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F H Schröder

Publications and source records attributed to F H Schröder.

At least 19 recordsLinked to original sources

Prediction of indolent prostate cancer: validation and updating of a prognostic nomogram.

PURPOSE: Screening with serum prostate specific antigen testing leads to the detection of many prostate cancers early in their natural history. Statistical models have been proposed to predict indolent cancer. We validated and updated model predictions for a screening setting. MATERIALS AND METHODS: We selected 247 patients with clinical stage T1C or T2A from the European Randomized Study on Screening for Prostate Cancer who were treated with radical prostatectomy. We validated a nomogram that had previously been developed in a clinical setting. Predictive characteristics were serum prostate specific antigen, ultrasound prostate volume, clinical stage, prostate biopsy Gleason grade, and total length of cancer and noncancer tissue in biopsy cores. Indolent cancer was defined as pathologically organ confined cancer 0.5 cc or less in volume without poorly differentiated elements. Logistic regression was used to update the previous model and examine the contribution of other potential predictors. RESULTS: Overall 121 of 247 patients (49%) had indolent cancer, while the average predicted probability was around 20% (p <0.001). Effects of individual variables were similar to those found before and discriminative ability was adequate (AUC 0.76). An updated model was constructed, which merely recalibrated the nomogram and did not apply additional predictors. CONCLUSIONS: Prostate cancers identified in a screening setting have a substantially higher likelihood of being indolent than those predicted by a previously proposed nomogram. However, an updated model can support patients and clinicians when the various treatment options for prostate cancer are considered.

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Anxiety and depression after prostate cancer diagnosis and treatment: 5-year follow-up.

To document anxiety and depression from pretreatment till 5-year follow-up in 299 men with localized prostate cancer. To assess, if baseline scores were predictive for anxiety and depression at 1-year follow-up. Respondents completed four assessments (pretreatment, at 6 and 12 months, and at 5-year follow-up) on anxiety, depression and mental health. Respondents were subdivided according to therapy (prostatectomy or radiotherapy) and high vs low-anxiety. Pretreatment 28% of all patients were classified as 'high-anxiety'; their average anxiety scores decreased significantly post-treatment, that is towards less anxiety. At all assessments, high-anxiety men treated by prostatectomy reported less depression than high-anxiety men treated by radiotherapy. Of men treated by radiotherapy, 27% reported clinical significant levels of depression while 20% is expected in a general population. The improvement in mental health at 6-months follow-up was statistically significant and clinically meaningful in all respondent groups. Sensitivity of anxiety at baseline as a screening tool was 71% for anxiety and 60% for symptoms of depression. We recommend clinicians to attempt early detection of patients at risk of high levels of anxiety and depression after prostate cancer diagnosis since prevalence is high. STAI-State can be a useful screening tool but needs further development.

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Very late local recurrence after surgery for prostate cancer unaccompanied by detectable PSA levels.

The possibility and possible aetiology of local prostate cancer (PC) recurrence despite undetectable prostate-specific antigen (PSA) levels are highlighted. A case of a local recurrence 8.5 years after radical prostatectomy for Gleason 3+4 PC is presented. It demonstrates that PC can recur, even after a prolonged period of time (8.5 years), despite undetectable levels (i.e. <0.02 ng/ml) of PSA. In conclusion, the decision to omit digital rectal examination from the follow-up regimens of men with undetectable PSA levels could be justified. In such exceptional cases, however, PC recurrence would be either missed or would only be diagnosed after a considerable delay.

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Innovations in serum and urine markers in prostate cancer current European research in the P-Mark project.

An overview is given of serum and urine prostate cancer markers that are currently under investigation and subsequently the P-Mark project is introduced. There are many markers showing promise to overcome the limitations of prostate specific antigen (PSA). Eventually, these markers should be able to increase the specificity in diagnosis, differentiate between harmless and aggressive disease and identify progression towards androgen independence at an early stage. In the P-Mark project, several recently developed, promising markers will be evaluated using clinically well-defined biorepositories. Following successful evaluation, these markers will be validated on a sample set derived from two large, European, prostate cancer studies and used for the identification of special risk groups in the general population. In addition, novel markers will be identified in the same biorepositories by different mass spectrometry techniques.

