The Impact of Baseline PSMA PET/CT Versus CT on Outcomes of 223Ra Therapy in Metastatic Castration-Resistant Prostate Cancer Patients.

Imaging before 223Ra-dichloride (223Ra) therapy is crucial for selecting metastatic castration-resistant prostate cancer (mCRPC) patients with bone-only disease. The purpose of this study was to evaluate if baseline prostate-specific membrane antigen (PSMA) PET/CT (bPSMA) versus CT is associated with outcomes of 223Ra therapy. Methods: A secondary analysis of the data of a prospective observational study (NCT04995614) was performed. Patients received a maximum of 6 223Ra cycles and were retrospectively divided into the bPSMA or baseline CT (bCT) groups. All patients received baseline bone scintigraphy. Primary endpoints were alkaline phosphatase and prostate-specific antigen response. Secondary endpoints were overall survival (OS) and radiologic response. Results: Between 2017 and 2020, 122 mCRPC patients were included: 18 (14.8%) in the bPSMA group and 104 (85.2%) in the bCT group. All baseline characteristics were comparable. No significant differences in alkaline phosphatase or prostate-specific antigen response were found. The bCT group showed an OS significantly shorter than that of the bPSMA group (12.4 vs. 19.9 mo, P = 0.038). In 31 of 76 patients (40.1%) in the bCT group who also received posttherapy CT, lymph node or visceral metastases (soft-tissue involvement [STI]) were detected after 223Ra therapy, compared with 0 of 15 patients in the bPSMA group who received posttherapy PSMA PET/CT or CT. No significant difference in OS was found between patients in the bCT or posttherapy CT subgroup without STI (46/76) and the bPSMA group. Conclusion: bPSMA versus CT does not seem to impact biochemical response during 223Ra therapy in mCRPC patients. Nevertheless, patients in the bCT group had a significantly shorter OS, most likely due to underdetection of STI in this group. Therefore, replacing bCT with PSMA PET/CT appears to be a valuable screening method for identifying patients who will benefit most from 223Ra therapy.

Health-related quality of life, psychological distress, and fatigue in metastatic castration-resistant prostate cancer patients treated with radium-223 therapy.

BACKGROUND: Radium-223 is a registered treatment option for symptomatic bone metastatic castration-resistant prostate cancer (mCRPC). Aim of this multicenter, prospective observational cohort study was to evaluate health-related quality of life (HR-QoL), psychological distress and fatigue in mCRPC patients treated with radium-223. METHODS: Primary endpoint was cancer-specific and bone metastases-related HR-QoL, as measured by the EORTC QLQ-C30 and BM-22 questionnaires. Secondary endpoints were psychological distress and fatigue, evaluated by the HADS and CIS-Fatigue questionnaires. Outcomes were analyzed for the total cohort and between subgroups (1-3 versus 4-5 versus 6 radium-223 injections). A trajectory analysis was performed to explore HR-QoL patterns over time. RESULTS: In total, 122 patients were included for analysis. Baseline HR-QoL, pain intensity, psychological distress and fatigue were worse in patients who did not complete radium-223 therapy. In patients who completed therapy, stabilization of HR-QoL was perceived and psychological distress and fatigue remained stable, whereas clinically meaningful and statistically significant deterioration of HR-QoL, psychological distress and fatigue over time was observed in patients who discontinued radium-223 therapy. Trajectory analysis revealed that HR-QoL deterioration over time was more likely in patients with baseline opioid use, low hemoglobin and high alkaline phosphatase levels. CONCLUSIONS: Patients who discontinued radium-223 therapy showed worse HR-QoL, psychological distress and fatigue at baseline and more frequent deterioration of HR-QoL, psychological distress and fatigue over time when compared to patients who completed therapy. Specific attention with regard to HR-QoL during follow-up is indicated in patients with opioid use, low hemoglobin and high alkaline phosphatase levels before radium-223 therapy initiation. CLINICAL TRIAL REGISTRATION NUMBER: NCT04995614.

Evaluation of Quantitative Ga-68 PSMA PET/CT Repeatability of Recurrent Prostate Cancer Lesions Using Both OSEM and Bayesian Penalized Likelihood Reconstruction Algorithms.

