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Posterior rhabdosphincter reconstruction (PRR) has been proposed to improve early urinary continence (UC) recovery after radical prostatectomy (RP). In order to generate level 1b evidence, we designed a double-blind randomised controlled trial powered to detect a 20% increase in early UC recovery after robot-assisted RP (RARP). A group of 153 patients with cT1c–3a N0M0 prostate cancer were randomised (73 to control arm and 80 to PRR arm) and 152 completed 12-mo follow-up. For UC defined as no pad use, the recovery hazard ratio at 1-mo follow-up was 2.312 (95% confidence interval [CI] 1.081–4.937; p = 0.030). UC recovery was observed in 33.8% of patients in the PRR arm and 18.1% of patients in the control arm (p = 0.022). At 3-mo follow-up the corresponding rates were 58.8% and 43.1% (p = 0.038). The median time to UC recovery was 106 d (95% CI 73–139) in the control arm and 64 d (95% CI 39–89) in PRR arm (p = 0.897). No differences in pathological outcomes or early and late surgical complications were observed between the arms. We conclude that PRR is safe and increases early UC recovery after RARP. Patient summary We investigated reconstruction of a muscular ring that controls the flow of urine, called the rhabdosphincter, after removal of the prostate in robot-assisted surgery. The procedure is safe and increases early recovery of urinary continence. This trial is registered at ClinicalTrials.gov as NCT03302169.

Multiparametric magnetic resonance; Prostate cancer; Tumor staging Resonancia magnética multiparamétrica; Cáncer de próstata; Estadificación tumoral Ressonància magnètica multiparamètrica; Càncer de pròstata; Estadificació tumoral The correct identification of extracapsular extension (ECE) of prostate cancer (PCa) on multiparametric magnetic resonance imaging (mpMRI) is crucial for surgeons in order to plan the nerve-sparing approach in radical prostatectomy. Nerve-sparing strategies allow for better outcomes in preserving erectile function and urinary continence, notwithstanding this can be penalized with worse oncologic results. The aim of this study was to assess the ability of preoperative mpMRI to predict ECE in the final prostatic specimen (PS) and identify other possible preoperative predictive factors of ECE as a secondary end-point. We investigated a database of two high-volume hospitals to identify men who underwent a prostate biopsy with a pre-biopsy mpMRI and a subsequent RP. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of mpMRI in predicting ECE were calculated. A univariate analysis was performed to find the association between image staging and pathological staging. A multivariate logistic regression was performed to investigate other preoperative predictive factors. A total of 1147 patients were selected, and 203 out of the 1147 (17.7%) patients were classified as ECE according to the mpMRI. ECE was reported by pathologists in 279 out of the 1147 PS (24.3%). The PPV was 0.58, the NPV was 0.72, the sensitivity was 0.32, and the specificity was 0.88. The multivariate analysis found that PSA (OR 1.057, C.I. 95%, 1.016–1.100, p = 0.006), digital rectal examination (OR 0.567, C.I. 95%, 0.417–0.770, p = 0.0001), ratio of positive cores (OR 9.687, C.I. 95%, 3.744–25.006, p = 0.0001), and biopsy grade in prostate biopsy (OR 1.394, C.I. 95%, 1.025–1.612, p = 0.0001) were independent factors of ECE. The mpMRI has a great ability to exclude ECE, notwithstanding that low sensitivity is still an important limitation of the technique.

Prostate cancer (PCa) aggressiveness can be assessed from clinical and pathologic surrogate endpoints as the International Society of Uropathology grade group (GG) in prostate biopsies, the type of pathology from surgical specimens, the clinical stage, and the risk of biochemical recurrence after treatment of localised PCa. Low evidence exists about the association between prostate magnetic resonance imaging (MRI) and PCa aggressiveness beyond the known increased risk of clinically significant PCa (csPCa) as Prostate Imaging and Data Report System (PI-RADS) increase. Therefore, we confirm previous data and generate new evidence from all the previous surrogate endpoints of PCa aggressiveness, confirming that MRI grades the aggressiveness of PCa. We sought to find further evidence showing the increase in PCa aggressiveness as PI-RADS score increases from four surrogates of PCa aggressiveness: i. prostate biopsy GG (≤3 vs. >3), ii. type of pathology in surgical specimens (favourable vs. unfavourable), iii. clinical stage (localised vs. advanced), and risk of recurrence of localised PCa after primary treatment (low-intermediate vs. high). A group of 692 PCa patients were diagnosed after 3-T multiparametric MRI (mpMRI) and guided and/or systematic biopsies, showing csPCa (GG ≥ 2) in 547 patients (79%) and insignificant PCa (iPCa) in 145 (21%). The csPCa rate increased from 32.4% in PI-RADS < 3 to 95.5% in PI-RADS 5 (p < 0.001). GG ≥ 3 was observed in 7.6% of PCa with PI-RADS < 3 and 32.6% in those with PI-RADS > 3 (p < 0.001). Unfavourable pathology was observed in 38.9% of PCa with PI-RAD < 3 and 68.3% in those with PI-RADS > 3 (p = 0.030). Advanced disease was not observed in PCa with PI-RADS ≤ 3, while it existed in 12.7% of those with PI-RADS > 3 (p < 0.001). High-risk recurrence localised PCa was observed in 9.5% of PCa with PI-RADS < 3 and 35% in those with PI-RADS > 3 (p = 0.001). The PI-RADS score was an independent predictor of all surrogates of PCa aggressiveness as PSA density. We confirmed that mpMRI grades PCa aggressiveness

