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Item does not contain fulltext, OBJECTIVES: To assess the proportion of clinically significant (cs) prostate cancer (PCa) found during follow-up in patients with negative systematic biopsy (SB) followed by non-suspicious multiparametric magnetic resonance imaging (mpMRI) and persistent clinical suspicion of PCa compared to the general population. PATIENTS AND METHODS: A prospective study in a subgroup of patients from a multicentre randomized controlled trial was conducted between 2014 and 2017, including 665 men with prior negative SB with a persistent elevated prostate-specific antigen and/or suspicious digital rectal examination undergoing mpMRI. All patients with negative SB and Prostate Imaging-Reporting and Data System (PI-RADS) ≤2 on mpMRI entered biochemical follow-up. Follow-up data until December 2021 were collected by reviewing institutional hospital records and the Dutch Pathology Registry (PALGA). The primary outcome was the observed number of csPCa (Gleason ≥3 + 4/International Society of Urological Pathology grade group ≥2) cases during follow-up compared to the expected number in the general population (standardized incidence ratio [SIR]). RESULTS: In total, 431 patients had non-suspicious mpMRI and entered biochemical follow-up. After a median (interquartile range) follow-up of 41 (23-57) months, 38 patients were diagnosed with PCa, of whom 13 (3.0%) had csPCa. The SIR for csPCa was 4.3 (95% confidence interval 2.3-7.4; total excess of eight cases). A higher risk of a positive biopsy for (cs)PCa based on the European Randomized Study of Screening for Prostate Cancer risk calculator and a suspicious repeat MRI (PI-RADS ≥3) were significant predictive factors for csPCa. CONCLUSION: After negative prior biopsy and non-suspicious mpMRI the risk of csPCa is low. However, compared to the general population, the risk of csPCa is increased despite the high negative predictive value of mpMRI. More research focusing on biochemical and image-guided risk-adapted diagnostic surveillance strate

Item does not contain fulltext, BACKGROUND: The objective of this real-world population study is to investigate incidence and treatment of visceral metastases (VMs) in castration resistant prostate cancer (CRPC) patients and their survival. METHODS: CRPC-patients in the CAPRI-registry between 2010 and 2016 were included in the analyses and followed till 2017. Outcomes were proportion of patients radiologically screened for VMs and proportion of patients with VMs at CRPC-diagnosis and at the start of every treatment line. Groups have been created based on location of VMs (lung, liver, or both) at date of first VM diagnosis. The outcome for these groups was overall survival (OS). Statistics included descriptive analyses, Kaplan-Meier method, and Cox proportional hazard regression analysis for survival analyses. RESULTS: Of 3602 patients from the CAPRI registry, 457 patients (12.7%) were diagnosed with VMs during follow-up: 230 patients with liver, 161 with lung, and 66 with both liver and lung metastases. The proportion of patients radiologically screened for VMs increased per treatment line as did the occurrence rate of VMs. However, 80% of patients at CRPC diagnosis to 40% in the 6th line were not screened for VMs at the start of a systemic treatment. Median OS was 8.6 months for patients with liver, 18.3 with lung and 10.9 with both liver and lung metastases (p < 0.001) from date of first VM diagnosis. After correction for prognostic factors patients with lung metastases had significantly better OS than patients with liver metastases (HR 0.650, p = 0.001). CONCLUSION: This real-world analysis showed that despite the increased rate of radiological staging during follow-up, still 80% to 40% of the patients (CRPC diagnosis to 6th treatment line respectively) were not screened for VMs at the start of a systemic treatment. VMs and location of VMs are key prognostic patient characteristics, impacts survival and have implications for treatment decisions, so routine staging of CRPC-patients is warranted.

Item does not contain fulltext, BACKGROUND: Whereas neoadjuvant cisplatin-based chemotherapy (NAC) followed by a radical cystectomy remains the standard treatment for patients with muscle-invasive bladder cancer (MIBC), increasing evidence suggests that checkpoint inhibitors, either alone or in combination with chemotherapy, are effective in the (neo)adjuvant setting. The major aim of this study was to improve our understanding of the immune-modulating effects of NAC in MIBC. METHODS: Tumor tissue of 81 patients was used, including 60 patients treated with NAC and 21 patients undergoing upfront cystectomy. Multiplex immunohistochemistry was performed to assess CD3(+), CD3(+)CD8(+), CD3(+)CD8(-)FoxP3(-), CD3(+)FoxP3(+), and CD20(+) cells. Patients were classified into a favorable or unfavorable outcome group based on the development of a recurrence within a year. RESULTS: The density of intratumoral CD3(+) T cells decreased following NAC in patients with a recurrence at one year, while it remained stable in patients without a recurrence (median fold change 0.6 [95CI 0.3; 1.0] versus 1.0 [95CI 0.6; 2.2]). This decrease was mainly attributable to a decrease in CD3(+)CD8(-)FoxP3(-) and CD3(+)FoxP3(+) T cells and was not observed in patients with an early recurrence after upfront cystectomy. Additionally, in cystectomy tissue of patients treated with NAC, median CD3(+) and CD3(+)CD8(+) T cell densities were significantly lower in patients with versus patients without a recurrence (CD3: 261. cells/mm(2) [95CI 22.4; 467.2]; CD8: 189.6 cells/mm(2) [95CI 2.0;462.0]). CONCLUSION: T cell density decreases following NAC in MIBC patients with poor clinical outcome. Further research is needed to investigate whether this decrease in T cell density affects the efficacy of subsequent checkpoint inhibitors. PReCIS: The major aim of this study was to improve our understanding of the immune-modulating effects of NAC in patients with MIBC. We reveal a decline in intratumoral CD3(+) T cell density following NAC in pati

