C.H. Bangma

Diagnostic and prognostic signatures from the small non-coding RNA transcriptome in prostate cancer

Prostate cancer (PCa) is the most frequent male malignancy and the second most common cause of cancer-related death in Western countries. Current clinical and pathological methods are limited in the prediction of postoperative outcome. It is becoming increasingly evident that small non-coding RNA (ncRNA) species are associated with the development and progression of this malignancy. To assess the diversity and abundance of small ncRNAs in PCa, we analyzed the composition of the entire small transcriptome by Illumina/Solexa deep sequencing. We further analyzed the microRNA (miRNA) expression signatures of 102 fresh-frozen patient samples during PCa progression by miRNA microarrays. Both platforms were cross-validated by quantitative reverse transcriptase–PCR. Besides the altered expression of several miRNAs, our deep sequencing analyses revealed strong differential expression of small nucleolar RNAs (snoRNAs) and transfer RNAs (tRNAs). From microarray analysis, we derived a miRNA diagnostic classifier that accurately distinguishes normal from cancer samples. Furthermore, we were able to construct a PCa prognostic predictor that independently forecasts postoperative outcome. Importantly, the majority of miRNAs included in the predictor also exhibit high sequence counts and concordant differential expression in Illumina PCa samples, supported by quantitative reverse transcriptase–PCR. Our findings provide miRNA expression signatures that may serve as an accurate tool for the diagnosis and prognosis of PCa.

Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study

Study Type – Diagnostic (validating cohort)
Level of Evidence 1b

Cutaneous Metastasis Following Laparoscopic Pelvic Lymphadenectomy for Prostatic Carcinoma

A case of implantation metastasis in the abdominal wall following transabdominal laparoscopic pelvic lymphadenectomy is reported. A cutaneous nodule was palpated at 1 of the laparoscopic ports 6 months after laparoscopic lymphadenectomy in a 66-year-old patient with stage T3pN1M0, grade 2 adenocarcinoma of the prostate. Aspiration cytology confirmed metastatic adenocarcinoma.

Evaluation of diffusion-weighted MR imaging at inclusion in an active surveillance protocol for low-risk prostate cancer

PurposeWe aimed to determine whether diffusion-weighted magnetic resonance imaging, by means of the apparent diffusion coefficient (ADC), is able to guide magnetic resonance–guided biopsy in patients fit for active surveillance (AS) and identify patients harboring high-grade Gleason components not suitable for AS. Materials and MethodsOur study was approved by the institutional review board of all participating hospitals, and all patients signed informed consent at inclusion. Fifty-four consecutive patients with low-risk prostate cancer (PCa) underwent multiparametric magnetic resonance imaging (MP-MRI) at inclusion for AS. Cancer-suspicious regions (CSRs) upon 3-T MP-MRI were identified in all patients, and magnetic resonance–guided biopsy was performed in all CSRs to obtain histopathological verification. For all CSRs, a median ADC (mADC) was calculated. Wilcoxon signed ranks and Mann-Whitney tests was performed to detect differences between the groups. We used the area under the receiver operating characteristic curve to evaluate the accuracy of mADC to predict the presence of PCa in a CSR. Level of statistical significance was set at P < 0.05. ResultsMean mADC in the CSRs with PCa was 1.04 × 10−3 mm2/s (SD, 0.29), whereas the CSRs with no PCa displayed a mean mADC of 1.26 × 10−3 mm2/s (SD, 0.25; P < 0.001). Cancer-suspicious regions with a high-grade Gleason component displayed a mean mADC of 0.84 × 10−3 mm2/s (SD, 0.35) vs a mean mADC for the low-grade CSRs of 1.09 × 10−3 mm2/s (SD, 0.25; P < 0.05). A diagnostic accuracy of mADC for predicting the presence of PCa in a CSR with an area under the receiver operating characteristic curve of 0.73 was established (95% confidence interval, 0.61–0.84). ConclusionsMedian ADC is able to predict the presence and grade of PCa in CSRs identified by MP-MRI.

1 Screening for prostate cancer: Results of the Rotterdam section of the European Randomized study of Screening for Prostate Cancer (ERSPC)

a Erasmus University Medical Center, Department of Urology, Rotterdam, The Netherlands; Comprehensive Cancer Center, Rotterdam, The Netherlands; c Erasmus University Medical Center, Department of Pathology, Rotterdam, The Netherlands; d Erasmus University Medical Center, Department of Clinical Chemistry, Rotterdam, The Netherlands; e Erasmus University Medical Center, Department of Public Health, Rotterdam, The Netherlands E U RO P E AN URO LOG Y 6 4 ( 2 0 1 3 ) 5 3 0 – 5 3 9