Magnetic resonance imaging; Predictive model; Prostate cancer Imágenes por resonancia magnética; Modelo predictivo; Cáncer de próstata Imatges per ressonància magnètica; Model predictiu; Càncer de pròstata A predictive model including age, PCa family history, biopsy status (initial vs repeat), DRE (normal vs abnormal), serum prostate-specific antigen (PSA), and DRE prostate volume ca-tegory was developed to stratify initial PCa suspicion in 1486 men with PSA > 3 ng/mL and/or abnormal DRE, in whom mpMRI followed; 2- to 4-core TRUS-guided biopsies where Prostate Imaging Report and Data System (PI-RADS) > 3 lesions and/or 12-core TRUS systematic biopsies were performed in one academic institution between 1 January 2016–31 December 2019. The csPCa detection rate, defined as International Society of Uro-Pathology grade group 2 or higher, was 36.9%. An external validation of designed BCN-RC 1 was carried out on 946 men from two other institutions in the same metropolitan area, using the same criteria of PCa suspicion and diagnostic approach, yielded a csPCa detection rate of 40.8%. The areas under the receiver operating characteristic curves of BCN-RC 1 were 0.823 (95% CI: 0.800–0.846) in the development cohort and 0.837 (95% CI: 0.811–0.863) in the validation cohort (p = 0.447). In both cohorts, BCN-RC 1 exhibited net benefit over performing mpMRI in all men from 8 and 12% risk thresholds, respectively. At 0.95 sensitivity of csPCa, the specificities of BCN-RC 1 were 0.24 (95% CI: 0.22–0.26) in the development cohort and 0.34 (95% CI: 0.31–0.37) in the validation cohort (p < 0.001). The percentages of avoided mpMRI scans were 17.2% in the development cohort and 22.3% in the validation cohort, missing between 1.8% and 2% of csPCa among men at risk of PCa. In summary, BCN-RC 1 can stratify initial PCa suspicion, reducing the demand of mpMRI, with an acceptable loss of csPCa. This research was funded by Instituto de Salut Carlos III (SP) and European Union, grant number PI20/01666.

Background: Lymph node (LN) status is a key prognostic factor in the decision-making process of prostate cancer (PCa) management. Sectioning and haematoxylin and eosin (H&E) staining technique remain the gold standard for the evaluation of LN metastases despite some limitations, especially low sensitivity in detecting an accurate tumour burden within the LN, as well as a subjective and time-consuming result. One-step nucleic acid amplification (OSNA) quantifies mRNA copies of cytokeratin 19 (CK19) in a fast, objective, automated, and reproducible way, raising a general interest to explore its utility for lymphatic metastasis identification in different malignancies.Methods: To present the latest evidence related to the detection of LN metastases in several tumours by using OSNA compared with the conventional H&E method, a systematic review of articles published since March 2021 was conducted using PubMed, Cochrane Library, and Web of Science databases. References from primary papers and review articles were checked to obtain further potential studies. Our procedure for evaluating records identified during the literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria.Results: Twenty five studies were included. LN from six different groups of tumours: breast, gastrointestinal, gynecological, lung, head and neck and prostate cancers has been assessed. OSNA was compared with post-operative formalin-fixed paraffin-embedded tissue sections with H&E staining as the reference standard. Contingency tables were created, and concordance rate, sensitivity, specificity and predictive values were reported. Seventeen studies analysed the discordant cases using different techniques.Conclusion: OSNA method has a high diagnostic accuracy for the detection of LN metastases in several CK19 expressing tumours. Available evidence encourages its usage in PCa patients to improve LN staging and prognosis.

INTRODUCTION AND OBJECTIVE:Lymph node (LN) status is a key prognostic factor in the decision-making process for prostate cancer (PC) management. Sectioning and haematoxylin-eosin (HE) staining tech...

Diagnosis; Proclarix; Prostate cancer Diagnóstico; Proclarix; Cáncer de próstata Diagnòstic; Proclarix; Càncer de pròstata Purpose To analyze how Proclarix is valuable to appropriately select candidates for multiparametric magnetic resonance imaging (mpMRI) and derived biopsies, among men with suspected prostate cancer (PCa). Proclarix is a new marker computing the clinically significant PCa (csPCa) risk, based on serum thosmbospondin-1, cathepsin D, prostate-specific antigen (PSA) and percent free PSA, in addition to age, that has been developed in men with serum PSA 2 to 10 ng/mL, prostate volume ≥35 mL, and normal digital rectal examination (DRE). Materials and Methods Proclarix score (0%–100%) is analyzed in a prospective frozen serum collection of 517 correlative men scheduled for guided and/or systematic biopsies after mpMRI. Outcome variables were csPCa detection (grade group ≥2), insignificant PCa (iPCa) overdetection and avoided mpMRIs. Results The area under the curve of Proclarix was 0.701 (95% CI 0.637–0.765) among 281 men with serum PSA 2 to 10 ng/mL, prostate volume ≥35 mL, and -normal DRE, and 0.754 (95% CI 0.701–0.807) in the others, p=0.038. Net benefit of Proclarix existed in all men. After selecting 10% threshold, Proclarix was integrated in an algorithm which also used the serum PSA level and DRE. A reduction of 25.4% of mpMRIs request was observed and 17.7% of prostate biopsies. Overdetection of iPCa was reduced in 18.2% and 2.6% of csPCa were misdiagnosed. Conclusions Proclarix is valuable in all men with suspected PCa. An algorithm integrating Proclarix score, serum PSA, and DRE can avoid mpMRI requests, unnecessary prostate biopsies and iPCa overdetection, with minimal loss of csPCa detection.

