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Background and Objective: The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) recommendations standardise the reporting of prostate magnetic resonance imaging (MRI) in patients on active surveillance (AS) for prostate cancer. An international consensus group recently updated these recommendations and identified the areas of uncertainty., Methods: A panel of 38 experts used the formal RAND/UCLA Appropriateness Method consensus methodology. Panellists scored 193 statements using a 1-9 agreement scale, where 9 means full agreement. A summary of agreement, uncertainty, or disagreement (derived from the group median score) and consensus (determined using the Interpercentile Range Adjusted for Symmetry method) was calculated for each statement and presented for discussion before individual rescoring., Key Findings and Limitations: Participants agreed that MRI scans must meet a minimum image quality standard (median 9) or be given a score of 'X' for insufficient quality. The current scan should be compared with both baseline and previous scans (median 9), with the PRECISE score being the maximum from any lesion (median 8). PRECISE 3 (stable MRI) was subdivided into 3-V (visible) and 3-NonV (nonvisible) disease (median 9). Prostate Imaging Reporting and Data System/Likert ≥3 lesions should be measured on T2-weighted imaging, using other sequences to aid in the identification (median 8), and whenever possible, reported pictorially (diagrams, screenshots, or contours; median 9). There was no consensus on how to measure tumour size. More research is needed to determine a significant size increase (median 9). PRECISE 5 was clarified as progression to stage ≥T3a (median 9)., Conclusions and Clinical Implications: The updated PRECISE recommendations reflect expert consensus opinion on minimal standards and reporting criteria for prostate MRI in AS., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Careful assessment of the reasons for discontinuation of active surveillance (AS) is required for men with prostate cancer (PCa)., Objective: Using Movember's Global Action Plan Prostate Cancer Active Surveillance initiative (GAP3) database, we report on reasons for AS discontinuation., Design, Setting, and Participants: We compared data from 10296 men on AS from 21 centres across 12 countries., Outcome Measurements and Statistical Analysis: Cumulative incidence methods were used to estimate the cumulative incidence rates of AS discontinuation., Results and Limitations: During 5-yr follow-up, 27.5% (95% confidence interval [CI]: 26.4-28.6%) men showed signs of disease progression, 12.8% (95% CI: 12.0-13.6%) converted to active treatment without evidence of progression, 1.7% (95% CI: 1.5-2.0%) continued to watchful waiting, and 1.7% (95% CI: 1.4-2.1%) died from other causes. Of the 7049 men who remained on AS, 2339 had follow-up for >5yr, 4561 had follow-up for <5yr, and 149 were lost to follow-up. Cumulative incidence of progression was 27.5% (95% CI: 26.4-28.6%) at 5yr and 38.2% (95% CI: 36.7-39.9%) at 10yr. A limitation is that not all centres were included due to limited information on the reason for discontinuation and limited follow-up., Conclusions: Our descriptive analyses of current AS practices worldwide showed that 43.6% of men drop out of AS during 5-yr follow-up, mainly due to signs of disease progression. Improvements in selection tools for AS are thus needed to correctly allocate men with PCa to AS, which will also reduce discontinuation due to conversion to active treatment without evidence of disease progression., Patient Summary: Our assessment of a worldwide database of men with prostate cancer (PCa) on active surveillance (AS) shows that 43.6% drop out of AS within 5yr, mainly due to signs of disease progression. Better tools are needed to select and monitor men with PCa as part of AS., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Published data on prostate magnetic resonance imaging (MRI) during follow-up of men on active surveillance are lacking. Current guidelines for prostate MRI reporting concentrate on prostate cancer (PCa) detection and staging. A standardised approach to prostate MRI reporting for active surveillance will facilitate the robust collection of evidence in this newly developing area., Objective: To develop preliminary recommendations for reporting of individual MRI studies in men on active surveillance and for researchers reporting the outcomes