01 april 2023, Item does not contain fulltext, BACKGROUND: Culture-based antibiotic prophylaxis is a plausible strategy to reduce infections after transrectal prostate biopsy (PB) related to fluoroquinolone-resistant pathogens. OBJECTIVE: To assess the cost effectiveness of rectal culture-based prophylaxis compared with empirical ciprofloxacin prophylaxis. DESIGN SETTING AND PARTICIPANTS: The study was performed alongside a trial in 11 Dutch hospitals investigating the effectiveness of culture-based prophylaxis in transrectal PB between April 2018 and July 2021 (trial registration number: NCT03228108). INTERVENTION: Patients were 1:1 randomized for empirical ciprofloxacin prophylaxis (oral) or culture-based prophylaxis. Costs for both prophylactic strategies were determined for two scenarios: (1) all infectious complications within 7 d after biopsy and (2) culture-proven Gram-negative infections within 30 d after biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Differences in costs and effects (quality-adjusted life-years [QALYs]) were analyzed from a healthcare and societal perspective (including productivity losses, and travel and parking costs) using a bootstrap procedure presenting uncertainty surrounding the incremental cost-effectiveness ratio in a cost-effectiveness plane and acceptability curve. RESULTS AND LIMITATIONS: For the 7-d follow-up period, culture-based prophylaxis (n = 636) was €51.57 (95% confidence interval [CI] 6.52-96.63) more expensive from a healthcare perspective and €16.95 (95% CI -54.29 to 88.18) from a societal perspective than empirical ciprofloxacin prophylaxis (n = 652). Ciprofloxacin-resistant bacteria were detected in 15.4%. Extrapolating our data, from a healthcare perspective, 40% ciprofloxacin resistance would lead to equal cost for both strategies. Results were similar for the 30-d follow-up period. No significant differences in QALYs were observed. CONCLUSIONS: Our results should be interpreted in the context of local ciprofloxacin resistance rates. In our setting, fr

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01 augustus 2023, Item does not contain fulltext, Darolutamide is a next-generation androgen receptor signaling inhibitor (ARSI) currently approved for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC) and metastatic hormone sensitive prostate cancer (mHSPC). Studies suggest that darolutamide also has the potential to be used to treat other stages of prostate cancer (PC), suggesting that its indications will broaden in the near future. Since ARSIs show similar efficacy for the treatment of PC, pharmacokinetic properties of these drugs and patient characteristics could help physicians decide which drug to select. This review provides an overview of the pharmacokinetic and pharmacodynamic properties of darolutamide. One of the most important pharmacological advantages of darolutamide is its low brain distribution and therefore limited seizure potential and central nervous system adverse effects. In addition, darolutamide has little drug-drug interaction potential and is unlikely to alter the exposure of other cytochrome P450 or P-glycoprotein substrates. Nevertheless, it may significantly increase the exposure of breast cancer resistant protein (BCRP) substrates. The limited solubility and bioavailability of darolutamide increases when taken together with food, regardless of the fat content. Darolutamide is excessively metabolized by oxidation and glucuronidation and excreted in the urine and feces. For this reason, dose reduction is required in patients with moderate and severe renal or severe hepatic impairment. Although no exposure-response relationship was observed with darolutamide, less advanced stages of PC showed better PSA response on treatment. Overall, darolutamide has some advantageous pharmacological properties that may lead to its preferred use, when broader registered, in selected patients across different disease stages.