Objective To assess the current ability of atypical small acinar proliferation (ASAP), multifocal high-grade prostatic intraepithelial neoplasia (mHGPIN), HGPIN with atypia (PINATYP) and other non-malignant lesions to predict clinically significant prostate cancer (csPCa) in repeat prostate biopsies. Methods This retrospective study analyzed 377 repeat prostate biopsies, carried out between 2.014 and 2.017, and excluding those with previous PCa or 5-alpha reductase inhibitors treatment. ASAP, mHGPIN, PINATYP, prostatic atrophy, prostatic hyperplastic atrophy, proliferative inflammatory atrophy (PIA), chronic prostatitis, acute prostatitis, or granulomatous prostatitis, were prospectively reported after 12-core transrectal ultrasound (TRUS) systematic negative previous biopsies. 3T-multiparametric magnetic resonance imaging (mpMRI) was performed previous repeat biopsies. At least 2-core TRUS targeted biopsies of Prostate Imaging-Reporting and Data Systemv2 lesions ≥3, and/or 12-core TRUS systematic biopsy were performed in repeat prostate biopsies. The main outcome measurements were csPCa detection, which was defined when the International Society of Uro-Pathology group grade >1 and avoided biopsies. After logistic regression analysis the most efficient model was selected, nomogram was designed with internal validation, and clinical utility was analyzed. Results Normal benign tissue alone was present in less than 2% of previous negative biopsies. mHGPIN (39.7%), ASAP (4.3%) and PINATYP (3.7%) failed to predict csPCa risk in repeat biopsies. The finding of PIA (38.2%) associated with a decreased the risk of csPCa with an Odd ratio of 0.54 (95% confidence interval: 0.31–0.95), P= 0.031. The area under the curve, to predict csPCa, of mpMRI was 0.736, increasing up to 0.860 (95% confidence internal:0.82–0.90) when PSA density, age, digital rectal examination, and differential PSA between biopsies and PIA finding were integrated in a predictive model. At 6% threshold, more than 20% of repeat prostate biopsies were saved without missing csPCa. Conclusion Currently, mHGPIN in negative prostate biopsy seems not able to predict the risk of future csPCa. The low incidence of ASAP and PINATYP, in our series, did not allow us to draw conclusions. PIA finding associated with a reduced risk of csPCa, and it could be integrated in a useful based-mpMRI predictive nomogram.

To analyze prostatic-specific antigen density (PSAD) according to the Prostate Imaging Reporting and Data System (PIRADSv.2) score, in order to determine how it should be used.This correlative series considered 952 men with prostatic-specific antigen3 ng/ml and/or abnormal digital rectal examination who were subjected to prostatic biopsy (PB) between 2016 and 2017. Of these men, 768 had no previous 5-α-reductase inhibitor use or history of prostate cancer (CaP) and had previously undergone 3-T multiparametric magnetic resonance imaging (mpMRI). In this sample, 549 men were biopsy-naïve and 219 had at least 1 previous negative PB. A 12-core transrectal ultrasound-guided PB was performed in all participants, as well as at least 2-core targeted biopsies of every detected lesion with a PIRADSv.2 score ≥3. Significant CaP (sCaP) was defined as an International Society of Uropathologist grade1 or tumor length4 mm.The overall CaP detection was 41.7%, with sCaP detected in 37.4%. sCaP was detected in 4.3% of PIRADSv.23, 21.5% of PIRADSv.2 =3, 56.6% of PIRADSv.2 =4, and 78.5% of PIRADSv.2 =5, (P0.001). Insignificant CaP detection ranged from 6.5% to 1.5% respectively (P = 0.099). PSAD was an independent predictor of sCaP (odds ratios 1.971, 95% confidence interval [1.633, 2.378], P0.001) and mpMRI (OR 3.179, 95%CI [2.593, 4.950], P0.001). Age (P = 0.013), family history of CaP (P = 0.021), and the type of PB (initial vs. repeated, P0.001) were also independent predictors of sCaP. PSAD was determined by PIRADSv.2 (P = 0.013) and the presence of sCaP (P0.001). PSAD increased with PIRADSv.2 score, even in men with CaP (P0.001) and slightly in men without CaP (P = 0.019). The area under the curve for mpMRI increased from 0.830 to 0.869 when PSAD was associated, (P0.001). The area under the curve of PSAD decreased from 0.727 in men with a PIRADSv.2 score3 to 0.706 in those with a score of 5.The efficacy of PSAD to detect sCaP decreases with PIRADSv.2. Predictors other than mpMRI and PSAD exist. Considering these conditions, independent predictors should be integrated in a nomogram and risk-calculator to personalize PB recommendation.

