Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial.

Importance: Prostate-specific antigen (PSA) screening has potential to reduce prostate cancer mortality but frequently detects prostate cancer that is not clinically important. Objective: To describe rates of low-grade (grade group 1) and high-grade (grade groups 2-5) prostate cancer identified among men invited to participate in a prostate cancer screening protocol consisting of a PSA test, a 4-kallikrein panel, and a magnetic resonance imaging (MRI) scan. Design, Setting, and Participants: The ProScreen trial is a clinical trial conducted in Helsinki and Tampere, Finland, that randomized 61 193 men aged 50 through 63 years who were free of prostate cancer in a 1:3 ratio to either be invited or not be invited to undergo screening for prostate cancer between February 2018 and July 2020. Interventions: Participating men randomized to the intervention underwent PSA testing. Those with a PSA level of 3.0 ng/mL or higher underwent additional testing for high-grade prostate cancer with a 4-kallikrein panel risk score. Those with a kallikrein panel score of 7.5% or higher underwent an MRI of the prostate gland, followed by targeted biopsies for those with abnormal prostate gland MRI findings. Final data collection occurred through June 31, 2023. Main Outcomes and Measures: In descriptive exploratory analyses, the cumulative incidence of low-grade and high-grade prostate cancer after the first screening round were compared between the group invited to undergo prostate cancer screening and the control group. Results: Of 60 745 eligible men (mean [SD] age, 57.2 [4.0] years), 15 201 were randomized to be invited and 45 544 were randomized not to be invited to undergo prostate cancer screening. Of 15 201 eligible males invited to undergo screening, 7744 (51%) participated. Among them, 32 low-grade prostate cancers (cumulative incidence, 0.41%) and 128 high-grade prostate cancers (cumulative incidence, 1.65%) were detected, with 1 cancer grade group result missing. Among the 7457 invited men (49%) who refused participation, 7 low-grade prostate cancers (cumulative incidence, 0.1%) and 44 high-grade prostate cancers (cumulative incidence, 0.6%) were detected, with 7 cancer grade groups missing. For the entire invited screening group, 39 low-grade prostate cancers (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected. During a median follow-up of 3.2 years, in the group not invited to undergo screening, 65 low-grade prostate cancers (cumulative incidence, 0.14%) and 282 high-grade prostate cancers (cumulative incidence, 0.62%) were detected. The risk difference for the entire group randomized to the screening invitation vs the control group was 0.11% (95% CI, 0.03%-0.20%) for low-grade and 0.51% (95% CI, 0.33%-0.70%) for high-grade cancer. Conclusions and Relevance: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT03423303.

Infectious complications after transrectal MRI-targeted and systematic prostate biopsy.

PURPOSE: To compare infectious complications after transrectal systematic prostate biopsy (SB) and magnetic resonance imaging (MRI)-targeted biopsy (TB) in a large retrospective cohort to assess whether one technique is superior to the other regarding infectious complications. METHODS: A total of 4497 patients underwent 5288 biopsies, 2875 (54%) SB and 2413 (46%) MRI-TB only. On average, 12 SB cores and 3.7 MRI-TB cores were taken per biopsy session during the study period. Infection-related complications within 30 days were compared. The primary endpoint was a positive urine culture. Secondary endpoints were positive blood cultures, urine tests with elevated leukocytes ≥ 100 E6/L and elevated C-reactive protein (CRP) ≥ 100 mg/L. Chi-square test was used to compare the cohorts. RESULTS: Positive urine cultures were found in 77 (2.7%) after SB and in 42 (1.7%) after MRI-TB (p = 0.022). In total, 46 (0.9%) blood culture positive infections were found, 23 (0.9%) occurred after SB and 23 (1.0%) after MRI-TB, (p = 0.848). Urine tests with elevated leukocytes ≥ 100 E6/L were found in 111 (3.9%) after SB and in 61 (2.5%) after MRI-TB (p = 0.006). Elevated CRP ≥ 100 mg/L was found in 122 (4.2%) after SB and in 72 (3.0%) after MRI-TB (p = 0.015). Blood cultures were drawn more often after SB than after MRI-TB, but the difference was not statistically significant. However, urine cultures and CRP were taken more often after SB than MRI-TB. CONCLUSION: Blood culture positive infections were equally rare after SB and MRI-TB. However, all other infectious complications were more common after SB than MRI-TB.