of cohorts of men having MRI on active surveillance., Design, Setting, and Participants: The RAND/UCLA Appropriateness Method was used. Experts in urology, radiology, and radiation oncology developed a set of 394 statements relevant to prostate MRI reporting in men on active surveillance for PCa. Each statement was scored for agreement on a 9-point scale by each panellist prior to a panel meeting. Each statement was discussed and rescored at the meeting., Outcome Measurements and Statistical Analysis: Measures of agreement and consensus were calculated for each statement. The most important statements, derived from both group discussion and scores of agreement and consensus, were used to create the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) checklist and case report form., Results and Limitations: Key recommendations include reporting the index lesion size using absolute values at baseline and at each subsequent MRI. Radiologists should assess the likelihood of true change over time (ie, change in size or change in lesion characteristics on one or more sequences) on a 1-5 scale. A checklist of items for reporting a cohort of men on active surveillance was developed. These items were developed based on expert consensus in many areas in which data are lacking, and they are expected to develop and change as evidence is accrued., Conclusions: The PRECISE recommendations are designed to facilitate the development of a robust evidence database for documenting changes in prostate MRI findings over time of men on active surveillance. If used, they will facilitate data collection to distinguish measurement error and natural variability in MRI appearances from true radiologic progression., Patient Summary: Few published reports are available on how to use and interpret magnetic resonance imaging for men on active surveillance for prostate cancer. The PRECISE panel recommends that data should be collected in a standardised manner so that natural variation in the appearance and measurement of cancer over time can be distinguished from changes indicating significant tumour progression., (Copyright © 2016 European Association of Urology. All rights reserved.)

Background: Technology development to enable the culture of human prostate cancer (PCa) progenitor cells is required for the identification of new, potentially curative therapies for PCa., Objective: We established and characterized patient-derived conditionally reprogrammed cells (CRCs) to assess their biological properties and to apply these to test the efficacies of drugs., Design, Setting, and Participants: CRCs were established from seven patient samples with disease ranging from primary PCa to advanced castration-resistant PCa (CRPC). The CRCs were characterized by genomic, transcriptomic, protein expression, and drug profiling., Outcome Measurements and Statistical Analysis: The phenotypic quantification of the CRCs was done based on immunostaining followed by image analysis with Advanced Cell Classifier using Random Forest supervised machine learning. Copy number aberrations (CNAs) were called from whole-exome sequencing and transcriptomics using in-house pipelines. Dose-response measurements were used to generate multiparameter drug sensitivity scores using R-statistical language., Results and Limitations: We generated six benign CRC cultures which all had an androgen receptor-negative, basal/transit-amplifying phenotype with few CNAs. In three-dimensional cell culture, these cells could re-express the androgen receptor. The CRCs from a CRPC patient (HUB.5) displayed multiple CNAs, many of which were shared with the parental tumor. We carried out high-throughput drug-response studies with 306 emerging and clinical cancer drugs. Using the benign CRCs as controls, we identified the Bcl-2 family inhibitor navitoclax as the most potent cancer-specific drug for the CRCs from a CRPC patient. Other drug efficacies included taxanes, mepacrine, and retinoids., Conclusions: Comprehensive cancer pharmacopeia-wide drug testing of CRCs from a CRPC patient highlighted both known and novel drug sensitivities in PCa, including navitoclax, which is currently being tested in clinical trials of CRPC., Patient Summary: We describe an approach to generate patient-derived cancer cells from advanced prostate cancer and apply such cells to discover drugs that could be applied in clinical trials for castration-resistant prostate cancer., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Literature