Publications by authors named "Harm H E van Melick"

35 Publications

Long-term Outcomes of Focal Cryotherapy for Low- to Intermediate-risk Prostate Cancer: Results and Matched Pair Analysis with Active Surveillance.

Eur Urol Focus 2021 Apr 26. Epub 2021 Apr 26.

Department of Urology, Institut Mutualiste Montsouris and Université Paris Descartes, Paris, France.

Background: To date, only one trial compared focal therapy and active surveillance (AS) for low-risk prostate cancer (PCa). In addition, long-term outcomes of focal cryotherapy (FC) are lacking.

Objective: Our aim was to evaluate long-term outcomes of FC and compare them with AS.

Design, Setting, And Participants: We included two prospective series of 121 (FC) and 459 (AS) consecutive patients (2008-2018) for low- to intermediate-risk PCa.

Outcome Measurements And Statistical Analysis: Study outcomes were radical therapy-free or androgen deprivation therapy (ADT)-free, any treatment-free, metastasis-free, and overall survival. A matched pair analysis was performed using seven covariates.

Results And Limitations: The median FC follow-up was 85 mo (interquartile range 58-104); 92 (76%) men had International Society of Urological Pathology (ISUP) grade 1. Among matched variables, no significant differences were present except for cT stage and year of entry (both p < 0.01). Ten-year radical therapy-free or ADT-free, any treatment-free, metastasis-free, and overall survival were 51%, 40.2%, 93.9%, and 97%, respectively for FC. No differences were noted with AS (all p > 0.05), with the exception of time to radical therapy, time to radical therapy and ADT, and time to any treatment, all being shorter for AS (all p < 0.01). Freedom from radical treatment or ADT was higher for FC (AS 10 yr 39.3%; p = 0.04). Complications were relatively rare (26.5%) and mainly of low grade (Clavien >2, n = 3); three men developed incontinence (p = 0.0814), while both International Index of Erectile Function 5 and International Prostate Symptom Score scores increased (p = 0.0287 and p = 0.0165, respectively). Limitations include absence of randomization.

Conclusions: At an early long-term follow-up, FC in the context of mainly low-risk PCa is safe and increases time to radical therapy but does not provide meaningful oncological advantages compared with AS.

Patient Summary: We compared focal cryotherapy with active surveillance mainly for low-risk prostate cancer. Focal cryotherapy, despite having fewer complications, did not yield meaningful advantages over active surveillance at 10 yr. Active surveillance should be preferred to focal cryotherapy for these patients.
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http://dx.doi.org/10.1016/j.euf.2021.04.008DOI Listing
April 2021

Evaluation of Ureteroenteric Anastomotic Strictures after the Introduction of Robot-Assisted Radical Cystectomy with Intracorporeal Urinary Diversion: Results from a Large Tertiary Referral Center.

J Urol 2021 Apr 30;205(4):1119-1125. Epub 2020 Nov 30.

Department of Urology, St. Antonius Hospital Nieuwegein/Utrecht, Nieuwegein, The Netherlands.

Purpose: Benign ureteroenteric anastomotic strictures following radical cystectomy are a critical complication The incidence is highly dependent on study design, surgical technique and surgeon experience. We studied the incidence of ureteroenteric anastomotic strictures after open vs robot-assisted radical cystectomy with an intracorporeal urinary diversion, and determined the influence of the introduction of robot-assisted radical cystectomy in our clinic.

Materials And Methods: A retrospective, single center, cohort study was performed between January 2012 and December 2017 in all patients undergoing radical cystectomy. Multivariate analysis was performed to determine which patient or disease-specific factors were associated with development of ureteroenteric anastomotic strictures.

Results: Of 279 patients, 192 (69%) underwent open radical cystectomy and 87 (31%) underwent robot-assisted radical cystectomy with intracorporeal urinary diversion. In total, 47/279 patients (17%) developed ureteroenteric anastomotic strictures after a median of 3.0 months (95% CI 2.4-3.7). The difference in incidence of ureteroenteric anastomotic strictures was statistically significant between open and robot-assisted radical cystectomy (13% vs 25%, p <0.001). On multivariate analysis, only surgical technique (open vs robot-assisted radical cystectomy) was independently associated with development of ureteroenteric anastomotic strictures (p=0.004). There was a peak incidence of ureteroenteric anastomotic strictures after robot-assisted radical cystectomy of 47% during the first year after introduction of the robot-assisted procedure.

Conclusions: Introducing robot-assisted radical cystectomy with intracorporeal urinary diversion can result in an initial peak incidence of strictures, highlighting the importance of surgeon experience and the presence of a learning curve. Nonetheless, after experience has been gained, our results show that patients undergoing robot-assisted radical cystectomy with intracorporeal urinary diversion are still more likely to develop ureteroenteric anastomotic strictures compared to those undergoing open radical cystectomy.
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http://dx.doi.org/10.1097/JU.0000000000001518DOI Listing
April 2021

Multiparametric Magnetic Resonance Imaging Should Be Preferred Over Digital Rectal Examination for Prostate Cancer Local Staging and Disease Risk Classification.

Urology 2021 Jan 28;147:205-212. Epub 2020 Oct 28.

Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.

Objective: To assess the impact of multiparametric magnetic resonance imaging (mp-MRI) local tumor staging on prostate cancer risk stratification and choice of treatment.

Materials And Methods: Prostate cancer patients, newly diagnosed from 2017 to 2018 at 7 Dutch teaching hospitals were included. Risk group classification was done twice, using either digital rectal examination (DRE) or mp-MRI information. Risk group migration and rates of treatment intensification associated with mp-MRI upstaging were established. Diagnostic accuracy measures for the detection of nonorgan-confined disease (stage ≥T3a), for both DRE and mp-MRI, were assessed in patients undergoing robot-assisted radical prostatectomy.

Results: A total of 1683 patients were included. Upstaging due to mp-MRI staging occurred in 493 of 1683 (29%) patients and downstaging in 43 of 1683 (3%) patients. Upstaging was associated with significant higher odds for treatment intensification (odds ratio [OR]: 3.5 95% confidence interval [CI] 1.9-6.5). Stage ≥T3a on mp-MRI was the most common reason for risk group upstaging (77%). Sensitivity for the detection of stage ≥T3a was higher for mp-MRI compared to DRE (51% vs 12%, P <.001), whereas specificity was lower (82% vs 97%, P <.001). Mp-MRI resulted in a significantly higher cumulative rate of true positive and true negative stage ≥T3a predictions compared with DRE (67% vs 58%, P <.001).

Conclusion: Use of mp-MRI tumor stage for prostate cancer risk classification leads to upstaging in 1 of 3 patients. Mp-MRI enables superior detection of nonorgan-confined disease compared with DRE, and should be the preferred tool for determining clinical tumor stage.
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http://dx.doi.org/10.1016/j.urology.2020.08.089DOI Listing
January 2021

Comparison of risk-calculator and MRI and consecutive pathways as upfront stratification for prostate biopsy.

World J Urol 2020 Oct 22. Epub 2020 Oct 22.

Department of Urology, St. Antonius Hospital Utrecht/Nieuwegein, Koekoekslaan 1, Utrecht, 3435CM, The Netherlands.

Purpose: In biopsy naïve men suspected for prostate cancer (PCa), it is uncertain how a risk-calculator and bi-parametric (bp) MRI should be combined to decide on prostate biopsy, balancing cancer detection rates and diagnostic burden.