Population-based randomized trial of screening for clinically significant prostate cancer ProScreen: a pilot study.

OBJECTIVES: To evaluate the feasibility of a population-based screening trial using prostate-specific antigen (PSA), a kallikrein panel and multiparametric magnetic resonance imaging (MRI) aimed at minimizing overdiagnosis, while retaining mortality benefit. PATIENTS AND METHODS: Feasibility of the screening algorithm was evaluated in terms of participation, screening test results and cancer detection. A random sample of 400 men aged 65 years was identified from the population registry and invited for screening with three stepwise tests (PSA, kallikrein panel and MRI). Men with PSA levels ≥3 ng/mL were further tested with the kallikrein panel, and those with positive findings (risk >7.5%) were referred for prostate MRI. Men with positive MRI (Prostate Imaging Reporting and Data System [PI-RADS] score 3-5) had targeted biopsies only. Men with negative MRI, but PSA density ≥0.15 underwent systematic biopsies. RESULTS: Of the 399 men invited, 158 (40%) participated and 27 had PSA levels ≥3 ng/mL (7% of the invited and 17% of the participants). Of these, 22 had a positive kallikrein panel (6% of the invited and 81% of the PSA-positive men). Finally, 10 men (3% of the invited and 45% of 4Kscore [kallikrein panel]-positive) had a suspicious MRI finding (PI-RADS score ≥3) and five were diagnosed with a clinically significant prostate cancer (Gleason Grade Group [GG] ≥2) at fusion biopsy (3% of the participants), with two GG 1 cases (1%). Additional testing (kallikrein panel and MRI) after PSA reduced biopsies by 56%. CONCLUSION: The findings constitute proof of principle for our screening protocol, as we achieved a substantial detection rate for clinically significant cancer with few clinically insignificant cases. Participation, however, was suboptimal.

Associations of PTEN and ERG with Magnetic Resonance Imaging Visibility and Assessment of Non-organ-confined Pathology and Biochemical Recurrence After Radical Prostatectomy.

BACKGROUND: Diagnosing clinically significant prostate cancer (PCa) is challenging, but may be facilitated by biomarkers and multiparametric magnetic resonance imaging (MRI). OBJECTIVE: To determine the association between biomarkers phosphatase and tensin homolog (PTEN) and ETS-related gene (ERG) with visible and invisible PCa lesions in MRI, and to predict biochemical recurrence (BCR) and non-organ-confined (non-OC) PCa by integrating clinical, MRI, and biomarker-related data. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of a population-based cohort of men with PCa, who underwent preoperative MRI followed by radical prostatectomy (RP) during 2014-2015 in Helsinki University Hospital (n = 346), was conducted. A tissue microarray corresponding to the MRI-visible and MRI-invisible lesions in RP specimens was constructed and stained for PTEN and ERG. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations of PTEN and ERG with MRI-visible and MRI-invisible lesions were examined (Pearson's χ2 test), and predictions of non-OC disease together with clinical and MRI parameters were determined (area under the receiver operating characteristic curve and logistic regression analyses). BCR prediction was analyzed by Kaplan-Meier and Cox proportional hazard analyses. RESULTS AND LIMITATIONS: Patients with MRI-invisible lesions (n = 35) had less PTEN loss and ERG-positive expression compared with patients (n = 90) with MRI-visible lesions (17.2% vs 43.3% [p = 0.006]; 8.6% vs 20.0% [p = 0.125]). Patients with invisible lesions had better, but not statistically significantly improved, BCR-free survival probability in Kaplan-Meier analyses (p = 0.055). Rates of BCR (5.7% vs 21.1%; p = 0.039), extraprostatic extension (11.4% vs 44.6%; p < 0.001), seminal vesicle invasion (0% vs 21.1%; p = 0.003), and lymph node metastasis (0% vs 12.2%; p = 0.033) differed between the groups in favor of patients with MRI-invisible lesions. Biomarkers had no independent role in predicting non-OC disease or BCR. The short follow-up period was a limitation. CONCLUSIONS: PTEN loss, BCR, and non-OC RP findings were more often encountered with MRI-visible lesions. PATIENT SUMMARY: Magnetic resonance imaging (MRI) of the prostate misses some cancer lesions. MRI-invisible lesions seem to be less aggressive than MRI-visible lesions.

