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Background and Objectives: To evaluate the representativeness of Dutch patients participating in the European Organization for Research and Treatment of Cancer EORTC boost-no-boost trial to the target breast cancer patient population. Methods: All female breast cancer patients diagnosed between 1989 and 1996, aged < 70 years, treated with breast-conserving surgery and radiation therapy, were selected from the Netherlands Cancer Registry (NCR) and linked to the EORTC trial database. Baseline characteristics were compared between trial and non-trial participants, for the Dutch population and according to seven participating institutions. Kaplan-Meier curves and multivariable Cox regression were used to explore potential heterogeneity in overall survival between low, medium and high-volume institutes. Results: Overall, 20,880 patients were identified from the NCR: 2,445 of 2,602 (94%) trial participants could be linked, and 18,435 were treated outside the trial. Trial participants had similar age, morphology, topography, laterality and socioeconomic status as non trial participants, but more often stage I (62.7% vs. 56.4%) tumours and less often adjuvant treatment (22.9% vs. 26.5%). Crude 20 year survival ranged from 52.5% to 57.4%, without significant differences in multivariable analyses. Conclusion: This case study showed that participants in the boost-no-boost trial well represented the Dutch target population. Data linkage comes with challenges, but can close the gap between research and clinical practice. (C) 2022 The Author(s). Published by Elsevier Inc.

Purpose: To evaluate testicular function in men with previously acquired undescended testes (AUDT) in whom spontaneous descent was awaited until puberty followed by orchiopexy in case of nondescent. Methods: Andrological evaluation including paternity, scrotal ultrasound, reproductive hormones, and semen analysis was performed in three groups: men with AUDT, healthy controls, and men with previously congenital undescended testes (CUDT). Results: In comparison with controls, men with AUDT more often had significantly abnormal testicular consistency, smaller testes, lower sperm concentration, and less motile sperm. Except for more often a normal testicular consistency in men with AUDT, no differences were found between men with AUDT and men with CUDT. Also, no differences were found between men with AUDT which had spontaneously descended and men who underwent orchiopexy. Conclusions: Fertility potential in men with AUDT is compromised in comparison with healthy controls, but comparable with men with CUDT. This suggests that congenital and acquired UDT share the same etiology. No significant difference was found between men who had spontaneous descent and men needing orchiopexy. However, fertility potential is unknown for men after immediate surgery at diagnosis, and this should be a subject for future studies. (C) 2014 Elsevier Inc. All rights reserved.

Objective In addition to disease-specific mortality, a randomized controlled cancer screening trial may be evaluated in terms of excess mortality, in which case no patient-specific information on causes of death is needed. We studied the effect of not accounting for attendance on the calculated excess mortality in a prostate cancer screening trial. Methods The numerator of the excess mortality rate related to prostate cancer diagnoses in each study arm equals the excess number of deaths observed in the cancer patients. The estimation of the expected number of deaths in the absence of the prostate cancer diagnoses has to account for the self-selection of those participating in the trial, particularly if the proportion of non-participants is substantial. Setting The European prostate cancer screening trial (ERSPC). Results In the screening arm, non-attendees had roughly twice the mortality rate of attendees. Approximately twice as many cancers were detected in the screening arm compared with the control arm, primarily in attendees. Unless attendance is properly accounted for, the expected mortality of prostate cancer patients in the screening arm is overestimated by 0.9–3.6 deaths per 1000 person-years. Conclusions Attendees have a lower all-cause mortality rate (are healthier) and a higher probability of a prostate cancer diagnosis than non-attendees and the men randomized to the control arm. If attendance is not accounted for, the excess mortality and the between-arm excess mortality rate ratio are underestimated and screening is considered more effective than it actually is. These effects may be sizeable, notably if non-attendance is common. Correcting for attendance status is important in the calculation of the excess mortality rate in prostate cancer patients that can be used in conjunction with a disease-specific mortality analysis in a randomized controlled cancer screening trial.

Men with a history of congenital undescended testes (UDT) have an increased risk of fertility problems. Despite no definitive proof, current guidelines recommend early surgical intervention because this may have a positive effect on future fertility potential by preventing degenerative changes of the testes in early life. Also surgical intervention facilitates observability of the testes in view of possible malignancy. We evaluated testicular function in adult men with previous UDT treated at different ages before puberty. A long-term follow-up study of men with previous UDT was performed. Andrological evaluation included medical history taking, physical examination, scrotal ultrasound, determination of reproductive hormones, and semen analysis. Findings were compared with those of a control group of men with normal testicular descent. The influence of age at orchiopexy on future fertility parameters was evaluated in a multivariate regression analysis. 62 men were included of whom seven had had bilateral UDT. Twenty-four patients had had their orchiopexy before the age of 24 months of whom eight men had it before 12 months of age. Forty-eight men had had unsuccessful luteinizing-hormone-releasing-hormone (LHRH) nasal spray treatment during childhood, whereas 14 of 24 men operated before 24 months of age had not received LHRH treatment before orchiopexy. Fertility potential in men with a history of UDT is compromised in comparison with controls. We could not detect any influence of age at orchiopexy on fertility parameters. However, the number of patients operated before the age of 12 months is limited. This study does not support the assumption that early orchiopexy results in better fertility potential.

Background: Prediction models need validation to assess their value outside the development setting.Objective: To assess the external validity of the European Randomised study of Screening for Prostate Cancer (ERSPC) Risk Calculator (RC) in a contemporary clinical cohort.Methods: The RC calculates the probability of a positive sextant prostate biopsy (P(posb)) using serum prostate-specific antigen (PSA), results of digital rectal examination, transrectal ultrasound (TRUS) and ultrasound assessed prostate volume. We prospectively validated the RC in 320 biopsied men (55-75 years), with no previous prostate biopsy, included in five Dutch hospitals in 2008-2011. If the P(posb) was >= 20% a biopsy was recommended. The performance of the RC was tested by comparing the observed outcomes to predicted probabilities, using the area under the curve (AUC) and decision curves analyses.Results: Compared to the screening cohort, men in the clinical cohort differed. They had higher PSA levels (median 6.8 versus 4.3 ng/ml, p Conclusions: The ERSPC RC performs well in a Dutch clinical cohort in men with previous PSA tests and contemporary biopsy schemes, and outperforms a PSA and DRE-based approach in the decision to perform a biopsy. (C) 2012 Elsevier Ltd. All rights reserved.