To combine multiparametric MRI (mpMRI) findings and clinical parameters to provide nomograms for diagnosing different scenarios of aggressiveness of prostate cancer (PCa). A cohort of 346 patients with suspicion of PCa because of abnormal finding in digital rectal examination (DRE) and/or high prostate specific antigen (PSA) level received mpMRI prior to prostate biopsy (PBx). A conventional 12-core transrectal PBx with two extra cores from suspicious areas in mpMRI was performed by cognitive fusion. Multivariate logistic regression analysis was performed combining age, PSA density (PSAD), DRE, number of previous PBx, and mpMRI findings to predict three different scenarios: PCa, significant PCa (ISUP-group ≥ 2), or aggressive PCa (ISUP-group ≥ 3). We validate models by ROC curves, calibration plots, probability density functions (PDF), and clinical utility curves (CUC). Cut-off probabilities were estimated for helping decision-making in clinical practice. Our cohort showed 39.6% incidence of PCa, 32.6% of significant PCa, and 23.4% of aggressive PCa. The AUC of predictive models were 0.856, 0.883, and 0.911, respectively. The PDF and CUC showed 11% missed diagnoses of significant PCa (35 cases of 326 significant PCa expected in 1000 proposed Bx) when choosing

Purpose: It remains unclear whether patients with prostate cancer suspicion and negative magnetic resonance imaging (M.R.I.) can safely obviate biopsy. The purpose of this study was to assess the clinical negative predictive value (N.P.V.) of M.R.I. in excluding prostate cancer. The secondary end-point was to compare N.P.V. to detect significant prostate cancer of M.R.I.The secondary end-point was to compare N.P.V. to detect significant prostate cancer in M.R.I. classified as P.I.-R.A.D.S.1 and as P.I.-R.A.D.S.2 Methods: From December 2012 to January 2017, 1128 M.R.I.s were performed consecutively due to prostate cancer clinical suspicion. The absence of suspicious and presence of low-risk areas were considered as negative M.R.I., P.I.-R.A.D.S.1 and 2. Biopsy results were compared according to P.I.-R.A.D.S. classification. The clinically significant disease was defined as International Society of Urological Pathology group higher than 1. Results: Two hundred and twenty-two (20%) M.R.I.s didn’t highlight targetable imaging suspicious areas, which were recorded as negative tests: 130 (59%) P.I.-R.A.D.S.1 and 92 (41%) P.I.-R.A.D.S.2. Detection of clinically significant prostate cancer in at least one biopsy core was higher in the P.I.-R.A.D.S.2 group, 9% (8/92) vs 3% (4/130), p = 0.047. The N.P.V. in biopsy-naïve men and P.I.-R.A.D.S.1 was 95% for significant disease, while in patients subjected to repeated biopsies and P.I.-R.A.D.S.1, the N.P.V. found was 99%. Those rates differ from the P.I.-R.A.D.S.2 group: N.P.V. in biopsy-naïve patients was 84%, and 95% in repeated biopsy. Conclusions: P.I.-R.A.D.S.2 shouldn’t be considered as a negative M.R.I. A biopsy cannot be routinely omitted in biopsy-naïve men with clinical suspicion of cancer and a low-suspicious area in M.R.I., giving the possibility of missing clinically significant tumors.

Introduction and aims Urinary incontinence is a common complication after radical prostatectomy. The aim of our study was to describe the preoperative anatomical features using magnetic resonance imaging in order to predict early continence recovery after robotic radical prostatectomy. Material and methods 72 patients who underwent robotic radical prostatectomy were prospectively analysed. EPIC questionnaire (1, 6 and 12 mo) and first self-reported continence were used to assess functional outcomes. Membranous urethral length (MUL) and MUL-prostate axis angle (aMULP) were assessed preoperatively on T2 weighted sagittal images. Results Continence rate was 67.2%, 92.6% and 95.2% at 1, 6 and 12 months, respectively. Early continence was achieved in patients with the lower aMULP. At 1 month, average aMULP in continent patients was 107.21° (CI 95% 90.3–124.6) vs. 118.5° (CI 95% 117.7–134) in incontinent ones (p = 0.014). At 6 month differences in aMULP among groups were found: 114.24° (CI 95% 104.6–123.9) in continents vs. 142° (CI 95% 126.5–157.6) in incontinents (p = 0.015). At 12 month, continent group showed a significantly higher preoperative aMULP. aMULP was revealed as the only independent predictor of urinary continence at 6 mo in multivariate analysis, OR 0.007 (CI 95% 0.002–0.012), p = 0.012. Conclusions Preoperative anatomical parameters assessment prior surgery can help to identified those patients will achieve early continence recovery and it supports therapeutic decisions making.

The aim of this study was to evaluate hormonal recovery after cessation of androgen deprivation therapy (ADT) in a group of elderly prostate cancer patients.Forty patients with locally advanced or metastatic prostate cancer, with a mean age of 71.5 years [95% confidence interval (CI) 69.1-73.9], were treated with ADT for a mean duration of 74.6 months (95% CI 59.7-89.5 months). Mean follow-up time after ADT cessation was 36.5 months (95% CI 30.6-42.3 months). Serum testosterone and luteinizing hormone (LH) were determined at 6 month intervals after ADT cessation.After 18 months of follow-up, all patients had recovered normal LH levels, while 38% of patients still presented castration levels of testosterone ( 50 ng/dl). A multivariate analysis was performed to find factors related to testosterone recovery (testosterone50 ng/dl). Neither age at start of ADT nor clinical stage reached statistical significance. Only time under ADT was correlated with testosterone recovery (p = .031). Kaplan-Meier curves were obtained. Mean time for testosterone recovery was 14.5 months (95% CI 6.5-22.6 months) in patients treated with ADT for less than 60 months compared to 29.3 months (95% CI 19.6-39.1 months) in patients treated with ADT for more than 60 months (log-rank p = .029).Age did not correlate with testosterone recovery in a group of elderly prostate cancer patients in whom ADT was stopped. Testosterone recovery after ADT cessation was significantly correlated with time under ADT treatment. Significant implications related to economic aspects of the dosage schedule may be considered.