on the health-related quality of life (HRQoL) for men with localized prostate cancer (PCa) on active surveillance (AS) shows a need for methodological guidance regarding HRQoL issues and how to address them., Objective: The European School of Oncology Task Force (ESO TF) aimed to identify a core set of research questions and related measures to include in AS HRQoL studies., Design, Setting, and Participants: A modified Delphi study was used to reach consensus on AS HRQoL research topics and tools between 2014 and 2015. Data were collected by engaging a multidisciplinary team of 15 experts., Outcome Measurements and Statistical Analysis: An open-ended questionnaire was used to collect information from ESO TF members regarding issues in AS HRQoL research. Then a structured questionnaire was used to collect ratings on the usefulness/importance of different AS HRQoL aspects. Items that ≥80% of ESO TF members rated as useful/important were retained. Items with a 50-80% rating were discussed to reach final agreement., Results and Limitations: Six main research questions concerning the selection of outcome measures, measurement tools, and comparison groups were identified as relevant. The core set of measures identified were related to individual characteristics, psychological dimensions; decision-making-related issues, and physical functioning. The multidisciplinary expertise of ESO TF members was a significant asset, even if bringing different backgrounds to the discussion table represented a challenge., Conclusions: HRQoL measures have to be sensitive to the specific needs of men on AS. The definition of HRQoL outcomes will enhance a broader understanding of the HRQoL of men on AS and sustain patient-centered medicine., Patient Summary: An international panel agreed on a set of health-related quality-of-life aspects to be assessed among men on active surveillance for prostate cancer. Valid relevant questionnaires were identified. The experts' indications lay a foundation for future research and clinical practice., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The Prostate Cancer Research International Active Surveillance (PRIAS) study was initiated a decade ago to study the most optimal selection and follow-up of men on active surveillance (AS)., Objective: We report on 10 yr of follow-up of men on AS in the PRIAS study and evaluate if criteria used to recommend a switch to active treatment truly predict unfavorable outcome on subsequent radical prostatectomy (RP)., Design, Setting, and Participants: Men with low-risk prostate cancer were included and followed prospectively on AS. Follow-up consisted of regular prostate-specific antigen (PSA) tests, digital rectal examinations, and biopsies. Men with Gleason >3+3, more than two positive biopsy cores, or stage higher than cT2 were advised to switch to active treatment (until 2014, a PSA doubling time [PSA DT] of 0-3 yr was also used)., Outcome Measurements and Statistical Analysis: Reclassification rates, treatment after discontinuation, and outcome on RP after discontinuing AS were reported. Regression analysis on the outcome of RP was used to evaluate the predictive value of criteria currently used to recommend a switch to active treatment. Kaplan-Meier and competing risk analysis were used to report discontinuation rates over time and long-term oncologic end points., Results and Limitations: A total of 5302 men were included in PRIAS across 18 countries. Reclassification rates remained stable on all subsequent biopsies, with 22-33% of men having either Gleason >3+3 or more than two positive cores on any repeat biopsy. At 5 and 10 yr of follow-up, 52% and 73% of men, respectively, had discontinued AS, most of them because of protocol-based reclassification. A third of men undergoing subsequent RP had favorable pathologic tumor features (Gleason 3+3 and pT2). Of the criteria used to recommend a switch to active treatment, more than two positive cores and a PSA DT of 0-3 yr were not predictive of unfavorable pathologic outcome on RP., Conclusions: A substantial group of men discontinued AS without subsequent unfavorable tumor features on RP; therefore, we propose Gleason upgrading and cT3 as the only indicators for an immediate switch to active treatment. Surrogate indicators (eg, more than two positive cores and a fast-rising PSA) should not trigger immediate active treatment but rather further investigation to confirm the suspicion of higher risk disease., Patient