Ethnicity and prostate cancer: The way to solve the screening problem?

In their analysis in BMC Medicine, Lloyd et al. provide individual patient lifetime risks of prostate cancer diagnosis and prostate cancer death stratified by ethnicity. This easy to understand information is helpful for men to decide whether to start prostate-specific antigen testing (i.e. screening). A higher lifetime risk of prostate cancer death in some ethnic groups is not automatically a license to start screening. The potential benefit in the form of reducing metastases and death should still be weighed against the potential risk of over diagnosis. In case of ethnicity, this harm-to-benefit ratio does not differ between groups. Stratifying men for screening based on ethnicity is therefore not optimal and will not solve the current screening problem. Other methods for risk-stratifying men have been proven to produce a more optimal harm-to-benefit ratio

Long-term follow-up after active surveillance or curative treatment: quality-of-life outcomes of men with low-risk prostate cancer

Purpose: To compare long-term (4–10 years) quality of life (QoL) of men with low-risk prostate cancer (PCa) treated by different modalities and a reference group without PCa. Methods: In this cross-sectional study, four groups were sent a one-time QoL-questionnaire; PCa patients (1) following the structured Prostate cancer Research International Active Surveillance protocol, (2) who underwent radical prostatectomy (RP) in the context of t

Rule-based versus probabilistic selection for active surveillance using three definitions of insignificant prostate cancer

To study whether probabilistic selection by the use of a nomogram could improve patient selection for active surveillance (AS) compared to the various sets of rule-based AS inclusion criteria currently used. We studied Dutch and Swedish patients participating in the European Randomized study of Screening for Prostate Cancer (ERSPC). We explored which men who were initially diagnosed with cT1-2, Gleason 6 (Gleason pattern a parts per thousand currency sign3 + 3) had histopathological indolent PCa at RP [defined as pT2, Gleason pattern a parts per thousand currency sign3 and tumour volume (TV) a parts per thousand currency sign0.5 or TV a parts per thousand currency sign 1.3 ml, and TV no part of criteria (NoTV)]. Rule-based selection was according to the Prostate cancer Research International: Active Surveillance (PRIAS), Klotz, and Johns Hopkins criteria. An existing nomogram to define probability-based selection for AS was refitted for the TV1.3 and NoTV indolent PCa definitions. 619 of 864 men undergoing RP had cT1-2, Gleason 6 disease at diagnosis and were analysed. Median follow-up was 8.9 years. 229 (37 %), 356 (58 %), and 410 (66 %) fulfilled the TV0.5, TV1.3, and NoTV indolent PCa criteria at RP. Discriminating between indolent and significant disease according to area under the curve (AUC) was: TV0.5: 0.658 (PRIAS), 0.523 (Klotz), 0.642 (Hopkins), 0.685 (nomogram). TV1.3: 0.630 (PRIAS), 0.550 (Klotz), 0.615 (Hopkins), 0.646 (nomogram). NoTV: 0.603 (PRIAS), 0.530 (Klotz), 0.589 (Hopkins), 0.608 (nomogram). The performance of a nomogram, the Johns Hopkins, and PRIAS rule-based criteria are comparable. Because the nomogram allows individual trade-offs, it could be a good alternative to rigid rule-based criteria

Evaluation of a short RNA within Prostate Cancer Gene 3 in the predictive role for future cancer using non-malignant prostate biopsies.

BACKGROUND: Prostate Cancer 3 (PCA3) is a long non-coding RNA (ncRNA) upregulated in prostate cancer (PCa). We recently identified a short ncRNA expressed from intron 1 of PCA3. Here we test the ability of this ncRNA to predict the presence of cancer in men with a biopsy without PCa. METHODS: We selected men whose initial biopsy did not identify PCa and selected matched cohorts whose subsequent biopsies revealed PCa or benign tissue. We extracted RNA from the initial biopsy and measured PCA3-shRNA2, PCA3 and PSA (qRT-PCR). RESULTS: We identified 116 men with and 94 men without an eventual diagnosis of PCa in 2-5 biopsies (mean 26 months), collected from 2002-2008. The cohorts were similar for age, PSA and surveillance period. We detected PSA and PCA3-shRNA2 RNA in all samples, and PCA3 RNA in 90% of biopsies. The expression of PCA3 and PCA3-shRNA2 were correlated (Pearson's r = 0.37, p<0.01). There was upregulation of PCA3 (2.1-fold, t-test p = 0.02) and PCA3-shRNA2 (1.5-fold) in men with PCa on subsequent biopsy, although this was not significant for the latter RNA (p = 0.2). PCA3 was associated with the future detection of PCa (C-index 0.61, p = 0.01). This was not the case for PCA3-shRNA2 (C-index 0.55, p = 0.2). CONCLUSIONS: PCA3 and PCA3-shRNA2 expression are detectable in historic biopsies and their expression is correlated suggesting co-expression. PCA3 expression was upregulated in men with PCa diagnosed at a future date, the same did not hold for PCA3-shRNA2. Futures studies should explore expression in urine and look at a time course between biopsy and PCa detection

Active surveillance: Oncologic outcome

PURPOSE OF REVIEW: To give insight into recent literature (during the past 12-18 months) reporting on oncologic outcomes of men on active surveillance. RECENT FINDINGS: From recent published trials comparing radical prostatectomy vs. watchful waiting, we learn that radical treatment only benefits a small proportion of men and that a substantial part of men is overtreated. Therefore, active surveillance should aim at postponing treatment for most, but still generate the same disease-specific mortality as radical prostatectomy by treating only those who benefit. In this review some recent published data on prostate cancer-specific mortality under active surveillance as well as intermediate outcomes are described. SUMMARY: Prostate cancer-specific mortality under active surveillance is very low; however, longer follow-up is warranted. When deferred radical treatment and immediate radical treatment are compared, results seem to be quite similar, suggesting that postponing treatment does not affect the outcomes of men under active surveillance. Furthermore, in the majority of men active treatment could be avoided completely, without compromising oncologic outcome