Response evaluation of bone metastasis in prostate cancer: Preliminary comparison of computerized bone scan index versus standardized clinical criteria.

OBJECTIVE: The correlation between the computer-assisted bone scan index (BSI) responses versus clinical response classification if bone metastases in prostate cancer patients are not clear. We compared changes in BSI with Prostate Cancer Working Group-3 (PCWG3) and MD Anderson (MDA) criteria. MATERIALS AND METHODS: Fifty-six consecutive patients with at least two bone scans (BS) within 12 months were included, who had BS before and after treatment with the same anticancer agent. RESULTS: Progressive disease (PD) by PCWG3 criteria was seen in 28% of the cases (median BSI increased by 1.69 units) versus non-PD in 72% (BSI change -0.13). MDAnderson showed PD in 34% (BSI increase 0.49), 45% stable disease (BSI change 0.00), and 20% partial responses (BSI decrease 1.44). Absolute BSI changes differed significantly among response categories by PCWG3 and MDA criteria (both P<0.0001). Response classification using dichotomized BSI data (>0/≤0 and >0.3/≤0.3 BSI units) showed a significant correlation with PCWG3 and MDA criteria (all P<0.001). Absolute BSI changes and dichotomized BSI correlated to prostate-specific antigen responses (both P<0.001) but not to clinical responses. CONCLUSION: Absolute changes in BSI and BSI response classification correlated significantly with standardized clinical response criteria for the assessment of treatment responses of skeletal metastases in prostate cancer.

(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.

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.

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.

Treatment with bone-seeking radionuclides for painful bone metastases in patients with lung cancer: a systematic review.

Treatment with bone-seeking radionuclides may provide palliation from pain originating from bone metastases. However, most studies have been conducted in patients with prostate cancer and patients with breast cancer. We aimed to perform a systematic review of the use of radionuclide treatment in lung cancer in accordance with the PRISMA guidelines. In the eligible trials, pain relief was reported in 75% of the patients included in the studies. The onset of pain relief was seen within 1-5 weeks after treatment, lasting up to 6 months. However, the methodology in the included trials was poor-only two randomised trials were eligible, and none of them compared radionuclide treatments with placebo or best standard of care. The remaining trials were case series with inherent problems of methodology reporting. Particularly challenging was the lack of reporting of baseline disease status and use of prior/concomitant analgaesics. Large randomised controlled trials are needed to clarify the efficacy of radionuclide treatment in lung cancer.

Observer agreement of treatment responses on planar bone scintigraphy in prostate cancer patients: importance of the lesion assessment method.

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.

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.