Methods: Prospective, single centre cohort study (August 2018-April 2019). All patients referred with serum PSA ≥ 3 ng/ml or abnormal digital rectal examination received bpMRI and risk for PCa was calculated using the ERSPC risk-calculator. Men with either PI-RADS ≥ 3 or calculator risk-score > 20% were recommended to undergo systematic biopsy (SB) and targeted biopsy (TB) of any visible lesion (reference pathway). Eight different derived diagnostic pathways were compared to the reference pathway regarding cancer detection, number of biopsies and bpMRIs performed.

Results: Of 496 patients; 233 (47%) had a risk-calculator score of > 20%; 201 (41%) had PI-RADS score ≥ 3. The reference pathway detected PCa in 32.1%, clinically significant (cs) PCa in 19.4%, with 41% avoided biopsies, but 0% avoided bpMRI. Stratification with only risk-calculator: 76% csPCa diagnosed, 53% avoided biopsies and 100% avoided bpMRI. Stratification with only bpMRI: 97% csPCa diagnosed, 59% avoided biopsies, but 0% avoided bpMRI. A pathway with risk-calculator first, followed only with bpMRI when high-risk: 81% csPCa diagnosed, 72% avoided biopsies and 53% avoided bpMRI.

Conclusion: Upfront bpMRI as a risk stratification tool outperforms risk-calculator in detecting significant disease. Applying the risk-calculator first to decide on performing an MRI, avoids 1 out of 2 MRIs, but up to 1 out of 5 significant cancers are missed.
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http://dx.doi.org/10.1007/s00345-020-03488-2DOI Listing
October 2020

Treatment patterns and clinical outcomes of chemotherapy treatment in patients with muscle-invasive or metastatic bladder cancer in the Netherlands.

Sci Rep 2020 09 25;10(1):15822. Epub 2020 Sep 25.

Urology Department, St. Antonius Hospital, Koekoekslaan 1, 3435CM, Nieuwegein/Utrecht, The Netherlands.

This retrospective study was performed to evaluate real-world oncological outcomes of patients treated with chemo-based therapy for muscle-invasive or metastatic bladder cancer (MIBC/mBC) and compare results to data from RCTs and other cohorts. Among 1578 patients diagnosed, 470 (30%) had MIBC/mBC. Median overall survival (mOS) for RC alone (47 months), first-line (13 months) and second-line (7 months) chemotherapy, and chemotherapy for recurrent disease (8 months) were similar to literature. Treatment with neoadjuvant and induction chemotherapy (NAIC) was only utilized in 9% of patients, and often in patients with poor disease status, resulting in a lower mOS compared to literature (35 and 20 months, respectively). Patients treated with chemotherapy had many adversities to treatment, with only 50%, 13%, 18% and 7% of patients in NAIC, first-line, salvage after RC, and second-line setting completing the full pre-planned chemotherapy treatment. Real-world data shows NAIC before RC is underutilized. Adversities during chemotherapy treatment are frequent, with many patients requiring dose reduction or early treatment termination, resulting in poor treatment response. Although treatment efficacy between RCTs and real-world patients is quite similar, there are large differences in baseline characteristics and treatment patterns. Possibly, results from retrospective studies on real-world data can deliver missing evidence on efficacy of chemotherapy treatment on older and 'unfit' patients.
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http://dx.doi.org/10.1038/s41598-020-72820-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519076PMC
September 2020

Development and External Validation of a Novel Nomogram to Predict Side-specific Extraprostatic Extension in Patients with Prostate Cancer Undergoing Radical Prostatectomy.

Eur Urol Oncol 2020 Sep 21. Epub 2020 Sep 21.

Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.

Background: Prediction of side-specific extraprostatic extension (EPE) is crucial in selecting patients for nerve-sparing radical prostatectomy (RP).

Objective: To develop and externally validate nomograms including multiparametric magnetic resonance imaging (mpMRI) information to predict side-specific EPE.

Design, Setting, And Participants: A retrospective analysis of 1870 consecutive prostate cancer patients who underwent robot-assisted RP from 2014 to 2018 at three institutions.

Outcome Measurements And Statistical Analysis: Four multivariable logistic regression models were established, including combinations of patient-based and side-specific variables: prostate-specific antigen (PSA) density, highest ipsilateral International Society of Urological Pathology (ISUP) biopsy grade, ipsilateral percentage of positive cores on systematic biopsy, and side-specific clinical stage assessed by both digital rectal examination and mpMRI. Discrimination (area under the curve [AUC]), calibration, and net benefit of these models were assessed in the development cohort and two external validation cohorts.

Results And Limitations: On external validation, AUCs of the four models ranged from 0.80 (95% confidence interval [CI] 0.68-0.88) to 0.83 (95% CI 0.72-0.90) in cohort 1 and from 0.77 (95% CI 0.62-0.87) to 0.78 (95% CI 0.64-0.88) in cohort 2. The three models including mpMRI staging information resulted in relatively higher AUCs compared with the model without mpMRI information. No major differences between the four models regarding net benefit were established. The model based on PSA density, ISUP grade, and mpMRI T stage was superior in terms of calibration. Using this model with a cut-off of 20%, 1980/2908 (68%) prostatic lobes without EPE would be found eligible for nerve sparing, whereas non-nerve sparing would be advised in 642/832 (77%) lobes with EPE.

Conclusions: Our analysis resulted in a simple and robust nomogram for the prediction of side-specific EPE, which should be used to select patients for nerve-sparing RP.

Patient Summary: We developed a prediction model that can be used to assess accurately the likelihood of tumour extension outside the prostate. This tool can guide patient selection for safe nerve-sparing surgery.
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http://dx.doi.org/10.1016/j.euo.2020.08.008DOI Listing
September 2020

Preoperative frailty and outcome in patients undergoing radical cystectomy.

BJU Int 2020 09 4;126(3):388-395. Epub 2020 Aug 4.

Department of, Anesthesiology and Intensive Care, St. Antonius Hospital, Nieuwegein, The Netherlands.

Objective: To determine the value of preoperative frailty screening in predicting postoperative severe complications and 1-year mortality in patients undergoing radical cystectomy (RC).

Patients And Methods: Prospective cohort single-centre study in patients undergoing RC from September 2016 to December 2017. Preoperative frailty screening was implemented as standard care and was used to guide shared decision-making during multidisciplinary team meetings. Frailty screening consisted of validated tools to assess physical, mental and social frailty. Patients were considered frail when having two or more frailty characteristics. The primary endpoint was the composite of a severe complication (Clavien-Dindo Grade III-V) within 30 days and 1-year all-cause mortality. The secondary endpoints included any complication (Clavien-Dindo II-V), length of stay, readmission within 30 days, and all-cause mortality. Logistic regression analysis and the concordance statistic (c-statistic) were used to describe the association and predictive value of preoperative frailty screening.

Results: A total of 63 patients were included; 39 (61.9%) were considered frail. Preoperative frailty was associated with a seven-fold increased risk of a severe complication or death 1 year after RC [adjusted odds ratio (OR) 7.36, 95% confidence interval (CI) 1.7-31.8; 22 patients]. Compared to the American Society of Anesthesiologists (ASA) score and Charlson Comorbidity Index, frailty showed the best model performance (Nagelkerke R 0.20) and discriminative ability(c-statistic 0.72, P < 0.01) for the primary endpoint. After adding frailty to the conventional ASA risk score, the c-statistic improved by 11% (P < 0.01). Overall survival was significantly worse in frail patients (23.2 months, 95% CI 18.7-30.1) vs non-frail patients (32.9 months, 95% CI 30.0-35.9; P = 0.01).