Prostate MRI added to CAPRA, MSKCC and Partin cancer nomograms significantly enhances the prediction of adverse findings and biochemical recurrence after radical prostatectomy.

BACKGROUND: To determine the added value of preoperative prostate multiparametric MRI (mpMRI) supplementary to clinical variables and their role in predicting post prostatectomy adverse findings and biochemically recurrent cancer (BCR). METHODS: All consecutive patients treated at HUS Helsinki University Hospital with robot assisted radical prostatectomy (RALP) between 2014 and 2015 were included in the analysis. The mpMRI data, clinical variables, histopathological characteristics, and follow-up information were collected. Study end-points were adverse RALP findings: extraprostatic extension, seminal vesicle invasion, lymph node involvement, and BCR. The Memorial Sloan Kettering Cancer Center (MSKCC) nomogram, Cancer of the Prostate Risk Assessment (CAPRA) score and the Partin score were combined with any adverse findings at mpMRI. Predictive accuracy for adverse RALP findings by the regression models was estimated before and after the addition of MRI results. Logistic regression, area under curve (AUC), decision curve analyses, Kaplan-Meier survival curves and Cox proportional hazard models were used. RESULTS: Preoperative mpMRI data from 387 patients were available for analysis. Clinical variables alone, MSKCC nomogram or Partin tables were outperformed by models with mpMRI for the prediction of any adverse finding at RP. AUC for clinical parameters versus clinical parameters and mpMRI variables were 0.77 versus 0.82 for any adverse finding. For MSKCC nomogram versus MSKCC nomogram and mpMRI variables the AUCs were 0.71 and 0.78 for any adverse finding. For Partin tables versus Partin tables and mpMRI variables the AUCs were 0.62 and 0.73 for any adverse finding. In survival analysis, mpMRI-projected adverse RP findings stratify CAPRA and MSKCC high-risk patients into groups with distinct probability for BCR. CONCLUSIONS: Preoperative mpMRI improves the predictive value of commonly used clinical variables for pathological stage at RP and time to BCR. mpMRI is available for risk stratification prebiopsy, and should be considered as additional source of information to the standard predictive nomograms.

PTEN and ERG expression in MRI-ultrasound guided fusion biopsy correlated with radical prostatectomy findings in men with prostate cancer.

BACKGROUND: Conventional systematic prostate biopsies (SBx) have multiple limitations, and magnetic resonance imaging (MRI)-ultrasound fusion targeting is increasingly applied (fusion biopsies [FBx]). In our previous studies, we have shown that loss of the tumor suppressor gene phosphatase and tensin homolog (PTEN) in radical prostatectomy (RP) specimens predicts poor disease-specific survival, and in active surveillance (AS), PTEN loss in SBx predicts an adverse AS outcome, although SBx PTEN status does not correlate well with the corresponding RP status. Here, we have hypothesized that PTEN and erythroblast transformation-specific related gene (ERG) status in FBx correlate better with RP than they would in SBx. METHODS: A total of 106 men, who had undergone FBx and subsequent RP in a single center between June 2015 and May 2017 were included. Fifty-three of the men had concomitant or previous SBx's. All biopsy and RP specimens were collected, and tissue microarrays (TMA) were constructed from RP specimens. Immunohistochemical stainings for PTEN and ERG expression were conducted on biopsies and RP TMAs and results were compared by using Fisher's exact test. RESULTS: The immunohistochemical predictive power of FBx, determined by the concordance of biopsy PTEN and ERG status with RP, is superior to SBx (77.6% vs 66.7% in PTEN, 92.4% vs 66.6% in ERG). FBx was superior to SBx in correlation with RP Gleason Grade Groups and MRI prostate imaging reporting and data system scores. CONCLUSION: FBx grading correlates with RP histology and MRI findings and predicts the biomarker status in the RP specimens more accurately than SBx. A longer follow-up is needed to evaluate if this translates to better prediction of disease outcomes, especially in AS and radiation therapy where prostatectomy specimens are not available for prognostication.