To determine the influence of radical prostatectomy (RP) and external beam radiation therapy (EBRT) on the hypothalamic pituitary axis of 120 men with clinically localized prostate cancer treated with RP or EBRT exclusively.120 patients with localized prostate cancer were enrolled. Ninety two patients underwent RP and 28 patients EBRT exclusively. We measured serum levels of luteinizing hormone, follicle stimulating hormone (FSH), total testosterone (T), free testosterone, and estradiol at baseline and at 3 and 12 months after treatment completion.Patients undergoing RP were younger and presented a higher prostate volume (64.3 vs. 71.1 years, p0.0001 and 55.1 vs. 36.5 g, p0.0001; respectively). No differences regarding serum hormonal levels were found at baseline. Luteinizing hormone and FSH levels were significantly higher in those patients treated with EBRT at three months (luteinizing hormone 8,54 vs. 4,76 U/l, FSH 22,96 vs. 8,18 U/l, p0,0001) while T and free testosterone levels were significantly lower (T 360,3 vs. 414,83ng/dl, p 0,039; free testosterone 5,94 vs. 7,5pg/ml, p 0,018). At 12 months FSH levels remained significantly higher in patients treated with EBRT compared to patients treated with RP (21,01 vs. 8,51 U/l, p0,001) while T levels remained significantly lower (339,89 vs. 402,39ng/dl, p 0,03).Prostate cancer treatment influences the hypothalamic pituitary axis. This influence seems to be more important when patients with prostate cancer are treated with EBRT rather than RP. More studies are needed to elucidate the role that prostate may play as an endocrine organ.

To analyse the relationship between daily calcium intake (DCI) and bone mineral density (BMD) in patients with prostate cancer, and to assess if DCI is a risk factor for osteoporosis in this group of patients.DCI was assessed by a standard questionnaire answered by men with prostate cancer who had had bone densitometry. BMD was measured by dual-energy X-ray absorptiometry in the lumbar spine and different hip sites, in a cross-sectional study including 372 men with prostate cancer free of bone metastases, 71.5% (266) under androgen-deprivation therapy (ADT) and 28.5% (106) after radical prostatectomy (RP). Osteoporosis was defined according to the International Society for Clinical Densitometry official position (2005).A DCI of1000 mg, the National Institute of Health recommendation, was detected in 93% of the men, (93.5% under ADT and 91.5% after RP). Osteoporosis was identified in 49.2% (183) of the patients, 54.9% (146) under ADT and 34.9% (37) after RP. The mean DCI was 609.7 mg in men with osteoporosis and 682.8 mg in those without (P0.001); in men under ADT the mean DCI remained significantly lower in those with osteoporosis (615.5 vs 700.4 mg, P0.001). A multivariate analysis showed that DCI was an independent risk factor for osteoporosis, together with patient age, ADT and its duration.DCI seems to be related to BMD; a low DCI was an independent risk factor for osteoporosis in men with prostate cancer. In the study population overall the DCI was inadequate. Urologists should recommend a DCI of1000 mg in patients with prostate cancer, especially in those under ADT.

Objectives To know the prevalence of osteoporosis in patients with prostate cancer according to the duration of androgen deprivation therapy (ADT). Methods Dual energy x-ray absorptiometry was used to assess the bone mineral density (BMD) at the lumbar spine, femoral neck, Ward's triangle, trochanter, and total hip in 390 patients free of bone metastases. Osteoporosis was diagnosed if a T-score of less than 2.5 was detected at any measurement site. A subset of 124 patients were hormone naive at BMD testing, and 112 had undergone ADT for 2 years, 61 for 4 years, 37 for 6 years, 35 for 8 years, and 21 for 10 years or longer. Results The osteoporosis rate was 35.4% in hormone-naive patients, 42.9% after 2 years of ADT, 49.2% after 4 years, 59.5% after 6 years, 65.7% after 8 years, and 80.6% after 10 or more years. Conversely, the rate of normal BMD decreased from 19.4% in hormone-naive patients to 17.8% after 2 years of ADT, 16.4% after 4 years, 10.8% after 6 years, 5.7% after 8 years, and 0% after 10 or more years of ADT. Conclusions The prevalence of osteoporosis seemed high in hormone-naive patients with prostate cancer, and it increased to more than 80% after 10 years of ADT. Because of the increased risk of bone fractures in those patients, clinicians should be aware of the impact of ADT on BMD to prevent bone mass loss.

Objectives: It was the aim of this study to analyze the failure rates in achieving or maintaining castrate levels of serum testosterone in patients with advanced prostate cancer treated with the 3-month luteinizing hormone-releasing hormone agonist (LH-RH) therapy. Methods:Total serum testosterone was determined in 234 patients with prostate cancer in a cross-sectional study. A subset of 90 patients submitted to radical prostatectomy was used as the control group (group 1), and 144 patients with advanced prostate cancer under androgen suppression therapy were included in the study group (groups 2 and 3). The study group was divided into 93 patients (group 2) treated with 50 mg daily bicalutamide and LH-RH agonist (maximal androgen blockade, MAB) and 51 patients treated with the LH-RH agonist alone (group 3). Median follow-up after androgen suppression was 42 months. The castrate testosterone level was defined below 50 ng/dl. Results: The mean serum testosterone level was 29.1 ng/dl in patients undergoing MAB (group 2) and 29.5 ng/dl in patients treated with the LH-RH agonist (group 3; p > 0.05). In group 1, the mean serum testosterone was 445.2 ng/dl (p < 0.0001). The rate of patients with a serum testosterone level higher than 50 ng/dl was 10.9% in patients undergoing androgen suppression, 10% in patients with MAB treatment and 12.5% in those with LH-RH agonist therapy (p > 0.05). In group 1, 98.9% of the patients had a serum testosterone level higher than 50 ng/dl. Conclusions: A small but clinically significant rate of patients under 3-month LH-RH agonist therapy fail to achieve or maintain castrate testosterone serum levels. This finding supports the need of monitoring testicular response during LH-RH agonist therapy.

