http://repub.eur.nl/res/aut/5571/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/34720/ 2012-01-01T00:00:00Z Background: The rate of decrease in advanced cancers is an estimate for determining prostate cancer (PCa) screening program effectiveness. Objective: Assess the effectiveness of PCa screening programs using a 2- or 4-yr screening interval. Design, setting, and participants: Men aged 55-64 yr were participants at two centers of the European Randomized Study of Screening for Prostate Cancer: Gothenburg, Sweden (2-yr screening interval, n = 4202), and Rotterdam, the Netherlands (4-yr screening interval, n = 13 301). We followed participants until the date of PCa, the date of death, or the last follow-up at December 31, 2008, or up to a maximum of 12 yr after initial screening. Potentially life-threatening (advanced) cancer was defined as cancer with at least one of following characteristics: clinical stage ≥T3a, M1, or N1; serum prostate-specific antigen (PSA) >20.0 ng/ml; or Gleason score ≥8 at biopsy. Intervention: We compared the proportional total (advanced) cancer incidence (screen-detected and interval cases), defined as the ratio of the observed number of (advanced) cancers to the expected numbers of (advanced) cancers based on the control arm of the study. Measurements: The proportional cancer incidence from the second screening round until the end of observation was compared using a 2- or 4-yr screening interval. Results and limitations: From screening round 2 until the end of observation, the proportional cancer incidence was 3.64 in Gothenburg and 3.08 in Rotterdam (relative risk [RR]: 1.18; 95% confidence interval [CI], 1.04-1.33; p = 0.009). The proportional advanced cancer incidence was 0.40 in Gothenburg and 0.69 in Rotterdam (RR: 0.57; 95% CI, 0.33-0.99; p = 0.048); the RR for detection of low-risk PCa was 1.46 (95% CI, 1.25-1.71; p < 0.001). This study was limited by the assumption that PSA testing in the control arm was similar in both centers. Conclusions: A 2-yr screening interval significantly reduced the incidence of advanced PCa; however, the 2-yr interval increased the overall risk of being diagnosed with (low-risk) PCa compared with a 4-yr interval in men aged 55-64 yr. Individualized screening algorithms must be improved to provide the strategy for this issue. http://repub.eur.nl/res/pub/34740/ 2012-01-01T00:00:00Z Aim The incidence, patterns of care and survival were determined in patients with stage IV colorectal cancer (CRC) in a population-based series. Method Computer records for patients diagnosed with stage IV CRC diagnosed from 1 January 1995 to 31 December 2007 were retrieved from the Rotterdam Cancer Registry. Surgical resection of the primary tumour, chemotherapy use, hepatic surgery and survival were evaluated according to year of diagnosis, age, gender and primary tumour site. Results In the southwestern part of the Netherlands, 19014 new patients with CRC were diagnosed and synchronous metastatic disease was found in 3482 (18%). This proportion increased during the study period, from 16% to 21%. Surgical resection of the primary tumour was performed in approximately 50% of the patients and did not change over time. Postoperative 30-day mortality was 8%. Chemotherapy use increased from 18% in the first period to 56% in the latest period. Liver surgery increased from 4% in the first period to 10% in the latest period. Median survival increased from 7months to 12months and 2-year survival increased from 14% to 28%. Two-year survival declined with increasing age and was significantly worse for right-sided tumours (14%). Conclusion Survival of patients with stage IV CRC has improved over time and this is probably a result of the increased use of chemotherapy and the increased numbers of patients who underwent hepatic surgery. © 2011 The Authors. Colorectal Disease http://repub.eur.nl/res/pub/25542/ 2011-04-05T00:00:00Z Background: A noticeable proportion of colorectal cancer (CRC) patients are diagnosed with synchronous CRC. Large population-based studies on the incidence, risk factors and prognosis of synchronous CRC are, however, scarce, and are needed for better determination of risks of synchronous CRC in patients diagnosed with colonic neoplasia. Methods: All newly diagnosed CRC between 1995 and 2006 were obtained from the Rotterdam Cancer Registry in The Netherlands, and studied for synchronous CRC. Results: Of the 13,683 patients diagnosed with CRC, 534 patients (3.9%) were diagnosed with synchronous CRC. The risk of having synchronous CRC was significantly higher in men (OR 1.54, 95% CI 1.29-1.84) and in patients aged >70 years (OR 1.83, 95% CI 1.39-2.40). Synchronous CRC patients had a significantly higher risk of distant metastases (OR 1.69, 95% CI 1.27-2.26). In 34% (184/534) the two tumours were located in different