01 juli 2023, Contains fulltext : 294532.pdf (Publisher’s version ) (Open Access), PURPOSE: Incomplete resection of prostate cancer (PCa) results in increased risk of disease recurrence. Combined fluorescence-guided surgery with tumor-targeted photodynamic therapy (tPDT) may help to achieve complete tumor eradication. We developed a prostate-specific membrane antigen (PSMA) ligand consisting of a DOTA chelator for (111)In labeling and a fluorophore/photosensitizer IRDye700DX (PSMA-N064). We evaluated the efficacy of PSMA-tPDT using PSMA-N064 in cell viability assays, a mouse xenograft model and in an ex vivo incubation study on fresh human PCa tissue. METHODS: In vitro, therapeutic efficacy of PSMA-N064 was evaluated using PSMA-positive LS174T cells and LS174T wild-type cells. In vivo, PSMA-N064-mediated tPDT was tested in immunodeficient BALB/c mice-bearing PSMA-positive LS174T xenografts. Tumor growth and survival were compared to control mice that received either NIR light or ligand injection only. Ex vivo tPDT efficacy was evaluated in excised fresh human PCa tissue incubated with PSMA-N064. RESULTS: In vitro, tPDT led to a PSMA-specific light- and ligand dose-dependent loss in cell viability. In vivo, tPDT-induced tumor cell apoptosis, delayed tumor growth, and significantly improved survival (p = 0.004) of the treated PSMA-positive tumor-bearing mice compared with the controls. In fresh ex vivo human PCa tissue, apoptosis was significantly increased in PSMA-tPDT-treated samples compared to non-treated control samples (p = 0.037). CONCLUSION: This study showed the feasibility of PSMA-N064-mediated tPDT in cell assays, a xenograft model and excised fresh human PCa tissue. This paves the way to investigate the impact of in vivo PSMA-tPDT on surgical outcome in PCa patients.

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Item does not contain fulltext, BACKGROUND: Patients with metastatic castration resistant prostate cancer (mCRPC) are at risk of symptomatic skeletal events (SSE). Bone health agents (BHA, ie bisphosphonates and denosumab) and new life-prolonging drugs (LPDs) can delay SSEs. The aim of this study is to investigate the use of BHAs in relation to SSEs in treated real-world mCRPC population. PATIENTS AND METHODS: We included patients from the CAPRI registry who were treated with at least one LPD and diagnosed with bone metastases prior to the start of first LPD (LPD1). Outcomes were SSEs (external beam radiation therapy (EBRT) to the bone, orthopedic surgery, pathologic fracture or spinal cord compression) and SSE-free survival (SSE-FS) since LPD1. RESULTS: One-thousand nine hundred and twenty-three patients were included with a median follow-up from LPD1 of 16.7 months. Fifty-two percent (n = 996) started BHA prior or within 4 weeks after the start of LPD1 (early BHA). In total, 41% experienced at least one SSE. SSE incidence rate was 0.29 per patient year for patients without BHA and 0.27 for patients with early BHA. Median SSE-FS from LPD1 was 12.9 months. SSE-FS was longer in patients who started BHA early versus patients without BHA (13.2 vs. 11.0 months, P = .001). CONCLUSION: In a real-world population we observed an undertreatment with BHAs, although patients with early BHA use had lower incidence rates of SSEs and longer SSE-FS. This finding was irrespective of type of SSE and presence of risk factors. In addition to LPD treatment, timely initiation of BHAs is recommended in bone metastatic CRPC-patients with both pain and/or opioid use and prior SSE.

Item does not contain fulltext, BACKGROUND: This study aims to evaluate the predictive value of lymph nodes (LN) suspicious for metastases on preoperative prostate-specific membrane antigen (PSMA) PET/CT for biochemical persistence (BCP) and early biochemical recurrence (BCR) following robotic-assisted radical prostatectomy (RARP) with extended pelvic LN dissection (ePLND). METHODS: We evaluated 213 patients with intermediate and high-risk prostate cancer (PCa) who underwent clinical staging with preoperative (68)Ga- or (18)F-PSMA-PET/CT scan and subsequent RARP with ePLND. Patients were grouped as PSMA- or PSMA+ depending on their LN status on PSMA-PET/CT and subdivided according to histological LN status in pN0 or pN1. Diagnostic accuracy of PSMA-PET/CT for the detection of pN1 was evaluated. BCP was defined as a first postoperative serum PSA level ≥0.1 ng/mL 6-12 weeks following RP. Early BCR was defined as detectable PSA > 0.2 ng/mL within 12 months of follow-up. Univariable logistic regression analyses were used to evaluate the effect of PSMA+ on BCP and BCR. RESULTS: Forty patients (19%) were PSMA+. The overall incidence of pN1 was 23%. Sensitivity, specificity, PPV and NPV on a per patient level for the detection of pN1 was 29%, 84%, 35%, and 80% respectively. BCP was observed in 26 of 211 patients (12%) and early BCR in 23 of 110 patients (21%). The presence of PSMA+ was a significant predictor for BCP (OR 7.1, 2.9-17.1 95% CI) and BCR (OR 8.1, 2.9-22.6 95% CI). CONCLUSION: Preoperative PSMA-PET/CT may be a valuable tool for patient counseling for RARP and ePLND as it is a significant predictor for the risk of postoperative BCP and early BCR. We conclude that an ePLND should not be avoided in men with intermediate or high-risk PCa and preoperative negative PSMA-PET/CT, as 20% have microscopic LN metastasis.