Biomarkers, Tumor↗

[Diagnosis based on prostate needle biopsy: inadequate correlation between pathologic results and clinical course for individual prognosis].

Since the introduction of serum testing for prostate-specific antigen (PSA) in 1990 for the early detection of prostate cancer, the number of men undergoing a prostate needle-biopsy procedure has increased dramatically. In order to highlight the significance of the various diagnostic outcomes of a prostate needle biopsy, the pathological findings from needle biopsies were compared with those from samples taken during radical prostatectomy and in follow-up biopsies, using data from the 'European randomised screening for prostate cancer' (ERSPC) trial. In men with an elevated PSA value and a benign or negative needle-biopsy result, 10-15% were found to have prostate cancer in follow-up biopsies. In men with a needle-biopsy diagnosis of adenocarcinoma, 29% were found to have questionable histopathological characteristics or minimal cancer that did not require therapy. The incidence of minimal cancer increased to 70% among men with a needle-biopsy diagnosis of focal carcinoma, i.e. a small focus (< 3 mm diameter) of well-differentiated adenocarcinoma, based on one biopsy from a series of six. In men with a needle-biopsy diagnosis of 'suspected malignancy' 36.5% were found to have prostate cancer in follow-up biopsies. In men with a needle-biopsy diagnosis of 'high grade prostatic intra-epithelial neoplasia' 13% were found to have prostate cancer in follow-up biopsies. This percentage was not significantly higher than the percentage of cancers detected after an initially benign biopsy outcome. To avoid over-treatment of a substantial number of men who lack symptoms of prostate cancer but are diagnosed on the basis of biopsy results, it is vital that clinical/pathologic parameters are developed and validated that can help in deciding whether to initiate curative treatment immediately.

Adenocarcinoma↗

Screening for prostate cancer.

Epidemiologically, prostate cancer is the most common cancer in the Western world after skin cancer. To date, it is still unknown whether screening for prostate cancer is justified, because results of randomised clinical trials are not yet available. The available screening tests (i.e. prostate-specific antigen (PSA) test) do not always detect cancers that otherwise would have resulted in prostate cancer mortality. Favourable results from prostate cancer screening include an increasing number of men with localised disease and an increase in the number of well-differentiated tumours. However, the risk of overdiagnosis and subsequent over-treatment (due to the diagnosis of localised disease), using aggressive therapies fuels arguments against screening. Therefore, until more evidence is available proving otherwise, prostate cancer screening can only be justified in the context of clinical trials.

Biopsy↗

Atrophy in prostate needle biopsy cores and its relationship to prostate cancer incidence in screened men.

OBJECTIVES: To evaluate whether the incidence of atrophy reported on sextant biopsies is associated with subsequent prostate cancer detection and to obtain a more thorough analysis of the different categories and extent of atrophy, we performed a review of benign biopsy cores. METHODS: In the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer, 4117 and 1840 men underwent sextant biopsy in the first and second screening round (4-year interval), respectively. Sextant biopsy was prompted by elevated prostate-specific antigen levels. For review, randomly taken benign sextant biopsies (n = 202) with a follow-up of at least 8 years were chosen. RESULTS: Before review, atrophy was reported in the biopsies of 11.4% and 8.7% of the first and second round, respectively. The prostate cancer incidence during 8 years of follow-up after an initial diagnosis of atrophy was 10.4%, which was not significantly different than the 12.3% of cancers detected after a benign diagnosis without reference to atrophy. After review, the incidence of simple atrophy, post-atrophic hyperplasia, and sclerotic atrophy in sextant biopsies was 91%, 47%, and 9%, respectively. Extensive atrophy was observed in 5% of biopsies. Only 2 men (4.7%) in the reviewed group had a subsequent diagnosis of prostate cancer in the 8 years of follow-up. Additionally, prostatic intraepithelial neoplasia was diagnosed in 3 men (7.0%) in the second screening round. CONCLUSIONS: Atrophy, especially its simple form, is a very common lesion in prostate biopsy cores (94%). Atrophy in an asymptomatic population undergoing screening was not associated with a greater prostate cancer or prostatic intraepithelial neoplasia incidence during subsequent screening rounds.