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

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

Watchful waiting in prostate cancer: Review and policy proposals

proportion. Because of the resulting uncertainties in assigning clinical stage, most studies have given preference to the use of histological and cytological grade as the most important prognostic variable for stratification. Table 2 summarizes some of the results [3–5]. Data on overall survival are not age-corrected and therefore reflect to a large part the intercurrent mortality. Data on cancer-specific survival and mortality may be flawed by the uncertainties of the clinical determination of death from prostate cancer. However, the data are informative. There is a steep decline in the 5-, 10and 15-year cancer-specific survival with increasing grade and, in [4], a steep increase in cancer-specific mortality with increasing Gleason scores. It is important to realise that most cases diagnosed with present diagnostic techniques fall into the moderately differentiated group (grade 2, Gleason 6). The cancer-specific 10–15-year mortality of moderately differentiated cases in the data cited in Table 2 is 18–30%. Obviously, the favourable group of prostate cancer which may not require immediate treatment must primarily be found within the groups of men diagnosed with grade 1 and 2 or Gleason 4–6 cancers. However, biopsy grade alone does not discriminate sufficiently. In using biopsybased grading the lack of correlation between biopsy grade and the true histological grade determined on radical prostatectomy (RP) specimens must be considered. Narain et al. [6] found that a biopsy Gleason score of <7 identified the same grading only in 54.8% of cases; 40.9% and 4.3% were found to have Gleason 7 or Gleason >7 tumours in their RP specimens. Kaplan-Meier curves constructed according to Gleason grade <7 in biopsy and RP specimens showed a small but statistically significantly difference in disease-free survival against the biopsy grade. Despite these limitations the cited natural history data show that there are subgroups of patients who are not at risk of dying from prostate cancer even within 15 years. The identification of cancers which can be treated by watchful waiting (WW) with acceptable safety, the pattern and duration of follow-up, and the trigger points for treatment will be crucial elements for developing policies aiming at delaying or completely avoiding aggressive treatment.

Prostate-specific antigen: its clinical use and application in screening for prostate cancer

Prostate cancer in most European countries is the second most frequent cancer in males and the second most frequent cause of cancer death. Prostate specific antigen (PSA) is an important tumour marker, which relates to many aspects of this disease. It has been shown that PSA is helpful in the early diagnosis of prostate cancer and in this respect is superior to other available tests like rectal examination and transrectal ultrasonography. PSA is also helpful in staging of locally confined disease. It can be used to identify or exclude local extension of disease, if combined with T category and grade of differentiation determined on biopsy. The same parameters also give an indication of the presence of lymph node metastases, which may prevent unnecessary and invasive staging procedures in certain groups of patients with favourable prognostic factors and a low PSA value. PSA is less suitable as a marker for metastatic disease. Progression of untreated prostate cancer in various stages can be monitored by PSA. The true value of the marker in this respect is still underexplored. It may be possible that PSA will be shown to differentiate effectively between aggressive and non-progressive disease. In this respect, it could become an essential tool to identify those patients that may not require treatment at all. PSA is also a useful marker for therapy response. An elevation of PSA after radical prostatectomy indicates local or metastatic progression, which will occur within 1-2 years. PSA is an androgen dependent enzyme and decreases under endocrine treatment. It is unexplained why in spite of its endocrine dependent character, PSA rises with endocrine independent progression of prostate cancer.

Volume adjustment for intermediate prostate- specific antigen values in a screening population

In a screening population of 812 men, between the ages of 55 and 77 years, and prostate-specific antigen (PSA) below 10.0 ng/ml (Hybritech), digital rectal examination (DRE) and transrectal ultrasonography of the prostate (TRUS) were performed. Seventeen prostate carcinomas were detected. Four methods of prostate volumetry were used to determine volume-adjusted PSA levels. These were PSA density for the total gland volume (PSAD), for the inner zone volume (PSAT) and population-specific excess PSA values. There was a significant difference between the benign and the malignant population for age, PSA, PSAD, PSAT and excess PSA values. The maximal discriminatory potential, analysed by the area under receiver ROC curve, was 0.90, reached for prolate spheroid determined excess PSA. For PSA alone this was 0.86. Volume-adjusted PSA values have no additional benefit beyond unadjusted values in screening for prostate carcinoma in this study.

Serial Prostate Specific Antigen Measurements and Progression in Untreated Confined (Stages T0 to 3NxM0, Grades 1 to 3) Carcinoma of Prostate

PURPOSE The contribution of serial prostate specific antigen (PSA) determinations was studied to obtain better understanding of the natural history of clinically confined prostate carcinoma. MATERIALS AND METHODS Serial PSA determinations in 29 patients with untreated confined prostate carcinoma were correlated to the clinical course for a mean of 39 months. RESULTS Disease progressed locally in 13 patients after a mean of 31 months. Metastatic progression was not observed. Neither grade, stage, PSA changes nor initial PSA showed significant differences with respect to interval of progression between patients with and without progression. CONCLUSIONS PSA does not parallel clinical progression in patients selected for watchful waiting.