Publications by authors named "Joep G H van Roermund"

23 Publications

  • Page 1 of 1

Management of upper urinary tract problems after radical cystectomy for urothelial carcinoma: tips and tricks.

Curr Opin Urol 2021 Jun 16. Epub 2021 Jun 16.

Department of Urology, Maastricht University Medical Centre +, Maastricht Department of Urology, Zuyderland Hospital, Heerlen, Netherlands.

Purpose Of Review: After radical cystectomy (RC) patients are at risk for both benign and malignant problems regarding the upper urinary tract (UUT). This review summarizes the recent literature and provides tips on how to manage problems of the UUT after RC.

Recent Findings: Disease recurrence, kidney stones and ureteroenteric strictures (UES) are common after RC. Endourological techniques can be used to treat low-grade disease recurrence, either with a retrograde or antegrade approach. Treatment success depends on getting access to the UUT and on tumor characteristics; selecting the right approach is key. Kidney stones can be treated endourologically with good results. With use of minimal invasive techniques such as robot cystectomy, a higher incidence of UES is observed. The use of indocyanine green could help to prevent this complication. In case of a stricture, primary reconstruction should be the treatment strategy of choice.

Summary: After RC, recurrence of the UUT remains a complicated problem. Choice of treatment method should be tailored to the patient and tumor characteristics. Kidney stones after cystectomy can be successfully managed endourological. Robot assisted RC introduced a higher rate of UES, which should be managed by primary revision.
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http://dx.doi.org/10.1097/MOU.0000000000000905DOI Listing
June 2021

Development of a Management Algorithm for Acute and Chronic Radiation Urethritis and Cystitis.

Urol Int 2021 Jun 15:1-12. Epub 2021 Jun 15.

Department of Urology, St. Antonius Hospital, Gronau, Germany.

Objective: The purpose of this review was to summarize the current literature on the assessment and treatment of radiation urethritis and cystitis (RUC) for the development of an evidenced-based management algorithm.

Material And Methods: The PubMed/MEDLINE database was searched by a multidisciplinary group of experts in January 2021.

Results: In total, 48 publications were identified. Three different types of RUC can be observed in clinical practice: inflammation-predominant, bleeding-predominant, and the combination of inflammation- and bleeding-RUC. There is no consensus on the optimal treatment of RUC. Inflammation-predominant RUC should be treated symptomatically based on the existence of bothersome storage or voiding lower urinary tract symptom as well as on pain. When bleeding-predominant RUC has occurred, hydration and hyperbaric oxygen therapy (HOT) should be used first and, if HOT is not available, oral drugs instead (sodium pentosane polysulfate, aminocaproic acid, immunokine WF 10, conjugated estrogene, or pentoxifylline + vitamin E). If local bleeding persists, focal therapy of bleeding vessels with a laser or electrocoagulation is indicated. In case of generalized bleeding, intravesical installation should be initiated (formalin, aluminium salts, and hyaluronic acid/chondroitin). Vessel embolization is a less invasive treatment with potentially less complications and good clinical outcomes. Open- or robot-assisted surgery is indicated in patients with permanent, life-threatening bleeding, or fistulae.

Conclusions: Treatment of RUC, if not self-limiting, should be done according to the type of RUC and in a stepwise approach. Conservative/medical treatment (oral and topic agents) should primarily be used before invasive (transurethral) treatments.
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http://dx.doi.org/10.1159/000515716DOI Listing
June 2021

Is prostate cancer radiotherapy using implantable rectum spacers safe and effective in inflammatory bowel disease patients?

Clin Transl Radiat Oncol 2021 Mar 25;27:121-125. Epub 2021 Jan 25.

Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, the Netherlands.

Background: Prostate cancer radiotherapy (RT) in patients with (active) inflammatory bowel disease (IBD) remains controversial. We hypothesized that RT in combination with a biodegradable prostate-rectum spacer balloon implantation, might be a safe treatment approach with acceptable toxicities for these high risk for rectal toxicity patients.

Materials And Methods: We report on a small prospective mono-centric series of 8 patients with all-risk prostate cancer with the comorbidity of an IBD. Four patients had Crohn's disease and 4 patients had ulcerative colitis. One out of four had an active status of IBD. All patients were intended to be treated with curative high-dose RT: 5 patients were treated with external beam RT (70 Gray (Gy) in 28 fractions), and 3 patients were treated with I-implant (145 Gy). Toxicities were scored according to the CTCAE v4.03: acute side effects occur up to 3 months after RT, and late side effects start after 3 months.

Results: Median follow-up was 13 months (range: 3-42 months). Only one acute grade 2 gastro-intestinal (GI) toxicity was observed: an increased diarrhea (4-6 above baseline) during RT, which resolved completely 6 weeks after treatment. No late grade 3 or more GI toxicity was reported, and no acute and late grade ≥2 genitourinary toxicity events were observed.