Summary: We confirmed the safety of active surveillance as a treatment option for men with low-risk prostate cancer; however, some changes could be made to the follow-up protocol to safely increase the number of men who remain on active surveillance., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Men with prostate cancer on active surveillance (AS) are advised to follow strict follow-up schedules and switch to definitive treatment on risk reclassification. However, some men might not adhere to these strict protocols., Objective: To determine the number of noncompliers and disease reclassification rates in men not complying with the follow-up protocol of the Prostate Cancer Research International Active Surveillance (PRIAS) study., Design, Setting, and Participants: A total of 4547 men with low-risk prostate cancer were included and prospectively followed on AS. Men were regularly examined using prostate-specific antigen (PSA), digital rectal examination, and repeat biopsies, and were advised to switch to definitive treatment on disease reclassification (>cT2c, Gleason score > 3+3, >2 cores positive, or PSA doubling time [PSA-DT] 0-3 yr)., Outcome Measurements and Statistical Analysis: Rates of men not complying with follow-up visits or a recommendation to discontinue AS are reported. Biopsy outcome (Gleason ≥7 or >2 cores positive) was compared between compliers and noncompliers using Cox proportional hazards analysis., Results and Limitations: The compliance rate for PSA visits was 91%. By contrast, the compliance rate for standard repeat biopsies decreased over time (81%, 60%, 53%, and 33% at 1, 4, 7, and 10 yr after diagnosis, respectively). Yearly repeat biopsies in men with faster rising PSA (PSA-DT 3-10 yr) was low at <30%, although these men had higher upgrading rates at repeat biopsy (25-30% vs 16%). PSA-DT of 0-3 yr was the most common recommendation for discontinuation, but 71% continued on AS. Men with PSA-DT of 0-3 yr were at higher risk of upgrading on repeat biopsy (hazard ratio 2.02, 95% confidence interval 1.36-3.00) compared to men without fast rising PSA., Conclusion: Some men and their physicians do not comply with AS follow-up protocols. In particular, yearly repeat biopsies in men with fast rising PSA are often ignored, as is the recommendation to discontinue AS because of very fast rising PSA. Although these men are at greater risk of higher Gleason scores on repeat biopsy, the majority still exhibit favorable tumor characteristics. Fast rising PSA should therefore not trigger a recommendation to receive active treatment, but should rather serve as a criterion for stricter follow-up. In addition, we should aim to find ways of safely reducing the number of biopsies to increase adherence to AS protocols., Patient Summary: We looked at compliance with an active surveillance protocol for low-risk prostate cancer in a large active surveillance study. We observed reluctance to undergo yearly biopsies because of fast rising prostate-specific antigen, despite a higher risk of disease progression. Further research should aim to safely reduce the number of repeat biopsies in men on active surveillance to increase protocol adherence., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

This study investigated the effects of resistance training (RT) on the metabolism of testosterone (T) in younger (n=5, 28±3yrs.) and older (n=8, 70±2yrs.) men. Experimental heavy resistance exercises (5×10RM leg presses) were performed before and after a 12-month of RT. No age differences were found in the production or metabolic clearance rate of T (determined by stable isotope dilution method), skeletal muscle androgen receptor content or serum LH concentrations due to acute or chronic RT. The T production capacity response to gonadotropin stimulation and the concentrations of the urinary T metabolites (androsterone and etiocholanolone) were lower in the older compared to younger men (p<0.05-0.01). This study further showed that RT may have acute effect on T production and clearance rates, while the exercise-induced increases in serum T appeared to be induced by decreased metabolic clearance rate of T. Attenuated T production capacity and urinary excretion of T metabolites in older men may reflect the known reduction in testicular steroidogenesis upon aging. No changes were observed in T metabolism due to RT indicating a homeostatic stability for this hormone in men of different ages., (Copyright © 2015. Published by Elsevier Inc.)