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Additional use of [-2] precursor prostate-specific antigen and "benign" PSA at diagnosis in screen-detected prostate cancer.

OBJECTIVES: To evaluate the adjuvant clinical use of [-2] precursor prostate-specific antigen ([-2]pPSA), which is associated with prostate cancer (PCa), and "benign" PSA, related to benign prostatic hyperplasia, in selecting a treatment strategy in patients with screen-detected PCa. METHODS: Research-use immunoassays (Beckman Coulter) were used to measure [-2]pPSA, sum [-7, -5, -4, and -2]pPSA, and benign PSA from the frozen serum of participants from the screen arm of the European Randomized Study of Screening for Prostate Cancer, section Rotterdam, diagnosed with PCa with a serum PSA level lower than 15 ng/mL. We compared men with relatively benign PCa (Epstein's criteria; group 1) and men with arbitrarily defined aggressive PCa characteristics (Gleason score greater than 4 + 4 and more than four cores with PCa invasion or pT3C disease; group 2). RESULTS: The data of 61 patients were evaluated. The median age in both groups was 68 years. Total PSA performed best in a univariate analysis, although in the multivariate analysis, the combination of pPSA and percent free PSA could correctly predict 95.5% of group 1 and 82.4% of group 2. The pPSA and percent free PSA forms remained statistically significant in the multivariate analysis of a subgroup of 30 participants normalized for PSA level and prostate volume; combined they correctly identified 89.5% and 54.5% of patients identified as having relatively favorable and aggressive PCa characteristics, respectively. CONCLUSIONS: Adjuvant clinical use of pPSA over traditional parameters in selecting treatment strategies for men with PCa cannot yet be definitely determined. However, the promising results in a subgroup analysis warrant further investigation.

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Features of prostate cancers detected during a prevalence screening round. The Rotterdam experience.

INTRODUCTION: Prostate-specific antigen (PSA) testing of asymptomatic men may lead to the detection of "minimal" prostate cancers that are less likely to be associated with morbidity or mortality. OBJECTIVE: To examine the significance of various diagnostic outcomes from needle biopsies of the prostate in an asymptomatic population of men. METHODS: Prostatic needle biopsy findings were matched with those from radical prostatectomy specimens using data from the Rotterdam section of the European Randomized study of Screening for Prostate Cancer (ERSPC). Men, aged between 55 and 75 years, with elevated PSA levels underwent lateralized sextant needle biopsies. In corresponding radical prostatectomy specimens, the tumor categories (minimal, moderate, or advanced) were determined. RESULTS: Prostate cancer was diagnosed in 5.1% of 19,970 screened men, and 31.6 % of the men had cancers that were categorized as "minimal." Repeat biopsies performed after initial diagnoses of either isolated prostatic intra-epithelial neoplasia (PIN) or "suspicious for malignancy," detected adenocarcinoma in 12.1%and 36.5 % of the men, respectively. In a substudy of 510 men with a benign biopsy outcome 12 months previously, repeat biopsies detected adenocarcinoma in 12.4 of the men. Of men who were subsequently treated with radical prostatectomy, the cancers were classified as "minimal" in 27.8% of the men with previously benign biopsies and in 47.4% of the men with previously suspicious lesions, CONCLUSIONS: The chance of finding a "minimal" prostate cancer in an asymptomatic population is substantial and increases when a repeat biopsy is performed following a biopsy with a suspicious outcome.