Conclusion: Prostate cancer patients with IBD are a challenge to treat with RT. Our results suggest that RT in combination with a balloon implant in selective patients with (active) IBD may be promising, however additional validation is needed.
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http://dx.doi.org/10.1016/j.ctro.2021.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875819PMC
March 2021

Exhaled-breath Testing for Prostate Cancer Based on Volatile Organic Compound Profiling Using an Electronic Nose Device (Aeonose™): A Preliminary Report.

Eur Urol Focus 2020 11 24;6(6):1220-1225. Epub 2018 Nov 24.

Department of Urology, Maastricht University Medical Centre, Maastricht, The Netherlands. Electronic address:

Background: Prostate biopsy, an invasive examination, is the gold standard for diagnosing prostate cancer (PCa). There is a need for a novel noninvasive diagnostic tool that achieves a significantly high pretest probability for PCa, reducing unnecessary biopsy numbers. Recent studies have shown that volatile organic compounds (VOCs) in exhaled breath can be used to detect different types of cancers via training of an artificial neural network (ANN).

Objective: To determine whether exhaled-breath analysis using a handheld electronic nose device can be used to discriminate between VOC patterns between PCa patients and healthy individuals.

Design, Setting, And Participants: This prospective pilot study was conducted in the outpatient urology clinic of the Maastricht University Medical Center, the Netherlands. Patients with histologically proven PCa were already included before initial biopsy or during follow-up, with no prior treatment for their PCa. Urological patients with negative biopsies in the past year or patients with prostate enlargement (PE) with low or stable serum prostate-specific antigen were used as controls. Exhaled breath was probed from 85 patients: 32 with PCa and 53 controls (30 having negative biopsies and 23 PE).

Outcome Measurements And Statistical Analysis: Patient characteristics were statistically analyzed using independent sample t test and Pearson's chi-square test. Data analysis was performed by Aethena software after data compression using the TUCKER3 algorithm. ANN models were trained and evaluated using the leave-10%-out cross-validation method.

Results And Limitations: Our trained ANN showed an accuracy of 0.75, with an area under the curve of 0.79 with sensitivity and specificity of 0.84 (95% confidence interval [CI] 0.66-0.94) and 0.70 (95% CI 0.55-0.81) respectively, comparing PCa with control individuals. The negative predictive value was found to be 0.88. The main limitation is the relatively small sample size.

Conclusions: Our findings imply that the Aeonose allows us to discriminate between patients with untreated, histologically proven primary PCa and control patients based on exhaled-breath analysis.

Patient Summary: We explored the possibility of exhaled-breath analysis using an electronic nose, to be used as a noninvasive tool in clinical practice, as a pretest for diagnosing prostate cancer. We found that the electronic nose was able to discriminate between prostate cancer patients and control individuals.
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http://dx.doi.org/10.1016/j.euf.2018.11.006DOI Listing
November 2020

Multifaceted Mechanisms of Cisplatin Resistance in Long-Term Treated Urothelial Carcinoma Cell Lines.

Int J Mol Sci 2018 Feb 16;19(2). Epub 2018 Feb 16.

Department of Urology, Medical Faculty, Heinrich Heine University, 40225 Duesseldorf, Germany.

Therapeutic efficacy of cisplatin-based treatment of late stage urothelial carcinoma (UC) is limited by chemoresistance. To elucidate underlying mechanisms and to develop new approaches for overcoming resistance, we generated long-term cisplatin treated (LTT) UC cell lines, characterised their cisplatin response, and determined the expression of molecules involved in cisplatin transport and detoxification, DNA repair, and apoptosis. Inhibitors of metallothioneins and Survivin were applied to investigate their ability to sensitise towards cisplatin. Cell growth, proliferation, and clonogenicity were examined after cisplatin treatment by MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, EdU (5-ethynyl-2'-deoxyuridine) incorporation assay, and Giemsa staining, respectively. Cell cycle distribution and apoptosis were quantified by flow cytometry. mRNA and protein expressions were measured by real-time quantitative (qRT)-PCR, western blot, or immunofluorescence staining. LTTs recovered rapidly from cisplatin stress compared to parental cells. In LTTs, to various extents, cisplatin exporters and metallothioneins were induced, cisplatin adduct levels and DNA damage were decreased, whereas expression of DNA repair factors and specific anti-apoptotic factors was elevated. Pharmacological inhibition of Survivin, but not of metallothioneins, sensitised LTTs to cisplatin, in an additive manner. LTTs minimise cisplatin-induced DNA damage and evade apoptosis by increased expression of anti-apoptotic factors. The observed diversity among the four LTTs highlights the complexity of cisplatin resistance mechanisms even within one tumour entity, explaining heterogeneity in patient responses to chemotherapy.
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http://dx.doi.org/10.3390/ijms19020590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855812PMC
February 2018

Prostate Cancer Radiation Therapy: What Do Clinicians Have to Know?

Biomed Res Int 2016 28;2016:6829875. Epub 2016 Dec 28.