Patients with colorectal cancer are at risk for developing metachronous colorectal cancer. The purpose of posttreatment surveillance is to detect and remove premalignant lesions to prevent metachronous colorectal cancer.The aim of this study was to investigate the incidence of and predictive factors for metachronous colorectal cancer in patients with newly diagnosed colorectal cancer.The data on all patients with newly diagnosed colorectal cancer between 1995 and 2006 were obtained from the Rotterdam Cancer Registry in The Netherlands and studied for metachronous colorectal cancer.The annual incidence rate and the standardized incidence ratios were calculated.In total, colorectal cancer was diagnosed in 10,283 patients; there were 39,974 person-years of follow-up. The mean annual incidence rate of metachronous colorectal cancer was 314/100,000 person-years at risk during 10 years of follow-up, corresponding with a mean annual incidence of 0.3% and a cumulative incidence of 1.1% at 3 years, 2.0% at 6 years, and 3.1% at 10 years. The incidence of metachronous colorectal cancer after resection of a first colorectal cancer is significantly higher than the incidence of colorectal cancer in an age- and sex-matched general population (standardized incidence ratio 1.3, 95% CI 1.1-1.5). This difference is especially seen during the first 3 years after first colorectal cancer diagnosis (standardized incidence ratio 1.4, 95% CI 1.1-1.8). The presence of synchronous colorectal cancer was the only significant risk factor for developing metachronous colorectal cancer (relative risk 13.9, 95% CI 4.7-41.0).Despite the availability of colonoscopy, metachronous colorectal cancer is still seen during follow-up in patients with colorectal cancer; the highest risk is during the first 3 years after initial diagnosis. For this reason, a follow-up colonoscopy is useful at a short-term interval after colorectal cancer diagnosis. The presence of synchronous colorectal cancer at the time of first colorectal cancer diagnosis is the only predictive risk factor for developing metachronous colorectal cancer. Tailored surveillance programs may be considered in patients with a diagnosis of synchronous tumors.

Study Type – Prognosis (case control) Level of Evidence 3a What's known on the subject? and What does the study add? Treatment of advanced PC might put patients at an increased risk of cardiovascular events. Recent studies have suggested that the excess mortality is lower among men who were diagnosed with screen detected PC in comparison to men with clinically diagnosed PC, possibly due to the use of medications for cardiovascular disease and the change to a healthier lifestyle of men with a screen detected PC. Men with clinically diagnosed PC have an increased risk of death unrelated to PC itself, i.e., the excess mortality is based on an increased risk of dying from other neoplasm and diseases of the circulatory or respiratory system. OBJECTIVE • To assess the cause-specific mortality unrelated to prostate cancer (PC) itself in patients with screen- and clinically diagnosed PC. PATIENTS AND METHODS • The present study was conducted among participants of the European Randomized Study of Screening for Prostate Cancer. • Based on consensus of the causes of death committee (CODC), all patients who died from PC were excluded. • In the intervention arm, cases were patients with a screen-detected PC, aged 55–74 years, between 1993 and 2001. • These cases were matched to two controls in whom no cancer was found after biopsy, and two controls in whom no cancer was suspected after screening. In the control arm, cases were patients with clinically diagnosed PC, aged 55–74 years, between 1993 and 2001. These cases were matched to four controls without PC. Matching was done with respect to date of birth, screening and/or diagnosis. Men were followed up to 31 December 2007. RESULTS • No statistically significant difference in overall mortality between cases and controls in the intervention arm was observed: relative risk (RR) 1.26 (95% confidence interval [CI] 0.96–1.65; P = 0.102) and RR 1.13 (95% CI 0.86–1.47; P = 0.381). • In the control arm, the overall mortality was statistically significantly higher in cases relative to controls: RR 1.43 (95% CI 1.03–2.00; P = 0.033). • This difference was because of an increased risk of dying from neoplasms and disease of the circulatory or respiratory system among cases: RR 1.61 (95% CI 1.12–2.29; P = 0.009). • The present study was limited by the relatively small sample size. CONCLUSIONS • Increased mortality unrelated to PC itself was observed in men with clinically diagnosed PC, but not in screen-detected PC. • The excess mortality in men with clinically diagnosed PC seems to be as a result of a significantly increased risk of dying from neoplasm and disease of the circulatory or respiratory system. • Results have to be studied more thoroughly in further clinical trials.

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. (C) 2011 Elsevier Ltd. All rights reserved.

The advantages and disadvantages of two different methods of analyzing the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial with respect to the effect of prostate-specific antigen (PSA) screening on prostate cancer (PCa) mortality (ie, disease-specific mortality analysis and excess mortality analysis) are discussed in depth. The traditional disease-specific mortality is the best end point, but it could be biased by misclassification of causes of death, and it does not take into account the possible effect of the screening process on other causes of death. Excess mortality analysis overcomes these problems, but the results could be biased if the expected mortality is not corrected for attendance status. Both methods, when applied to the ERSPC trials, demonstrate that no increase in non-PCa mortality occurred in the screening group and confirm that PSA screening decreases PCa mortality. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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 person-years 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.

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)

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.

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

PSA-driven screening has been applied to a large part of the male population in many countries. An elevated PSA in secondary screens may indicate benign enlargement of the prostate rather than prostate cancer. In such cases the yearly rate of increase of PSA (PSA velocity [PSAV]) may improve the test characteristics of PSA. Materials and Methods Data from the European Randomized Study of Screening for Prostate Cancer Rotterdam are used to study the issue. Relative sensitivity, relative specificity, and positive predictive value (PPV) are calculated. Logistic regression analysis is used to compare odds ratios for positive biopsies. The relationship between PSAV and parameters of tumour aggressiveness is investigated. Results Five hundred eighty-eight consecutive participants were identified who presented at their first screening with PSA values 4.0ng/ml four years later. None were biopsied in round one, all were biopsied in round two. Relative sensitivity and specificity depend strongly on PSAV cut-offs of 0.25–1.0ng/ml/yr. The use of PSAV cut-offs does not improve the PPV of the PSA cut-off of 4.0ng/ml, nor do any of the PSAV cut-offs improve the odds ratio for identifying prostate cancer with respect to the cut-off value of 4.0ng/ml. The rate of aggressive cancers seems to increase with increasing PSAV. Conclusions PSAV does not improve the detection characteristics of a PSA cut-off of 4.0ng/ml in secondary screening after four years.