Conclusions: Frail patients undergoing RC are at high risk of postoperative adverse outcomes including death. Preoperative frailty screening improves preoperative risk stratification and may be used to guide patient selection for RC.
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http://dx.doi.org/10.1111/bju.15132DOI Listing
September 2020

[Fracture prevention in metastatic prostate cancer].

Ned Tijdschr Geneeskd 2020 02 18;164. Epub 2020 Feb 18.

St. Antonius ziekenhuis, afd. Urologie, Nieuwegein/Utrecht.

Patients with metastatic prostate cancer are living longer than they used to, thanks to a wider range of therapeutic options. This means that an increasing number of men will receive long-term treatment with anti-hormonal therapy - androgen-deprivation therapy (ADT) - and the risk of side effects from this therapy is increasing. A relevant decrease in bone density is increasingly seen in patients receiving ADT, which means that a disproportionate increase in risk of fractures is seen in aging patients. Urologists are confronted with these patients in clinical practice. The question is how urologist-care for these patients is organised in the Netherlands. A survey among urologists in the Netherlands revealed that there is great diversity in how they think and act, and that there is a need for national guidelines and additional training on this subject.
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February 2020

External validation of the Martini nomogram for prediction of side-specific extraprostatic extension of prostate cancer in patients undergoing robot-assisted radical prostatectomy.

Urol Oncol 2020 05 19;38(5):372-378. Epub 2020 Feb 19.

Department of Urology, Canisius Wilhelmina Hospital, Santeon-group, Nijmegen, The Netherlands.

Introduction: To establish oncological safe nerve-sparing robot-assisted radical prostatectomy, accurate assessment of extraprostatic extension (EPE) is critical. A recently developed nomogram including magnetic resonance imaging parameters accurately predicted side-specific EPE in the development cohort. The aim of this study is to assess this model's performance in an external patient population.

Patients And Methods: Model fit was assessed in a cohort of 550 patients who underwent robot-assisted radical prostatectomy in 2014 to 2017 for prostate cancer. Model calibration was evaluated using calibration slopes. Discriminative ability was quantified using the area under the receiver operating characteristic curve. Model updating was done by adjusting the linear predictor to minimize differences in expected and observed risk for EPE.

Results: A total of 792 prostate lobes were included for model validation. Discriminative ability expressed in terms of receiver operating characteristic curve was 0.78, 95%CI 0.75-0.82. Graphical evaluation of the calibration showed poor fit with a high disagreement between predicted probabilities and observed probabilities of EPE in the population. Model updating resulted in excellent agreement between mean predicted and observed probabilities. However, calibration plots showed substantial miscalibration; including both under- and overestimation.

Conclusion: External validation of the novel nomogram for the prediction of side specific EPE developed by Martini and co-workers showed good discriminative ability but poor calibration. After updating, substantial miscalibration was still present. Use of this nomogram for individualized risk predictions is therefore not recommended.
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http://dx.doi.org/10.1016/j.urolonc.2019.12.028DOI Listing
May 2020

Treatment Preferences of Patients With Benign Prostatic Hyperplasia Before and After Using a Web-based Decision Aid.

Urology 2020 Mar 30;137:138-145. Epub 2019 Dec 30.

Department of Urology, Elisabeth-Tweesteden Hospital, Tilburg, the Netherlands.

Objective: To evaluate treatment preferences of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) before and after using a web-based decision aid (DA).

Patients And Methods: Between July 2016 and January 2017 patients were invited to use a web-based LUTS/BPH DA. Treatment preferences (for lifestyle advices, medication or surgery) before and after DA use and responses on values clarification exercises were extracted from the DA.

Results: In total, 126 patients were included in the analysis. Thirty-four percent (43/126) had not received any previous treatment and were eligible for (continuation of) lifestyle advices or to start medication, as initial treatment. The other 66% (83/126) did use medication and were eligible, either for continuing medication or to undergo surgery. Before being exposed to the DA, 67 patients (53%) were undecided and 59 patients (47%) indicated an initial treatment preference. Half of the patients who were initially undecided were able to indicate a preference after DA use (34/67, 51%). Of those with an initial preference, 80% (47/59) confirmed their initial preference after DA use. Five out of 7 values clarification exercises used in the DA were discriminative between final treatment preferences. In 79%, the treatment preferred after DA use matched the received treatment. Overall, healthcare providers were positive about DA feasibility.

Conclusion: Our findings suggest that a LUTS/BPH DA may help patients to confirm their initial treatment preference and support them in forming a treatment preference if they did not have an initial preference.
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http://dx.doi.org/10.1016/j.urology.2019.12.026DOI Listing
March 2020

Reply by Authors.

J Urol 2020 03 3;203(3):545. Epub 2019 Dec 3.

Department of Radiology and Nuclear Medicine, University Medical Center, Utrecht, The Netherlands.

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http://dx.doi.org/10.1097/JU.0000000000000531.02DOI Listing
March 2020

Complications and Adverse Events of Three Magnetic Resonance Imaging-based Target Biopsy Techniques in the Diagnosis of Prostate Cancer Among Men with Prior Negative Biopsies: Results from the FUTURE Trial, a Multicentre Randomised Controlled Trial.

Eur Urol Oncol 2019 11 11;2(6):617-624. Epub 2019 Sep 11.

Department of Urology, St. Antonius Hospital, Nieuwegein/Utrecht, The Netherlands.

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 (ΔIPSS 0.3, p = 0.1) and erectile function (ΔIIEF-5 -0.4, p = 0.5). The main limitation was that additional SB was performed in FUS-TB and COG-TB, and was omitted in MRI-TB, making comparison difficult.

Conclusions: There was a significant difference in minor AEs among groups. An increase in the number of cores increased the overall risk of AEs. A low AE occurrence in MRI-TB was likely caused by the omission of SB. Prostate biopsy did not impact self-reported urinary and erectile functions.

Patient Summary: In this study, we compared the complication rates of three techniques of magnetic resonance imaging (MRI)-based targeted biopsy of the prostate. We found a significant difference in the occurrence of minor complication rates among three groups in favour of transrectal in-bore MRI targeted biopsy, likely caused by the omission of additional systematic biopsy in this group.
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http://dx.doi.org/10.1016/j.euo.2019.08.007DOI Listing
November 2019

Prospective Validation of Gallium-68 Prostate Specific Membrane Antigen-Positron Emission Tomography/Computerized Tomography for Primary Staging of Prostate Cancer.

J Urol 2020 03 6;203(3):537-545. Epub 2019 Sep 6.

Department of Radiology and Nuclear Medicine, University Medical Center, Utrecht, The Netherlands.

Purpose: Prospective validation of Ga prostate specific membrane antigen positron emission tomography/computerized tomography is lacking in initial staging of prostate cancer. In this study we evaluated the diagnostic accuracy of Ga prostate specific membrane antigen positron emission tomography/computerized tomography for detecting lymph node metastasis in patients with intermediate-high risk prostate cancer.