Context: There is great interest in using magnetic resonance imaging (MRI) for men on active surveillance for prostate cancer., Objective: To systematically review evidence regarding the use of MRI in men with low- or intermediate-risk prostate cancer suitable for active surveillance., Evidence Acquisition: Ovid Medline and Embase databases were searched for active surveillance, prostate cancer, and MRI from inception until April 25, 2014 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses process. Identified reports were critically appraised according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria., Evidence Synthesis: A lesion on MRI suspicious for prostate cancer (positive MRI) is seen in two-thirds of men otherwise suitable for active surveillance. A positive MRI makes the identification of clinically significant disease at repeat biopsy more likely, especially when biopsies are targeted to suspicious MRI lesions. Radical prostatectomy data show that positive MRI is more likely to be associated with upgrading (Gleason score>3+3) than a negative MRI (43% vs 27%). A positive MRI is not significantly more likely to be associated with upstaging at radical prostatectomy (>T2) than a negative MRI (10% vs 8%). Although MRI is of interest in the monitoring of men on active surveillance, robust data on the use of repeat MRI in active surveillance are lacking. Prospective studies with clear definitions of radiological significance and progression are needed before this approach can be adopted., Conclusions: MRI is useful for detection of clinically significant disease at initial assessment of men considering active surveillance. To use MRI as a monitoring tool in surveillance, it will be necessary to define both radiological significance and radiological progression., Patient Summary: This review assesses evidence for the use of magnetic resonance imaging (MRI) in men on active surveillance for prostate cancer. MRI at the start of surveillance can detect clinically significant disease in one-third to half of men. There are few data to assess the use of MRI as a monitoring tool during surveillance, so there is a need to define significant disease on MRI and significant changes over time., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Overdiagnosis and subsequent overtreatment are important side effects of screening for, and early detection of, prostate cancer (PCa). Active surveillance (AS) is of growing interest as an alternative to radical treatment of low-risk PCa., Objective: To update our experience in the largest worldwide prospective AS cohort., Design, Setting, and Participants: Eligible patients had clinical stage T1/T2 PCa, prostate-specific antigen (PSA) ≤ 10 ng/ml, PSA density <0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score ≤ 6. PSA was measured every 3-6 mo, and volume-based repeat biopsies were scheduled after 1, 4, and 7 yr. Reclassification was defined as more than two positive cores or Gleason >6 at repeat biopsy. Recommendation for treatment was triggered in case of PSA doubling time <3 yr or reclassification., Outcome Measurements and Statistical Analysis: Multivariate regression analysis was used to evaluate predictors for reclassification at repeat biopsy. Active therapy-free survival (ATFS) was assessed with a Kaplan-Meier analysis, and Cox regression was used to evaluate the association of clinical characteristics with active therapy over time., Results and Limitations: In total, 2494 patients were included and followed for a median of 1.6 yr. One or more repeat biopsies were performed in 1480 men, of whom 415 men (28%) showed reclassification. Compliance with the first repeat biopsy was estimated to be 81%. During follow-up, 527 patients (21.1%) underwent active therapy. ATFS at 2 yr was 77.3%. The strongest predictors for reclassification and switching to deferred treatment were the number of positive cores (two cores compared with one core) and PSA density. The disease-specific survival rate was 100%. Follow-up was too short to draw definitive conclusions about the safety of AS., Conclusions: Our short-term data support AS as a feasible strategy to reduce overtreatment. Clinical characteristics and PSA kinetics during follow-up can be used for risk stratification. Strict monitoring is even more essential in men with high-risk features to enable timely recognition of potentially aggressive disease and offer curative intervention. Limitations of using surrogate end points and markers in AS should be recognized., Trial Registration: The current program is registered at the Dutch Trial Register with ID NTR1718 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1718)., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Little is known about the outcome of radical prostatectomy (RP) in men initially followed on active surveillance (AS) for low-risk prostate cancer (PCa)., Objective: Evaluate pathology findings after RP in our prospective AS cohort., Design, Setting, and Participants: All men participated in the Prostate Cancer Research International: Active Surveillance (PRIAS) study. Eligible men were initially diagnosed with low-risk PCa (clinical stage ≤ T2, prostate-specific antigen [PSA] ≤ 10 ng/ml, PSA density <0.2 ng/ml per ml, one or two positive biopsy cores, and Gleason score ≤ 6) and underwent RP between December 2006 and July 2011. The study protocol recommends RP in case of risk reclassification on repeat biopsy (Gleason score >6 and/or more than two positive cores) or a PSA