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Aim: To evaluate the clinical consequences of prostate specific membrane antigen (PSMA) PET/CT for primary staging in patients with ISUP grade 5 (Gleason score ≥9) prostate cancer (PCa), and no definitive distant metastases based on standard imaging., Methods: At our tertial referral center, PSMA PET/CT became standard of care from August 2018 for primary staging of prostate cancer given the following criteria: (1) no prior treatment for prostate cancer, (2) ISUP grade 5, (3) no definitive metastases on standard imaging (contrast enhanced CT and bone scintigraphy), and (4) deemed suitable for treatment with curative intent based on comorbidity and life expectancy. We present the preliminary results of first six months recruitment with 12 months of follow-up., Results: Forty-eight patients (mean age 69 years, median PSA 13.0 ng/mL, 20 patients with locally advanced PCa) were included. CT was positive in pelvic lymph nodes in two patients, bone scintigraphy was equivocal in three patients. PSMA PET/CT showed pathological uptake outside the prostatic bed in 22 patients (46%) of which 13 patients (27%) showed lesions confined to regional lymph nodes, and nine patients (19%) showed nonregional lymph node metastases and/or bone metastases. PSMA PET/CT changed the treatment strategy from curatively intended treatment to palliative treatment in 18 patients (38%)., Conclusion: PMSA PET/CT revealed pathological uptake in a large proportion of high-risk patients at primary staging among patients with no definite metastases on standard imaging leading to change of patient management in 38% of the patients.

Objective: To determine whether preoperative staging of high-risk prostate cancer with 18 F-sodium-fluoride ( 18 F-NaF) positron emission tomography (PET) reduces the risk of skeletal metastases., Design: Nationwide, population-based cohort study using real-world data., Setting: The study used national health registries, including all sites in Denmark from 2011 to 2018., Participants: Newly diagnosed high-risk prostate cancer patients who underwent radical prostatectomy from 2011 to 2018. Patients were stratified into two groups according to the preoperative imaging modality of either 18 F-NaF PET or bone scintigraphy., Main Outcome Measures: The risk of skeletal-related events (SREs) as a proxy for skeletal metastases following radical prostatectomy. The secondary endpoint was overall survival., Results: Between 1 January 2011 and 31 December 2018, 4183 high-risk patients underwent radical prostatectomy. Of these patients, 807 (19.3%) underwent 18 F-NaF PET and 2161 (51.7%) underwent bone scintigraphy. The remaining 30% were examined by a different imaging method or did not undergo imaging. Using the inverse probability of treatment weighting to control potential confounding, the HR of experiencing an SRE for patients in the 18 F-NaF PET group versus the bone scintigraphy group was 1.15 (95% CI 0.86 to 1.54). The 3-year survival rates were 97.4% (95% CI 96.1 to 98.7) and 97.1% (95% CI 96.4 to 97.9) for patients receiving 18 F-NaF PET and bone scintigraphy, respectively., Conclusion: Patients with high-risk prostate cancer undergoing preoperative staging with 18 F-NaF PET did not display a lower risk of developing SREs after prostatectomy compared with patients undergoing bone scintigraphy. The survival rates were similar between the two groups., Competing Interests: Competing interests: One author received grants from Bayer and Novo Nordisk for the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the diagnostic accuracy of observers with different levels of experience in reading 18F-sodium fluoride (NaF) PET/CT images for the diagnosis of bone metastases in prostate cancer (PCa) patients., Methods: Nine observers with varying NaF PET/CT experience, ranging from no experience to 2000+ examinations, evaluated 211 NaF PET/CT scans from PCa patients participating in one of four prospective trials. Each observer evaluated each NaF PET/CT on a patient level using a trichotomous scale: M0 (no bone metastases), Me (equivocal for bone metastases) and M1 (bone metastases). Subsequently, a dichotomous evaluation was conducted (M0/M1). The final diagnosis was retrieved from the original study. For each observer, ROC curves and the diagnostic accuracy were calculated based on dichotomous and trichotomous scales; in the latter case, Me was first regarded as M1 and then M0., Results: Across all experience levels, the sensitivity, specificity and accuracy using the dichotomous scale ranged from 0.81 to 0.89, 0.93 to 1.00 and 0.91 to 0.94, respectively. Employing the trichotomous scale, novice and experienced observers chose Me in up to 20 vs. 10% of cases, respectively. Considering Me as M0, the sensitivity, specificity and accuracy ranged from 0.78 to 0.89, 0.95 to 1.00 and 0.91 to 0.95, respectively. Considering Me as M1, the sensitivity, specificity and accuracy ranged from 0.86 to 0.92, 0.71 to 0.96 and 0.77 to 0.94, respectively., Conclusion: Novice observers used the equivocal option more frequently than observers with NaF PET/CT experience. However, on the dichotomous scale, all observers exhibited high and satisfactory accuracy for the detection of bone metastases, making NaF PET/CT an effective imaging modality even in unexperienced hands., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Gallium-68-prostate-specific membrane antigen positron emission tomography/computed tomography ( 68 Ga-PSMA PET/CT) has become a well-established imaging method for the evaluation of patients with prostate cancer. However, several cases have revealed PSMA uptake in a large variety of conditions other than prostate cancer. Prostate-specific membrane antigen uptake in thyroid cancer has also been reported. The aim of the present study was to systematically investigate the prevalence and clinical significance of thyroid incidental findings in patients undergoing 68 Ga-PSMA PET/CT., Materials and Methods: We retrospectively identified all patients referred for 68 Ga-PSMA PET/CT at the Department of Nuclear Medicine, Aalborg University Hospital, Denmark between May 2015 and May 2019. Patients with increased PSMA uptake in the thyroid gland were included in the analysis. Follow-up included imaging, biochemical, and/or histopathological collected over six months., Results: A total of 341 patients were included. Increased 68 Ga-PSMA uptake in the thyroid gland was observed in 13 patients (4%). Focal uptake was observed in seven patients, diffuse uptake in five patients and mixed focal and diffuse uptake in one patient. Malignancy was verified in two patients (2/13 patients, 15%), both patients with focal PSMA uptake., Conclusion: Gallium-68-PSMA thyroid incidental findings are rare in prostate cancer patients. However, cases of focal PSMA uptake in the thyroid gland should be further investigated, as these findings may represent metastatic or primary malignancy of the thyroid gland.