Materials And Methods: Patients with newly diagnosed prostate cancer and negative bone scan findings at greater than 10% MSKCC (Memorial Sloan Kettering Cancer Center) risk for lymph node metastasis were prospectively included in study from October 2017 to October 2018. In candidates for extended pelvic lymph node dissection Ga prostate specific membrane antigen positron emission tomography/computerized tomography was performed prior to planned surgery. Scan results were evaluated in a second tumor board meeting to assess a potential change of management. Sensitivity, specificity, and positive and negative predictive value for detecting lymph node metastasis were calculated per patient and per resection template using histopathology as the reference. A positron emission tomography based change of management was also reported.

Results: A total of 103 patients were eligible for analysis and 97 extended pelvic lymph node dissections were performed. In 41 patients (42.3%) there was a total of 85 lymph node metastases. Positron emission tomography was positive in 17 patients, resulting in 41.5% patient based sensitivity (95% CI 26.7-57.8) for detecting lymph node metastasis. The patient based specificity rate was 90.9% (95% CI 79.3-96.6), and positive and negative predictive values were 77.3% (95% CI 54.2-91.3) and 67.6% (95% CI 55.6-77.7), respectively. A positron emission tomography based change of treatment was observed in 13 patients (12.6%).

Conclusions: In patients with newly diagnosed prostate cancer at greater than 10% MSKCC risk for lymph node involvement Ga prostate specific membrane antigen positron emission tomography/computerized tomography detected lymph node metastasis with high specificity and moderate sensitivity. This led to a treatment change in 12.6% of patients.
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http://dx.doi.org/10.1097/JU.0000000000000531DOI Listing
March 2020

Follow-up in Active Surveillance for Prostate Cancer: Strict Protocol Adherence Remains Important for PRIAS-ineligible Patients.

Eur Urol Oncol 2019 09 10;2(5):483-489. Epub 2019 Feb 10.

Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.

Background: Active surveillance (AS) is a safe treatment strategy for men with low-risk prostate cancer (PC) when performed in a research setting using strict follow-up. However, less is known about the protocol adherence and outcomes for AS in real-world practice.

Objective: To evaluate Prostate Cancer Research International Active Surveillance (PRIAS) protocol adherence in a real-world cohort and to relate follow-up intensity to oncological safety.

Design, Setting, And Participants: Patients with biopsy-detected PC diagnosed from 2008 to 2014 treated with AS at six teaching hospitals in The Netherlands.

Intervention: AS included regular prostate-specific antigen (PSA) testing (every 3-6mo) combined with a confirmatory biopsy 1yr after diagnosis and every 3yr thereafter.

Outcome Measurements And Statistical Analysis: The proportions of patients complying with the PRIAS biopsy and PSA monitoring protocol were determined. We assessed if PRIAS-discordant follow-up was associated with a higher risk of metastasis compared with PRIAS-concordant follow-up using Cox regression analysis. Analysis was performed for separate risk groups (PRIAS-eligible and PRIAS-ineligible) on the basis of the PRIAS inclusion criteria.

Results And Limitations: Of all patients on AS for >6mo, 706/958 (74%) had PRIAS-concordant PSA monitoring. Overall concordant follow-up (PSA and repeat biopsy) was observed in 415/958 patients (43%). The percentage of patients with overall concordant follow-up varied between hospitals (range 34-60%; p<0.001). Among PRIAS-ineligible patients, PRIAS-discordant PSA monitoring was associated with a higher risk of developing PC metastases during AS compared with patients with concordant follow-up (hazard ratio 5.25, 95% confidence interval 1.02-27.1). In the PRIAS-eligible population, we found no significant differences regarding rates of metastases between patients with discordant and concordant follow-up.

Conclusions: We observed substantial variation in AS follow-up intensity between large urological practices in the Netherlands. Overall, 43% of patients on AS in daily clinical practice receive PRIAS-concordant follow-up. Noncompliance with the PRIAS follow-up protocol was associated with a higher rate of metastasis among PRIAS-ineligible patients, indicating that strict protocol adherence is important when these patients opt for AS.

Patient Summary: Fewer than half of patients with prostate cancer on active surveillance are monitored according to the follow-up protocol of the largest ongoing active surveillance study. Lower-intensity monitoring may be less safe for patients who are not in the lowest risk group.
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http://dx.doi.org/10.1016/j.euo.2019.01.010DOI Listing
September 2019

Is There Still a Need for Repeated Systematic Biopsies in Patients with Previous Negative Biopsies in the Era of Magnetic Resonance Imaging-targeted Biopsies of the Prostate?

Eur Urol Oncol 2020 04 22;3(2):216-223. Epub 2019 Jun 22.

Department of Urology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.

Background: The role of targeted prostate biopsies (TBs) in patients with cancer suspicious lesions on multiparametric magnetic resonance imaging (mpMRI) following negative systematic biopsies (SBs) is undebated. However, whether they should be combined with repeated SBs remains unclear.

Objective: To evaluate the value of repeated SBs in addition to TBs in patients with a prior negative SB and a persistent suspicion of prostate cancer (PCa).

Design, Setting, And Participants: A prospective study as part of a multicenter randomized controlled trial conducted between 2014 and 2017, including 665 men with a prior negative SB and a persistent suspicion of PCa (suspicious digital rectal examination and/or prostate-specific antigen >4.0ng/ml).

Intervention: All patients underwent 3T mpMRI according to Prostate Imaging Reporting and Data System (PI-RADS) v2. Patients with PI-RADS ≥3 were randomized 1:1:1 for three TB techniques: MRI-TRUS fusion TB (FUS-TB), cognitive registration fusion TB (COG-TB), or in-bore MRI TB. FUS-TB and COG-TB were combined with repeated SBs.

Outcome Measurements And Statistical Analysis: Clinically significant prostate cancer (csPCa) was defined as Gleason ≥3+4. Differences in detection rates of csPCa, clinically insignificant PCa (cisPCa), and overall PCa between TBs (FUS-TB and COG-TB) and repeated SBs were compared using McNemar's test.

Results And Limitations: In the 152 patients who underwent both TB and SB, PCa was detected by TB in 47% and by SB in 32% (p<0.001, 95% confidence interval [CI]: 6.0-22%). TB detected significantly more csPCa than SB (32% vs 16%; p<0.001, 95% CI: 11-25%). Clinically significant PCa was missed by TB in 1.3% (2/152). Combining SB and TB resulted in detection rate differences of 6.0% for PCa, 5.0% for cisPCa, and 1.0% for csPCa compared with TB alone.

Conclusions: In case of a persistent suspicion of PCa following a negative SB, TB detected significantly more csPCa cases than SB. The additional value of SB was limited, and only 1.3% of csPCa would have been missed when SB had been omitted.

Patient Summary: We evaluated the role of systematic biopsies and magnetic resonance imaging (MRI)-targeted biopsies for the diagnosis of prostate cancer in patients with prior negative systematic biopsies. MRI-targeted biopsies perform better in detecting prostate cancer in these patients. The value of repeated systematic biopsies is limited.
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http://dx.doi.org/10.1016/j.euo.2019.06.005DOI Listing
April 2020

Active Surveillance for Prostate Cancer in a Real-life Cohort: Comparing Outcomes for PRIAS-eligible and PRIAS-ineligible Patients.

Eur Urol Oncol 2018 08 15;1(3):231-237. Epub 2018 May 15.

Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.

Background: In daily practice, a wider range of patients with prostate cancer (PCa) are selected for active surveillance (AS) compared to those in AS trials, including higher-risk patients. However, less is known about the outcomes for off-protocol selected PCa patients who opt for AS.

Objective: To compare AS outcomes for higher-risk patients and very low-risk patients in a large cohort of patients diagnosed with PCa.