doubling time ≤ 3 yr., Measurements: Descriptive statistics were used to report on pathology findings for staging and grading., Results and Limitations: Pathology results were available in 167 out of 189 RP cases (88.4%). Median time to RP was 1.3 yr (range: 1.1-1.9). Protocol-based recommendations led to deferred RP in 143 men (75.7%); 24 men (12.7%) switched because of anxiety, and 22 (11.6%) had other reasons. Pathology results showed 134 (80.8%) organ-confined cases and 32 (19.2%) cases with extracapsular extension. Gleason scores ≤ 6, 3+4, 4+3, and 8 were found in 79 (47.3%), 64 (38.3%), 21 (12.6%), and 3 (1.8%) cases, respectively. Unfavourable RP results (pT3-4 and/or Gleason score ≥ 4+3) were found in 49 patients (29%), of whom 33 (67%) had a biopsy-related reason for deferred RP., Conclusions: RP results in men initially followed on AS show organ-confined disease and favourable Gleason grading in a majority of cases. Most men in our cohort had a protocol-based reason to switch to deferred RP. A main focus for AS protocols should be to improve the selection of patients at the time of inclusion to minimise reclassification of risk and preserve the chance for curative treatment, if indicated., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Active surveillance (AS) protocols for low-risk prostate cancer (PCa) generally include repeat prostate biopsies at predefined follow-up intervals., Objective: To study the outcome of routinely obtained 1-yr repeat biopsies and factors predicting reclassification to higher risk, to contribute to risk stratification for men on AS., Design, Setting, and Participants: We analysed men with low-risk PCa (clinical stage ≤ T2, prostate-specific antigen (PSA) ≤ 10 ng/ml, PSA density <0.2 ng/ml per millilitre, one or two positive biopsy cores, and Gleason score ≤ 6) who had been included in a prospective AS protocol., Interventions: PSA was measured 3-monthly and the first volume-dependent repeat biopsy was scheduled 1 yr after diagnosis, independent of PSA doubling time (PSA-DT). Reclassification to higher risk disease on repeat biopsy was defined as Gleason score ≥ 7 or ≥ 3 positive cores., Measurements: We analysed whether baseline patient characteristics and PSA-DT were associated with reclassification to more aggressive PCa on repeat biopsy., Results and Limitations: A first repeat biopsy was taken in 757 patients after median follow-up of 1.03 yr. The results of repeat biopsies were favourable (no or low-risk PCa) in 594 patients (78.5%) and led to reclassification of risk in 163 (21.5%). Analysis showed that reclassification to higher risk was significantly influenced by the number of initial positive cores (two vs one) (odds ratio [OR]: 1.8; p=0.002) and higher PSA density (OR: 2.1; p=0.003). The outcome was not significantly influenced by age, clinical stage, total number of biopsy cores, or PSA. Adding PSA-DT at time of repeat biopsy to the model showed PSA-DT <3 yr to be significantly associated with reclassification to higher risk (OR: 1.7; p=0.015). Data on tumour involvement per biopsy core were not available., Conclusions: Clinical features at baseline and during follow-up in our AS cohort are significantly associated with short-term reclassification to higher risk on repeat biopsy. These characteristics can potentially be used for risk stratification of men with PCa who are apparently at favourable risk., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The incidence of small, localised, well-differentiated prostate cancer (PCa) is increasing, mainly as a result of screening. Many of these cancers will not progress, and radical therapy may lead to substantial overtreatment. Active surveillance (AS) has emerged as an alternative., Objective: To retrospectively validate the currently used criteria for eligibility for AS., Design, Setting, and Participants: For this cohort study, data from 616 men who were diagnosed with PCa between 1994 and 2007 at a mean age of 66.3 yr in four centres of the European Randomized Study of Screening for Prostate Cancer (ERSPC) were combined. All patients fit the criteria for AS (prostate-specific antigen [PSA] < or = 10.0 ng/ml, PSA-density < 0.2 ng/ml per ml, stage T1C/T2, Gleason score < or = 3 + 3 = 6, and < or = 2 positive biopsy cores), and initially they were managed expectantly. Median follow-up was 3.91 yr., Measurements: Disease specific-, overall-, and treatment-free survival were studied. Present PSA characteristics were assessed and also compared between men who were switching to deferred active therapy during follow-up and men remaining untreated., Results and Limitations: The calculated (Kaplan-Meier) 10-yr PCa-specific survival (21 patients at risk) was 100%, which sharply contrasted with 77% overall survival. Men still alive showed favourable PSA characteristics. Although the calculated 10-yr treatment-free survival was only 43%, objective signs of progression often did not indicate the shift to radical treatment. The cohort consisted of men on AS and those on watchful waiting (WW); information on comorbidity or psychological distress was not available., Conclusions: AS seems justified in selected men with screen-detected PCa. Prospective protocol-based AS programs are necessary to optimise selection criteria and to find the appropriate trigger points for switching to active therapy. Possible negative psychological reactions with AS against improved quality of life by withholding side-effects from radical treatment should be considered.