Background: Equivocal scanning results occur. It remains unclear how these results are presented and their management influence diagnostic characteristics., Purpose: To investigate the reporting and handling of equivocal imaging findings in diagnostic studies of bone metastases, and to assess the impact on diagnostic performance of the methods used to analyze equivocal findings. The conceptual issue was reified based on two actual observations., Material and Methods: A recent meta-analysis of bone metastases in prostate cancer was conducted and data were obtained from a large clinical trial with a true reference of bone metastasis, where diagnostic characteristics were calculated with equivocal scans handled by: removal; considered malignant; considered benign; and intention-to-diagnose., Results: The meta-analysis included 18 trials where the median proportion of reported equivocal results was 27%. Eleven (61%) studies reported an equivocal option for the index test, 42% reported equivocal results and described how these were analyzed. The clinical trial included 583 prostate cancer patients with 20% equivocal results. The different methods of managing equivocal findings resulted in highly variable outcomes: sensitivity = 85%-100%; specificity = 78%-99%; and positive and negative predictive values = 44%-94% and 97%-100%, respectively. The diagnostic performances obtained using the four methods were differentially susceptible to the proportion of equivocal imaging findings and the prevalence of bone metastases., Conclusion: Reporting of equivocal results was inadequate in bone imaging trials. The handling of equivocal findings strongly influenced diagnostic accuracy.

Background: The aim was to compare the diagnostic accuracy of 68 Ga-PSMA PET/CT with conventional cross-sectional imaging and diffusion-weighted MRI (DW-MRI) for detecting lymph node metastasis (LNM) to stage prostate cancer patients. Twenty consecutive, newly- diagnosed prostate cancer patients were prospectively enrolled and underwent 68 Ga-PSMA-11 PET/CT, anatomical MRI or contrast-enhanced CT, and DW-MRI prior to laparoscopic, template-based, extended lymph node dissection. Histopathological findings served as the reference test., Results: Histopathology showed LNM in 13 of 20 patients (19 high-risk, 1 intermediate risk). Five patients had metastasis-suspected lymph nodes on 68 Ga-PSMA PET/CT. Patient-based analysis showed that the sensitivity and specificity for detecting LNM were 39% and 100% with 68 Ga-PSMA PET/CT, 8% and 100% with MRI/CT, and 36% and 83% with DW-MRI, respectively. The positive and negative predictive values were 100% and 49% with 68 Ga-PSMA PET/C, 100% and 37% with MRI/CT, and 80% and 42% with DW-MRI. Of 573 dissected lymph nodes, 33 were LNM from 26 regions. True-positive LNM on 68 Ga-PSMA PET/CT was 9-11 mm in diameter, whereas false-negative LNM had a median diameter of 4 mm, with only 3 of 30 lymph nodes being larger than 10 mm. LNM were positive for PSMA by immunostaining., Conclusions: The sensitivity of 68 Ga-PSMA PET/CT was notably better than that of MRI/CT and comparable to that of DW-MRI. Some false positive findings with DW-MRI reduced its specificity and positive predictive value compared with those of 68 Ga-PSMA PET/CT and MRI/CT.