Design, Setting, And Participants: Patients diagnosed with PCa between 2008 and 2015 with clinical stage ≥T1c and managed with AS at six large teaching hospitals.

Intervention: AS included regular prostate-specific antigen (PSA) testing (every 3-6 mo) and a confirmatory biopsy 1 yr after diagnosis and every 3 yr thereafter.

Outcomes Measurements And Statistical Analysis: Using the inclusion criteria of the PRIAS study, outcomes for PRIAS-eligible patients (ie, cT1c-T2, Gleason sum score ≤6, ≤2 positive biopsy cores, PSA ≤10 ng/ml, and PSA density <0.2 ng/ml/ml) were compared to outcomes for PRIAS-ineligible patients. Unfavourable outcomes following deferred surgery, biochemical recurrence, and risk of metastasis were calculated using univariate and multivariate Cox regression analyses. Time to tumour progression was established using survival analysis.

Results And Limitations: Of the 1000 patients included and managed with AS, almost half of the patients (49%) had higher-risk disease characteristics than the PRIAS inclusion criteria. PRIAS-ineligible patients discontinued AS because of tumour progression significantly earlier than PRIAS-eligible patients (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.44-2.11); they also had a higher risk of positive surgical margins (odds ratio [OR] 2.15, 95% CI 1.11-4.17) and unfavourable pathological findings (OR 3.20, 95% CI 1.61-6.35) following deferred radical prostatectomy. PSA density ≥0.2 ng/ml/ml was the most important individual predictor and, in addition to a higher risk of tumour progression and unfavourable surgical outcomes, was also associated with a significantly higher risk of biochemical progression following deferred radical prostatectomy (OR 3.26, 95% CI 1.23-8.64). In the overall population, PSA density ≥0.2 ng/ml/ml was also associated with a higher risk of metastasis (HR 2.71, 95% CI 1.23-5.96).

Conclusions: In this cohort, approximately half of the patients did not meet the inclusion criteria of the PRIAS study. These patients had a two- to threefold higher risk of disease progression and unfavourable outcomes following deferred prostatectomy. PSA density is an important individual predictor of unfavourable outcomes and should be taken into account when selecting patients for AS.

Patient Summary: A large proportion of patients with prostate cancer on active surveillance are not in the lowest risk group. These patients have a higher risk of experiencing tumour progression to a stage requiring curative intervention. They also have worse disease prognosis compared to patients on active surveillance in the lowest risk group.
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http://dx.doi.org/10.1016/j.euo.2018.03.015DOI Listing
August 2018

Effectiveness of a web-based treatment decision aid for men with lower urinary tract symptoms due to benign prostatic hyperplasia.

BJU Int 2019 07 4;124(1):124-133. Epub 2019 Mar 4.

Department of Urology, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands.

Objectives: To evaluate the effectiveness of a web-based decision aid (DA), with values clarification exercises compared with usual care, for men with lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH).

Patients And Methods: Between July 2016 and January 2017, all new patients with LUTS/BPH who consulted the urologist were invited to use the DA and participate in this prospective questionnaire study. Patients who consulted the urologist between December 2015 and February 2016 served as controls. The DA was designed to support patients in making a well-informed treatment decision, corresponding with their personal preferences and values. Well-informed decision was measured by using a knowledge questionnaire. Value congruent decision was measured by the correspondence between responses on nine value statements and chosen treatment. The primary outcome, decision quality, was defined as the combination of well-informed decision and value congruent decision. Secondary outcomes were decisional conflict, involvement and received role in shared decision-making, decisional regret, and treatment choice.

Results: A total of 109 DA-users and 108 controls were included. DA-users were younger (68.4 vs 71.5 years; P = 0.003) and their education level was higher (P = 0.047) compared with the controls. Patients who used the DA made a well-informed and value congruent decision more often than the control group (43% vs 21%; P = 0.028). DA-users had less decisional conflict (score 33.2 vs 46.6; P = 0.003), experienced a less passive role in decision-making (22% vs 41%; P = 0.038), and reported less process regret (score 2.4 vs 2.8; P = 0.034). Furthermore, DA-users who had not used prior medication chose lifestyle advices more often than the control group (43% vs 11%; P = 0.002). Outcomes were adjusted for significantly different baseline characteristics.

Conclusion: The LUTS/BPH DA seems to improve the decision quality by supporting patients in making more well-informed and value congruent treatment decisions. Therefore, further implementation of this DA into routine care is suggested.
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http://dx.doi.org/10.1111/bju.14646DOI Listing
July 2019

Comparison of Immediate vs Deferred Cytoreductive Nephrectomy in Patients With Synchronous Metastatic Renal Cell Carcinoma Receiving Sunitinib: The SURTIME Randomized Clinical Trial.

JAMA Oncol 2019 02;5(2):164-170

The Netherlands Cancer Institute, Amsterdam, the Netherlands.

Importance: In clinical practice, patients with primary metastatic renal cell carcinoma (mRCC) have been offered cytoreductive nephrectomy (CN) followed by targeted therapy, but the optimal sequence of surgery and systemic therapy is unknown.

Objective: To examine whether a period of sunitinib therapy before CN improves outcome compared with immediate CN followed by sunitinib.

Design, Setting, And Participants: This randomized clinical trial began as a phase 3 trial on July 14, 2010, and continued until March 24, 2016, with a median follow-up of 3.3 years and a clinical cutoff date for this report of May 5, 2017. Patients with mRCC of clear cell subtype, resectable primary tumor, and 3 or fewer surgical risk factors were studied.

Interventions: Immediate CN followed by sunitinib therapy vs treatment with 3 cycles of sunitinib followed by CN in the absence of progression followed by sunitinib therapy.

Main Outcomes And Measures: Progression-free survival was the primary end point, which needed a sample size of 458 patients. Because of poor accrual, the independent data monitoring committee endorsed reporting the intention-to-treat 28-week progression-free rate (PFR) instead. Overall survival (OS), adverse events, and postoperative progression were secondary end points.

Results: The study closed after 5.7 years with 99 patients (80 men and 19 women; mean [SD] age, 60 [8.5] years). The 28-week PFR was 42% in the immediate CN arm (n = 50) and 43% in the deferred CN arm (n = 49) (P = .61). The intention-to-treat OS hazard ratio of deferred vs immediate CN was 0.57 (95% CI, 0.34-0.95; P = .03), with a median OS of 32.4 months (95% CI, 14.5-65.3 months) in the deferred CN arm and 15.0 months (95% CI, 9.3-29.5 months) in the immediate CN arm. In the deferred CN arm, 48 of 49 patients (98%; 95% CI, 89%-100%) received sunitinib vs 40 of 50 (80%; 95% CI, 67%-89%) in the immediate arm. Systemic progression before planned CN in the deferred CN arm resulted in a per-protocol recommendation against nephrectomy in 14 patients (29%; 95% CI, 18%-43%).

Conclusions And Relevance: Deferred CN did not improve the 28-week PFR. With the deferred approach, more patients received sunitinib and OS results were higher. Pretreatment with sunitinib may identify patients with inherent resistance to systemic therapy before planned CN. This evidence complements recent data from randomized clinical trials to inform treatment decisions in patients with primary clear cell mRCC requiring sunitinib.