The objective of this study was to analyze the value of the nadir level of prostate-specific antigen (PSA) to predict androgen-independent progression (AIP) in metastatic prostate cancer patients after androgen deprivation therapy. In a group of 185 metastatic prostate cancer patients who received androgen deprivation therapy serum PSA was determined every three months until AIP occurred. Multiple regression analysis was performed to define independent clinical and PSA-related predictors of AIP. AIP was assumed to be present after two consecutive increases in serum PSA after the PSA nadir. Independent predictors of the duration of AIP-free survival (less than 12 months versus more than 12 months) were the extent of bone involvement (six or fewer hot spots versus more than six) with an odds ratio (O.R.) of 3.95, Gleason score (7 or less versus more than 7) with an O.R. of 3.47, and PSA nadir (2 μg/L or less versus more than 2 μg/L) with an O.R. of 14.63. AIP was independently predicted by the extent of bone involvement with an O.R. of 1.72, Gleason score with an O.R. of 1.74, PSA nadir with an O.R. of 3.22, and time to reach the PSA nadir (9 months or less versus more than 9 months) with an O.R. of 2.84. When patients were stratified according to these predictors, those with three good prognostic factors had a median AIP-free survival of 58 months while those with two, one or no good prognostic factors had a median AIP-free survival of 19 months, 12 months and 7 months, respectively. We conclude that the PSA nadir seems to be a good predictor of AIP in patients with metastatic prostate cancer after androgen deprivation therapy. Time to PSA nadir, extent of bone involvement and Gleason score are also independent predictors. The combination of these prognostic factors allows to stratify metastatic prostate cancer patients for the prediction of AIP.

We have assessed the effect of androgen deprivation therapy (ADT) in the thyroid function test in prostate cancer patients. Serum levels of tri-iodothyronine (T3), thyroxine (T4), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were determined in a cross-sectional study that included 279 patients diagnosed with prostate cancer. A subset of 96 patients free of prostate-specific antigen relapse after radical prostatectomy became a control group and 183 patients under continuous ADT formed the study group. Sixty-four patients out of the study group were treated with luteinizing hormone-releasing hormone (LHRH) agonist and 119 with LHRH agonist plus bicalutamide. The average time of ADT was 42.5 months (3-218). Results were as follows. Mean T3 level was 122.7 ng/dl (72.6-213.0) in the control group and 123.8 ng/dl (64.4-228.2) in patients under ADT, p=0.472. Mean T4 level was 7.66 (1.81-4.30) and 7.66 microg/dl (3.60-13.30), respectively, p=0.884. Mean TSH level was 1.58 (0.44-11.70) and 1.81 mU/dl (0.15-6.58), respectively, p=0.007. Mean FT4 level was 1.24 (0.80-1.90) and 1.18 ng/dl (0.80-1.90), respectively, p=0.018. No statistically significant differences between the T3, T4, TSH and FT4 serum levels were detected according to the modality of ADT. The serum level of TSH was higher than 5 mU/l in six patients (2.1%); however, all cases had a normal FT4 serum level. This mild hypothyroidism was detected in two of the 96 patients of the control group (2.1%) and in four of the 183 under ADT (2.2%). Our data show that ADT seems to alter the thyroid function test. A statistically significant increase in TSH serum level and a decrease in FT4 serum level were detected in patients under ADT. However, only a mild hypothyroidism was detected in about 2% of the patients with prostate cancer, independently of ADT.

Objective: The percentage of free prostatic-specific antigen (PSA) has been introduced as a tool to avoid unnecessary biopsies in men with normal digital rectal examination (DRE) and serum PSA between 4.1 and 10ng/ml. In this series we also analyze its utility in men with normal DRE and serum PSA between 10.1 and 20ng/ml. Materials and Methods: A series of 1149 consecutive men with normal DRE and serum PSA between 4.1 and 20ng/ml submitted for the first ultrasound guided sextant biopsy is analyzed. In 921 (80.2%) the serum PSA was from 4.1 to 10ng/ml and in 228 (19.8%) from 10.1 to 20ng/ml. Total and free serum PSA determinations were done by the inmunoradiometric assays Tandem and Tandem free PSA (Hybritech Inc.). Results: The overall detection rate of prostate cancer was 27.9%. In the group of men which serum PSA ranged from 4.1 to 10ng/ml the rate of detection was 25.4% and 37.7% when it was between 10.1 and 20ng/ml. Using 25% or less of percent free PSA as a criterion for performing prostatic biopsy it would have detected 95.3% and 95.4% of the prostate cancers, respectively. The rate of unnecessary avoided biopsies would be 17.5% when serum PSA ranged from 4.1 to 10ng/ml and 17.6% between 10.1 and 20ng/ml. Conclusions: This prospective study demonstrates that the percentage of free PSA seems to have similar utility when serum PSA levels are between 4.1 and 10ng/ml and between 10.1 and 20ng/ml, at the time of the first prostatic biopsy indication.