Department of Radiation Oncology (MAASTRO Clinic), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands.

Radiotherapy (RT) for prostate cancer (PC) has steadily evolved over the last decades, with improving biochemical disease-free survival. Recently population based research also revealed an association between overall survival and doses ≥ 75.6 Gray (Gy) in men with intermediate- and high-risk PC. Examples of improved RT techniques are image-guided RT, intensity-modulated RT, volumetric modulated arc therapy, and stereotactic ablative body RT, which could facilitate further dose escalation. Brachytherapy is an internal form of RT that also developed substantially. New devices such as rectum spacers and balloons have been developed to spare rectal structures. Newer techniques like protons and carbon ions have the intrinsic characteristics maximising the dose on the tumour while minimising the effect on the surrounding healthy tissue, but clinical data are needed for confirmation in randomised phase III trials. Furthermore, it provides an overview of an important discussion issue in PC treatment between urologists and radiation oncologists: the comparison between radical prostatectomy and RT. Current literature reveals that all possible treatment modalities have the same cure rate, but a different toxicity pattern. We recommend proposing the possible different treatment modalities with their own advantages and side-effects to the individual patient. Clinicians and patients should make treatment decisions together () while using patient decision aids.
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http://dx.doi.org/10.1155/2016/6829875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225325PMC
February 2017

Phenotype plasticity rather than repopulation from CD90/CK14+ cancer stem cells leads to cisplatin resistance of urothelial carcinoma cell lines.

J Exp Clin Cancer Res 2015 Nov 25;34:144. Epub 2015 Nov 25.

Department of Urology, Medical Faculty, Heinrich-Heine-University Duesseldorf, Universitaetsstrasse 1, 40225, Düsseldorf, Germany.

Background: Tumour heterogeneity and resistance to systemic treatment in urothelial carcinoma (UC) may arise from cancer stem cells (CSC). A recent model describes cellular differentiation states within UC based on corresponding expression of surface markers (CD) and cytokeratins (CK) with CD90 and CK14 positive cells representing the least differentiated and most tumourigenic population. Based on the fact that this population is postulated to constitute CSCs and the origin of cisplatin resistance, we enriched urothelial carcinoma cell lines (UCCs) for CD90 and studied the tumour-initiating potential of these separated cells in vitro.

Methods: Magnetic- and fluorescence-activated- cell sorting were used for separation of CD90(+) and CD90(-) UCCs. Distribution of cell surface markers CD90, CD44, and CD49f and cytokeratins CK14, CK5, and CK20 as well as the effects of short- and long-term treatment with cisplatin were assessed in vitro and measured by qRT-PCR, immunocytochemistry, reporter assay and flow cytometry in 11 UCCs.

Results: We observed cell populations with surface markers according to those reported in tumour xenografts. However, expression of cytokeratins did not concord regularly with that of the surface markers. In particular, expression of CD90 and CK14 diverged during enrichment of CD90(+) cells by immunomagnetic sorting or following cisplatin treatment. Enriched CD90(+) cells did not exhibit CSC-like characteristics like enhanced clonogenicity and cisplatin resistance. Moreover, selection of cisplatin-resistant sublines by long-term drug treatment did not result in enrichment of CD90(+) cells. Rather, these sublines displayed significant phenotypic plasticity expressing EMT markers, an altered pattern of CKs, and WNT-pathway target genes.

Conclusions: Our findings indicate that the correspondence between CD surface markers and cytokeratins reported in xenografts is not maintained in commonly used UCCs and that CD90 may not be a stable marker of CSC in UC. Moreover, UCCs cells are capable of substantial phenotypic plasticity that may significantly contribute to the emergence of cisplatin resistance.
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http://dx.doi.org/10.1186/s13046-015-0259-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4660687PMC
November 2015

[Rectal bleeding after radiotherapy for prostate cancer].

Ned Tijdschr Geneeskd 2014 ;158:A7698

Maastricht Universitair Medisch Centrum, Maastricht.

This clinical lesson, based on two case histories, illustrates a complication seen after manipulation of the rectal wall in patients who have undergone radiotherapy for localised prostate cancer. Rectal bleeding, which is feared by patients, can be the first sign of radiation proctitis. Manipulation of the rectal wall, for example by taking biopsies or Argon plasma coagulation, should be done with caution and only if absolutely necessary, because it can lead to fistula formation.
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April 2015

Prostate brachytherapy and second primary cancer risk: a competitive risk analysis.

J Clin Oncol 2011 Dec 24;29(34):4510-5. Epub 2011 Oct 24.

Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.

Purpose: To assess the risk of second primary cancer (SPC) after [(125)I]iodine prostate cancer brachytherapy compared with prostatectomy and the general population.

Patients And Methods: In a cohort consisting of 1,888 patients with prostate cancer who received monotherapy with brachytherapy (n = 1,187; 63%) or prostatectomy (n = 701; 37%), SPC incidences were retrieved by linkage with the Dutch Cancer Registry. Standardized incidence rates (SIRs) and absolute excess risks (AERs) were calculated for comparison.