Adenocarcinoma↗

Prostate-specific antigen velocity at low prostate-specific antigen levels as screening tool for prostate cancer: results of second screening round of ERSPC (ROTTERDAM).

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.

Adenocarcinoma↗

No reason for immediate repeat sextant biopsy after negative initial sextant biopsy in men with PSA level of 4.0 ng/mL or greater (ERSPC, Rotterdam).

OBJECTIVES: In the early detection of prostate cancer (CaP) uncertainty exists concerning the most appropriate biopsy procedure. Within the European Randomized Study of Screening for Prostate Cancer (ERSPC) lateralized sextant biopsies are used. False-negative results of sextant biopsies have led to the extensive use of procedures using 12 or more biopsy cores. The ERSPC offers the opportunity to study the yield of repeat biopsies after 4 years in men who had negative sextant biopsies and a prostate-specific antigen (PSA) level of 4.0 mg/mL or more at the first screening round. METHODS: Between August 1996 and May 1998, a total of 6876 men (age 55 to 74 years) were randomized to the screening arm and actually underwent screening. The numbers and levels of biopsy indicators, as well as possible predictors for biopsy outcome, in the second screening round, such as prostate volume, volume change over time, prostate-specific antigen density (PSAD), PSA velocity, and age, were calculated and compared for participants with positive and negative biopsies in round 2. The positive predictive value (PPV) and detection rates, as well as parameters of aggressiveness, were evaluated for second-round biopsy-detected and interval CaP cases. RESULTS: Of the 728 men with a PSA level of 4.0 mg/mL or more who underwent biopsy at initial screening, 553 were eligible for a second screening visit after 4 years. Of these, 272 (49.2%) actually underwent screening. Eighteen CaP cases were detected with 217 biopsies, indicated by a PSA level of 3.0 ng/mL or more (PPV 8.3%). Eight interval cases were identified by linking to the Cancer Registry. These 26 cases would have increased the PPV and detection rate of the initial screening round from 36.1% to 39.7% and from 3.8% to 4.2%, respectively. Most of these cases (23 of 26 or 88.5%) were organ confined and amenable to potentially curative treatment. CONCLUSIONS: Although the results of this study may have been biased by the low rate of availability/eligibility of participants for rescreening (after 4 years), the proportion of cancers detected after a previous lateral sextant biopsy indicated by a PSA value of 4.0 mg/mL or more (PPV 8.3%) fell far short of the overall PPV at rescreening (PPV 20%). The features of most cancers that were possibly missed during the first round allowed a potentially curative approach. The ERSPC study group found no reason to change the ERSPC protocol.

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Prostate cancer characteristics and prostate specific antigen changes in screening detected patients initially treated with a watchful waiting policy.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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The value of (-7, -5)pro-prostate-specific antigen and human kallikrein-2 as serum markers for grading prostate cancer.

OBJECTIVE: To assess the value of the precursor form (-7,5pro) of prostate-specific antigen (PSA) and human kallikrein-2 (hK2) for detecting and grading prostate cancer, as better serum markers with improved specificity are needed in men with lower ranges of total (t)PSA. PATIENTS AND METHODS: tPSA, free PSA (fPSA), the precursor (-7,5)proPSA and hK2 were measured in a subset of participants of the European Randomised Study of Screening of Prostate Cancer. In a pilot study, sera from 143 men biopsied but with no prostate cancer, 142 with BPH, and 146 with prostate cancer were analysed to determine the relative value of serum markers for differentiating between the groups. Then, in 141 men with prostate cancer who had a radical prostatectomy, these serum markers were related to the pathological grading to analyse their value as prognostic variables. RESULTS: Levels of (-7,5)proPSA, hK2 and fPSA could be used to distinguish between BPH and cancer, but proPSA and hK2, alone or combined, did not improve the specificity of fPSA for discriminating BPH and cancer. There was also no correlation between these serum markers and pathological tumour grade. CONCLUSION: The clinical effect of using (-7,5)proPSA or hK2 for detecting and grading prostate cancer remains limited.