The objective of this study was to show or to exclude an effect of dietary supplement on rising prostate-specific antigen (PSA) levels. We have studied the effect of a dietary supplement (verum, administered for 6 weeks) containing plant estrogens, antioxidants, including carotenoids, selenium and other putative prostate cancer inhibiting substances in a randomized placebo-controlled double-blind crossover study in 37 hormonally untreated men with prostate cancer and increasing PSA levels. Outcome measures were changes in the rates of change of serum concentrations of total and free PSA and changes in male sex hormone levels. Male sex hormone levels were significantly lower during the verum phase (DHT: -0.11 nmol/L, p = 0.005; testosterone: -1 nmol/L, p = 0.02). Total PSA doubling time was unaffected. Free PSA, which increased during the placebo phase (average doubling time of 68 weeks), decreased during the verum period (average half-life of 13 weeks; p = 0.02). In those men in whom the free androgen index decreased (21 out of 32), a significant decrease in the slopes of both total and free PSA was observed (p = 0.04). Overall total PSA doubling times did not increase significantly during verum. However, the study demonstrates that this dietary intervention reduces DHT and testosterone levels and increases free PSA doubling time (and total PSA doubling time in a relevant subgroup). If future studies confirm that these observations translate into a slowing of disease progression, a dietary intervention may become an attractive option for prostate cancer treatment and prevention.

for cancer. I was one of the architects of the National Health Service Breast Screening Programme (NHSBSP) in the United Kingdom in the late 1980s and also have enjoyed the privilege of acting as independent chairman of the Prostate Testing for Cancer and Treatment (ProtecT) trial of PCa screening in the United Kingdom for the last 12 yr [3]. I was also one of the first to break ranks with the NHSBSP as emergingdata started to suggest that breast cancer screening was failing to liveup to itspromise.Most recently, I published a paper in the BMJ inwhich I returned to basics and posed the question in the introduction of the editorial, ‘‘Does screening for breast cancer improve LoL andorQoL?’’ The answerwas a resounding no [4]. If we are not to repeat the errors of the past, then all cancer-screening trials must be reported using absolute numbers, numbers needed to screen to avoid a causespecific death, all-cause mortality, and some measure of QoL. Impotence and incontinence might be good surrogates for the latter. Some biostatisticians get very cross with me when they argue that the trials were not powered to determine any impact on all-cause deaths. Yet hundreds of thousands of men have been randomised in screening trials, so if the signal has been lost in the background noise, it must be a very small signal. If that is indeed the case, there is the issue of opportunity costs when the same money might be used with greater wisdom to save more lives. I am confident that the ProtecT trial will not repeat the mistakes of the past.

Objectives. To study retrospectively whether the prostate-specific antigen (PSA) velocity, that is, the change in PSA level over time, might serve as a screening tool in this PSA range. It is estimated that 40% of detectable prostate cancers are present in men with a PSA level of 4.0 ng/mL or less. Digital rectal examination and/or transrectal ultrasonography have been used as screening tools at these low PSA levels, but this approach is not very efficient. Methods. The possible predictors (including PSA velocity) for biopsy outcome were studied using univariate and multivariate logistic regression analysis in 774 men who underwent biopsy between November 1997 and January 2002 in the second screening round of the European Randomised Study of Screening for Prostate Cancer (ERSPC). The clinical stage of the tumors was determined, and the Gleason scores of the biopsies were studied. Results. A total of 149 cancers were found (positive predictive value 19.2%). The odds ratio for the PSA velocity determined by univariate logistic regression analysis was 2.2 (95% confidence interval 0.7 to 6.9, P = 0.19) and was 0.73 (95% confidence interval 0.20 to 2.6, P = 0.64) by multivariate analysis. The distribution of the clinical stage of the detected tumors was 64.4% T1c, 32.2% T2, and 3.4% T3. The biopsy Gleason score was 6 in 84.5%, 7 in 14.2%, and 8 in 1.3%. Conclusions. The number of cancers detected in this study and the distribution of clinical stage and biopsy Gleason score confirmed that a relatively large proportion of potentially curable cancers can be found in the low PSA ranges. The PSA velocity did not appear to be a useful screening tool for the identification of these cancers.

We evaluated prostate cancer (PCa) characteristics at diagnosis and changes in prostatic specific antigen (PSA) with time in males with screening detected PCa that was initially managed with a watchful waiting policy.Patients with histologically proven PCa and PSA less than 10 ng/ml were selected from the European Randomized Study of Screening for Prostate Cancer, section Rotterdam. The choice of initiating a watchful waiting policy was patient desire or physician advice. PSA slope and PSA doubling time (PSADT) were calculated in patients with 3 or more PSA tests results available.A total of 191 patients were included. Mean age at diagnosis was 69 years and mean PSA was 3.9 ng/ml. Of the patients 92.6% had a Gleason score of 3 + 3 or lower, 133 had a followup of greater than 12 months (mean 40) and 35 (29.2%) had a negative PSA slope. Mean PSADT was 9.7 years (range 0.3 to 155) in 85 males with a positive PSA slope. During followup 30 patients changed therapy.Watchful waiting remains a controversial prostate cancer treatment strategy. In select screening detected patients with PCa there appears to be a subgroup with stable or even decreasing PSA values with time. These males could profit from a watchful waiting policy with possible deferred treatment. Together with conventional tumor parameters at diagnosis PSADT and PSA slope during followup could be used to monitor tumor activity and possibly aid in determining the time of deferred treatment. Further followup is mandatory to validate these results.

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.