Contains fulltext : 251781.pdf (Publisher’s version ) (Open Access), BACKGROUND: Real-world disease models spanning multiple treatment lines can provide insight into the (cost) effectiveness of treatment sequences in clinical practice. OBJECTIVE: Our objective was to explore whether a disease model based solely on real-world data (RWD) could be used to estimate the effectiveness of treatments for patients with castration-resistant prostate cancer (CRPC) that could then be suitably used in a cost-effectiveness analysis. METHODS: We developed a patient-level simulation model using patient-level data from the Dutch CAPRI registry as input parameters. Time to event (TTE) and overall survival (OS) were estimated with multivariate regression models, and type of event (i.e., next treatment or death) was estimated with multivariate logistic regression models. To test internal validity, TTE and OS from the simulation model were compared with the observed outcomes in the registry. RESULTS: Although patient characteristics and survival outcomes of the simulated data were comparable to those in the observed data (median OS 20.6 vs. 19.8 months, respectively), the disease model was less accurate in estimating differences between treatments (median OS simulated vs. observed population: 18.6 vs. 17.9 [abiraterone acetate plus prednisone], 24.0 vs. 25.0 [enzalutamide], 20.2 vs. 18.7 [docetaxel], and 20.0 vs. 23.8 months [radium-223]). CONCLUSIONS: Overall, the disease model accurately approximated the observed data in the total CRPC population. However, the disease model was unable to predict differences in survival between treatments due to unobserved differences. Therefore, the model is not suitable for cost-effectiveness analysis of CRPC treatment. Using a combination of RWD and data from randomised controlled trials to estimate treatment effectiveness may improve the model.

Contains fulltext : 251755.pdf (Publisher’s version ) (Open Access), PURPOSE: The aim of our study was to compare infectious complication rates between different prostate biopsy techniques with various number of biopsy cores. MATERIALS AND METHODS: In this retrospective study, all patients from 2 hospitals who underwent prostate biopsy between 2012 and 2019 were identified. Cohorts with different types of prostate biopsies were compiled within these hospitals. Primary outcome measure was any registered infectious complication within 7 days post-biopsy. Secondary outcomes were infectious complications within 30 days, hospitalization and bacteremia. To compare the risk of infection following different prostate biopsy techniques, data was fitted into a logistic regression model adjusting for potential confounders. RESULTS: In total, 4,233 prostate biopsies in 3,707 patients were included. After systematic transrectal ultrasound-guided prostate biopsy (TRUSPB; 12±1.4 biopsy cores), 4.0% (2,607) of all patients had infectious complications within 7 days post-biopsy. Transperineal magnetic resonance imaging (MRI)-ultrasound fusion guided prostate biopsy (16±3.7 biopsy cores) was associated with significantly lower infection rates than systematic TRUSPB (adjusted OR: 0.29 [0.09-0.73] 95% confidence interval [CI]). Transrectal targeted MRI-ultrasound fusion guided prostate biopsy (3.1±0.8 biopsy cores) and transrectal targeted in-bore MRI guided prostate biopsy (2.8±0.8 biopsy cores) also showed fewer infectious complications than systematic TRUSPB (adjusted OR: 0.41 [0.12-1.12] 95% CI and 0.68 [0.37-1.20] 95% CI, respectively). CONCLUSIONS: Transperineal prostate biopsy, or transrectal prostate biopsy with reduced number of biopsy cores, could lower the risk of infectious complications.

Item does not contain fulltext, In recent years, clinical use of novel advanced imaging modalities in prostate cancer detection, staging, and therapy has intensified and is currently reforming clinical guidelines. In the future, advanced imaging technologies will continue to develop and become even more accurate, which will offer new opportunities for improving patient selection, surgical treatment, and radiotherapy, with the potential to guide prostate cancer therapy.

Item does not contain fulltext, 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.

Contains fulltext : 244285.pdf (Publisher’s version ) (Open Access), Treatment evaluation in metastatic castration-resistant prostate cancer is challenging. There is an urgent need for biomarkers to discriminate short-term survivors from long-term survivors, shortly after treatment initiation. Thereto, the added value of early RNA biomarkers on predicting progression-free survival (PFS) and overall survival (OS) were explored. The RNA biomarkers: KLK3 mRNA, miR-375, miR-3687, and NAALADL2-AS2 were measured in 93 patients with mCRPC, before and 1 month after start of first-line abiraterone acetate or enzalutamide treatment, in two prospective clinical trials. The added value of the biomarkers to standard clinical parameters in predicting PFS and OS was tested by Harell's C-index. To test whether the biomarkers were independent markers of PFS and OS, multivariate Cox regression was used. The best prediction model for PFS and OS was formed by adding miR-375 and KLK3 (at baseline and 1 month) to standard clinical parameters. Baseline miR-375 and detectable KLK3 after 1 month of therapy were independently related to shorter PFS, which was not observed for OS. In conclusion, the addition of KLK3 and miR-375 (at baseline and 1 month) to standard clinical parameters resulted in the best prediction model for survival assessment.