Objectives: To determine whether short-term treatment of patients about to undergo transurethral resection of the prostate (TURP) with tranexamic acid (TXA) would be beneficial in reducing the associated blood loss., Methods: A prospective and randomized trial was conducted with 136 men requiring TURP for obstructive urinary symptoms. The treatment group received 2 g TXA three times daily on the day of, and first day after, the operation., Results: Short-term TXA treatment significantly reduced the operative blood loss associated with TURP (128 mL versus 250 mL, P = 0.018), and this difference was not a result of the amount of tissue resected between the two groups (16 g versus 16 g, P = 0.415). In addition, TXA treatment reduced the amount of blood loss per gram of resected tissue (8 mL/g versus 13 mL/g, P = 0.020). Furthermore, the volume of irrigating fluid required (15 L versus 18 L, P = 0.004) and operating time (36 minutes versus 48 minutes, P = 0.001) were also reduced. However, TXA treatment did not influence the number of patients requiring a blood transfusion. Six patients in the treatment group (7.2%) and five in the control group (6.8%) required a transfusion (P = 0.709). Moreover, TXA treatment did not affect the duration of catheterization (1 day versus 1 day, P = 0.342) or hospitalization (3 days versus 3 days, P = 0.218)., Conclusions: Short-term TXA treatment is effective in reducing the operative blood loss associated with TURP.

Objective: The role of estrogens and androgens in the etiology and progression of testicular germ cell cancer is poorly understood. To gain insight into the role of sex steroid action in testicular tumorigenesis, we have measured mRNAs encoding estrogen receptor beta (ERbeta), androgen receptor (AR), and their coregulators SNURF/RNF4, PIASx, and PIAS1 in testicular germ cell tumors., Methods: We used real-time quantitative reverse transcription-PCR assay to compare the steroid receptor and coregulator mRNA levels in 12 matched samples of testicular tumors and adjacent normal tissues (seminomas n=8, nonseminomas n=4). In addition, ERbeta and SNURF/RNF4 protein immunoreactivity was analyzed from paraffin-embedded normal testis and tumor specimens., Results: ERbeta mRNA levels were down-regulated by 59% in seminomas (p=0.017), and those of AR and SNURF/RNF4 mRNAs were decreased by 75% and 67%, respectively, in seminomas and teratocarcinomas compared to paired normal samples (p=0.034 for both, Wilcoxon signed rank test), whereas the PIASx and PIAS1 mRNA were unaltered. ERbeta and SNURF/RNF4 were also clearly down-regulated at the protein level in testicular tumors., Conclusions: Expression of ERbeta and SNURF/RNF4 was significantly lower in cancerous than in noncancerous testis tissue. Down-regulation of the ERbeta and the coregulator SNURF/RNF4 genes may play a role in testicular tumorigenesis.