Results: A total of 223 patients were diagnosed with SPC, 136 (11%) after brachytherapy and 87 (12%) after prostatectomy, with a median follow-up of 7.5 years. The SIR for all malignancies, bladder cancer, and rectal cancer were 0.94 (95% CI, 0.78 to 1.12), 1.69 (95% CI, 0.98 to 2.70), and 0.90 (95% CI, 0.41 to 1.72) for brachytherapy and 1.04 (95% CI, 0.83 to 2.28), 1.82 (95% CI, 0.87 to 3.35), and 1.50 (95% CI, 0.68 to 2.85) for prostatectomy, respectively. Bladder SPC risk was significantly increased after brachytherapy for patients age 60 years or younger (SIR, 5.84; 95% CI, 2.14 to 12.71; AER, 24.03) and in the first 4 years of follow-up (SIR, 2.14; 95% CI, 1.03 to 3.94; AER, 12.24). Adjusted for age, the hazard ratio (brachytherapy v prostatectomy) for all SPCs combined was 0.87 (95% CI, 0.64 to 1.18).

Conclusion: Overall, we found no difference in SPC incidence between patients with prostate cancer treated with prostatectomy or brachytherapy. Furthermore, no increased tumor incidence was found compared with the general population. We observed a higher than expected incidence of bladder SPC after brachytherapy in the first 4 years of follow-up, probably resulting from lead time or screening bias. Because of power limitations, a small increased SPC risk cannot be formally excluded.
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http://dx.doi.org/10.1200/JCO.2011.35.0991DOI Listing
December 2011

Prostate specific antigen bounce is related to overall survival in prostate brachytherapy.

Int J Radiat Oncol Biol Phys 2012 Feb 6;82(2):883-8. Epub 2011 Feb 6.

Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.

Purpose: To investigate the association between prostate specific antigen (PSA) bounce and disease outcome after prostate brachytherapy.

Methods And Materials: We analyzed 975 patients treated with (125)I implantation monotherapy between 1992 and 2006. All patients had tumor Stage ≤ 2c, Gleason score ≤ 7 prostate cancer, a minimum follow-up of 2 years with at least four PSA measurements, and no biochemical failure in the first 2 years. Median follow-up was 6 years. Bounce was defined as a PSA elevation of +0.2 ng/mL with subsequent decrease to previous nadir. We used the Phoenix +2 ng/mL definition for biochemical failure. Additional endpoints were disease-specific and overall survival. Multivariate Cox regression analysis was performed to adjust for potential confounding factors.

Results: Bounce occurred in 32% of patients, with a median time to bounce of 1.6 years. More than 90% of bounces took place in the first 3 years after treatment and had disappeared within 2 years of onset. Ten-year freedom from biochemical failure, disease-specific survival, and overall survival rates were, respectively, 90%, 99%, and 88% for the bounce group and 70%, 93%, and 82% for the no-bounce group. Only 1 patient (0.3%) died of prostate cancer in the bounce group, compared with 40 patients (6.1%) in the no-bounce group. Adjusted for confounding, a 70% biochemical failure risk reduction was observed for patients experiencing a bounce (hazard ratio 0.31; 95% confidence interval 0.20-0.48).

Conclusions: A PSA bounce after prostate brachytherapy is strongly related to better outcome in terms of biochemical failure, disease-specific survival, and overall survival.
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http://dx.doi.org/10.1016/j.ijrobp.2010.11.049DOI Listing
February 2012

Body mass index is not a predictor of biochemical recurrence after radical prostatectomy in Dutch men diagnosed with prostate cancer.

World J Urol 2011 Oct 16;29(5):695-701. Epub 2010 Dec 16.

Department of Urology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.

Purpose: To determine the effect of body mass index (BMI) on clinical and pathological characteristics at time of diagnosis and on risk of biochemical recurrence after radical prostatectomy among Dutch men diagnosed with prostate cancer.

Methods: In total, 1,116 prostate cancer patients with known BMI, diagnosed between 2003 and 2006, were identified from the population-based cancer registry held by the Comprehensive Cancer Centre East, The Netherlands. Of these, 504 patients underwent a radical prostatectomy. Patients were categorized as normal weight (BMI < 25 kg/m(2)), overweight (BMI 25-30 kg/m(2)), or obese (BMI ≥ 30 kg/m(2)). Multivariable proportional hazards regression models, adjusted for age, prediagnostic PSA levels, and pathological characteristics were used to evaluate BMI as a prognostic factor for biochemical recurrence after radical prostatectomy.