Item does not contain fulltext, BACKGROUND: In 2004 docetaxel was the first life-prolonging drug (LPD) registered for metastatic castration-resistant prostate cancer (mCRPC) patients. Between 2011 and 2014 new LPDs for mCRPC (cabazitaxel, abiraterone, enzalutamide, and radium-223) were introduced in the Netherlands. The objective of this study is to assess the impact of the introduction of new LPDs on treatment patterns and overall survival (OS) over time. PATIENTS AND METHODS: CRPC patients diagnosed in the years 2010-2016 in the observational, retrospective CAPRI registry (20 hospitals) were included and followed up to 2018. Two subgroups were analyzed: treatment-naïve patients (subgroup 1, n = 3600) and post-docetaxel patients (subgroup 2, n = 1355). RESULTS: In both subgroups, the use of any LPD increased: from 57% (2010-2011) to 69% (2014-2015) in subgroup 1 and from 65% (2011-2012) to 79% (2015-2016) in subgroup 2. Chemotherapy as first mCRPC-treatment (i.e., docetaxel) and first post-docetaxel treatment (i.e., cabazitaxel or docetaxel rechallenge) decreased (46-29% and 20-9% in subgroup 1 and 2, respectively), while the use of androgen-receptor targeting treatments (ART) increased from 11% to 39% and 46% to 64% in subgroup 1 and 2, respectively. In subgroup 1, median OS (mOS) from diagnosis CRPC increased from 28.5 months to 31.0 months (p = 0.196). In subgroup 2, mOS from progression on docetaxel increased from 7.9 months to 12.5 months (p < 0.001). After multiple imputations of missing values, in multivariable cox-regression analysis with known prognostic parameters, the treatment period was independent significant for OS in subgroup 1 (2014-2015 vs. 2010-2011 with HR 0.749, p < 0.001) and subgroup 2 (2015-2016 vs. 2011-2012 with HR 0.811, p = 0.037). CONCLUSION: Since 2010, a larger proportion of mCRPC patients was treated with LPDs, which was related to an increased mOS.

Contains fulltext : 235310.pdf (Publisher’s version ) (Closed access), PURPOSE: [(177)Lu]Lu-PSMA-617 radioligand therapy ((177)Lu-PSMA) is a novel treatment for metastatic castration-resistant prostate cancer (mCRPC), which could also be applied to patients with metastatic hormone-sensitive prostate cancer (mHSPC) with PSMA expression. In this prospective study (NCT03828838), we analyzed toxicity, radiation doses, and treatment effect of (177)Lu-PSMA in pateints with low-volume mHSPC. PATIENTS AND METHODS: Ten progressive patients with mHSPC following local treatment, with a maximum of ten metastatic lesions on [(68)Ga]Ga-PSMA-11 PET/diagnostic-CT imaging (PSMA-PET) and serum PSA doubling time <6 months received two cycles of (177)Lu-PSMA. Whole-body single-photon emission CT/CT (SPECT/CT) and blood dosimetry was performed to calculate doses to the tumors and organs at risk (OAR). Adverse events (AE), laboratory values (monitoring response and toxicity), and quality of life were monitored until week 24 after cycle 2, the end of study (EOS). All patients underwent PSMA-PET at screening, 8 weeks after cycle 1, 12 weeks after cycle 2, and at EOS. RESULTS: All patients received two cycles of (177)Lu-PSMA without complications. No treatment-related grade III-IV adverse events were observed. According to dosimetry, none of the OAR reached threshold doses for radiation-related toxicity. Moreover, all target lesions received a higher radiation dose than the OAR. All 10 patients showed altered PSA kinetics, postponed androgen deprivation therapy, and maintained good quality of life. Half of the patients showed a PSA response of more than 50%. One patient had a complete response on PSMA-PET imaging until EOS and two others had only minimal residual disease. CONCLUSIONS: (177)Lu-PSMA appeared to be a feasible and safe treatment modality in patients with low-volume mHSPC.