Objective To assess the magnitude of prostate cancer detection by serendipity (the coincidental detection of prostate cancer during the evaluation of an abnormal screening test result) when a digital rectal examination (DRE) and transrectal ultrasonography (TRUS) are used as initial screening tests for prostate cancer in men with low levels of prostate-specific antigen (PSA; 0.0–3.9 ng/mL). Patients and methods In all, 117 participants of a population-based screening study were diagnosed with prostate cancer after a standard evaluation of an abnormal screening test result; 49 underwent radical prostatectomy. Serendipity was defined as either: (i) the presence of prostate cancer opposite to the side that raised suspicion for cancer on DRE and/or TRUS; (ii) a negative lesion-directed biopsy while cancer was present in one or more of the cores of the sextant biopsy; (iii) a tumour volume of

Objective: To study the effects of the application of flow rate prescreening to select men for invasive pressure–flow studies, notably the reduction of invasive pressure–flow measurements that can be achieved and the proportion of men in whom, on the basis of the application of a prescreening, an invasive measurement is unjustly not indicated (false negatives). In addition, the variables on which these effects depend are studied. Materials and Methods: Two hundred and sixty-two pressure–flow measurements in 131 patients (2 measurements/patient) and 89 free-flow measurements that preceded the invasive measurements in some patients were studied. A mathematical model was developed based on the outcomes of the invasive measurements. By means of the model the effects of several flow rate prescreening scenarios were estimated. A comparison of the model predicted and actually observed effects of flow rate prescreening was made for those measurements that were preceded by a free-flow rate measurement. Results: The application of a free-flow rate prescreening may result in a reduction of the number of invasive measurements of 20–30% at a 5% false negative rate. The reduction that may be achieved at an assumed constant false negative rate depends on the distribution of the maximum flow rate in the population and on the definition of bladder outlet obstruction used. When the measurement selection procedure was applied to the free-flow rate measurements that were available in 89 patients, a 21% reduction in invasive measurement indications was found (25% expected). Four patients (4.5%) would have been unjustly excluded from invasive procedures (maximally 5% expected), three of these four patients were borderline obstructed. Conclusion: Considering the bother and risk to the patient and the cost of invasive measurements we think that a 20–30% gain in efficiency at a 5% risk of unjustly declaring a patient unobstructed makes a flow rate prescreening procedure cost effective in the diagnosis of bladder outlet obstruction.

Objectives. To determine whether an additional subclassification of the assessed clinical stage for prostate cancer before biopsy increases our ability to predict the biopsy outcome. A suspicious digital rectal examination (DRE) and/or a suspicious transrectal ultrasound (TRUS) investigation increases the likelihood of prostate cancer given a certain prostate-specific antigen level. Methods. Biopsies done in 2199 men with suspicious DRE and/or TRUS findings were studied. The clinical stage was assessed according to the 1992 TNM classification. Univariate and multivariate statistical analyses were performed. Results. The assessed extent of disease classified as intracapsular or extracapsular (ie, clinical Stage T2 versus T3 and T4) was a significant independent predictor for the biopsy outcome. Men with suspected extracapsular disease on the basis of the DRE findings before the sextant biopsy had a twofold increased odds ratio of having prostate cancer detected compared with men with suspected intracapsular disease. A suspicion of extracapsular disease on the basis of TRUS findings, however, significantly decreased the risk of having prostate cancer detected in a biopsy. Conclusions. We found a modified version of the clinical stage (ie, extracapsular, clinical T3 or T4 cancer versus intracapsular) to be significantly better in predicting the presence of prostate cancer at a given prostate-specific antigen level than a simple “yes or no abnormality found on DRE and/or TRUS” qualification. A suspicion of extracapsular disease raised on the basis of the DRE findings should be valued differently than a similar suspicion raised on the basis of the TRUS findings. Apparently, the extracapsular lesions seen by TRUS are primarily nonmalignant.

Two large-scale randomized screening trials, the Prostate, Lung, Colorectal and Ovary (PLCO) cancer trial in the USA and the European Randomized Screening for Prostate Cancer (ERSPC) trial in Europe are currently under way, aimed at assessing whether screening reduces prostate cancer mortality. Up to the end of 1998, 102,691 men have been randomized to the intervention arm and 115,322 to the control arm (which represents 83% of the target sample size) from 7 European countries and 10 screening centers in the USA. The principal screening method at all centers is determination of serum prostate-specific antigen (PSA). The PLCO trial and some European centers use also digital rectal examination (DRE) as an ancillary screening test. In the core age group (55-69 years), 3,362 of 32,486 men screened (10%) had a serum PSA concentration of 4 ng/ml or greater, which is 1 cut-off for biopsy (performed in 84%). An additional 6% was referred for further assessment based on other criteria, with much less efficiency. Differences in PSA by country are largely attributable to the age structure of the study population. The mean age-specific PSA levels are lower in the PLCO trial (1.64 ng/ml [in the age group 55-59 years], 1.80 [60-64 years] and 2.18 [65-69 years) than in the ERSPC trial (1.28-1.71 [55-59], 1.75-2.87 [60-64] and 2.48-3.06 [65-69 years]). Detection rates at the first screen in the ERSPC trial range from 11 to 42/1,000 men screened and reflect underlying differences in incidence rates and screening procedures. In centers with consent to randomization design, adherence in the screening arm is 91%, but less than half of the men in the target population are enrolled in the trial. In population-based centers in which men were randomized prior to consent, all eligible subjects are enrolled, but only about two-thirds of the men in the intervention arm undergo screening. Considerable progress has been made in both trials. Enrollment will be completed in 2001. A substantial number of early prostate cancers have been detected. The differences between countries seem to reflect both underlying prostate cancer incidence and screening policy. The trials have the power to show definitive results in 2005-2008.

Purpose: Worldwide 2 large-scale randomized screening trials for prostate cancer have been initiated. Determining prostate specific antigen (PSA) involves a simple test that may influence the outcome of these trials if frequently done in the control arm or before study enrollment. We quantified PSA and digital rectal examination before and during the screening trial in Rotterdam, The Netherlands and in the general population.Materials and Methods: Trial participants were administered study intake questionnaires on tests done before study participation. Data on PSA from the regional general practice laboratory were correlated with participant data. Various sources were used to quantify PSA tests and digital rectal examinations in the general population.Results: Of men 55 to 74 years old 45% underwent digital rectal examination at 1 time and 13% reported that PSA was tested before trial participation. Each rate increased with age. No statistically significant effect of former PSA testing or digital rectal e...