RATIONALE: To formally determine the repeatability of Ga-68 PSMA lesion uptake in both relapsing and metastatic tumor. In addition, it was hypothesized that the BPL algorithm Q. Clear has the ability to lower SUV signal variability in the small lesions typically encountered in Ga-68 PSMA PET imaging of prostate cancer. METHODS: Patients with biochemical recurrence of prostate cancer were prospectively enrolled in this single center pilot test-retest study and underwent two Ga-68 PSMA PET/CT scans within 7.9 days on average. Lesions were classified as suspected local recurrence, lymph node metastases or bone metastases. Two datasets were generated: one standard PSF + OSEM and one with PSF + BPL reconstruction algorithm. For tumor lesions, SUVmax was determined. Repeatability was formally assessed using Bland-Altman analysis for both BPL and standard reconstruction. RESULTS: A total number of 65 PSMA-positive tumor lesions were found in 23 patients (range 1 to 12 lesions a patient). Overall repeatability in the 65 lesions was -1.5% ± 22.7% (SD) on standard reconstructions and -2.1% ± 29.1% (SD) on BPL reconstructions. Ga-68 PSMA SUVmax had upper and lower limits of agreement of +42.9% and -45.9% for standard reconstructions and +55.0% and -59.1% for BPL reconstructions, respectively (NS). Tumor SUVmax repeatability was dependent on lesion area, with smaller lesions exhibiting poorer repeatability on both standard and BPL reconstructions (F-test, p < 0.0001). CONCLUSION: A minimum response of 50% seems appropriate in this clinical situation. This is more than the recommended 30% for other radiotracers and clinical situations (PERCIST response criteria). BPL does not seem to lower signal variability in these cases.

Diagnostic accuracy of 18F-fluciclovine PET/CT in primary lymph node staging of prostate cancer.

INTRODUCTION: To determine preoperative diagnostic accuracy of 18F-fluciclovine PET/CT-scan in detection (or exclusion) of lymph node metastases (LNM) in men with prostate cancer (PCa) in comparison to the histopathological results of the extended pelvic lymph node dissection (e-PLND). METHODS: A retrospective medical records-based cohort study, including 47 men with primary PCa who received 18F-fluciclovine PET/CT and subsequent e-PLND for lymph node staging. Incidence and number of visualized LNM, their locations and diameters on 18F-fluciclovine PET/CT were recorded in comparison to the histopathological results of the e-PLND as reference. Positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity and diagnostic accuracy of 18F-fluciclovine PET/CT were calculated on the basis of histopathology results after e-PLND. RESULTS: Forty-seven men were eligible for analysis. Median lymph node yield was 19 (range 10-70). A total of 996 lymph nodes were removed, and 59 metastases were found in 21 cases (45%). Preoperative PET was issued 'positive' in 11 men and in 9 of them (82%) this was histopathologically confirmed resulting in a PPV of 82% (95% CI, 51-96). On the contrary, PET was issued 'negative' in 36 cases, but in 12 of them (33%) metastases were detected in the e-PLND specimen, resulting in an NPV of 67% (95% CI, 50-80). The patient-based sensitivity was 43% (95% CI, 24-64) and the patient-based specificity rate was 92% (95% CI, 75-99), whereas overall diagnostic accuracy was established to be 70% in the present cohort. CONCLUSION: 18F-Fluciclovine PET/CT has a high specificity and positive predicted value for the presence of LNM in men with prostate cancer. However, the sensitivity and NPV seem to be limited to exclude the absence of LNM at a clinically acceptable level. Prospective evaluation is necessary to define patients who may benefit from 18F-fluciclovine PET/CT as a triage test for the indication for e-PLND.

Screening for distant metastases in patients with ipsilateral breast tumor recurrence: the impact of different imaging modalities on distant recurrence-free interval.

PURPOSE: In patients with ipsilateral breast tumor recurrence (IBTR), the detection of distant disease determines whether the intention of the treatment is curative or palliative. Therefore, adequate preoperative staging is imperative for optimal treatment planning. The aim of this study is to evaluate the impact of conventional imaging techniques, including chest X-ray and/or CT thorax-(abdomen), liver ultrasonography(US), and skeletal scintigraphy, on the distant recurrence-free interval (DRFI) in patients with IBTR, and to compare conventional imaging with 18F-FDG PET-CT or no imaging at all. METHODS: This study was exclusively based on the information available at time of diagnoses of IBTR. To adjust for differences in baseline characteristics between the three imaging groups, a propensity score (PS) weighted method was used. RESULTS: Of the 495 patients included in the study, 229 (46.3%) were staged with conventional imaging, 89 patients (19.8%) were staged with 18F-FDG PET-CT, and in 168 of the patients (33.9%) no imaging was used (N = 168). After a follow-up of approximately 5 years, 14.5% of all patients developed a distant recurrence as first event after IBTR. After adjusting for the PS weights, the Cox regression analyses showed that the different staging methods had no significant impact on the DRFI. CONCLUSIONS: This study showed a wide variation in the use of imaging modalities for staging IBTR patients in the Netherlands. After using PS weighting, no statistically significant impact of the different imaging modalities on DRFI was shown. Based on these results, it is not possible to recommend staging for distant metastases using 18F-FDG PET-CT over conventional imaging techniques.