surgical segments. Five-year relative survival of synchronous CRC was similar to patients with solitary CRC after multivariate adjustment for the presence of distant metastases. Conclusion: One out of 25 patients diagnosed with CRC presents with synchronous CRC. In the multivariate analysis, survival of patients with synchronous CRC was similar to patients with solitary CRC, when corrected for the presence of distant metastases at first presentation. One third of the synchronous CRC were located in different surgical segments, which stresses the importance of performing total colon examination preferably prior to surgery. http://repub.eur.nl/res/pub/34085/ 2011-04-01T00:00:00Z Background: Prediction models need external validation to assess their value beyond the setting where the model was derived from. Objective: To assess the external validity of the European Randomized study of Screening for Prostate Cancer (ERSPC) risk calculator (www.prostatecancer-riskcalculator.com) for the probability of having a positive prostate biopsy (P(posb)). Design, setting and participants: The ERSPC risk calculator was based on data of the initial screening round of the ERSPC section Rotterdam and validated in 1825 and 531 men biopsied at the initial screening round in the Finnish and Swedish sections of the ERSPC respectively. P(posb) was calculated using serum prostate specific antigen (PSA), outcome of digital rectal examination (DRE), transrectal ultrasound and ultrasound assessed prostate volume. Measurements: The external validity was assessed for the presence of cancer at biopsy by calibration (agreement between observed and predicted outcomes), discrimination (separation of those with and without cancer), and decision curves (for clinical usefulness). Results and limitations: Prostate cancer was detected in 469 men (26%) of the Finnish cohort and in 124 men (23%) of the Swedish cohort. Systematic miscalibration was present in both cohorts (mean predicted probability 34% versus 26% observed, and 29% versus 23% observed, both p < 0.001). The areas under the curves were 0.76 and 0.78, and substantially lower for the model with PSA only (0.64 and 0.68 respectively). The model proved clinically useful for any decision threshold compared with a model with PSA only, PSA and DRE, or biopsying all men. A limitation is that the model is based on sextant biopsies results. Conclusions: The ERSPC risk calculator discriminated well between those with and without prostate cancer among initially screened men, but overestimated the risk of a positive biopsy. Further research is necessary to assess the performance and applicability of the ERSPC risk calculator when a clinical setting is considered rather than a screening setting. http://repub.eur.nl/res/pub/22978/ 2010-12-01T00:00:00Z Objectives To study the difference between the disease-specific and excess mortality rate in the European Randomized Study of Screening for Prostate Cancer section Rotterdam. Methods A total of 42,376 men were randomized to systematic screening or usual care. The excess number of deaths was defined as the difference between the observed number of deaths in the prostate cancer (PC) patients and the expected number of deaths up to 31 December 2006. The expected number was derived from mortality of all study participants before a possible diagnosis with PC. The disease-specific mortality rate was based on the number of men who died from PC. The excess mortality rate based on the arm-specific excess number of deaths and the disease-specific mortality rate were compared between the two study arms. Results The overall mortality rate was not significantly different between the intervention and the control arms of the study: RR 1.02 (95% CI 0.98-1.07). The disease-specific mortality rate was 0.42 men per 1000 person-years in the intervention and 0.48 men per 1000 person-years in the control arm: RR 0.86 (95% CI 0.64-1.17). The excess mortality rate was 0.40 per 1000 personyears in the intervention arm and 0.61 men per 1000 person-years in the control arm, and the RR for excess mortality was 0.66 (95% CI 0.39-1.13). Conclusions In contrast to the disease-specific mortality rates an increased difference in the excess mortality rates was observed between the two arms. This observation may be due to a systematic underestimation of the disease-specific deaths, and/or an additional disease-related mortality that is measured by an excess mortality analysis but not by a disease-specific mortality. http://repub.eur.nl/res/pub/27465/ 2010-10-15T00:00:00Z BACKGROUND: The benefits of prostate cancer screening on an individual level remain unevaluated. METHODS: Between 1993 and 1999, a total of 43,987 men, aged 55-74 years, were included in the intervention arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC) section in the