Purpose: Although early detection of prostate cancer by prostate specific antigen based screening results in a shift towards more clinically organ confined tumors, changes in prostate cancer characteristics after radical prostatectomy are less clear.Materials and Methods: We studied 121 totally embedded radical prostatectomy specimens that were obtained from consecutive participants of the European Randomized Study of Screening for Prostate Cancer who were systematically screened and treated surgically. In each specimen pathological stage, Gleason score and proportion of high grade cancer (Gleason pattern 4 or 5) were determined. Lymph node status at operation, stage and grade were compared to a historical series of 72 surgical procedures performed for clinically localized prostate cancer at our hospital before the introduction of serum prostate specific antigen as a diagnostic tool.Results: Although none of the screen detected cases had positive lymph nodes at surgery, operation was discontinued in 13 (1...

A randomized screening trial was started in Europe to show the effect of early detection and treatment of prostate cancer on mortality (European Study on Screening of Prostate Cancer). In one centre (Rotterdam), the screening protocol initially consisted of 3 screening tests for all men: prostate-specific antigen (PSA), digital rectal examination (DRE) and transrectal ultrasonography (TRUS). A PSA value of ≥4 ng/ml and/or an abnormality on DRE and/or TRUS were taken to indicate that biopsy was required. In this study, we examined the possibilities for a more efficient screening protocol. A logistic-regression model was used to predict the number of cancers for PSA < 4 ng/ml if all men were biopsied (predictive index, PI). Effects of a change in PSA cut-off on the screening results were explored. Weights were applied to procedures and cancers to explore the possibility of expressing differences between protocols in one overall figure. Biopsies in men with PSA < 1 ng/ml and a positive DRE or TRUS were very inefficient. Applying DRE and TRUS only in the PSA ranges 1.5 to 3.9 and 2 to 3.9 ng/ml to determine whether a biopsy was required would result in a decrease of 29 to 36% in biopsies and a decrease of 5 to 8% in cancers. However, the results of DRE and TRUS could not be duplicated entirely. A protocol with only PSA ≥ 3 ng/ml as a direct biopsy indicator resulted in a decrease of detected cancers by 7.6% and of biopsies by 12%, also a much simpler screening procedure. Use of the PI would give more efficient protocols, but this should be viewed as a preliminary finding, with the disadvantage of necessitating many additional screening visits. Since the results of DRE and TRUS could not be duplicated, a change in protocol towards PSA ≥ 3 ng/ml appears acceptable. If this proves effective, a final judgement about the optimal combination of screening tests may be made. Int. J. Cancer (Pred. Oncol.) 84:437–441, 1999. © 1999 Wiley-Liss, Inc.

Background: Despite low specificity, serum prostate-specific antigen (PSA) is widely used in screening for prostate cancer. Specificity can be improved by measuring free and total PSA and by combining these results with clinical findings. Methods such as neural networks and logistic regression are alternatives to multistep algorithms for clinical use of the combined findings. Methods: We compared multilayer perceptron (MLP) and logistic regression (LR) analysis for predicting prostate cancer in a screening population of 974 men, ages 55–66 years. The study sample comprised men with PSA values >3 μg/L. Explanatory variables considered were age, free and total PSA and their ratio, digital rectal examination (DRE), transrectal ultrasonography, and a family history of prostate cancer. Results: When at least 90% sensitivity in the training sets was required, the mean sensitivity and specificity obtained were 87% and 41% with LR and 85% and 26% with MLP, respectively. The cancer specificity of an LR model comprising the proportion of free to total PSA, DRE, and heredity as explanatory variables was significantly better than that of total PSA and the proportion of free to total PSA (P Conclusion: The probability calculated by logistic regression provides better diagnostic accuracy for prostate cancer than the presently used multistep algorithms for estimation of the need to perform biopsy.

BACKGROUND The finding of isolated high grade prostatic intraepithelial neoplasia (PIN) or borderline lesions (lesions suspicious for malignancy) in prostate needle biopsies warrants repeat biopsies. The reported frequency of these lesions in prostate needle biopsies varies considerably. The authors evaluated the frequency and clinical impact of high grade PIN and borderline lesions in sextant prostate needle biopsies obtained from screened participants in the European Randomized study of Screening for Prostate Cancer (ERSPC). METHODS A total of 8763 participants in the Rotterdam section of the ERSPC ages 55-75 years were screened systematically for prostate carcinoma. Systematic sextant prostate needle biopsies were prompted by an abnormal digital rectal examination and/or abnormal transrectal ultrasonography findings at serum prostate specific antigen (PSA) levels ≥ 1.0 ng/mL or a PSA level ≥ 4.0 ng/mL. Repeat biopsies were obtained within 6 months after initial biopsy. RESULTS Of 1824 biopsied men, 384 (21.1%) were found to have prostate carcinoma on initial biopsy. Twelve participants (0.7%) had isolated high grade PIN and 43 (2.4%) had borderline lesions. Repeat biopsies yielded no carcinoma in 7 participants with initial high grade PIN and 15 tumors (38.5%) in 39 participants with borderline lesions. CONCLUSIONS In prostate needle biopsies obtained from a screened population, indications for repeat biopsy such as high grade PIN and borderline lesions do not represent large diagnostic subsets. Borderline lesions comprise the most important indication for a repeat biopsy. The low frequency of equivocal biopsy diagnoses in the current study supports the clinical applicability of sextant needle biopsies in population-based screening for prostate carcinoma. Cancer 1999;85:145–52. © 1999 American Cancer Society.

Screening for prostate cancer is controversial. While in some parts of the world screening is practised as a healthcare policy, it is strongly rejected in other areas, because solid evidence of effectiveness of screening combined with early treatment with respect to lowering the mortality of prostate cancer has not been shown. It is for this reason that a large European study is installed to establish or rule out the value of screening for this frequent disease. The present paper presents the goal of the study and elaborates on the value of presently available screening tests. Preliminary results with respect to the first round of screening in the Rotterdam area relating to 32,000 randomized men are presented. Evidence of effectiveness of screening through other studies and mechanisms is discussed.