Impact noise of prostate biopsy devices.

Objective: To analyse the impact noise generated by prostate biopsy devices.Materials and methods: In a laboratory setting, repeated impact noise was recorded at distances of 50 cm and 100 cm using five brands of device on chicken meat, an apple and an empty target. In a clinical setting, the impact noise levels of prostate biopsy devices were recorded in 40 real patient cases using three brands of device.Results: In the laboratory setting, the average SPL (sound pressure level) peak level ranged from 104.3 to 121.3 dB. The highest impact noise levels were measured with the Monopty device, ranging from 114.8 to 122.4 dB. In the clinical setting, there were no statistical differences between repeated SPL values for each specific target. Also, the noise levels were equal when the same device brand was used at 50 cm and 100 cm. The highest SPLs were recorded with the Monopty device, which ranged from 110 to 127 dB. The corresponding values for the Max-Core and Multicore were from 106 to 122.5 dB and from 108 to 116.5 dB, respectively.Conclusions: Biopsy devices generate high peak levels of impact noise. Personnel performing biopsies are advised to consider using hearing protection, even though the impact noise may not induce permanent hearing loss.

Fast prostate retrieval in robot-assisted laparoscopic prostatectomy for next-generation biobanking.

Robotic-assisted laparoscopic radical prostatectomy (RALP) has become the most widespread treatment for organ-confined prostate cancer. Here, we describe a fast specimen retrieval technique for RALP to obtain high-quality tissue specimen with minimal warm ischemia time for next-generation biobanking. Here, we show that using fast retrieval technique, short warm ischemia times can be achieved while not increasing the surgical time. Patients undergoing RALP with written informed consent participated in Helsinki Urological Bank study. Previously operated RALP patients and those, who were not willing to participate in the study, served as a control group. The study consisted of 1685 patients, 684 in fast retrieval and 1001 in control group. We developed a novel fast retrieval technique in which fascia is opened for camera port according to the prostate size and a running suture is placed and tightened against the camera port in the beginning of the operation. Immediately after prostate is freed from attachments, suture is loosened and the prostate is extirpated inside the endoscopic bag through the camera port fascial opening, then the fascial suture is again tightened against the camera port and the RALP procedure is completed. The mean warm ischemia times in fast retrieval group were 20 min 18 s and 22 min 30 s, respectively, in patients without and with lymphadenectomy. The mean console and surgery times with and without lymphadenectomy were similar in both groups. There were no technique-related complications associated with Fast Retrieval procedure. Tissue integrity test results for the RNA and DNA quality showed good quality for the specimen. Fast retrieval technique can easily and safely be utilized to maximize usefulness of RALP tissue specimen in downstream biobank applications.

Randomised Trial of Adjuvant Radiotherapy Following Radical Prostatectomy Versus Radical Prostatectomy Alone in Prostate Cancer Patients with Positive Margins or Extracapsular Extension.