The aim of this study was to evaluate bone mass changes after 1 year of four different types of pharmacological intervention. Ninety-seven prostate cancer patients treated with androgen deprivation therapy, and severe osteopenia or osteoporosis were retrospectively studied. Patients were divided in four groups. Group 1: 28 patients treated with denosumab, Group 2: 24 patients treated with alendronate, Group 3: 24 patients with no antiresorptive treatment and Group 4: 21 patients previously treated with alendronate and switched to denosumab. Dual X-ray absorptiometry was performed at baseline and after 1 year. Bone mass changes at the L2–L4 lumbar spine, femoral neck and total hip were evaluated. No differences were found at baseline. After 1 year, men receiving denosumab or alendronate (Group 1 and 2) showed a significant bone mass increase at the lumbar spine (+2.4 and +5.0 %, respectively), while no significant changes were observed in Group 3 and 4. At the femoral neck, Group 1 and 2 patients showed a significant bone mass increase (+3.7 and +3.6 %, respectively), while no significant changes were observed in Group 3 and 4. At the total hip, we observed a significant bone mass increase in Group 1 (+2.9 %) and a significant bone mass loss in Group 3 patients (−1.9 %). No significant changes were observed in Group 2 and 4. Denosumab increased significantly bone mass in all three dual X-ray absorptiometry standard sites, while alendronate did not at total hip. No benefit was observed in men previously treated with alendronate who switched to denosumab treatment.

Objective: To analyse changes in lipid profiles observed in patients receiving androgen deprivation therapy (ADT) and to evaluate differences between medical castration and maximal androgen blockade (MAB). Material and Methods: Serum levels of total cholesterol (TC), high-density lipoproteins (HDL), low-density lipoproteins (LDL) and triglycerides (TG) were prospectively evaluated in 33 patients with locally advanced or metastatic prostate cancer treated with ADT. The median age was 73.4 years. Serum lipids were measured at baseline and thereafter at 6 and 12 months. The modality of ADT was medical, with 3 months depot LHRH agonist, in 11 patients and MAB, by addition of 50 mg/day of bicalutamide, in 22 patients. Results: TC increased from 210 to 227 mg/dl (p < 0.05), while LDL increased from 132 to 148 mg/dl (p < 0.05) at 6 months. There were no significant changes in HDL or TG levels. There were no significant differences in any of the analysed parameters after 12 months of ADT. The comparison between the group of patients treated with LHRH agonists alone and the group treated with MAB demonstrated no significant differences in any of the analysed parameters at 6 and 12 months (p > 0.05). Conclusions: Changes observed in TC and LDL after 6 months of ADT were transitory. No significant differences were observed according to the modality of ADT.

Introduction: To determine clinical and biopsy features with predictive capacity to identify pathologically insignificant prostate cancer (pIPCa). Material and Methods: pIPCa was defined as cancer volume 3 and a Gleason score (GS) of ≤6 in radical prostatectomy (RP) specimens. Clinical and biopsy parameters were studied as predictors of pIPCa and validated by applying them to d’Amico’s low-risk cases: T1c-T2a, prostate-specific antigen (PSA) Results: 280 patients were evaluated; 11.8% (33) had pIPCa, increasing to 23% in low-risk cases. In patients fulfilling d’Amico’s low-risk criteria, variables significantly different in pIPCa were: volume, number of positive cylinders (NPC), percentage of positive cylinders (%PC), percentage of the most affected cylinder (%MAC) and uni/bilaterality. In these cases, volume and the NPC increased as independent variables on logistic regression and when adding a volume threshold of 45 cm3 and 1 positive core, specificity reached 95.8%. Conclusions: The incidence of pIPCa in RP specimens is relevant, especially in low-risk cases. Prostate volume and NPC are independent predictors of pIPCa. We propose a simple predictive model by adding the features of 1 positive core and volume ≧45 cm3 to d’Amico’s criteria. This allows to preoperatively distinguish between patients that most probably would benefit from radical treatment and patients that might be offered active surveillance.

We determined the testosterone castration level with clinical relevance in patients with prostate cancer on continuous androgen deprivation therapy. Secondary objectives were to analyze the role of associated bicalutamide in breakthrough increases of serum testosterone in these patients and the possible benefit of maximal androgen blockade.Serum testosterone was determined 3 times (in 6 months) in 73 patients with nonmetastatic prostate cancer treated with medical castration, 28 (38.4%) of whom also received bicalutamide (maximal androgen blockade). During a mean followup of 51 months (range 12 to 240) 41 (67.1%) events of androgen independent progression were identified, and correlated with breakthrough testosterone increases of 50 ng/dl (classic level) and 20 ng/dl (surgical castration level).Testosterone was less than 20 ng/dl in all determinations in 32 patients (43.6%). Breakthrough increases between 20 and 50 ng/dl were observed in 23 patients (31.5%), and increases greater than 50 ng/dl were observed in the remaining 18 (24.7%). The lowest testosterone level with a significant impact on survival free of androgen independent progression was 32 ng/dl. Mean survival free of androgen independent progression in patients with breakthrough increases greater than 32 ng/dl was 88 months (95% CI 55-121) while it was 137 months (95% CI 104-170) in those without breakthrough increases (p0.03). Patients on maximal androgen blockade had an incidence of testosterone increase similar to those receiving monotherapy. However, maximal androgen blockade provided a significantly longer survival free of androgen independent progression in those with breakthrough increases greater than 50 ng/dl.In the current report the lowest testosterone castration level with clinical relevance in medically castrated patients with prostate cancer was 32 ng/dl. Breakthrough increases greater than this threshold predicted a lower survival free of androgen independent progression. Maximal androgen blockade might benefit medically castrated cases of prostate cancer with breakthrough increases of more than 50 ng/dl.