Background The utility of digital rectal examination (DRE) as a screening test for early detection of prostate cancer has not been established. Therefore, we evaluated the usefulness of DRE as a stand-alone screening test and in conjunction with measured serum prostate-specific antigen (PSA) levels of 0-3.9 ng/mL and transrectal ultrasonography (TRUS). Methods Our study population consisted of 10,523 men aged 54-76 years who were randomly assigned to the screening arm of the Rotterdam, The Netherlands, section of the European Randomized Study of Screening for Prostate Cancer. The underlying prevalence of detectable prostate cancer was estimated by logistic regression analysis and used for calculating the sensitivity of DRE as a test. Pathologic characteristics of 105 radical prostatectomy specimens were used to determine the aggressiveness of the tumors diagnosed (and missed) by DRE. Results The overall detection rate for prostate cancer in this population when serum PSA measurement, DRE, and TRUS were used was 4.5%, and the detection rate with DRE alone was 2.5%. The positive predictive value of DRE ranged from 4% to 11% in men with PSA levels of 0-2.9 ng/mL and from 33% to 83% in men with PSA levels of 3.0-9.9 ng/mL or more. Most tumors detected by DRE in men with PSA levels of less than 4.0 ng/mL were small (mean volumes = 0.24-0.83 mL), and most were well differentiated (Gleason scores of 6 or less). Minimal, moderate, and advanced cancers were seen in 42%, 42%, and 16% of men, respectively, with a PSA level of 4.0 ng/mL or less. DRE alone allowed detection of 264 (55.8%) of 473 cancers; 82 (17.3%) of the 473 cancers would have remained undetected by PSA-based screening alone (i.e., no follow-up procedures for PSA values of 0-3.9 ng/mL). Conclusions For PSA values of 0-3.9 ng/mL, the positive predictive value and sensitivity of DRE, tumor volume, and tumor grade were strongly dependent on PSA level. DRE has a poor performance in low PSA ranges.

Objective: To investigate the clinical significance of vascular invasion in prostate cancer patients treated by radical prostatectomy for clinically localized and locally advanced disease. Materials and Methods: Vascular invasion was determined during a routine work-up of radical prostatectomy specimens of 273 patients who underwent surgery for prostatic carcinoma. The correlation with other pathological variables was investigated. The prognostic influence for clinical progression, local recurrence, distant metastases, biochemical progression, overall survival and cancer-specific survival was determined. Results: Vascular invasion was present in 33 patients (12%). Vascular invasion correlated significantly with capsular perforation, seminal vesicle invasion, positive margins of resection, perineural invasion, high grade, and pathological stage. Vascular invasion was a significant prognostic factor for clinical progression (p < 0.001), local recurrence (p = 0.007), distant metastases (p < 0.001), biochemical progression (p < 0.001), overall survival (p = 0.02), and cancer-specific survival (p < 0.001). Multivariate analysis, adjusting for capsular perforation, high grade, and positive margins of resection, showed that vascular invasion was associated with a 2.5-fold increased risk for clinical progression. This relative risk was 2.3 for biochemical progression, and 2.7 for cancer-specific survival. Conclusion: Vascular invasion is a very important pathological variable for progression and survival, and must be evaluated on a routine basis during the work-up of radical prostatectomy specimens.

In recent years the introduction of serum prostate-specific antigen (PSA) determination as a screening tool for early detection of prostate cancer in asymptomatic men has led to a markedly increased detection of prostate cancers that are neither palpable nor visible with transrectal ultrasonography (stage Tlc). In this preliminary study we assessed pathologic features and aspects that are indicative of clinical significance in T1c tumors and tumors with palpable or visible lesions (non-Tlc tumors). Between June 1994 and December 1995, 51 consecutive radical prostatectomies were performed on screened participants in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). After determination of pathologic stage and Gleason score, morphometric analysis was performed to determine tumor volume. Radical prostatectomy specimens were divided into three mutually exclusive subsets: T1c tumors, non-Tlc tumors with preoperative PSA levels below 4 ng/ml, and non-Tlc tumors with PSA levels equal to or greater than 4 ng/ml. These subsets were compared for differences in the distribution of tumor volume, pathologic stage, and Gleason score. An arbitrarily constructed categorization model was used to assess clinical significance. In all, 17 (33%) of the patients had clinical stage T1c disease. In our categorization model, 88% of the T1c tumors fit the criteria for clinically significant tumors. T1c tumors, however, were significantly smaller (P < 0.01) and were more likely to be organ-confined (P = 0.01) as compared with non-T1c tumors in patients with an elevated preoperative serum PSA level. In contrast, tumors detected at preoperative PSA levels of < 4 ng/ml had comparably the lowest pathologic stages and tumor volumes in our series. In our categorization model, 42% of these tumors fit the criteria for minimal tumor. This group of radical prostatectomies was therefore most likely to harbor clinically insignificant cancer, a finding that was consistent in two other categorization models derived from earlier reports. T1c tumors comprise a large fraction of the tumors found in population-based screening. As judged by their pathologic characteristics, T1c tumors are clinically significant tumors. The over-all low pathologic stage and Gleason score of these tumors make these patients excellent candidates for curative treatment by radical prostatectomy or radiotherapy. In contrast, some concern should be raised on the detection of tumors at low serum PSA levels by means of digital rectal examination and transrectal ultrasound alone, since a substantial proportion of these tumors could be considered clinically insignificant. Long-term follow-up, however, is necessary to substantiate this view.

Purpose: The ratio between free and total prostate specific antigen (PSA) in serum improves the specificity of total serum PSA for the detection of prostate carcinoma in select populations. The value of the free-to-total PSA ratio for a PSA of 4.0 to 10.0 ng./ml. was analyzed in a screening population.Materials and Methods: From 4,800 participants 55 to 76 years old 977 biopsies were obtained because of an abnormal digital rectal examination, suspicious transrectal ultrasonography and total serum PSA 4.0 ng./ml. or more. Of 191 patients with prostate carcinoma detected 101 had a serum PSA of 4.0 to 10.0 ng./ml. and 54 of them underwent radical prostatectomy. A free-to-total PSA ratio of 0.20, age specific PSA reference ranges and a PSA density of 0.12 ng./ml./cc were evaluated for the ability to increase the specificity of total serum PSA in predicting positive prostate biopsy results.Results: Receiver operating characteristics curves for the free-to-total PSA ratio showed a significant increase i...

