Interest in, willingness-to-pay for and willingness-to-recommend genetic testing for prostate cancer among affected men after radical prostatectomy.

Knowledge about interest in genetic testing and willingness-to-pay for a genetic test among men affected from prostate cancer (PCa) is limited. This study aimed to gain insight into men's attitudes in genetic testing for PCa. 4699 men with PCa from the German multicenter prospective database "Familial Prostate Cancer" were included. Interest in, Willingness-to-pay for and Willingness-to-recommend a genetic test for PCa were quantified. Associations with several sociodemographic and psychosocial variables were evaluated by logistic regression. 76.8% of the affected men with a median follow-up of 12.9 years were interested in a genetic test for PCa. Newly identified variables significantly associated with interest were having sons (OR 1.66, p < 0.001) and a high perceived severity of the PCa (OR 1.40, p < 0.001). 19% of men were willing to pay more than 500 € for a genetic test. Men with higher education, men with a better self-reported economic situation and men with a lethal PCa in their family were more likely to be willing to pay a larger sum for a test. 84.9% of men were willing to recommend a test to their relatives. Interest in genetic testing for PCa among affected men was generally high with most men willing to recommend a test to their relatives. Various characteristics associated with interest and willingness-to-pay larger sums for genetic testing were uncovered and need to be addressed when designing both future educational material and genetic tests for PCa.

Preliminary results on response assessment using 68Ga-HBED-CC-PSMA PET/CT in patients with metastatic prostate cancer undergoing docetaxel chemotherapy.

PURPOSE: To investigate the value of 68Ga-HBED-CC PSMA (68Ga-PSMA) PET/CT for response assessment in metastatic castration-sensitive and castration-resistant prostate cancer (mCSPC and mCRPC) during docetaxel chemotherapy. METHODS: 68Ga-PSMA PET/CT was performed in seven mCSPC patients before and after six cycles of upfront docetaxel chemotherapy and in 16 mCRPC patients before and after three cycles of palliative docetaxel chemotherapy. Radiographic treatment response was evaluated separately on the 68Ga-PSMA PET and CT datasets. Changes in 68Ga-PSMA uptake (SUVmean) were assessed on a per-patient and a per-lesion basis using the PERCIST scoring system with slight modification. Treatment response was defined as absence of any PSMA uptake in all target lesions on posttreatment PET (complete response, CR) or a decrease in summed SUVmean of ≥30% (partial response, PR). The appearance of a new PET-positive lesion or an increase in summed SUVmean of ≥30% (progressive disease, PD) indicated nonresponse. A moderate change in summed SUVmean (between -30% and +30%) without a change in the number of target lesions was defined as stable disease (SD). For treatment response assessment on CT, RECIST1.1 criteria were used. Radiographic responses on 68Ga-PSMA PET [RR(PET)] and on CT [RR(CT)] were compared and correlated with biochemical response (BR). A decrease in serum PSA level of ≥50% was defined as biochemical PR. RESULTS: Biochemical PR was found in six of seven patients with mCSPC (86%, 95% confidence interval 42% to 99.6%). The concordance rate was higher between BR and RR(PET) than between BR and RR(CT) (6/7 vs. 3/6 patients. 68Ga-PSMA PET and CT were concordant in only three patients (50%, 12% to 88%). In mCRPC patients, biochemical PR was found in six of 16 patients (38%, 15% to 65%). Outcome prediction was concordant between BR and RR(PET) in nine of 16 patients (56%), and between BR and RR(CT) in only four of 12 patients (33%) with target lesions on CT. 68Ga-PSMA PET and CT results corresponded in seven of 12 patients (58%, 28% to 85%). CONCLUSION: Our preliminary results suggest that 68Ga-PSMA PET might be a promising method for treatment response assessment in mCSPC and mCRPC. The data indicate that for different metastatic sites, the performance of 68Ga-PSMA PET in response assessment might be superior to that of the conventional CT approach and could help differentiate between progressive disease and treatment response. Because of the limited number of patients, the differences revealed in our study were not statistically significant. Thus larger and prospective studies are clearly needed and warranted to confirm the value of 68Ga-PSMA PET as an imaging biomarker for response assessment.

[11C]Choline PET/CT in therapy response assessment of a neoadjuvant therapy in locally advanced and high risk prostate cancer before radical prostatectomy.

PURPOSE: Recent studies have shown promising results of neoadjuvant therapy in prostate cancer (PC). The aim of this study was to evaluate the potential of [11C]Choline PET/CT in therapy response monitoring after combined neoadjuvant docetaxel chemotherapy and complete androgen blockade in locally advanced and high risk PC patients. RESULTS: In [11C]Choline PET/CT there was a significant decrease of SUVmax and SUVmean (p = 0.004, each), prostate volume (p = 0.005) and PSA value (p = 0.003) after combined neoadjuvant therapy. MRI showed a significant prostate and tumor volume reduction (p = 0.003 and 0.005, respectively). Number of apoptotic cells was significantly higher in prostatectomy specimens of the therapy group compared to pretherapeutic biopsies and the control group (p = 0.02 and 0.003, respectively). METHODS: 11 patients received two [11C]Choline PET/CT and MRI scans before and after combined neoadjuvant therapy followed by radical prostatectomy and pelvic lymph node dissection. [11C]Choline uptake, prostate and tumor volume, PSA value (before/after neoadjuvant therapy) and apoptosis (of pretherapeutic biopsy/posttherapeutic prostatectomy specimens of the therapy group and prostatectomy specimens of a matched control group without neoadjuvant therapy) were assessed and tested for differences and correlation using SPSS. CONCLUSIONS: The results showing a decrease in choline uptake after combined neoadjuvant therapy (paralleled by regressive and apoptotic changes in histopathology) confirm the potential of [11C]Choline PET/CT to monitor effects of neoadjuvant therapy in locally advanced and high risk PC patients. Further studies are recommended to evaluate its use during the course of neoadjuvant therapy for early response assessment.