Trial Registration: ClinicalTrials.gov identifier: NCT01099423.
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http://dx.doi.org/10.1001/jamaoncol.2018.5543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439568PMC
February 2019

The FUTURE Trial: A Multicenter Randomised Controlled Trial on Target Biopsy Techniques Based on Magnetic Resonance Imaging in the Diagnosis of Prostate Cancer in Patients with Prior Negative Biopsies.

Eur Urol 2019 04 3;75(4):582-590. Epub 2018 Dec 3.

Department of Urology, St. Antonius Hospital, Nieuwegein, Utrecht, The Netherlands.

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-TB (p>0.9, 95% CI -14% to 16%). The main study limitation was a low rate of PIRADS ≥3 lesions on mpMRI, causing underpowering for primary outcome.

Conclusions: We found no significant differences in the detection rates of (cs)PCa among the three MRI-based TB techniques.

Patient Summary: In this study, we compared the detection rates of (aggressive) prostate cancer among men with prior negative biopsies and a persistent suspicion of cancer using three different techniques of targeted biopsy based on magnetic resonance imaging. We found no significant differences in the detection rates of (aggressive) prostate cancer among the three techniques.
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http://dx.doi.org/10.1016/j.eururo.2018.11.040DOI Listing
April 2019

Comparing Three Different Techniques for Magnetic Resonance Imaging-targeted Prostate Biopsies: A Systematic Review of In-bore versus Magnetic Resonance Imaging-transrectal Ultrasound fusion versus Cognitive Registration. Is There a Preferred Technique?

Eur Urol 2017 04 25;71(4):517-531. Epub 2016 Aug 25.

Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.

Context: The introduction of magnetic resonance imaging-guided biopsies (MRI-GB) has changed the paradigm concerning prostate biopsies. Three techniques of MRI-GB are available: (1) in-bore MRI target biopsy (MRI-TB), (2) MRI-transrectal ultrasound fusion (FUS-TB), and (3) cognitive registration (COG-TB).

Objective: To evaluate whether MRI-GB has increased detection rates of (clinically significant) prostate cancer (PCa) compared with transrectal ultrasound-guided biopsy (TRUS-GB) in patients at risk for PCa, and which technique of MRI-GB has the highest detection rate of (clinically significant) PCa.

Evidence Acquisition: We performed a literature search in PubMed, Embase, and CENTRAL databases. Studies were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 checklist and START recommendations. The initial search identified 2562 studies and 43 were included in the meta-analysis.

Evidence Synthesis: Among the included studies 11 used MRI-TB, 17 used FUS-TB, 11 used COG-TB, and four used a combination of techniques. In 34 studies concurrent TRUS-GB was performed. There was no significant difference between MRI-GB (all techniques combined) and TRUS-GB for overall PCa detection (relative risk [RR] 0.97 [0.90-1.07]). MRI-GB had higher detection rates of clinically significant PCa (csPCa) compared with TRUS-GB (RR 1.16 [1.02-1.32]), and a lower yield of insignificant PCa (RR 0.47 [0.35-0.63]). There was a significant advantage (p = 0.02) of MRI-TB compared with COG-TB for overall PCa detection. For overall PCa detection there was no significant advantage of MRI-TB compared with FUS-TB (p=0.13), and neither for FUS-TB compared with COG-TB (p=0.11). For csPCa detection there was no significant advantage of any one technique of MRI-GB. The impact of lesion characteristics such as size and localisation could not be assessed.

Conclusions: MRI-GB had similar overall PCa detection rates compared with TRUS-GB, increased rates of csPCa, and decreased rates of insignificant PCa. MRI-TB has a superior overall PCa detection compared with COG-TB. FUS-TB and MRI-TB appear to have similar detection rates. Head-to-head comparisons of MRI-GB techniques are limited and are needed to confirm our findings.

Patient Summary: Our review shows that magnetic resonance imaging-guided biopsy detects more clinically significant prostate cancer (PCa) and less insignificant PCa compared with systematic biopsy in men at risk for PCa.
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http://dx.doi.org/10.1016/j.eururo.2016.07.041DOI Listing
April 2017

An Ex Vivo Phantom Validation Study of an MRI-Transrectal Ultrasound Fusion Device for Targeted Prostate Biopsy.

J Endourol 2016 06 16;30(6):685-91. Epub 2016 Mar 16.

1 Department of Urology, St. Antonius Hospital , Nieuwegein, The Netherlands .

Objectives: To evaluate the ex vivo accuracy of an MRI-TRUS fusion device for guiding targeted prostate biopsies, to identify the origin of errors, and to evaluate the likelihood that lesions can be accurately targeted.

Materials And Methods: Three prostate phantoms were used to perform 27 biopsies using transperineal MRI-TRUS fusion. All phantoms underwent 3-T MRI. The prostate contour and nine lesions were delineated onto the MRI. A 3D-US dataset was generated and fused with the MRI. Per lesion, one needle was virtually planned. The postbiopsy needle location was virtually registered. The needle trajectory was marked using an MRI-safe guidewire. Postinterventional MRI was performed. The coordinates of the lesion on preinterventional MRI, the virtually planned needle, the virtually registered needle, and the marked needle trajectory on postinterventional MRI were documented and used to calculate the planning error (PE), targeting error (TE), and overall error (OE). Using the OE in the transversal plane, an upper one-sided tolerance interval was calculated to assess the likelihood that a biopsy needle was on target.

Results: In the transversal plane, the mean PE, TE, and OE were 1.18, 0.39, and 2.33 mm, respectively. Using a single biopsy core, the likelihood that lesions with a diameter of 2 mm can be accurately targeted is 26%; lesions of 3 mm 61%; lesions of 4 mm 86%; lesions of 5 mm 96%; and lesions of 6 mm 99%. The likelihood of accurate sampling increases if more biopsy cores are used.

Conclusion: MRI-TRUS fusion allows for accurate sampling of MRI-identified lesions with an OE of 2.33 mm. Lesions with a diameter of 3 mm or more can be accurately targeted. These results should be considered the lower limit of in vivo accuracy.
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http://dx.doi.org/10.1089/end.2015.0864DOI Listing
June 2016

The Effects of Instrumentation on Urine Cytology and CK-20 Analysis for the Detection of Bladder Cancer.

Urology 2015 Oct 9;86(4):772-6. Epub 2015 Jul 9.

Department of Urology, St Antonius Hospital, Nieuwegein, The Netherlands.

Objective: To evaluate the effects of cystoscopy on urine cytology and additional cytokeratin-20 (CK-20) staining in patients presenting with gross hematuria.

Patients And Methods: For 83 patients presenting with gross hematuria, spontaneous and instrumented paired urine samples were analyzed. Three patients were excluded. Spontaneous samples were collected within 1 hour before cystoscopy, and the instrumented samples were tapped through the cystoscope. Subsequently, patients underwent cystoscopic evaluation and imaging of the urinary tract. If tumor suspicious lesions were found on cystoscopy or imaging, subjects underwent transurethral resection or ureterorenoscopy. Two blinded uropathological reviewers (DB, KK) evaluated 160 urine samples. Reference standards were results of cystoscopy, imaging, or histopathology.

Results: Thirty-seven patients (46.3%) underwent transurethral resection or ureterorenoscopy procedures. In 30 patients (37.5%) tumor presence was confirmed by histopathology. The specificity of urine analysis was significantly higher for spontaneous samples than instrumented samples for both cytology alone (94% vs 72%, P = .01) and for cytology combined with CK-20 analysis (98% vs 84%, P = .02). The difference in sensitivity between spontaneous and instrumented samples was not significant for both cytology alone (40% vs 53%) and combined with CK-20 analysis (67% vs 67%). The addition of CK-20 analysis to cytology significantly increases test sensitivity in spontaneous urine cytology (67% vs 40%, P = .03).