Objectives. Screening for prostate cancer to reduce the mortality and morbidity from this disease has become an important issue in recent years. Of all procedures used to diagnose prostate cancer, biopsy of the prostate is the cause of most complications. To evaluate the safety of the screening procedure, we have studied the complications and risk factors for complications within the screened population of the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam section. Methods. Between June 1994 and July 1996, 1687 transrectal ultrasound-guided systematic sextant biopsies were performed after screening 6198 men through prostate-specific antigen level, digital rectal examination, and transrectal ultrasonography. Results. From these 1687 biopsies, 302 cases of prostate cancer were diagnosed. Mild complications such as hematuria and hematospermia were reported frequently with rates of 23.6% and 45.3%, respectively. More severe complications were far less frequently seen. Fever, usually of low grade, was seen after 4.2% of biopsies. Seven men (0.4%) were admitted to a hospital after biopsy. Risk factors for complications could not be identified. Conclusions. Review of the literature concerning transrectal biopsies of the prostate shows that the complication rates within this screened population are comparable to those reported within referred patients. The admittance rate is slightly lower. Transrectal ultrasound-guided systematic sextant biopsy of the prostate is a safe procedure for the diagnosis of prostate cancer within the general population; however, identification of risk factors for complications might further improve the safety of the screening procedure.

Objective To evaluate the diagnosis, outcome and final pathology of radical prostatectomy for prostate cancer performed by urologists in a clinic where six urologists perform a total of 50 radical prostatectomies a year, using radical prostatectomy specimens processed routinely. Patients and methods Radical prostatectomy was performed in 273 patients who were followed prospectively. The radical prostatectomy specimens were evaluated for pathological stage, histological grade, capsular perforation, positive lateral and apical margins of resection, seminal vesicle invasion, perineural invasion and vascular invasion; the lymph node status was also determined. The relationship between these variables and clinical progression, local recurrence, distant metastases, biochemical progression, overall survival and cancer-specific survival was assessed. Results All evaluated variables were significantly predictive for clinical and biochemical progression in the univariate analyses, and all but perineural invasion and lymph node status for cancer-specific survival. Multivariate analysis showed vascular invasion to be the most important prognostic variable, followed by capsular perforation, positive margins of resection and poorly differentiated carcinoma. The overall results for the evaluated variables were comparable to the results from centres with greater experience. Conclusions The outcome of treatment in this small clinic was similar to that from larger clinics with more experience. The routine evaluation of the radical prostatectomy specimens identified pathological variables which were important prognostic factors, with vascular invasion, capsular perforation, positive margins of resection and poorly differentiated carcinoma being the most significant. The extent of vascular invasion should be part of the routine evaluation of radical prostatectomy specimens.

Purpose: We analyzed the relationship between the free-to-total PSA ratio and prostate cancer tumor stage and grade compared to total serum PSA.Materials and Methods: In 123 patients clinical and pathological grade and stage were related to total serum PSA and free-to-total PSA ratio.Results: Total serum PSA paralleled clinical staging of prostate cancer. The distributions of total serum PSA and the free-to-total PSA ratio were significantly different between benign and malignant diseases (any stage), and between any T category and nodal disease. For serum PSA significant differences were noted between the distributions of men with locally confined (stages T1 and T2) and locally extended (stage T3) disease, and between all T categories and systemic metastatic disease. This finding was not noted for the free-to-total PSA ratio.Conclusions: The free-to-total PSA ratio has no additional value in clinical staging of prostate carcinoma compared to serum PSA. The free-to-total PSA ratio may be considere...

To assess the extent of overestimation of the cumulative probability of death by the Kaplan-Meier method with the competing-risks regression analysis as reference approach.Data were derived from the screening arm of the Rotterdam branch of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The screening arm consisted of 21210 men between the ages of 55 and 74 at study entry. Follow up concerning mortality was complete through 2008. Endpoints were 5 and 10 year cumulative probabilities of prostate cancer death and death from other causes. Relative bias was defined as the ratio of the cumulative probability of death as determined by the Kaplan-Meier method, relative to the cumulative probability obtained by the competing-risks analysis.According to the Kaplan-Meier method, the 5 year cumulative probability of death from prostate cancer was 0.0101, compared with 0.0099 according to the competing-risk analysis [1.8% overestimation]. At 10 year, these numbers were 0.0347 and 0.0321, respectively [8.0% overestimation]. For death from other causes, the cumulative probabilities at 5 year were 0.0399 and 0.0397 according to the Kaplan-Meier and the competing-risks method [0.6% overestimation], respectively. At 10 year, the probabilities were 0.141 and 0.139 [1.7% overestimation], respectively.When competing events are present, the competing-risks regression analysis is to be preferred over the Kaplan-Meier method in the estimation of the cumulative probability of the event of interest.

Five randomized pilot studies of screening for prostate cancer (PC) have been conducted in the area of Rotterdam from 1991 to 1994. The purpose of these studies was to establish the feasibility of a randomized screening protocol with PC mortality as the major end point in The Netherlands and at a European level. All procedures related to recruitment of participants, to application of the screening tests and to data collection were evaluated. Men (7,200) aged 55–74 years were invited through the Rotterdam Population Registry. The recruitment rate over the 5 pilot studies averaged 38.2% (2,747 men). Recruitment procedures proved to be relevant for establishing higher participation rates (invitation and consent by mail). The screening tests were well accepted and tolerated. The general population-based character of the sample was confirmed by studying symptoms of prostatic disease in participants and in men who refused participation. Data based on one PSA serum determination, rectal examination and transrectal ultrasonography are presented; 204/1,403 men (14.5%) had a positive screening result by either test combination and underwent biopsy. Forty-nine cancers were found in 1,403 men (3.5%); 65% of prostate cancers (17/26) identified in men who eventually underwent radical prostatectomy proved to be locally confined. From the pilot studies, we conclude that a large contribution to a European Randomized Study of Screening for Prostate Cancer (ERSPC) can be made by recruiting about 40,000 men in the area of Rotterdam. The preliminary data suggest that after confirmation of the present data during the first years in the European study, DRE and TRUS can be withheld depending on the PSA result in a large proportion of the screening population. © 1996 Wiley-Liss, Inc.