Netherlands, Sweden, and Finland. A total of 42,503 men, aged 55-74 years, were included in a clinical population in Northern Ireland. Serum prostate-specific antigen (PSA) <20.0 ng/mL was measured in all men at study entry. All men were followed for prostate cancer incidence and causes of death until December 31, 2006. RESULTS: The adjusted absolute difference in prostate cancer specific mortality between the intervention population and the clinical population increased with increasing PSA level at study entry, ie, 0.05 per 10,000 person-years for men who had a serum PSA level of 0.0-1.9 ng/mL and 8.8 per 10,000 person-years for men who had a serum PSA level of 10-19.9 ng/mL. To evaluate the risks of early detection, the number needed to investigate (NNI) and number needed to treat (NNT) to save 1 death from prostate cancer were calculated. Both NNI and NNT were higher for those who had lower PSA levels at study entry. The NNI was 24,642 men for patients who had a serum PSA level of 0.0-1.9 ng/mL and was 133 men for patients who had a serum PSA level of 10-19.9 ng/mL; the NNT was 724 men for patients who had a serum PSA level of 0.0-1.9 ng/mL and was 60 men for patients with a serum PSA level of 10-19.9 ng/mL. CONCLUSIONS: For men with a low serum PSA level, the benefits of aggressive investigation and treatment may be limited because they are associated with a large increase in cumulative incidence and potential overtreatment. http://repub.eur.nl/res/pub/27963/ 2010-01-01T00:00:00Z Background: Screening for prostate cancer (PC) is controversial due to uncertainties about its efficiency. Objective: We aimed to develop strategies to reduce the number of unnecessary biopsies while still detecting most clinically important PC cases. Design, setting, and participants: In 1850 men initially screened and biopsied (prostate-specific antigen [PSA] value ≥3.0 ng/ml) in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer, we calculated both the probability of having a positive lateralized sextant biopsy [P(biop+)] and the probability of having an indolent cancer [P(ind)] if PC was detected at biopsy (n = 541). Analyses of repeat screening included 225 cancers in 1201 men. Interventions: The P(biop+) was based on applying a logistic regression model that included ultrasound volume, digital rectal exam, and transrectal ultrasound in addition to the PSA value. The P(ind) was based on a recently validated nomogram. Measurements and limitations: At initial screening the fraction of positive biopsies was 29% (541 of 1850). Applying an additional P(biop+) cut-off of 12.5% implied that 613 of the 1850 men (33%) would not have been biopsied. This would result in an increase in the positive predictive value (PPV) to 38% (468 of 1237). At repeat screening a similar P(biop+) cut-off would result in an increase in the PPV from 19% (225 of 1201) to 25% (188 of 760). Thirteen percent of PC cases would not have been diagnosed, of which 70% (initial screening) and 81% (repeat screening) could be considered as potentially indolent. None of the deadly PC cases would have been missed. A PSA cut-off of ≥4.0 ng/ml resulted in similar numbers of biopsied cases saved but considerably higher numbers of missed diagnoses. Conclusions: An individualized screening algorithm using other available prebiopsy information in addition to PSA level can result in a considerable reduction of unnecessary biopsies. Very few important PC cases, for which diagnosis at a subsequent screening visit might be too late for treatment with curative intent, would be missed. http://repub.eur.nl/res/pub/14412/ 2008-11-01T00:00:00Z BACKGROUND. Ongoing research on the best way to diagnose prostate cancer has yielded and will continue to yield vast amounts of information. Based on, for example, information from prostate cancer screening trials models have been made that enable urologists to predict which man has prostate cancer on the basis of pre-biopsy data. In patients with screen detected prostate cancer, the presence of indolent disease can now be identified with reasonable certainty by a different model. For these men active surveillance may be a better option than aggressive treatment with its possible side effects as impotence, incontinence and bowel damage. Both models mentioned above are logistic regression models. Nomograms enable their use in daily clinical practice. METHODS. Nomograms require the memorization and addition of intermediate results. We aimed to design a device that has the same function as a nomogram without this draw back. RESULTS. A new device that resembles a circular slide rule was developed and is currently being tested in prostate cancer diagnosis and in prostate cancer patient counseling. CONCLUSIONS. The new device has identical functionality to the nomogram without the drawback of the latter. The