less than T3 and Gleason score is less than 8 (n = 97). Approximately 50% of the patients enrolled in this study met these criteria. CONCLUSION: This is the first prospective trial to demonstrate that BS can be avoided in patients with low-risk PCa.