Results: Overall, clinical and biopsy characteristics did not significantly differ among BMI groups. Pathological characteristics after radical prostatectomy did not significantly differ among BMI groups, except for tumor stage, which was highest in obese patients (P = 0.017). For patients treated with radical prostatectomy, 5-year risk (95% Confidence Intervals) of biochemical recurrence was 30% (23-37%) for normal weight, 32% (25-39%) for overweight, and 25% (9-41%) for obese patients (log rank P = 0.810). BMI was not an independent prognostic factor for biochemical recurrence in multivariable proportional hazards regression analyses (HR 0.99 per kg/m(2), 95% CI: 0.93-1.06).

Conclusions: Compared with non-obese men, pathological tumor stage tended to be higher in obese men. Clinical relevance of this finding is unclear, because BMI was not an independent predictor of biochemical recurrence after radical prostatectomy.
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http://dx.doi.org/10.1007/s00345-010-0629-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189409PMC
October 2011

Survival after prostate brachytherapy in patients aged 60 years and younger.

BJU Int 2011 Jun 9;107(12):1906-11. Epub 2010 Nov 9.

Department of Radiation Oncology, University Medical Center Utrecht, The Netherlands.

Objective: • To compare survival after prostate brachytherapy in patients aged ≤60 years with patients aged >60 years.

Patients And Methods: • We analysed 419 locally confined prostate cancer patients, treated between 1989 and 2001 with I-125 implantation monotherapy. • Endpoints were biochemical failure (BF) according to the +2 ng/mL definition, disease-specific and overall survival. • Patients were subdivided into age ≤60 years and age >60 years. • Cox proportional-hazards regression analyses were performed to study the independent effect of age on BF and disease-specific survival.

Results: • The younger cohort consisted of 87 patients (21%), with smaller prostate volumes and a lower average prostate cancer risk class than the older cohort, consisting of 332 patients (79%). Mean follow-up was 9.1 years (±sd 2.8) for the younger cohort and 8.3 years (±sd 2.9) for the older cohort. • The 10-year (95% CI) freedom from BF, disease-specific survival and overall survival rates were 63% (51-75), 87% (78-96) and 81% (69-89), respectively, for the younger cohort and 46% (39-54), 83% (78-89) and 60% (54-66), respectively, for the older patient cohort. • Although a trend for better freedom from BF and disease-specific survival was observed in younger patients, the difference proved not clinically significant.

Conclusion: • Prostate cancer risk group and the year of treatment relate to outcome, but not age. With respect to prostate cancer curability, there seems no objection to offer brachytherapy to patients aged 60 years and younger.
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http://dx.doi.org/10.1111/j.1464-410X.2010.09769.xDOI Listing
June 2011

Periprostatic fat correlates with tumour aggressiveness in prostate cancer patients.

BJU Int 2011 Jun 2;107(11):1775-9. Epub 2010 Nov 2.

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

Study Type: Prognostic (case series).

Level Of Evidence: 4. What's known on the subject? and What does the study add? Nowadays more and more publications have been published about the topic prostate cancer aggressiveness and obesity with mixed results. However, most of the publications used the BMI as a marker for obesity, while the most metabolic active fat is the visceral fat. To learn more about these relations we measured and used the visceral fat in our paper.

Objective: To examine if the periprostatic fat measured on computed tomography (CT) correlates with advanced disease we examined patients who received radiotherapy for localized prostate cancer. Several USA reports found a positive association between obesity and prostate cancer aggressiveness. However, in recent European studies these conclusions were not confirmed. Studies concerning this issue have basically relied on body mass index (BMI), as a marker of general obesity. Visceral fat, however, is the most metabolically active and best measured on CT.

Patients And Methods: In 932 patients, who were treated with external radiotherapy (N=311) or brachytherapy (N=621) for their T1-3N0M0 prostate cancer, different fat measurements (periprostatic fat, subcutaneous fat thickness) were performed on a CT. Associations between the different fat measurements and risk of having high-risk (according to Ash et al., PSA>20 or Gleason score≥8 or T3) disease was measured.

Results: The median age (IQR) was 67.0 years (62.0-71.0) and median BMI (IQR) was 25.8 (24.2-28.3). Logistic regression analyses, adjusted for age, revealed a significant association between periprostatic fat density (PFD) and risk of having a high risk disease. (Odds ratio [95% CI] 1.06 [1.04-1.08], P<0.001)

Conclusion: Patients with a higher PFD had more often aggressive prostate cancer.
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http://dx.doi.org/10.1111/j.1464-410X.2010.09811.xDOI Listing
June 2011

Acute urinary retention after I-125 prostate brachytherapy in relation to dose in different regions of the prostate.

Int J Radiat Oncol Biol Phys 2011 May 3;80(1):76-84. Epub 2010 Jun 3.

Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.

Purpose: To assess the influence of dose in different prostate regions, and the influence of anatomic variation on the risk of acute urinary retention (AUR) after I-125 prostate brachytherapy.