Our aim was to evaluate the interobserver agreement in 18 F-sodium fluoride (NaF) PET/CT for the detection of bone metastases in patients with prostate cancer (PCa). Methods: 18 F-NaF PET/CT scans were retrieved from all patients who participated in 4 recent prospective trials. Two experienced observers independently evaluated the 18 F-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: 18 F-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 18 F-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 18 F-NaF PET/CT was satisfactory, rendering 18 F-NaF PET/CT a robust tool in the diagnostic armamentarium., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: PSMA PET is a promising method for primary lymph node staging in prostate cancer. However, recent systematic reviews have identified only a limited number of studies with histopathology as a reference test., Methods: A systematic search was performed in PubMed and the Cochrane Library. An expedited systematic review was performed where we identified diagnostic studies in prostate cancer where a preoperative PSMA PET for primary lymph node staging was compared to histopathology. The trials must have diagnostic data on a patient level., Results: Eighteen eligible clinical trials included 969 patients. The median patient number per study was 32 (range 10 to 208). Five trials were prospective, and nine trials had a consecutive enrolment of patients. Sixteen studies used Ga-68-PSMA-11; there was one study with Cu-64-PSMA and one study with F-18-DCDFPyL. Twelve studies used PET/CT, four trials used PET/MR. Most trials included patients with intermediate and high-risk. Diagnostic accuracy varied notably among the studies; sensitivity ranged from 23 to 100%, specificity 67-100%, positive predictive value 20-100%, and negative predictive value 41-100%. Weighted sensitivity was 59%, weighted specificity was 93%. Four studies compared PSMA PET with anatomical imaging (CT or MRI); in all cases, sensitivity and specificity were superior with PSMA PET. Three studies compared PSMA PET with multi-parametric or diffusion-weighted MRI with mixed results., Conclusions: PSMA PET showed promising diagnostic accuracy for primary lymph node staging with pathology as reference. Recommendation for PSMA PET for high-risk patients in clinical guidelines should be supported by confirmatory, prospective trials with patient-relevant outcomes.

The aim of this study was to determine if additional 18 F-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., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

A 69-year-old man with newly diagnosed prostate cancer PSA 274 ng/mL, Gleason 4+3, T-stage 3b) underwent Ga-PSMA PET/CT for staging with follow-up scans 6 and 13 weeks after androgen deprivation therapy (ADT) initiation. Six weeks after ADT initiation, lymph node metastases observed at staging showed metabolic and radiological regression, whereas the skeleton showed increased PSMA uptake in existing bone metastases and several new PSMA-avid lesions. Skeletal PSMA uptake decreased after 13 weeks of ADT, and prostate-specific antigen decreased to 16 ng/mL. These findings suggest the presence of the flare phenomenon to ADT in bone metastases seen on PSMA PET/CT.