Item does not contain fulltext, BACKGROUND: According to (inter-)national guidelines, (neo-)adjuvant and concurrent androgen deprivation therapy (ADT) in combination with external beam radiotherapy (EBRT) is optional for intermediate-risk prostate cancer (PCa) patients and is the recommended standard treatment for high-risk PCa patients. OBJECTIVE: The aim of this study is to provide insight into the prescription of ADT in intermediate- and high-risk PCa patients treated with EBRT in the Netherlands, and to evaluate adherence to European Association of Urology guidelines and factors affecting prescription. DESIGN, SETTING, AND PARTICIPANTS: All intermediate- and high-risk PCa patients between October 2015 and April 2016 were identified through the population-based Netherlands Cancer Registry. Variation in the prescription of ADT in patients with EBRT was evaluated. Multivariable multilevel logistic regression analyses were performed to determine the probability of ADT and to examine the role of patient-, tumour-, and hospital-related factors. RESULTS AND LIMITATIONS: Overall, 29% of patients with intermediate-risk PCa received ADT varying from 3% to 73% between institutions. From the multivariable regression analysis, higher Gleason grade, magnetic resonance imaging, and computed tomography (CT)-positron-emission tomography/CT prior to radiotherapy appeared to be associated with increased prescription of ADT. Among high-risk patients, 83% received ADT, varying from 57% to 100% between departments. A higher prostate-specific antigen level, more advanced tumour stage, and a higher Gleason grade were associated with increased prescription. CONCLUSIONS: Less than one-third of intermediate-risk PCa patients treated with EBRT receive ADT. The variation in the prescription of ADT between different institutions is substantial. This suggests that the prescription is largely dependent on different institutional policies. The guideline adherence in high-risk PCa is fairly good, as the vast majority of patien

Contains fulltext : 237673.pdf (Publisher’s version ) (Open Access), Circulating RNAs extracted from liquid biopsies represent a promising source of cancer- and therapy-related biomarkers. We screened whole blood from patients with metastatic castration-resistant prostate cancer (mCRPC) following their first-line treatment with abiraterone acetate and prednisone (AA-P) to identify circulating RNAs that may correlate with progression-free survival (PFS). In a prospective multicenter observational study, 53 patients with mCRPC were included after they started first-line AA-P treatment. Blood was drawn at baseline, 1, 3, and 6 months after treatment initiation. The levels of predefined circulating RNAs earlier identified as being upregulated in patients with mCRPC (e.g., microRNAs, long noncoding RNAs, and mRNAs), were analyzed. Uni- and multivariable Cox regression and Kaplan-Meier analyses were used to analyze the prognostic value of the various circulating RNAs for PFS along treatment. Detectable levels of kallikrein-related peptidase 3 (KLK3) mRNA at baseline were demonstrated to be an independent prognostic marker for PFS (201 vs 501 days, P = 0.00054). Three months after AA-P treatment initiation, KLK3 could not be detected in the blood of responding patients, but was still detectable in 56% of the patients with early progression. Our study confirmed that KLK3 mRNA detection in whole blood is an independent prognostic marker in mCRPC patients receiving AA-P treatment. Furthermore, the levels of circulating KLK3 mRNA in patients receiving AA-P treatment might reflect treatment response or early signs of progression.

Contains fulltext : 236937.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 221515.pdf (publisher's version ) (Open Access), For the treatment choice of localized prostate cancer, effective patient decision aids have been developed. The implementation of decision aids in routine care, however, lags behind. Main known barriers are lack of confidence in the tool, lack of training on its use, lack of resources and lack of time. A new implementation strategy addresses these barriers. Using this implementation strategy, the implementation rate of a decision aid was measured in eight hospitals and questionnaires were filled out by 24 care providers and 255 patients. The average implementation rate was 60 per cent (range 31%-100%). Hardly any barriers remained for care providers. Patients who did not use the decision aid appeared to be more unwilling than unable to use the decision aid. By addressing known barriers, that is, informing care providers on the effectiveness of the decision aid, providing instructions on its use, embedding it in the existing workflow and making it available free of charge, a successful implementation of a prostate cancer decision aid was reached.

Contains fulltext : 218778.pdf (Publisher’s version ) (Closed access)

Item does not contain fulltext, Aim: Timing of radium-223 (Ra-223) in metastatic castration-resistant prostate cancer (mCRPC) remains challenging due to alternative options and short window of opportunity. Methods: Ra-223 treated patients in the CAPRI-registry were included. Outcomes were evaluated based on treatment line of Ra-223. Results: Out of 285 patients, 49% received Ra-223 in line >/=3. 51% completed six Ra-223 injections and 34% had a symptomatic skeletal event after first Ra-223 without differences between subgroups. After correction of known prognostic factors Ra-223 in line >/=3 (HR: 3.267; 95% CI: 1.689-6.317; p < 0.01) remained associated with worse OS. Conclusion: In the Netherlands, Ra-223 was mainly started as second or third mCRPC-treatment in 2014-2018. Later timing of Ra-223 did affect OS, but not treatment completion and occurrence of symptomatic skeletal events.