application of the device is not limited to the field of prostate cancer research. http://repub.eur.nl/res/pub/29505/ 2008-06-15T00:00:00Z BACKGROUND. To analyze to what extent the percentage of suspicious digital rectal examination (DRE) findings vary between examiners and to what extent the percentage of prostate cancers (PCs) detected in men with these suspicious findings varies between examiners. METHODS. In the first screening round of the European Randomized study of Screening for PC (ERSPC) Rotterdam, 7,280 men underwent a PSA-determination and DRE of whom 2,102 underwent prostate biopsy (biopsy indication PSA ≥ 4.0 ng/ml and/or suspicious DRE and/or TRUS). Descriptive statistics of DRE-outcome per PSA-range were used to determine the observer variability of six examiners. Because this analysis did not correct properly for other predictors of a suspicious DRE (PSA-level, biopsy indication, TRUS-outcome, prostate volume and age), a logistic regression analysis controlling for these explanatory variables was performed as well. RESULTS. In 2,102 men biopsied, 443 PCs were detected (PPV = 21%). For all PSA levels the percentage suspicious DRE varied between examiners from 4% to 28% and percentage PC detected in men with a suspicious DRE varied from 18% to 36%. Logistic regression analysis showed that three of six examiners considered DRE significantly more often abnormal than others (ORs 3.48, 2.80, 2.47, P < 0.001). For all examiners the odds to have PC was statistically significantly higher in case of a suspicious DRE (ORs 2.21 -5.96, P < 0.05). This increased chance to find PC was not significantly observer-dependent. CONCLUSIONS. Three of six examiners considered DRE significantly more often suspicious than the others. However, under equal circumstances a suspicious DRE executed by each examiner increased the chance of the presence of PC similarly. http://repub.eur.nl/res/pub/36105/ 2007-04-01T00:00:00Z Objectives: The stage and grade shift of currently diagnosed prostate cancer has led to a diminished prognostic power of the Gleason score system. We investigated the predictive value of the amount of high-grade cancer (Gleason growth patterns 4/5) in the biopsy for prostate-specific antigen (PSA) and clinical relapse after radical prostatectomy. Methods: PSA-tested participants (N = 281) of the European Randomized Study of Screening for Prostate Cancer (ERSPC) who underwent radical prostatectomy were analyzed. Besides clinical features, and serum-PSA, histopathologic features as determined in the diagnostic biopsy and matching radical prostatectomy specimen were related to patient outcome. Results: At a median follow-up of 7 yr, 39 (13.9%), 24 (8.5%), and 12 (4.3%) patients had PSA ≥0.1 ng/ml, PSA ≥1.0 ng/ml, and clinical relapse after radical prostatectomy, respectively. Using Cox proportional hazards, PSA level (p = 0.002), length of tumour (p = 0.040), and length of high-grade cancer (p = 0.006) in the biopsy, but not Gleason score, were independent prognostic factors for biochemical relapse (PSA ≥0.1 ng/ml) when assessed as continuous variables. In radical prostatectomies, the proportion of high-grade cancer (p < 0.001) was most predictive of relapse (PSA ≥0.1 ng/ml). For PSA ≥1.0 ng/ml and clinical relapse, the amount of high-grade cancer, both in the biopsy specimen (p = 0.016 and p = 0.004, respectively) and radical prostatectomy specimen (p = 0.002 and p = 0.005, respectively), but not Gleason score, was an independent predictor. Conclusions: In biopsy and radical prostatectomy specimens of surgically treated prostate cancer, the amount of high-grade cancer is superior to the Gleason grading system in predicting patient outcome. We propose that, in addition to the Gleason score, the amount of Gleason growth patterns 4/5 in the biopsy (whether absolute length or proportion) should be mentioned in the pathology report. http://repub.eur.nl/res/pub/14370/ 2003-10-01T00:00:00Z OBJECTIVES: To investigate the weak correlation between bladder outlet obstruction (BOO), as diagnosed using the provisional International Continence Society nomogram for the definition of BOO in men, and postvoid residual urine volume. METHODS: The relationship between voiding to completion and several indexes for bladder outlet resistance and bladder contractility was studied in 131 pressure flow studies in male patients using multivariate logistic regression analysis. RESULTS: The International Continence Society nomogram and the related BOO index weakly predict for postvoid residual urine volume (areas under the receiver operating characteristic curve 0.63 and 0.64, respectively). The BOO index primarily measures bladder outlet resistance. If the nomogram or BOO index is augmented with bladder contractility information, the postvoid residual urine volume can be predicted significantly better (eg, area under the receiver operating characteristic curve [0.89] for the combination of the BOO index and bladder contractility information). CONCLUSIONS: The weak correlation between BOO and postvoid residual urine volume is related to the fact that emptying the bladder to completion depends on bladder contractility, as well as bladder outlet resistance. It is possible to estimate the probability to void to completion quite accurately on the basis of bladder outlet resistance and bladder contractility. We named this probability "relative bladder outlet resistance." A high probability of a postvoid residual urine volume may be assumed to indicate "relative BOO." By its very nature, the correlation between "relative BOO" and postvoid residual urine volume is good http://repub.eur.nl/res/pub/14369/ 2003-05-09T00:00:00Z OBJECTIVES: To study the causes for the variation between measurements, which is considerable, in maximal flow rate (Qmax) and the associated detrusor pressure (PdetQmax). Because of the central role of Qmax and PdetQmax in the diagnosis of bladder outlet obstruction, this is reason for concern. METHODS: Spectral analysis was carried out on two consecutive urodynamic measurements in 131 patients. The parameters for bladder outlet resistance and bladder contraction strength were determined, and difference plots were made to study the systematic variations. Logistic regression analysis was used to study whether the differences represent true changes of the function of the lower urinary tract. RESULTS: Signal components in the detrusor pressure and the flow rate signal with frequencies of 1 Hz or greater may be considered noise. Filtering out these frequencies changes the estimates of Qmax and PdetQmax, but not the between-measurement difference in them. Bladder contractility and bladder outlet resistance were systematically lower in the second measurement. Both the systematic and nonsystematic between-measurement variations were statistically significant predictors for postvoid residual urine volume. CONCLUSIONS: The nonsystematic between-measurement variability in Qmax and PdetQmax apparently reflects true variability in the physiologic state of the bladder outlet. It therefore does not discredit the pressure-flow study as the preferred method in the diagnosis of bladder outlet obstruction. Rather, the pressure-flow study is the only currently available method to study and quantify the apparent within-patient variability in bladder outlet resistance and bladder contractility http://repub.eur.nl/res/pub/14368/ 2003-02-11T00:00:00Z PURPOSE: We developed a method to objectively compare methods for the quantification of bladder outlet resistance. MATERIALS AND METHODS: We studied unselected voiding cystometries from 131 male patients. Several models proposed for bladder outlet resistance were fitted to the lowest monotonically increasing part (bottom) of the pressure flow plots. In conjunction with a parameter for bladder contractility, the model parameters were used as predictors of post-void residual greater than 20% of filled volume. RESULTS: The pressure decrease in relaxed bladder outlet was best described by a linear function of the flow rate. The flow rate independent and dependent parts of that function were statistically significant predictors for residual. However, they could be combined into 1 index that was as efficient as the 2 numbers separately in predicting residual. This index is the average pressure of the bottom of the pressure flow plot. CONCLUSIONS: We describe how different models for the quantification of bladder outlet resistance can be compared objectively on the basis of their ability to predict a significant post-void residual. Using this criterion in an unselected group of measurements, the average pressure of the bottom of the pressure flow plot performed best as an index for bladder outlet resistance quantification. It combines (or weights) 2 components (dependent and independent flow rates) without losing its power to predict post-void residual http://repub.eur.nl/res/pub/14366/ 2002-07-20T00:00:00Z PURPOSE: Currently bladder outlet obstruction in males is defined by the provisional International Continence Society nomogram which is partly based on expert opinion and partly on measurements before and after transurethral prostate resection. Recently there has been some interest in the development of a similar nomogram for females. MATERIALS AND METHODS: We studied the possibility of defining bladder outlet obstruction based on a sign that it causes, namely post-void residual urine. RESULTS: The probability of relative post-void residual urine exceeding 20% of bladder capacity was modeled in males and females using 1 parameter, that is URA/w20 or the ratio of the obstruction parameter urethral resistance factor (URA)-to-the bladder