Oligometastatic disease represents a clinical and anatomical manifestation between localised and polymetastatic disease. In prostate cancer, as with other cancers, recognition of oligometastatic disease enables focal, metastasis-directed therapies. These therapies potentially shorten or postpone the use of systemic treatment and can delay further metastatic progression, thus increasing overall survival. Metastasis-directed therapies require imaging methods that definitively recognise oligometastatic disease to validate their efficacy and reliably monitor response, particularly so that morbidity associated with inappropriately treating disease subsequently recognised as polymetastatic can be avoided. In this Review, we assess imaging methods used to identify metastatic prostate cancer at first diagnosis, at biochemical recurrence, or at the castration-resistant stage. Standard imaging methods recommended by guidelines have insufficient diagnostic accuracy for reliably diagnosing oligometastatic disease. Modern imaging methods that use PET-CT with tumour-specific radiotracers (choline or prostate-specific membrane antigen ligand), and increasingly whole-body MRI with diffusion-weighted imaging, allow earlier and more precise identification of metastases. The European Organisation for Research and Treatment of Cancer (EORTC) Imaging Group suggests clinical algorithms to integrate modern imaging methods into the care pathway at the various stages of prostate cancer to identify oligometastatic disease. The EORTC proposes clinical trials that use modern imaging methods to evaluate the benefits of metastasis-directed therapies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To prospectively compare diagnostic accuracies for detection of bone metastases by 68 Ga-PSMA PET/CT, 18 F-NaF PET/CT and diffusion-weighted MRI (DW 600 -MRI) in prostate cancer (PCa) patients with biochemical recurrence (BCR)., Methods: Sixty-eight PCa patients with BCR participated in this prospective study. The patients underwent 68 Ga-PSMA PET/CT, a 18 F-NaF PET/CT and a DW 600 -MRI (performed in accordance with European Society of Urogenital Radiology guidelines, with b values of 0 and 600 s/mm 2 ). Bone lesions were categorized using a three-point scale (benign, malignant or equivocal for metastases) and a dichotomous scale (benign or metastatic) for each imaging modality by at least two experienced observers. A best valuable comparator was defined for each patient based on study-specific imaging, at least 12 months of clinical follow-up and any imaging prior to the study and during follow-up. Diagnostic performance was assessed using a sensitivity analysis where equivocal lesions were handled as non-metastatic and then as metastatic., Results: Ten of the 68 patients were diagnosed with bone metastases. On a patient level, sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic analysis were, respectively, 0.80, 0.98-1.00 and 0.89-0.90 for 68 Ga-PSMA PET/CT (n = 68 patients); 0.90, 0.90-0.98 and 0.90-0.94 for 18 NaF PET/CT (n = 67 patients); and 0.25-0.38, 0.87-0.92 and 0.59-0.62 for DW 600 -MRI (n = 60 patients). The diagnostic performance of DW 600 -MRI was significantly lower than that of 68 Ga-PSMA PET/CT and 18 NaF PET/CT for diagnosing bone metastases (p < 0.01), and no significant difference in the AUC was seen between 68 Ga-PSMA PET/CT and 18 NaF PET/CT (p = 0.65)., Conclusion: 68 Ga-PSMA PET/CT and 18 F-NaF PET/CT showed comparable and high diagnostic accuracies for detecting bone metastases in PCa patients with BCR. Both methods performed significantly better than DW 600 -MRI, which was inadequate for diagnosing bone metastases when conducted in accordance with European Society of Urogenital Radiology guidelines.

Purpose of the Report: The aim of this study was to prospectively investigate the detection rate of Ga-PSMA PET/CT in biochemical recurrence (BCR) of prostate cancer and its impact on patient management., Materials and Methods: Patients with BCR after curatively intended treatment of prostate cancer were included. Each patient underwent a Ga-PSMA PET/CT. Changes in patient management based on the results of Ga-PSMA PET/CT were assessed., Results: Seventy patients were included. Sixty-four patients (91%) had radical prostatectomy, of whom 17 patients (24%) received salvage radiation therapy due to first biochemical relapse. Six patients (9%) underwent radiation therapy as the primary treatment. Ga-PSMA PET/CT detected recurrent disease in 37 patients (53%). The detection rate was 22% for prostate-specific antigen (PSA) levels up to 0.5 ng/mL compared with 83% for PSA levels greater than 0.5 ng/mL. Pathological uptake of Ga-PSMA was observed in 4 (16%) of 21, 4 (44%) of 9, 0 of 1, 7 (70%) of 10, and 22 (88%) of 25 patients with PSA levels from 0.2 to 0.3 ng/mL, 0.31 to 0.4 ng/mL, 0.41 to 0.5 ng/mL, 0.51 to 1 ng/mL, and greater than 1 ng/mL, respectively. Prostate-specific antigen was significantly higher in PSMA-positive patients than in PSMA-negative patients. In 15 (22%) of 69 patients, the results caused a definite change in patient management, and in another 15 (22%) of 69 patients, Ga-PSMA PET/CT guided the choice of treatment., Conclusions: Ga-PSMA PET/CT detects lesions in a large proportion of patients with BCR. Detection rates at low PSA levels (<0.5 ng/mL) were notably below the values reported in previous retrospective studies; however, detection rates improved with increasing PSA levels.

Background: The purpose of this study was to compare the agreement of the bone scan index (BSI) using EXINI Bone BSI 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 Bone BSI , 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.