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Contains fulltext : 218906.pdf (publisher's version ) (Open Access), BACKGROUND: The clinical landscape of prostate biopsy (PB) is evolving with changes in procedures and techniques. Moreover, antibiotic resistance is increasing and influences the efficacy of pre-biopsy prophylactic regimens. Therefore, increasing antibiotic resistance may impact on clinical care, which probably results in differences between hospitals. The objective of our study is to determine the (variability in) current practices of PB in the Netherlands and to gain insight into Dutch urologists' perceptions of fluoroquinolone resistance and biopsy related infections. METHODS: An online questionnaire was prepared using SurveyMonkey(R) platform and distributed to all 420 members of the Dutch Association of Urology, who work in 81 Dutch hospitals. Information about PB techniques and periprocedural antimicrobial prophylaxis was collected. Urologists' perceptions regarding pre-biopsy antibiotic prophylaxis in an era of antibiotic resistance was assessed. Descriptive statistical analysis was performed. RESULTS: One hundred sixty-one responses (38.3%) were analyzed representing 65 (80.3%) of all Dutch hospitals performing PB. Transrectal ultrasound guided prostate biopsy (TRUSPB) was performed in 64 (98.5%) hospitals. 43.1% of the hospitals (also) used other image-guided biopsy techniques. Twenty-three different empirical prophylactic regimens were reported among the hospitals. Ciprofloxacin was most commonly prescribed (84.4%). The duration ranged from one pre-biopsy dose (59.4%) to 5 days extended prophylaxis. 25.2% of the urologists experienced ciprofloxacin resistance as a current problem in the prevention of biopsy related infections and 73.6% as a future problem. CONCLUSIONS: There is a wide variation in practice patterns among Dutch urologists. TRUSPB is the most commonly used biopsy technique, but other image-guided biopsy techniques are increasingly used. Antimicrobial prophylaxis is not standardized and prolonged prophylaxis is common. The wide variation in p

Contains fulltext : 226662.pdf (Publisher’s version ) (Open Access), Uptake of decision aids (DAs) in daily routine is low, resulting in limited knowledge about successful DA implementation at a large scale. We assessed implementation rates after multi-regional implementation of three different prostate cancer (PCa) treatment DAs and patient-perceived barriers and facilitators to use a DA. Thirty-three hospitals implemented one out of the three DAs in routine care. Implementation rates for each DA were calculated per hospital. After deciding about PCa treatment, patients (n = 1033) completed a survey on pre-formulated barriers and facilitators to use a DA. Overall DA implementation was 40%. For each DA alike, implementation within hospitals varied from incidental (< 10% of eligible patients receiving a DA) to high rates of implementation (> 80%). All three DAs were evaluated positively by patients, although concise and paper DAs yielded higher satisfaction scores compared with an elaborate online DA. Patients were most satisfied when they received the DA within a week after diagnosis. Pre-formulated barriers to DA usage were experienced by less than 10% of the patients, and most patients confirmed the facilitators. Many patients received a DA during treatment counseling, although a wide variation in uptake across hospitals was observed for each DA. Most patients were satisfied with the DA they received. Sustained implementation of DAs in clinical routine requires further encouragement and attention.

Item does not contain fulltext, BACKGROUND: Oligometastatic prostate cancer (OMPC) is a heterogeneous disease state that is imperfectly understood, and its clinical implications are unclear. OBJECTIVE: To determine the consensus of a Dutch multidisciplinary expert panel on biological aspects, treatment goals, and management of OMPC in daily clinical practice. DESIGN, SETTING, AND PARTICIPANTS: The study comprised a modified Delphi method including an explorative survey with various statements and questions, followed by a consensus meeting to discuss and determine the agreement with revised statements and related items. The panel consisted of 34 Dutch representatives from urology, medical and radiation oncology, radiology, nuclear medicine, and basic research. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Agreement was determined with statements (five-point scale). Consensus was defined as >/=75% panel agreement with a statement. RESULTS AND LIMITATIONS: Consensus existed for 56% of statements. The panel agreed that OMPC comprises a limited metastatic spread in the hormone-sensitive setting, in both the synchronous and the metachronous presentation. Limited metastatic spread was believed to involve three to five metastases and a maximum of two organs. Prostate-specific membrane antigen positron emission tomography/computed tomography scan was currently perceived as the most accurate diagnostic imaging modality. Although there was a consensus that targeted treatment of all metastases in OMPC will delay further dissemination of the disease, opinions on specific treatment regimens were divided. Panel outcomes were limited by the lack of scientific evidence on OMPC. CONCLUSIONS: A multidisciplinary panel reached a consensus that OMPC is a specific disease state requiring a tailored treatment approach. OMPC registries and clinical studies should focus on both the biology and the clinical parameters in relation to optimal treatment strategies in synchronous and metachronous OMPC. PATIENT SUMMARY: A grou

Contains fulltext : 208152.pdf (publisher's version ) (Closed access)