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Circulating free insulin-like growth factor (IGF)-I, total IGF-I, and IGF binding protein-3 levels do not predict the future risk to develop prostate cancer: results of a case-control study involving 201 patients within a population-based screening with a 4-year interval.

Recent studies have reported that serum IGF-I levels in the highest quartile of the normal range and IGF binding protein-3 (IGFBP-3) in the lowest quartile of the normal range are associated with an increased risk of future prostate cancer and/or presence of prostate cancer. It has also been suggested that the measurement of circulating total IGF-I concentrations might be a useful tool for the early detection of prostate cancer in men with moderately increased prostate-specific antigen (PSA) levels. To determine whether circulating free IGF-I, total IGF-I, and IGFBP-3 levels can predict future prostate cancer risk, we prospectively studied prostate cancer characteristics in a cohort of men during two rounds (mean interval, 4 yr) of a population-based screening study for prostate cancer. Two hundred one prostate cancer cases were detected at the second-round screening (aged 55-70 yr), and all these subjects were enrolled in the case group for the present study. Prostate cancer had been confirmed by biopsy in all cases. These 201 subjects were matched with the 201 nonprostate cancer cases by age, serum PSA range at the first-round screening (PSA < 2 ng/ml, n = 67; PSA = 2-3 ng/ml, n = 67; and PSA = 3-4 ng/ml, n = 67), and residence area. At baseline, total IGF-I, free IGF-I, and IGFBP-3 levels and prostate volume of cases with prostate cancer were not different from those of healthy controls. PSA velocity was significantly different between cases and controls (P < 0.001).Stepwise forward logistic regression analysis showed that only PSA levels at baseline and PSA at round 2 after 4 yr are good predictors of prostate cancer, whereas total IGF-I, free IGF-I, and IGFBP-3 did not predict the development of prostate cancer. Only one of the 201 subjects with prostate cancer had metastases. Within the subjects with prostate cancer, there were no differences of IGF-I parameters with different tumor node metastasis categories and/or Gleason scores. Our study suggests that the measurement of serum IGF-I and/or IGFBP-3 concentrations in addition to PSA does not improve the identification of men at high risk to develop early stages of prostate cancer. In addition, our results indicate that the endocrine IGF-I system is not directly involved in the growth of the early stages of prostate cancer.

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Low all-cause mortality in the volunteer-based Rotterdam section of the European randomised study of screening for prostate cancer: self-selection bias?

OBJECTIVES: The likelihood of self-selection bias in a cohort of men that entered the volunteer-based randomised prostate cancer screening trial was assessed. In addition, the accuracy of the randomisation was evaluated by comparison amongst the trial arms. SETTING: The Rotterdam section of the European Randomised Study of Screening for Prostate Cancer (ERSPC). Participants were recruited from population registries and randomised after receipt of written informed consent (49% participation rate). METHODS: Data from 37,614 men who entered the Rotterdam trial between June 1994 and July 1999 were linked to the Causes of Death Registry of Statistics Netherlands. For the assessment of self-selection bias, mortality in the trial cohort and the area of Rotterdam was compared by calculating standardised mortality ratios (SMRs, 95% confidence interval [CI]). Comparisons between the screening and the control arm were made by means of relative risk (RR). RESULTS: There were a total of 1661 deaths (4.4%) in the trial cohort, during an average follow-up time of 2.8 years. The observed number of deaths in the two arms combined was lower than expected (SMR 86.7%, 95% CI 81.6-92.1), which was reflected in the major cause of death categories, especially in all malignant neoplasms. No difference was observed in the all-cause mortality rate among the screening and control arm, aged 55-69 years at entry (RR 1.00, 95% CI 0.89-1.12), nor when all causes, excluding prostate cancer mortality, were considered. CONCLUSIONS: The preliminary results show that the screening and the control arm were comparable, but men recruited for the trial seemed healthier than men in the target population.

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