Methods And Materials: In this case-control study, dosimetry and anatomy were compared between 50 patients with AUR (cases) and 50 patients without AUR (controls). Cases and controls were randomly selected from our database. The following structures were delineated on magnetic resonance imaging: prostate, urethra, peripheral zone, transitional zone, apex, base, midprostate, lower sphincter, and bladder neck. The dosimetric parameters analyzed were D(10), D(50), D(90), V(100), V(150), and V(200). The anatomic parameters analyzed were prostate protrusion into the bladder, bladder overlap, urethra angle, and urethra-bladder angle. The delineator was blinded to the patient's AUR status. Logistic regression analysis was used to investigate the association of these factors with AUR.

Results: The dose delivered to different regions of the prostate was not significantly associated with the risk of AUR. Only dose to the bladder neck was significantly associated with AUR (odds ratio 1.13 per 10 Gy; 95% CI 1.02;1.26; p = 0.023). Mean bladder neck D(90) was 65 Gy in AUR cases vs. 56 Gy in controls (p = 0.016), and mean bladder neck D(10) was 128 Gy vs. 107 Gy, respectively (p = 0.018). Furthermore, on univariate analysis, a larger extent of both bladder overlap and of prostate protrusion were associated with a higher risk of AUR (odds ratio 1.16; 95% CI 1.04-1.28; p = 0.005, and odds ratio 1.83; 95% CI 1.37-2.45; p < 0.001, respectively). The mean extent of prostate protrusion was 3.5 mm in AUR cases vs. 1.0 mm in controls (p < 0.001). Odds ratios did not change substantially after adjustment for potential confounders. On multivariate analysis, the extent of prostate protrusion seemed to be a stronger risk factor for AUR than bladder overlap.

Conclusion: The risk of AUR is not associated with dose delivered to different regions of the prostate. However, a higher dose to the bladder neck and a larger extent of prostate protrusion into the bladder are risk factors for the development of AUR after I-125 prostate brachytherapy.
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http://dx.doi.org/10.1016/j.ijrobp.2010.01.022DOI Listing
May 2011

Loose seeds versus stranded seeds in I-125 prostate brachytherapy: differences in clinical outcome.

Radiother Oncol 2010 Jul 8;96(1):30-3. Epub 2010 Mar 8.

Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands.

Purpose: To assess clinical outcome in terms of biochemical No evidence of disease (bNED) for patients with stranded seed implants versus loose seed implants in prostate brachytherapy.

Methods: From December 2000 until October 2006, we treated 896 T< or =2C Nx/0 Mx/0, prostate cancer patients with either stranded seed (n=538) or loose seed (n=358) I-125 implants. A total of 211 patients received a 6 months course of anti-androgen therapy, before treatment, for prostate volume reduction to <50 cc. Patients with very small and large gland volumes or a history of transurethral prostate resection, were preferably treated with stranded seeds, otherwise selection was arbitrary.

Results: The 5-year bNED rates (95% Confidence Interval) for stranded seed patients and loose seed patients were respectively 86% (82-90) and 90% (85-95), the total 5-year bNED rate was 87% (85-90). When adjusted for possible confounding factors in a Cox-regression analysis, type of seed was significantly associated with biochemical failure with a 43% risk reduction (hazard ratio: 0.57; 95% CI: 0.34-0.97) for loose seeds versus stranded seeds.

Conclusions: These results suggest that seed-type affects clinical outcome in prostate brachytherapy, with better bNED for patients with loose seed implants.
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http://dx.doi.org/10.1016/j.radonc.2010.02.012DOI Listing
July 2010

Periprostatic fat measured on computed tomography as a marker for prostate cancer aggressiveness.

World J Urol 2010 Dec 22;28(6):699-704. Epub 2009 Dec 22.

Department of Urology, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands.

Objective: Several reports found that obesity was associated with prostate cancer (PC) aggressiveness among men treated with radical prostatectomy or radiotherapy. Studies concerning this issue have basically relied on body mass index (BMI), as a marker for general obesity. Because visceral fat is the most metabolic active fat, we sought to evaluate if periprostatic fat measured on a computed tomography (CT) is a better marker than BMI to predict PC aggressiveness in a Dutch population who underwent brachytherapy for localized PC.

Patients And Methods: Of the 902 patients who underwent brachytherapy, 725 CT scans were available. Subcutaneous fat thickness (CFT), periprostatic fat area (cm(2)) and fat-density (%) were determined on the CT scan. Patients were stratified into three groups: <25, 25-75 and >75 percentile of the fat-density. Associations between the three fat-density subgroups and BMI and PC aggressiveness were examined.

Results: 237 patients were classified as having normal weight (37.2%), 320 as overweight (50.2%) and 80 as obese (12.6%). There was a strong significant association between BMI and fat-density and CFT. The strongest correlation was seen between BMI and CFT (Pearson r coefficient = 0.71). Logistic regression analysis revealed no statistically significant association between the different fat measurements and the risk of having a high-risk disease.