BACKGROUND: It remains unclear whether patients with positive surgical margins or extracapsular extension benefit from adjuvant radiotherapy following radical prostatectomy. OBJECTIVE: To compare the effectiveness and tolerability of adjuvant radiotherapy following radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: This was a randomised, open-label, parallel-group trial. A total of 250 patients were enrolled between April 2004 and October 2012 in eight Finnish hospitals, with pT2 with positive margins or pT3a, pN0, M0 cancer without seminal vesicle invasion. INTERVENTION: A total of 126 patients received adjuvant radiotherapy at 66.6Gy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was biochemical recurrence-free survival, which we analysed using the Kaplan-Meier method and Cox proportional hazard regression. Overall survival, cancer-specific survival, local recurrence, and adverse events were secondary endpoints. RESULTS AND LIMITATIONS: The median follow-up time for patients who were alive when the follow-up ended was 9.3yr in the adjuvant group and 8.6yr in the observation group. The 10-yr survival for biochemical recurrence was 82% in the adjuvant group and 61% in the observation group (hazard ratio [HR] 0.26 [95% confidence interval {CI} 0.14-0.48], p<0.001), and for overall survival 92% and 87%, respectively (HR 0.69 [95% CI 0.29-1.60], p=0.4). Two and four metastatic cancers occurred, respectively. Out of the 43 patients with biochemical recurrence in the observation group, 37 patients received salvage radiotherapy. In the adjuvant group, 56% experienced grade 3 adverse events, versus 40% in the observation group (p=0.016). Only one grade 4 adverse event occurred (adjuvant group). A limitation of this study was the number of patients. CONCLUSIONS: Adjuvant radiotherapy following radical prostatectomy is generally well tolerated and prolongs biochemical recurrence-free survival compared with radical prostatectomy alone in patients with positive margins or extracapsular extension. PATIENT SUMMARY: Radiotherapy given immediately after prostate cancer surgery prolongs prostate-specific antigen progression-free survival, but causes more adverse events, when compared with surgery alone.

Initiation of robot-assisted radical prostatectomies in Finland: Impact on centralization and quality of care.

Objective The aim of this study was to analyze the impact of introduction of robot-assisted prostate surgery and its quality measures in Finland from 2008 to 2012. Materials and methods Registry data were collected for time trends and national distribution of prostate cancer surgery in Finland, while preoperative, operative and follow-up data were collected for quality measures. Results The number and proportion of robot-assisted laparoscopic radical prostatectomies (RALPs) increased rapidly and they accounted for 68% of all radical prostatectomies in 2012. The number of centers performing prostatectomies diminished from 25 to 20 at the expense of low-volume centers. In total, 1996 patients were operated on in the four RALP centers in 2008-2012. As anticipated, the learning curve was uniform between the centers, as were mean blood loss (212 ml), hospitalization (1.8 days) and catheterization times (10.6 days). At 3 and 12 months, 49.4% and 71.2% of patients, respectively, were totally continent (no pads). After unilateral nerve-sparing surgery, 9.9% and 5.1% had partial or normal erection at 3 months postoperatively and 14.8% and 20.4% at 12 months, respectively. If bilateral nerve sparing was done, the figures were 13.0% and 13.5% at 3 months and 14.6% and 34.9% at 12 months. Clavien-Dindo grade 3, 4 or 5 complications were seen in 0.3%, 0.3% and 0.1% of patients, respectively. Limitations of the study include non-standardized collection of outcome parameters. Conclusions This report shows that the main impact of adoption of RALP on a national level was rapid spontaneous centralization of prostate cancer surgery. The main advantages of minimally invasive prostatectomy, i.e. low blood loss and short hospitalization, are easily achieved, while continuous effort is necessary for improvements in surgical outcomes.

Performance of transrectal prostate biopsies in detecting tumours and implications for focal therapy.

OBJECTIVE: The aim of this study was to investigate the performance of transrectal biopsies in predicting pathological outcomes after radical prostatectomy (RP) and in estimating possible candidates for focal therapies. MATERIAL AND METHODS: The study was a retrospective analysis of 96 prostate cancer patients treated by robot-assisted laparoscopic RP at Helsinki University Central Hospital in 2009-2010. Data from diagnostic biopsies were compared with data from reassessment of RP slides. At reanalysis, an index tumour was chosen for all patients and was determined as being the most dedifferentiated tumour or the largest tumour with Gleason pattern 3 in case Gleason patterns 4 or 5 were absent. The performance of prostate biopsies in predicting cancer laterality, tumour size and tumour location was analysed. Statistical methods included Spearman's correlation, linear regression analysis and Pearson's chi-squared test. Suitability for focal therapies was assessed based on tumour morphology and laterality. RESULTS: The extent of cancer in biopsies correlated with tumour size in the apex and middle of the prostate [standard coefficients in linear regression for the apex 2.479-2.553, 95% confidence interval (CI) 1.952-3.056, p < 0.001-0.007; and for the middle 1.936-2.388, 95% CI 1.504-2.861, p < 0.001]. Prostate biopsies performed moderately in predicting tumour location in RP slides (positive predictive value 34.1-90.9%). Thirty-six patients (37.5%) would possibly have been candidates for focal therapy and thirty-nine (40.6%) patients for hemiablation. CONCLUSIONS: Contemporary transrectal prostate biopsies are a suboptimal tool for predicting pathological findings at RP. Approximately 40% of patients would possibly have been suitable candidates for focal or hemiablative therapies.