Objectives The ratio between free and total prostate-specific antigen (PSA) in serum (F/T ratio) was shown to improve the specificity of total serum PSA for the detection of prostate carcinoma in selected populations. In this study, the value of the F/T ratio for screening of prostate cancer was compared with that of age-specific reference ranges for PSA and PSA density (PSAD) by a simulation experiment. Methods In 1726 men between 55 and 76 years old, 67 prostate carcinomas were detected by application of digital rectal examination (DRE), transrectal ultrasonography (TRUS), and total serum PSA. A serum PSA of 4.0 ng/mL or more, an abnormal DRE, or an abnormal TRUS were the indications to perform 308 biopsies. A simulation was performed in which an F/T ratio of 0.20 (ProStatus PSA Free/Total), age-specific PSA reference ranges, and a PSAD of 0.12 ng/mL/cc were used to study their capability to increase the specificity of total serum PSA in predicting prostate biopsy results. Results Using age-specific PSA reference ranges and DRE as indicators for biopsy, a reduction of 37% (113) of biopsies would have been obtained with a loss of detected cancers of 12% (11). For the use of PSAD and DRE, these numbers were 28% (96) and 11% (7), respectively. Application of a serum PSA of 4.0 ng/mL or more and an F/T ratio of 0.20 or less and an abnormal DRE as indicators for biopsy would reduce the number of biopsies by 37% (112) and the number of detected cancers by 11% (7). The biopsy to prostate cancer ratio of these simulations varied between 3.3 and 3.6. Minimal loss of cancer detection of 3% (2) with a reduction in the number of biopsies of 17% (53) is obtained when TRUS is omitted from the screening protocol. Selecting men by a total serum PSA value of 2.0 ng/mL for further diagnostic workup by TRUS and DRE would have reduced the number of biopsies by 30% (102), and the number of cancers detected by 6% (4). Conclusions The most cost-effective protocol for screening prostate carcinoma appears to be prescreening by total serum PSA. The F/T ratio might be used to detect carcinomas in the PSA range below 4.0 ng/mL, but the best threshold remains to be assessed.

Objectives The ratio between free and total prostate-specific antigen (PSA) in serum (F/T ratio) was shown to improve the differentiation between prostate carcinoma and benign conditions in selected series of patients. In this study the F/T ratio was analyzed for its ability to improve the specificity of total serum PSA, digital rectal examination (DRE), and transrectal ultrasonography (TRUS) for the detection of prostate cancer in an unselected screening population of men identified in the Rotterdam population. Methods In 1726 men between 55 and 76 years old, 67 prostate carcinomas were detected by DRE, TRUS, and total serum PSA (Abbott IMx, Hybritech Tandem E). The DELFIA ProStatus PSA EQM and ProStatus PSA Free/Total assays (Wallac) were applied in retrospect to determine total and free serum PSA. Age, total prostate and inner zone volumes were taken into consideration. Results Sixty-seven carcinomas were detected, two by TRUS and three by DRE alone. Total serum PSA was the most important single predictor of prostate cancer, followed by DRE. The F/T ratio increased the specificity of total serum PSA in the PSA range between 4.0 and 10.0 ng/mL. However, this improved specificity was not significant, nor for gland volumes restricted to 50 mL or less. Conclusions The combination of total serum PSA and DRE remains the standard for detection of prostate carcinoma in a screening population. Their specificity may be improved minimally by the F/T ratio, but not significantly in a sample of 1726 screened men. The threshold of the F/T ratio, and the optimal PSA range for its application, remains to be assessed prospectively.

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.

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.

In a urodynamic measurement setup there is a considerable spatial separation between the uroflowmeter and the location where the detrusor pressure is measured. Therefore, a “time shift” (or lag time correction) has to be applied to one of these signals in order to align related samples in studies where pressure and flow rate are considered simultaneously (e.g., assessment of bladder contractility or bladder outlet resistance). Currently, a heuristic value for this time shift of 0.8 s is applied. In this article, we present a method to estimate the lag time directly from the measurements. Using this method we have found, amongst others, that the mean lag time in our clinic is 0.6 s for males, 0.4 s for females voiding in sitting position, and 1.1 s for females voiding in standing position using a special receptacle in video urodynamics. Furthermore, we found that sphincter/urethral activity during voiding (which causes a drop in flow rate and an accompanying increase in detrusor pressure) is associated (on average) with shorter lag times than straining (when a positive pressure rise accompanies an increase in flow rate). Additionally strong evidence is provided that lag time correction is not a major source of error in urodynamics. © 1995 Wiley-Liss, Inc.

Background Given the fact that prostate cancer incidence will increase in the coming years, new prognostic biomarkers are needed with regard to the biological aggressiveness of the prostate cancer diagnosed. Since cytokines have been associated with the biology of cancer and its prognosis, we determined whether transforming growth factor beta 1 (TGFβ1), interleukin-7 (IL-7) receptor and IL-7 levels add additional prognostic information with regard to prostate cancer-specific survival. Materials and methods Retrospective survival analysis of forty-four prostate cancer patients, that underwent radical prostatectomy, was performed (1989–2001). Age, Gleason score and pre-treatment PSA levels were collected. IL-7, IL-7 receptor and TGFβ1 levels in prostate cancer tissue were determined by quantitative real-time RT-PCR and their additional prognostic value analyzed with regard to prostate cancer survival. Hazard ratios and their confidence intervals were estimated, and Akaike’s information criterion was calculated for model comparison. Results The predictive ability of a model for prostate cancer survival more than doubled when TGFβ1 and IL-7 were added to a model containing only the Gleason score and pre-treatment PSA (AIC: 18.1 and AIC: 6.5, respectively). Conclusion IL-7 and TGFβ1 are promising markers to indicate those at risk for poor prostate cancer survival. This additional information may be of interest with regard to the biological aggressiveness of the diagnosed prostate cancer, especially for those patients screened for prostate cancer and their considered therapy.

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. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.