contractility parameter Watts factor at 20% (w20). URA/w20 represents relative bladder outlet resistance or bladder outlet resistance normalized to bladder contractility. Above a threshold of URA/w20 = 6.8 in females and 8.2 in males a relative post-void residual exceeding 20% was noted in 90% of measurements. These thresholds may be used to define relative obstruction. The provisional International Continence Society nomogram for obstruction in males was transformed into an identical nomogram for females by equating the probabilities of post-void residual urine in each gender. The latter differed from that in men, in that the lines demarcating the zones were horizontal or flow rate independent but the intercepts were approximately the same at 20 and 40 cm. water. CONCLUSIONS: Instead of defining obstruction as an absolute level of bladder outlet resistance we suggest that it is better to define it relatively, that is as a level of bladder outlet resistance that depends on bladder contractility http://repub.eur.nl/res/pub/14819/ 1995-11-01T00:00:00Z http://repub.eur.nl/res/pub/9026/ 1995-01-01T00:00:00Z The influence of age, urethral resistance and bladder contractility on voiding efficiency was evaluated by pressure-flow studies in 138 men of a mean age of 60 years (range 18 to 86). From these studies the urethral resistance parameter was calculated and the maximum bladder contraction strength was determined. Premature fading of the bladder contraction was quantified by a bladder contraction strength decay factor. Voiding efficiency was expressed by the parameter of post-void residual urine volume as a percentage of the initial bladder volume. Multiple regression analysis showed that voiding efficiency depended significantly in descending order of importance on urethral resistance, maximum bladder contraction strength and bladder contraction strength decay factor. Patient age was not an independent factor. Maximum bladder contraction strength and bladder contraction strength decay factor were not correlated, suggesting that maximum bladder contraction strength and its decay constitute different properties of bladder contractile function. A voiding efficiency nomogram is proposed, making use of the values for maximum bladder contraction strength and urethral resistance in individual patients. Such a nomogram may have predictive value for the occurrence of acute retention but it must be tested prospectively. http://repub.eur.nl/res/pub/9027/ 1995-01-01T00:00:00Z In an attempt to increase our understanding of the clinical syndrome of benign prostatic hyperplasia (BPH) an analysis was made of the association between prostate volume as measured by transrectal ultrasound and several reported urodynamically determined urethral resistance parameters. Two types of obstruction can be recognized on the basis of urodynamic data: a compressive type characterized by a high urethral opening pressure and a prolonged isovolumetric contraction phase before urine flow can start, and a constrictive type characterized by a normal opening pressure and an increased slope of the urethral resistance relation. A combination of both types is often seen in BPH. In our study, parameters that selectively quantify compression correlate weakly to moderately with prostate volume, whereas parameters that mainly quantify constriction do not correlate at all with prostate volume. Parameters that combine a measure for compression and constriction correlate less well with prostate volume than parameters that mainly quantify compression. The variation in prostate volume was found to determine the variation in urethral resistance by 15% or less depending on the parameter used, which implies that the different pathophysiological mechanisms that can increase urethral resistance in the complex process of clinical BPH are mainly determined by factors other than the volume of the prostate. Thus, despite the lack of correlation between prostate volume and urethral resistance, pressure-flow studies and the determination of urethral resistance parameters provide a valuable contribution to the understanding of the pathophysiology of voiding dysfunction in men with symptoms of prostatism. http://repub.eur.nl/res/pub/14865/ 1994-08-12T00:00:00Z In this pilot study on 17 men who underwent urodynamic investigation for various dysuric complaints, real-time transrectal ultrasonography (TRUS) was performed. From the images anatomical parameters were identified that correlated with obstructive urodynamic findings and urethral resistance parameters based on pressure-flow analysis. This study gives support for further clinical investigations to determine the value of TRUS for male patients with dysuric disorders. It also illustrates the anatomical basis of prostatic obstruction as quantified by objective urodynamic parameters.