Conclusions: Periprostatic fat and fat-density as measured with CT were not correlated with PC aggressiveness in patients receiving brachytherapy. However, 31% of the patients with a normal BMI had a fat-density of >75 percentile of the periprostatic fat-density.
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http://dx.doi.org/10.1007/s00345-009-0497-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2966948PMC
December 2010

The impact of acute urinary retention after iodine-125 prostate brachytherapy on health-related quality of life.

Int J Radiat Oncol Biol Phys 2010 Aug 24;77(5):1322-8. Epub 2009 Nov 24.

Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.

Purpose: To evaluate the impact of acute urinary retention (AUR) in patients treated with (125)I prostate brachytherapy on short- and long-term health-related quality of life (HRQOL); and to assess whether pretreatment HRQOL has additional value in the prediction of AUR.

Methods And Materials: For 127 patients treated with (125)I brachytherapy for localized prostate cancer between December 2000 and June 2003, toxicity and HRQOL data were prospectively collected. Patients received a HRQOL questionnaire at five time points: before and 1 month, 6 months, 1 year, and 6 years after treatment. The questionnaire included the RAND-36 generic health survey, the cancer-specific European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30), the tumor-specific EORTC prostate cancer module (EORTC QLQ-PR25), and the American Urological Association (AUA) symptom index.

Results: Of 127 patients, 13 (10.2%) developed AUR. Patients with AUR had a significantly worse urinary QOL at all time points compared with patients without AUR. The mean difference over time (6 years) between both groups for the EORTC QLQ-PR25 urinary symptom score was 13.0 points (p < 0.001) and for the AUA urinary symptom score was 15.7 points (p = 0.001). Global QOL scores (EORTC QLQ-C30) over time for patients who developed AUR were significantly worse compared with patients without AUR (mean difference 6.7 points; p = 0.043). In multivariate logistic regression analysis, pretreatment International Prostate Symptom Score (p = 0.004) and neoadjuvant hormonal treatment (p = 0.034) were predictors of AUR. Quality of life did not have added predictive value.

Conclusion: Acute urinary retention after prostate brachytherapy has a significant negative impact on patient's HRQOL up to 6 years after treatment, in terms of both global QOL measures and urinary symptom scores. Furthermore, our results suggest limited value of pretreatment HRQOL measures for the prediction of AUR.
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http://dx.doi.org/10.1016/j.ijrobp.2009.06.083DOI Listing
August 2010

Long-term biochemical and survival outcome of 921 patients treated with I-125 permanent prostate brachytherapy.

Int J Radiat Oncol Biol Phys 2010 Apr 18;76(5):1433-8. Epub 2009 Jun 18.

Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.

Purpose: To assess long-term biochemical and survival outcome after permanent prostate brachytherapy (BT).

Methods And Materials: Data on 921 patients, treated with permanent interstitial BT monotherapy between 1989 and 2004 for or=50cc received 6 months of antiandrogen therapy before treatment. Patients were classified into risk groups with 232 defined as low-, 369 intermediate-, and 320 high-risk disease. The median follow-up was 69 months (range, 4-186 months); mean age was 67 years.

Results: Average 5- and 10-year biochemical no evidence of disease (bNED) rates were 79% and 57%. Average 10-year bNED rates by risk group were 88% for low-risk, 61% for intermediate-risk, and 30% for high-risk disease. The average 10-year overall and disease-specific survival rates were 59% and 82%. Ten-year overall and disease-specific survival rates by risk group were, respectively, 68% and 96% for low-risk, and 64% 87% for intermediate-risk, and 49% and 69% for high-risk disease. In multivariate Cox regression analysis, both risk group and treatment era were independent predictors of bNED and survival.

Conclusions: These data on long-term survival continue to support the use of I-125 monotherapy for prostate cancer in low-risk patients and, in particular, demonstrate its efficacy in intermediate-risk patients.
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http://dx.doi.org/10.1016/j.ijrobp.2009.03.049DOI Listing
April 2010

Body mass index is not a prognostic marker for prostate-specific antigen failure and survival in Dutch men treated with brachytherapy.

BJU Int 2010 Jan 10;105(1):42-8. Epub 2009 Jun 10.

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

Objective: To examine the relationship between body mass index (BMI) and biochemical recurrence (BCR), cancer-specific (CSS) and overall survival (OS) in men treated with permanent prostate brachytherapy (PPB), as there is limited information on the affect of obesity on treatment outcomes for prostate cancer.