Purpose: The aim of this study was to evaluate the clinical safety profile of the Ga-PSMA-11 ligand for PET/CT imaging in prospective clinical trials., Methods: Eighty-eight patients with newly diagnosed or recurrent prostate cancer participated in 2 prospective trials. Safety reporting was identical in the 2 trials. The Ga-PSMA-11 ligand was administered as 2 MBq/kg body weight (mean, 9.2 μg, 9.7 nmol). The reporting of clinical adverse events (AEs) and the measurement of blood pressure (BP) and heart rate (HR) were performed prior to injection (baseline); immediately after injection of Ga-PSMA-11 (postinjection); at 1, 10, and 60 minutes after injection; and after acquisition of the PET/CT scan (postscan). All hemodynamic assessments were performed in the supine position, except for the postscan measurement (sitting). The patients were interviewed regarding any AEs at baseline, postinjection, or postscan. In addition, the patients were instructed to report any AEs during the investigation and to contact the investigator if AEs occurred during the rest of the day. Adverse events were classified as mild, moderate, or severe by the patients and categorized by the investigator using the CTCAE (Common Terminology Criteria for Adverse Events) version 4.0., Results: There were no reported clinical AEs. There were significant decreases in systolic BP (P < 0.001) and HR (P < 0.001) over time. In comparison, the diastolic BP increased significantly (P < 0.001). After removal of the last observation (supine position), there was no time-dependent change in systolic or diastolic BP, but the significant change in HR remained. The mean changes over the entire observation period were minimal (systolic BP, -6 to 5 mm Hg; diastolic BP, -2 to 3 mm Hg; HR, decrease of 5 beats/min). No patients developed hypotension. Fifty-five patients presented with hypertension at baseline, which increased by 1 CTCAE grade in 15 patients and by 2 grades in 2 patients. A large number of cases of asymptomatic (grade 1) bradycardia were observed, primarily in patients with preexisting bradycardia. One patient developed transient grade 1 tachycardia. No patients required medical intervention for cardiovascular perturbations., Conclusions: Ga-PSMA-11 PET/CT was very well tolerated. We consider Ga-PSMA-11 to be safe for human application.

Ga-PSMA PET/CT is becoming the most promising imaging modality for detecting recurrent prostate cancer. The modality has the advantage of being able to detect recurrent disease, even at very low prostate-specific antigen levels. However, several studies report Ga-PSMA uptake in tissue unrelated to prostate cancer. We present a 74-year-old man who underwent Ga-PSMA PET/CT for recurrent prostate cancer 5 years after radical prostatectomy. The Ga-PSMA PET/CT showed an intramuscular lesion with increased PSMA uptake in the left vastus medialis muscle. The lesion was surgically removed, and histopathology found it to be an intramuscular myxoma that showed immunohistochemical PSMA expression.

Ga-PSMA PET/CT is increasingly used to assess prostate cancer. Avid Ga-PSMA uptake by thyroid cancer and renal cell carcinoma (RCC) has been reported in few cases. A 75-year-old man who received a diagnosis of RCC in 2006 and prostate cancer in 2009 presented with elevated prostate-specific antigen levels (0.7 ng/mL) following prostatectomy. Ga-PSMA PET/CT showed avid Ga-PSMA uptake in 1 pelvic and 1 retroperitoneal lymph node and focal Ga-PSMA accumulation in the thyroid. Excised retroperitoneal lymph node and thyroid tissues showed metastases from RCC, whereas the pelvic lymph node exhibited metastasis from prostate cancer.

Purpose: The aim of this study was to assess observer agreement on the evaluation of treatment responses of bone metastases by bone scintigraphy (BS) using different scoring methods in prostate cancer patients., Patients and Methods: Sixty-three paired BS from 55 patients were included. BS was performed before and after more than 12 weeks of anticancer treatment. A panel of experienced nuclear medicine physicians from several institutions evaluated treatment response using three different methods: (a) standard clinical assessment, (b) MD Anderson criteria, and (c) Prostate Cancer Working Group 2 (PCWG-2) criteria. All methods were based on the evaluation of paired before-after bone scans., Results: Readers were able to classify the presence of bone metastases at baseline with a high level of agreement [Cohen's κ=0.94, 95% confidence interval (CI) 0.82-1.00]. Observer agreement on bone response by PCWG-2 criteria showed considerable agreement (Cohen's κ=0.84, 95% CI: 0.69-0.99). Evaluation using standard clinical assessment and MD Anderson criteria showed moderate agreement (0.52, 95% CI: 0.36-0.69 and 0.64, 95% CI: 0.48-0.79, respectively). There was considerable variation among readers for regional lesion count on individual scans, with limits of agreement of -10 to 10 lesions or more for the majority of anatomical regions, including the thorax, spine, and pelvis., Conclusion: Observer agreement on treatment response by BS varied notably across methods. Optimal agreement was achieved by the PCWG-2 criteria. Variation in the classification of treatment response of bone metastases may have a significant impact on clinical decision-making, emphasizing the need for a uniform approach, including during clinical practice. Response assessment by lesion counting on repeated BS without access to previous scans cannot be recommended.