Dabigatran for thromboprophylaxis after robotic assisted laparoscopic prostatectomy: retrospective analysis of safety profile and effect on blood coagulation.

OBJECTIVE: The aims of this study were to analyse the efficacy and safety of orally administered dabigatran in prostate cancer patients who have undergone robotic assisted laparoscopic prostatectomy (RALP) and to analyse the effects of RALP on selected markers of coagulation activity. MATERIAL AND METHODS: Data were collected prospectively on the first 400 patients who underwent RALP at Helsinki University Central Hospital between 2009 and 2011. As thromboprophylaxis, intermittent compression devices were used in association with anaesthesia. Dalteparin sodium at 2500 IU was administered on the preoperative evening and at 5000 IU daily until discharge. Then patients were prescribed 220 mg dabigatran etexilate once daily for the next 15 days. Bleeding and thromboembolic complications were recorded. A set of routine coagulation analyses was undertaken in 61 patients preoperatively, on the first, second and eight postoperative days. RESULTS: One patient with obesity- and cancer-related risk factors developed venous thromboembolism 18 days after the operation. Nine patients (2.3%) had postoperative blood loss or bleeds, eight patients required blood transfusions and three underwent reoperation before dabigatran administration. Increased fibrinogen, factor VIII, d-dimer and thrombocytosis were observed postoperatively, reflecting coagulation activity. CONCLUSIONS: RALP activates coagulation, and thromboprophylaxis for high-risk patients even after minimally invasive surgery may be beneficial. Orally administered dabigatran after discharge from hospital appears safe for venous thromboembolism prophylaxis after RALP.

[Update on current care guidelines: benign prostatic hyperplasia]. / Eturauhasen hyvänlaatuinen liikakasvu.

Most benign prostatic hyperplasia (BPH) patients can be diagnosed and treated in primary care. Evaluation requires a medical history and a symptom score (DAN-PSS or IPSS) and a careful physical examination including a digital rectal examination. Careful follow-up and medical therapy are the usual first-line management options in uncomplicated BPH. Combination therapy with both alpha-blocker and 5alpha-reductase inhibitor is the most effective medical treatment modality. Transurethral resection (TURP) is a safe and effective way of treating BPH. The green laser is the most promising new endoscopic treatment modality.

[Robotic laparoscopic radical prostatectomy]. / Muutakin kuin lisää leluja kirurgeille? Robottiavusteinen laparoskooppinen radikaaliprostatektomia.

Robotic laparoscopic radical prostatectomy is an established method in the treatment of localized prostatic cancer. The equipment comprises a separate control console that makes ergonomic working possible. The optics creates a three-dimensional view and 10 to 15-fold magnification, thus enabling accurate operation. Recovery from the procedure is quicker and the number of blood transfusions lower than in open radical prostatectomy. The methods do not differ in regard to oncological results. Regardless of technique, radical prostatectomy is a demanding operation, in which the surgeon's skills and experience are decisive for the final result.

Duration of testosterone suppression after a 9.45 mg implant of the GnRH-analogue buserelin in patients with localised carcinoma of the prostate a 12-month follow-up study.