Conclusion: Instrumentation significantly decreases specificity of urine cytology. This may lead to unnecessary diagnostic procedures. Additional CK-20 staining in spontaneous urine cytology significantly increases sensitivity but did not improve the already high specificity. We suggest performing urine cytology and CK-20 analysis on spontaneously voided urine.
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http://dx.doi.org/10.1016/j.urology.2015.06.035DOI Listing
October 2015

The blind spots in follow-up after nephrectomy or nephron-sparing surgery for localized renal cell carcinoma.

World J Urol 2015 Jun 2;33(6):881-7. Epub 2014 Sep 2.

Department of Urology, Radboud University Medical Center, P.O. box 9101, 6525 GA, Nijmegen, The Netherlands,

Purpose: This study was conducted to identify time to and type of recurrence in relation to scheduled follow-up (FU) imaging after nephrectomy or nephron-sparing surgery for localized renal cell carcinoma (RCC). Using this information, future guidelines could improve the early detection of metastases.

Methods: Measured from moment of treatment, all recurrences after (partial) nephrectomy performed between 2000 and 2010 were categorized as being detected early (<6 months), late (>5 year for T1/T2 and >10 year for T3/T4), or intermediate (time within those two) based on European Association of Urology (EAU) guidelines. Also symptomatic presentation was screened.

Results: Recurrent disease developed in 80 of 396 patients after (partial) tumor nephrectomy. Mean time to recurrence in months was 56 (n = 21) for T1, 24 (n = 18) for T2, 21 (n = 38) for T3, and 11 (n = 2) for T4 tumors. Detection of early recurrence occurred in 22 patients (28%), of which 20 (91%) were T2-T4 tumors. In 10 (48%) of T1 tumors, late recurrence was found. Of the patients with symptoms due to recurrence, 65% (17/26) were detected outside the FU surveillance protocol (P = 0.01).

Conclusion: A more intensive FU the first 6 months after nephrectomy for T2-T4 and FU imaging ≥5 years after surgery for T1 tumors might improve early and asymptomatic detection of recurrent disease after nephrectomy for RCC.
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http://dx.doi.org/10.1007/s00345-014-1390-6DOI Listing
June 2015

3D cone-beam CT guidance, a novel technique in renal biopsy--results in 41 patients with suspected renal masses.

Eur Radiol 2012 Nov 2;22(11):2547-52. Epub 2012 Jun 2.

Department of Radiology, St Antonius Hospital, PO Box 2500, 3430 EM, Nieuwegein, The Netherlands.

Objective: To determine whether 3D cone-beam computed tomography (CBCT) guidance allows safe and accurate biopsy of suspected small renal masses (SRM), especially in hard-to-reach anatomical locations.

Materials And Methods: CBCT guidance was used to perform 41 stereotactic biopsy procedures of lesions that were inaccessible for ultrasound guidance or CT guidance. In CBCT guidance, a 3D-volume data set is acquired by rotating a C-arm flat-panel detector angiosystem around the patient. In the data set, a needle trajectory is determined and, after co-registration, a fusion image is created from fluoroscopy and a slice from the data set, enabling the needle to be positioned in real time.

Results: Of the 41 lesions, 22 were malignant, 17 were benign, and 2 were nondiagnostic. The two nondiagnostic lesions proved to be renal cell carcinoma. There was no growth during follow-up imaging of the benign lesions (mean 29 months). This resulted in a sensitivity, specificity, PPV, NPV, and accuracy of 91.7, 100, 100, 89.5, and 95.1%, respectively. Mean dose-area product value was 44.0 Gy·cm(2) (range 16.5-126.5). There was one minor bleeding complication.

Conclusion: With CBCT guidance, safe and accurate biopsy of a suspected SRM is feasible, especially in hard-to-reach locations of the kidney.

Key Points : • Cone-beam computed tomography has potential advantages over conventional CT for interventional procedures. • CBCT guidance incorporates 3D CBCT data, fluoroscopy, and guidance software. • In hard-to-reach renal masses, CBCT guidance offers an alternative biopsy method. • CBCT guidance offers good outcome and safety and has potential clinical significance.
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http://dx.doi.org/10.1007/s00330-012-2498-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472072PMC
November 2012

Incomplete thermal ablation stimulates proliferation of residual renal carcinoma cells in a translational murine model.

BJU Int 2012 Sep 22;110(6 Pt B):E281-6. Epub 2012 May 22.

Department of Urology, University Medical Center Utrecht, Utrecht, The Netherlands.

Unlabelled: What's known on the subject? and What does the study add? Thermal ablation influences the local tissue microenvironment. Several studies have reported that residual tumour cells may exhibit a more aggressive phenotype. This study shows that incomplete CA and RFA cause an increased proliferation and decreased apptosis of residual renal tumour cells. This may be caused by stimulatory factors such as hypoxia, HSPs and inflammatory cells.

Objective: To compare the effect of incomplete thermal ablation vs partial nephrectomy (PN) on growth stimulation and cellular survival in renal tumours.

Materials And Methods: Renca renal tumours were transplanted under the renal capsule of mice (four to six mice/group) after which incomplete radiofrequency ablation (RFA), cryoablation (CA) or PN was performed. At several time points after treatment, presence of cell proliferation, apoptosis, hypoxic areas, inflammatory factors and the heat-shock proteins (HSPs) 70 and 90 were evaluated using immunohistochemistry.

Results: At 2 h after thermal ablation residual tumour cells showed increased proliferation. This hyperproliferation was significantly stronger after RFA than CA (P < 0.05) and not present after PN. Residual cells showed increased apoptosis after 2 h and decreased apoptosis from 2 days after thermal ablation. Apoptotic cells were significantly less evident at 3 days after RFA (P < 0.001). Hypoxic areas and HSPs were increasingly present from 2 h up to 7 days after thermal ablation (P < 0.001). Inflammatory cells infiltrated mainly the necrotic areas after thermal ablation, and their abundance peaked at 1 week after ablation (P < 0.05). The increased cell growth was preceded by hypoxia and presence of HSPs.

Conclusions: CA and RFA result in an increased proliferation and decreased apoptosis of residual renal tumour cells. This hyperproliferation may be caused by stimulatory factors, e.g. hypoxia, HSPs and inflammatory cells, and could facilitate recurrences of renal tumours after thermal ablation. This study highlights the importance of achieving complete tumour destruction.
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http://dx.doi.org/10.1111/j.1464-410X.2012.11261.xDOI Listing
September 2012

Expression of nuclear FIH independently predicts overall survival of clear cell renal cell carcinoma patients.

Eur J Cancer 2010 Dec 13;46(18):3375-82. Epub 2010 Aug 13.

Department of Urology, University Medical Center Utrecht, The Netherlands.

Aim: The hypoxia inducible factor (HIF) pathway plays an important role in sporadic clear cell renal cell carcinoma (ccRCC) by stimulating processes of angiogenesis, cell proliferation, cell survival and metastases formation. Herein, we evaluate the significance of upstream proteins directly regulating the HIF pathway; the prolyl hydroxylases domain proteins (PHD)1, 2 and 3 and factor-inhibiting HIF (FIH), as prognostic markers for ccRCC.