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: The objective was to describe regional variations in M-staging in patients with newly diagnosed prostate cancer within a Danish county and to compare clinical practice with guideline recommendations., Methods: Data were as captured from 1) a prospective, non-interventional study counting 635 consecutive patients referred for M-staging in the 2008-2009 period at three regional hospitals within one county, and 2) a questionnaire on M-staging practice completed by the five sites performing M-staging in the same county in 2015., Results: All three sites referred patients for M-staging in 2008, irrespective of their risk factors. Two of the three sites maintained this practice in 2015. Furthermore, in 2015, three of five sites performed M-staging in intermediate and high-risk patients only. Planar whole-body bone scans were standard in all sites in 2008 with single photon emission computed tomography/computed tomography (SPECT/CT) being performed if required and if available. In 2015, two sites used choline positron emission tomography/CT for primary staging of high-risk patients against guideline recommendations. The use of SPECT/CT showed wide variations from "if required" to "mandatory" head-to-thigh imaging. There were notable variations between clinical practice and guidelines in 2008, and this was even more evident in 2015., Conclusion: Considerable variations existed with respect to the M-staging imaging practices in prostate cancer within a single Danish county. The variation was more pronounced in 2015 than in 2008. Clinical practice conflicted in part with European and national Danish guidelines., Funding: none., Trial Registration: not relevant.

Background: 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., Methods/design: 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., Discussion: 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.

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.

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.

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.

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.

Introduction: Painful bone metastases are common in advanced prostate cancer. We report the clinical outcome after administration of Samarium-153 ((153)Sm), an emitter of beta-particles that concentrates in the areas of enhanced osteoblastic activity., Methods: Twenty-two patients (median age 73 years) with metastatic, hormone-refractory prostate cancer received a single bolus infusion of (153)Sm (37 MBq/kg). All patients had painful bone metastases to more than one anatomical region, and most had inadequate pain relief to narcotic analgesics. Bone specific pain, analgesic score according to WHO, ECOG performance status, and blood count were evaluated before and up to 28 weeks after treatment., Results: Median follow-up was six weeks (mean 14 weeks). Eleven patients died within the 28 week observation period (ten from terminal disease), and four patients had their observation period truncated. Median pain score was 56.3%, 50.0%, and 50.0% of baseline values at week 4 (n = 20), 16 (n = 10), and 28 (n = 7), respectively. A reduction of baseline pain score by 50% or more was observed in 50%, 70% and 71% of patients at week 4, 16, and 28, respectively. Hematological toxicity was mild and reversible in most cases., Conclusion: Administration of (153)Sm to prostate cancer patients with painful bone metastases offered clinical relevant pain relief with tolerable hematological toxicity.

Bone scintigraphy is key in imaging skeletal metastases in newly diagnosed prostate cancer. Unfortunately, a notable proportion of scans are not readily classified as positive or negative but deemed indeterminate. The extent of reporting of indeterminate bone scans and how such scans are handled in clinical trials are not known. A systematic review was conducted using electronic databases up to October 2016. The main outcome of interest was the reporting of indeterminate bone scans, analyses of how such scans were managed, and exploratory analyses of the association of study characteristics and the reporting of indeterminate bone scan results. Seventy-four eligible clinical trials were identified. The trials were mostly retrospective (85%), observational (95%), large trials (median 195 patients) from five continents published over four decades. The majority of studies had university affiliation (72%), and an author with imaging background (685). Forty-five studies (61%) reported an indeterminate option for the bone scan and 23 studies reported the proportion of indeterminate scans (median 11.4%). Most trials (44/45, 98%) reported how to handle indeterminate scans. Most trials (n = 39) used add-on supplementary imaging, follow-up bone scans, or both. Exploratory analyses showed a significant association of reporting of indeterminate results and number of patients in the study (p = 0.024) but failed to reach statistical significance with other variables tested. Indeterminate bone scan for staging of prostate cancer was insufficiently reported in clinical trials. In the case of indeterminate scans, most studies provided adequate measures to obtain the final status of the patients. [ABSTRACT FROM AUTHOR]