OBJECTIVES: (1) To determine the duration of androgen deprivation after a single buserelin implant 9.45 mg in the neoadjuvant setting in combination with curative radiation therapy of carcinoma of the prostate, and (2) to evaluate the time to recovery of gonadal function, and the incidence and duration of hypogonadal symptoms. METHODS: We prospectively evaluated 21 men with carcinoma of the prostate who received one implant of 9.45 mg buserelin subcutaneously. Release of buserelin, changes in serum testosterone concentration, hot flushing and sexual function over a 12-month study period were recorded. RESULTS: Testosterone was suppressed below the castration limit (0.58 ng/ml=2 nmol/l) for 224 days (range, 139-309). The mean time to first return of testosterone above the castration limit was 246 days (range, 168-344); 50% of pre-treatment value was reached after 285 days (range, 218-370). The prevalence of hot flushing was 19 of 21 patients (90%) at 12 weeks. At the end of the study period, serum testosterone had reached 80% (range, 33%-166%) of pre-treatment concentration, sexual interest was present in 52%, erection was possible in 60%, and hot flushing remained in 24%. CONCLUSION: A single injection of 3-month buserelin implant 9.45 mg suppresses serum testosterone below the castration limit for at least 6 months. Testosterone secretion recovers by 8-12 months. Hypogonadal symptoms decreased with the restoration of serum testosterone secretion. These data are clinically relevant regarding the dose schedule for buserelin and the patient information provided.

The effects of short-term oral phytoestrogen supplementation on the hypothalamic-pituitary-testicular axis in prostate cancer patients.

BACKGROUND: Here we evaluate the effects of oral phytoestrogen supplementation on hypothalamic-pituitary-testicular (HPT) axis in CaP patients. METHODS: We recruited 40 men about to undergo radical prostatectomy for CaP to receive either 240 mg of clover phytoestrogens or placebo daily for 2 weeks. Serum hormone levels were measured before and after treatment. In addition, recombinant cell bioassay was used to measure serum androgen bioactivity (ABA). RESULTS: Phytoestrogen treatment increased serum LH from mean of 3.4-5.2 IU, P = 0.03. Concomitantly, non-significant trend towards decline in serum T, cfT and ABA values was noted. However, mean serum LH/T ratio was upregulated from 0.20 to 0.48 IU/nM, P = 0.004, suggesting compensated hypogonadism. During the course of treatment, serum concentration of equol correlated strongly with the concomitant decrease in ABA (r = -0.586, P = 0.022). CONCLUSIONS: Phytoestrogen treatment interferes with HPT axis in CaP patients by inducing testicular resistance to LH and compensated hypogonadism.

Plasma and prostate phytoestrogen concentrations in prostate cancer patients after oral phytoestogen supplementation.

BACKGROUND: Phytoestrogens have been suggested to reduce the risk of prostate cancer (CaP), but no data exists on how oral phytoestrogen supplementation influences phytoestrogen concentrations in prostate tissue. METHODS: Forty men with CaP, assigned for radical prostatectomy, received 240 mg of clover phytoestrogens or placebo daily for a 2-week period before their operation in a prospective and randomized study. Phytoestrogens were measured in plasma and prostate tissue by time-resolved fluoroimmunoassay (TR-FIA). RESULTS: All patients had low baseline phytoestrogen concentrations and only 35% had a detectable plasma concentration of equol. Oral supplementation with phytoestrogens induced a statistically significant (P<0.001) 23- and 7-fold increase in prostate tissue concentrations of the phytoestrogens genistein and daidzein, respectively. Supplemented patients demonstrated prostate tissue genistein and daidzein concentrations that were over twofold higher than their plasma. Interestingly, even though the placebo group did not receive phytoestrogen challenge, they also demonstrated twofold prostate tissue genistein and daidzein concentrations compared to their plasma values, suggesting that the prostate can concentrate available phytoestrogens. In addition, after the supplementation, 90% of the supplemented patients had a detectable plasma equol concentration. CONCLUSIONS: We conclude that prostate tissue can concentrate genistein and daidzein. Significant elevation of intraprostatic genistein and daidzein concentrations can be achieved with a short-term dietary phytoestrogen supplementation.

Tranexamic acid in control of primary hemorrhage during transurethral prostatectomy.

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.