Patients And Methods: In all, 1530 patients with clinically localized prostate cancer who underwent PPB were studied. Clinical and pathological data were retrospectively obtained from medical records. The BMI was classified as normal (< 25 kg/m(2)), overweight (25-30 kg/m(2)) and obese (> or = 30 kg/m(2)). BCR was defined as a rise in PSA levels of > or = 2 ng/mL after the nadir had been reached. The cause of death was determined for each deceased patient. Patients with metastatic prostate cancer who died of any cause were classified as prostate cancer deaths. RESULTS In all, 617 (40%) patients were classified as having a normal weight, 754 (49%) overweight and 159 (10%) were obese. The Kaplan-Meier 8-year risk of BCR (95% confidence interval) was 33.3% (27.2-39.4), 29.2% (23.5-34.9) and 29.3% (12.4-46.2) for patients with a BMI of < 25 kg/m(2), 25-30 kg/m(2) and > or = 30 kg/m(2), respectively. The 8-year CSS was 88.2% (83.1-93.3), 88.6% (83.7-93.5) and 90.6% (79.9-101.4) and the 8-year OS was 70.1% (63.6-76.6), 72.9% (66.6-79.2) and 81.8% (69.3-94.3) for these three groups, respectively. Multivariate proportional hazard regression analyses of BMI and established prognostic factors for BCR confirmed the absence of any prognostic value of BMI on BCR, CSS and OS.

Conclusions: BMI did not appear to have any prognostic value for BCR, CCS or OS in patients with clinically localized prostate cancer treated with PPB.
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http://dx.doi.org/10.1111/j.1464-410X.2009.08687.xDOI Listing
January 2010

Impact of obesity on surgical outcomes following open radical prostatectomy.

Urol Int 2009 11;82(3):256-61. Epub 2009 May 11.

Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Objective: The increasing incidence of both obesity and prostate cancer (PCa) detection will confront the urologist more often with obese men having PCa. It is unknown whether obesity affects the surgical and oncological outcomes following open radical retropubic prostatectomy (RRP). Knowledge concerning this issue is relevant when counselling obese patients with PCa for RRP.

Patients And Methods: A single institution cohort study was performed including 252 men who underwent a RRP between 1992 and 2003. The surgical complications (perioperative complications, post-RRP urinary incontinence, urethral strictures) were compared between obese (BMI >30) and nonobese (BMI
Results: Compared to nonobese (n = 221), obese men (n = 31) developed more frequently wound infections (16.1 vs. 4.5%; p < 0.05), urinary incontinence (25.8 vs. 8.7%; p < 0.05) as well as vesico-urethral strictures (46.2 vs. 12.3%; p < 0.05). The pathology results and the 5-year cumulative risk of PSA recurrence were comparable among both groups.

Conclusions: Compared to nonobese, obese men suffer more frequently from post-RRP urinary incontinence and vesicourethral strictures following open RRP.
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http://dx.doi.org/10.1159/000209353DOI Listing
July 2009

Body mass index as a prognostic marker for biochemical recurrence in Dutch men treated with radical prostatectomy.

BJU Int 2009 Aug 11;104(3):321-5. Epub 2009 Feb 11.

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

Objective: To investigate whether body mass index (BMI) is a prognostic factor for biochemical recurrence (BCR) in Dutch men after radical prostatectomy (RP), as although epidemiological studies of obesity in relation to prostate cancer have provided conflicting results, recent studies from the USA suggest that a higher BMI is a risk factor for progression of prostate cancer.

Patients And Methods: Of the 1417 patients with prostate cancer who had RP at two University hospitals, 1302 were included in the present study. BMI (kg/m(2)) classes were defined as normal (<25), overweight (25-30) and obese (> or =30). The median follow-up was 59 months and clinical data were obtained retrospectively from charts. BCR was defined as two consecutive prostate-specific antigen (PSA) levels of >0.1 ng/mL.

Results: In all, 600 patients were classified as having normal weight (43.9%), 665 as overweight (48.6%) and 103 as obese (7.5%). Overall, 297 patients developed BCR after RP; the 10-year risk (95% confidence interval) of BCR was 31.9 (26.6-37.2)%, 30.5 (25.8-35.2)% and 23.9 (14.9-32.9)% for patients in the three categories, respectively (P = 0.836). Multivariable proportional hazard regression analyses of BMI and established prognostic factors for BCR did not change these results.

Conclusion: BMI appeared to have no prognostic value for BCR in Dutch patients with clinically localized prostate cancer and treated with RP.
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http://dx.doi.org/10.1111/j.1464-410X.2009.08404.xDOI Listing
August 2009

The impact of obesity on prostate cancer.

World J Urol 2007 Oct 30;25(5):491-7. Epub 2007 May 30.

Department of Urology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.

Increasing prevalence of obesity in many parts of the world emphasizes the importance of learning more about the relationship between obesity and prostate cancer (PC). The present paper reviews the impact of obesity on PC using knowledge obtained from the available literature. Search of published literature in PUBMED database. Adipose tissue constitutes an active endocrine and metabolic organ which may be relevant in the development and progression of PC by different potential mechanisms. Furthermore, obesity could have an impact on the outcome of different treatment modalities for PC, both functionally as anatomically. Obesity is a growing problem, however, the exact role in the development and progression of PC has not been elucidated. Regarding the optimal treatment of PC in obese patients, comparative prospective studies are needed.
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http://dx.doi.org/10.1007/s00345-007-0178-3DOI Listing
October 2007
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