Methods: Immunohistochemical marker expression was examined on a tissue microarray containing tumour tissue derived from 100 patients who underwent nephrectomy for ccRCC. Expression levels of HIF, FIH and PHD1, 2 and 3 were correlated with overall survival (OS) and clinicopathological prognostic factors.

Results: HIF-1α was positively correlated with HIF-2α (p<0.0001), PHD1 (p = 0.024), PHD2 (p<0.0001), PHD3 (p = 0.004), FIH (p<0.0001) and VHL (p = 0.031). HIF-2α levels were significantly associated with FIH (p<0.0001) and PHD2 (p = 0.0155). Mutations in the VHL gene, expression variations of HIF-1α, HIF-2α and PHD1, 2, 3 did not show a correlation to OS or clinicopathological prognostic factors. Tumour stage, grade, diameter, metastastic disease and intensity of nuclear FIH were significantly correlated to OS in univariable analysis (p = 0.023). Low nuclear FIH levels remained a strong independent prognostic factor in multivariable analysis (p = 0.009).

Conclusion: These results show that low nuclear expression of FIH is a strong independent prognostic factor for a poor overall survival in ccRCC.
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http://dx.doi.org/10.1016/j.ejca.2010.07.018DOI Listing
December 2010

A 10-year follow-up after transurethral resection of the prostate, contact laser prostatectomy and electrovaporization in men with benign prostatic hyperplasia; long-term results of a randomized controlled trial.

BJU Int 2010 Sep 22;106(6):822-6. Epub 2010 Feb 22.

Departments of Urology, University Medical Center, Utrecht, the Netherlands.

Objective: To compare long-term results of transurethral resection of the prostate (TURP), contact laser prostatectomy (CLP) and electrovaporization of the prostate (EVAP) in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH).

Patients And Methods: Between 1996 and 2001, a prospective, randomized controlled trial was conducted in 150 men with LUTS suggestive of BPH, who had a prostate volume of 20-65 mL and a Schäfer's obstruction grade of > or =2. Outcome variables were the International Prostate Symptom Score (IPSS), Quality of Life (QoL) question, Symptom Problem Index (SPI), BPH Impact Index (BII), maximum urinary flow rate (Q(max)), prostate volume, prostate specific antigen (PSA) level, morbidity and mortality. In 2008 we carried out a long-term follow-up in these patients. Long-term values were compared with preoperative values for each treatment group (Wilcoxon signed-rank test), differences among groups were analysed (Kruskal-Wallis test) and actuarial failure-rates of the interventions were determined (Kaplan-Meier analysis).

Results: Although we could account for 91% of the initial participants in 2008, 66 (44%) patients (29 TURP, 20 CLP and 17 EVAP) were available for follow-up measurements after a mean (range) of 10.1(6.9-12.7) years Among the three treatment groups, there were no significant differences in IPSS, QoL, SPI, BII, Q(max), PSA level and prostate volume. The IPSS, QoL, SPI and BII were still improved (P < 0.05) from values before treatment for all treatments. Only in the TURP group were the long-term results of Q(max) still improved (P < 0.05). The mortality rate was comparable among the treatments. The 10-year actuarial failure rates (95% confidence interval) were 0.11 (0.03-0.20), 0.22 (0.10-0.35) and 0.23 (0.11-0.35) for TURP, CLP and EVAP, respectively.

Conclusions: After a mean follow-up of 10.1 years, there were similar and durable improvements in IPSS, QoL, SPI and BII for patients with LUTS suggestive of BPH after TURP, CLP and EVAP. Between the treatment groups there were no statistically significant differences in Q(max), PSA levels and prostate volume at any time during the follow-up. However, only patients treated with TURP showed minimal durable improvements in Q(max). There was no statistically significant difference in success rate and mortality rate among the three treatments.
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http://dx.doi.org/10.1111/j.1464-410X.2010.09229.xDOI Listing
September 2010

Diagnostic and predictive value of voiding diary data versus prostate volume, maximal free urinary flow rate, and Abrams-Griffiths number in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

Urology 2008 Mar;71(3):469-74

Department of Urology, University Medical Center, Utrecht, The Netherlands.

Objectives: To investigate the information of voiding data in relation to symptoms and well-being in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and to compare this information with that of prostate volume (Vprostate), maximal free urinary flow rate (Q(max,free)), and obstruction grade (OG).

Methods: We performed mandatory tests, recommended tests, and pressure-flow studies in 384 consecutive men with LUTS suggestive of BPH. We estimated nocturia, diuria, and mean voided volume (Vmean) from their voiding diaries. Symptoms and well-being were quantified by American Urological Association symptom index (SI), quality-of-life score (QoL), symptom problem index (SPI), and BPH impact index (BII). We investigated the influence of Vprostate, Q(max,free), OG, Vmean, nocturia, and diuria on SI, QoL, SPI, and BII. We re-evaluated 48 men 6 months after transurethral resection of the prostate (TURP). We analyzed the predictive value of preoperative Q(max,free), Vprostate, OG, Vmean, nocturia, and diuria for the improvements of SI, QoL, SPI, and BII after TURP. We studied the improvements of Q(max,free), OG, Vmean, nocturia, and diuria after TURP and the improvements of SI, QoL, SPI, and BII.

Results: Prostate volume, Q(max,free), and OG were only slightly associated with SI, QoL, SPI, and BII, in contrast to Vmean, nocturia, and diuria. The predictive value of all parameters on the outcome of TURP was poor. Improvements of all parameters were strongly associated with improvements of SI, QoL, SPI, and BII after TURP.

Conclusions: Voiding data should have a prominent role in the initial evaluation of men with LUTS suggestive of BPH.
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http://dx.doi.org/10.1016/j.urology.2007.11.033DOI Listing
March 2008

Cost aspects of transurethral resection of the prostate, contact laser prostatectomy, and electrovaporization.

Urology 2004 May;63(5):882-6

Department of Urology, University Medical Center Utrecht, Utrecht, The Netherlands.

Objectives: To compare the costs of transurethral resection of the prostate (TURP), contact laser prostatectomy (CLP), and electrovaporization in men with lower urinary tract symptoms associated with benign prostatic hyperplasia.

Methods: We conducted a randomized controlled trial that included men with lower urinary tract symptoms who met the criteria of the International Scientific Committee on benign prostatic hyperplasia. Subjective changes were quantified using questionnaires validated by the American Urological Association. The maximal free urinary flow rate was estimated. Morbidity and mortality were registered. These parameters were measured at regular intervals for up to 1 year and once during long-term follow-up. A cost analysis together with a sensitivity analysis was performed on the basis of a follow-up of 12 months.

Results: A total of 50 men were randomized to TURP, 45 to laser treatment, and 46 to electrovaporization. The subjective and objective changes were very similar during the 12 months of follow-up. The costs were highest for CLP (1885 dollars), followed by TURP (1707 dollars), and were lowest for electrovaporization (1489 dollars). However, the length of hospital stay decreased during the trial more for CLP and electrovaporization than for TURP. Recalculations demonstrated almost equal costs for CLP and TURP (1697 dollars and 1643 dollars, respectively) and the lowest costs for electrovaporization (1386 dollars).

Conclusions: Electrovaporization has a better cost-effectiveness than CLP and TURP in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia. CLP and TURP showed very similar cost-effectiveness ratios.
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http://dx.doi.org/10.1016/j.urology.2003.12.008DOI Listing
May 2004