Contains fulltext : 215769.pdf (publisher's version ) (Closed access), BACKGROUND: Three techniques of magnetic resonance imaging (MRI)-based targeted biopsy (TB) of the prostate exist. There is no superiority regarding diagnostic efficacy of prostate cancer (PCa) detection. OBJECTIVE: To compare adverse events (AEs) among three TB techniques and to evaluate the effect on urinary and erectile function. DESIGN, SETTING, AND PARTICIPANTS: Post hoc analysis of a multicentre randomised controlled trial among men with negative systematic biopsy (SB) and suspicion of PCa. INTERVENTION: In 234 patients, 3-T multiparametric MRI demonstrated PIRADS>/= 3 lesions, and patients were randomised 1:1:1 for TB: transrectal in-bore MRI TB (MRI-TB), transperineal MRI-transrectal ultrasound (TRUS) fusion TB (FUS-TB), and transrectal cognitive TRUS TB (COG-TB). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: AEs (Clavien-Dindo) were compared using Pearson chi-square test. Univariate logistic regression tests were performed for the number of cores, biopsy approach, and usage of anticoagulants. The participants filled in baseline and 30-d postbiopsy International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) questionnaires. The delta between measurements was compared using one-way analysis of variance. RESULTS AND LIMITATIONS: There were significant differences in minor AEs: 53% in MRI-TB, 71% in FUS-TB, and 85% in COG-TB (p<0.001). The number of cores was associated with AEs (odds ratio [OR] 1.11 per extra biopsy [95% confidence interval {CI} 1.06-1.17, p<0.001]). Anticoagulants were not associated with bleeding complications (OR 1.24 [95% CI 0.66-2.35, p=0.5]). Transrectal approach (MRI-TB+COG-TB) increased the risk of any AE (OR 2.54 [95% CI 1.16-5.77, p<0.05]) and nonsignificantly increased the risk of urinary tract infections (OR 3.69 [95% CI 0.46-168.4, p=0.3]). Biopsy did not impact urinary (DeltaIPSS 0.3, p=0.1) and erectile function (DeltaIIEF-5 -0.4, p=0.5). The main limitation was that additional SB was perfor

Contains fulltext : 215102.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 206894.pdf (publisher's version ) (Closed access), BACKGROUND: Guidelines advise multiparametric magnetic resonance imaging (mpMRI) before repeat biopsy in patients with negative systematic biopsy (SB) and a suspicion of prostate cancer (PCa), enabling MRI targeted biopsy (TB). No consensus exists regarding which of the three available techniques of TB should be preferred. OBJECTIVE: To compare detection rates of overall PCa and clinically significant PCa (csPCa) for the three MRI-based TB techniques. DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomised controlled trial, including 665 men with prior negative SB and a persistent suspicion of PCa, conducted between 2014 and 2017 in two nonacademic teaching hospitals and an academic hospital. INTERVENTION: All patients underwent 3-T mpMRI evaluated with Prostate Imaging Reporting and Data System (PIRADS) version 2. If imaging demonstrated PIRADS >/=3 lesions, patients were randomised 1:1:1 for one TB technique: MRI-transrectal ultrasound (TRUS) fusion TB (FUS-TB), cognitive registration TRUS TB (COG-TB), or in-bore MRI TB (MRI-TB). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary (overall PCa detection) and secondary (csPCa detection [Gleason score >/=3+4]) outcomes were compared using Pearson chi-square test. RESULTS AND LIMITATIONS: On mpMRI, 234/665 (35%) patients had PIRADS >/=3 lesions and underwent TB. There were no significant differences in the detection rates of overall PCa (FUS-TB 49%, COG-TB 44%, MRI-TB 55%, p=0.4). PCa detection rate differences were -5% between FUS-TB and MRI-TB (p=0.5, 95% confidence interval [CI] -21% to 11%), 6% between FUS-TB and COG-TB (p=0.5, 95% CI -10% to 21%), and -11% between COG-TB and MRI-TB (p=0.17, 95% CI -26% to 5%). There were no significant differences in the detection rates of csPCa (FUS-TB 34%, COG-TB 33%, MRI-TB 33%, p>0.9). Differences in csPCa detection rates were 2% between FUS-TB and MRI-TB (p=0.8, 95% CI -13% to 16%), 1% between FUS-TB and COG-TB (p>0.9, 95% CI -14% to 16%), and 1% between COG-TB and MRI

_Background:_ Cross resistance between androgen-receptor targeting therapies(ARTs) (abiraterone acetate plus prednisone [ABI + P] or enzalutamide [ENZ]) fortreatment of metastatic castration-resistant prostate cancer (mCRPC) may affectresponses to second ART (ART2). _Objective:_ To establish treatment duration and prostate-specific antigen (PSA)response of ART2 in real-world mCRPC patients treated with or without otherlife-prolonging drugs (LPDs; ie, docetaxel, cabazitaxel, or radium-223) betweenART1 and ART2. _Design, setting, and participants:_ Castration-resistant prostate cancer patients,diagnosed between 2010 and 2016 were retrospectively registered in Castra-tion-resistant Prostate Cancer Registry (CAPRI). Patients treated with both ARTswere clustered into two subgroups: ART1 > ART2 or ART1 > LPD > ART2.