Correction to: Dutch Economic Value of Radium-223 in Metastatic Castration-Resistant Prostate Cancer.

The article Dutch Economic Value of Radium-223 in Metastatic Castration-Resistant Prostate Cancer, written by Michel L. Peters, Claudine de Meijer, Dirk Wyndaele, Walter Noordzij, Annemarie M. Leliveld-Kors, Joan van den Bosch, Pieter H. van den Berg, Agni Baka, Jennifer G. Gaultney was originally published electronically on the publisher's internet portal (currently SpringerLink) on 2nd September, 2017 without open access.

Dutch Economic Value of Radium-223 in Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: The treatment of metastatic castration-resistant prostate cancer has changed with the introduction of radium-223, cabazitaxel, abiraterone and enzalutamide. To assess value for money, their cost effectiveness in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel from the Dutch societal perspective was investigated. METHODS: A cost-effectiveness analysis was conducted using efficacy, symptomatic skeletal-related event and safety data obtained from indirect treatment comparisons. Missing skeletal-related event data for cabazitaxel were conservatively assumed to be identical to radium-223. A Markov model combined these clinical inputs with Dutch-specific resource use and costs for metastatic castration-resistant prostate cancer treatment from a societal perspective. Total quality-adjusted life-years and costs in 2017 euros were calculated over a 5-year (lifetime) time horizon. RESULTS: Radium-223 resulted in €6092 and €4465 lower costs and 0.02 and 0.01 higher quality-adjusted life-years compared with abiraterone and cabazitaxel, respectively, demonstrating dominance of radium-223. Sensitivity analyses reveal a 64% (54%) chance of radium-223 being cost effective compared with abiraterone (cabazitaxel) at the informal €80,000 willingness-to-pay threshold. Compared with enzalutamide, radium-223 resulted in slightly lower quality-adjusted life-years (-0.06) and €7390 lower costs, revealing a 61% chance of radium-223 being cost effective compared with enzalutamide. The lower costs of radium-223 compared with abiraterone and enzalutamide are driven by lower drug costs and prevention of expensive skeletal-related events. Compared with cabazitaxel, the lower costs of radium-223 are driven by lower costs of the drug, administration and adverse events. CONCLUSION: Radium-223 may be a less costly treatment strategy offering similar gains in health benefits compared with abiraterone, cabazitaxel and enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel from the Dutch societal perspective.

Association between postprandial symptoms and gastric emptying after sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric procedure. However, postprandial symptoms can compromise its beneficial effect. It is not known if a changed gastric emptying and these symptoms are related. This study aimed to assess the association between postprandial symptoms and the gastric emptying pattern after LSG. METHODS: A gastric emptying study with a solid and liquid meal component was performed in the second year after LSG. Before the test, symptoms were assessed using a standardized questionnaire, and during the test, symptoms were scored on a visual analog scale (VAS). Gastric emptying results were expressed as lag phase, half time of gastric emptying (T½), and caloric emptying rate/minute. RESULTS: Twenty patients (14 F/6 M; age 45.6 ± 7.7 years, weight 93.4 ± 28.2 kg, BMI 31.6 ± 8.1 kg/m(2)) participated in this study; 13 had a low symptom score (≤9, group I), 7 a high symptom score (≥18, group II). VAS scores for epigastric pain, nausea, and belching were significantly higher in group II. Lag phase (solid) was 6.4 ± 4.5 min in group I, 7.3 ± 6.3 in group II (p = 0.94); T½ (solid) was 40.6 ± 10.0 min in group I, 34.4 ± 9.3 in group II (p = 0.27); caloric emptying rate was 3.9 ± 0.6 kcal/min in group I, 3.9 ± 1.0 kcal/min in group II (p = 0.32). CONCLUSIONS: Patients with postprandial symptoms after LSG reported more symptoms during the gastric emptying study than patients without symptoms. However, there was no difference between gastric emptying characteristics between both groups, suggesting that abnormal gastric emptying is not a major determinant of postprandial symptoms after LSG.