Prospective evaluation of [11C]Choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer.

PURPOSE: The aim of this study was to prospectively evaluate the value of [11C] Choline PET/CT in monitoring early and late response to a standardized first-line docetaxel chemotherapy in castration refractory prostate cancer (mCRPC) patients. METHODS: Thirty-two patients were referred for [11C] Choline PET/CT before the start of docetaxel chemotherapy, after one and ten chemotherapy cycles (or - in case of discontinuation - after the last administered cycle) for therapy response assessment. [11C] Choline uptake (SUVmax, SUVmean), CT derived Houndsfield units (HUmax, HUmean), and volume of bone, lung, and nodal metastases and local recurrence were measured semi-automatically at these timepoints. Change in SUVmax, SUVmean, HUmax, HUmean, and volume was assessed between PET 2 and 1 (early response assessment, ERA) and PET 3 and 1 (late response assessment, LRA) on a patient and lesion basis. Results of PET/CT were compared to clinically used RECIST 1.1 and clinical criteria based therapy response assessment including PSA for defining progressive disease (PD) and non-progressive disease (nPD), respectively. Relationships between changes of SUVmax and SUVmean (early and late) and changes of PSAearly and PSAlate were evaluated. Prognostic value of initial SUVmax and SUVmean was assessed. Statistical analyses were performed using SPSS. RESULTS: In the patient-based ERA and LRA there were no statistically significant differences in change of choline uptake, HU, and volume between PD and nPD applying RECIST or clinical response criteria. In the lesion-based ERA, decrease in choline uptake of bone metastases was even higher in PD (applying RECIST criteria), whereas in LRA the decrease was higher in nPD (applying clinical criteria). There were only significant correlations between change in choline uptake and PSA in ERA in PD, in LRA no significant correlations were discovered. Initial SUVmax and SUVmean were statistically significantly higher in nPD (applying clinical criteria). CONCLUSION: There is no significant correlation between change in choline uptake in [11C] Choline PET/CT and clinically routinely used objective response assessment during the early and late course of docetaxel chemotherapy. Therefore, [11C] Choline PET/CT seems to be of limited use in therapy response assessment in standardized first-line chemotherapy in mCRPC patients.

Value of 68Ga-PSMA HBED-CC PET for the Assessment of Lymph Node Metastases in Prostate Cancer Patients with Biochemical Recurrence: Comparison with Histopathology After Salvage Lymphadenectomy.

The purpose of this study was to evaluate the accuracy of Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)] PET compared with morphologic imaging for the assessment of lymph node metastases (LNM) in patients with recurrent prostate cancer. METHODS: Forty-eight patients (median age, 71 y; interquartile range, 66-74 y) with biochemical recurrence (median prostate-specific antigen level, 1.31 ng/mL; interquartile range, 0.75-2.55 ng/mL) who underwent 68Ga-prostate-specific membrane antigen (PSMA) HBED-CC PET/CT or PET/MR and salvage lymphadenectomy were retrospectively included. Institutional review board approval and written informed consent were obtained from all patients for the purpose of anonymized evaluation and publication of their data. Standardized predefined lymph node (LN) template fields (n = 10) were evaluated in 68Ga-PSMA HBED-CC PET and morphologic imaging for the presence of LNM using a 5-point-scale. Additionally, SUVmean/max and size of suspicious lesions were determined. Specificity of 68Ga-PSMA HBED-CC PET imaging for PET-positive LNs was defined by comparison to histopathology. The diagnostic accuracy of 68Ga-PSMA HBED-CC PET compared with morphologic imaging alone was assessed, and areas under the receiver-operating-characteristic curves are presented. RESULTS: LNM were found histologically in 68 of 179 resected anatomic LN fields (38.0%). The specificity of 68Ga-PSMA HBED-CC PET and morphologic imaging was 97.3% and 99.1%, respectively. However, 68Ga-PSMA HBED-CC PET detected LNM in 53 of 68 histopathologically proven metastatic LN fields (77.9%) whereas morphologic imaging was positive in only 18 of 67 (26.9%). 68Ga-PSMA HBED-CC PET imaging performed significantly superior to morphologic imaging for detection of LNM (difference in the areas under the receiver-operating-characteristic curves, 0.139; 95% confidence interval, 0.063-0.214; P < 0.001). In 68Ga-PSMA HBED-CC PET, the mean size of PET-positive LN measured by CT or MRI was 8.3 ± 4.3 mm (range, 4-25 mm), and LNs, which were suspicious only in CT or MRI, presented with a mean size of 13.0 ± 4.9 mm (range, 8-25 mm). CONCLUSION: 68Ga-PSMA HBED-CC PET imaging is a promising method for early detection of LNM in patients with biochemical recurrent prostate cancer. It is more accurate than morphologic imaging and thus might represent a valuable tool for guiding salvage lymphadenectomy.