Objetivo: La biopsia de próstata ecodirigida constituye el único método para obtener el diagnóstico de naturaleza de cáncer de próstata. Desde su introducción a finales de la década de los 80, se han producido múltiples modificaciones de la técnica con el objetivo de aumentar la tasa de detección de cáncer y disminuir la tasa de falsos negativos con el máximo confort y menor posibilidad de complicaciones. Métodos: Análisis crítico y revisión de conjunto de la literatura publicada sobre biopsia prostática hasta el momento. Resultados/Conclusiones: Los estudios publicados sugieren que los esquemas de biopsia extensos, tanto en las primeras biopsias como en las rebiopsias, aumentan la tasa de detección de cáncer en comparación con la biopsia por sextantes, siendo necesario incluir muestras procedentes de las porciones más laterales y apico-dorsales de la glándula donde el rendimiento diagnóstico es mayor. La rebiospia, tras una primera biopsia negativa, se indicará en los casos de primeras biopsias con PIN de AG y/o ASAP, elevación persistente de PSA y/o incremento del tiempo de doblaje de PSA total. No existe consenso respecto en que momento parar de rebiospiar, si bien parece que la tasa de detección de cáncer desciende a partir de la tercera rebiopsia. La introducción de las técnicas de bloqueo anestésico periprostático han permitido el control de dolor asociado en especial en la biopsias más extensas.

We characterized bone mineral density changes in patients with prostate cancer on androgen deprivation therapy during the first 2 years of uninterrupted therapy, and identified which location most reflects bone mass loss.Using dual energy x-ray absorptiometry, bone mineral density was prospectively assessed in patients with nonmetastatic prostate cancer at the lumbar spine and femoral neck, Ward's triangle, trochanter and total hip. Measurements were performed at baseline and yearly thereafter in patients on ADT, and at baseline and 1 year in controls (age matched patients with prostate cancer, free of biochemical progression after radical prostatectomy).A total of 62 patients were included in the study, 31 in each group. Median age (70 and 69 years, respectively), mean Gleason score and mean baseline serum testosterone did not significantly differ. Patients receiving ADT experienced a significant bone mass loss at 12 months in all locations, ranging from 2.29% to 5.55% (p0.001). In contrast, bone mineral density did not change significantly (0.64% to 1.68%) in patients not receiving ADT. In the 20 patients on ADT after 24 months, the second year decrease was not as severe, nor was it significant compared to first year values. The major bone mass loss occurred in Ward's triangle, with decreases of 5.55% at 12 months and 7.05% at 24 months.Bone mineral density decreases during the first 24 months of androgen suppression with the most relevant effect occurring in the first year. Ward's triangle is the axial skeletal site that reflects the major bone mass loss. Because the deleterious impact of long-term androgen suppression on bone mineral density is inversely related to fracture risk and indirectly related to survival in patients with prostate cancer, early diagnosis and prevention of bone mass loss are warranted in these patients.

The objective of our study was to analyze the value of prostate-specific antigen (PSA) levels before and after androgen suppression to predict the time to androgen-independent progression (AIP) in patients with advanced and metastatic prostate cancer. A series of 283 prostate cancer patients under androgen suppression as a single treatment was studied. The disease was locally advanced in 98 patients and metastatic in the remainder 185. AIP was defined after 2 consecutive increases of serum PSA after the nadir value. The mean follow-up before AIP was 29.2 months (3-198). AIP was detected in 205 patients (72.4%). In 152 patients (74.1%), the event was detected within 24 months, while in 53 patients (25.9%), it was observed beyond 24 months. The multivariate analysis showed that the nadir PSA and the time to reach the nadir PSA were the most significant predictors of the time to AIP. The odds ratio of having a biochemical response greater than 24 months was 20 times higher in patients that achieved an undetectable PSA level of 0.2 ng/mL or less. Moreover in those patients whose nadir PSA reached beyond 12 months after androgen suppression the odds ratio was 18 times higher. These results show that the ability to achieve an undetectable nadir PSA and the time to reach it are the most significant predictors of the time to AIP in patients with locally advanced and metastatic prostate cancer under androgen suppression as a single therapy.

PurposeTo analyze if the percentage of free prostate-specific antigen (PSA) can provide additional information to the combination of local clinical stage, serum PSA and Gleason score in the prediction of final stage and pathological features of prostate cancer.Materials and MethodsA group of 480 men with clinically localized prostate cancer underwent lymphadenectomy and radical prostatectomy. Total and free PSA were measured in preoperative serum. Clinical stage was T1 in 70.4% of patients and T2 in 29.6%. The biopsy Gleason score ranged between 2 and 4 in 5.6%, between 5 and 7 in 78.4%, and was higher than 7 in 16%. Total serum PSA was below 4.1 ng/mL in 4.3%, between 4.1 and 10 ng/mL in 66.4%, between 10.1 and 20 ng/mL in 22.5%, and higher than 20 in 6.7% of patients. The tumor was organ-confined in 49.8% and specimen-confined in 64.2%, and its pathological features were favorable in 35%.ResultsMultiple logistic regression analysis demonstrated that percent free PSA has independent predictive value for pathological stage only in the subset of patients with cT1 tumors and serum PSA between 4.1 and 10 ng/mL. In this group the probability of organ-confined cancer was 68.3% if the percent free PSA was above 15 and 56.3% if it was lower (pConclusionsPercent free PSA seems to provide additional information to the combination of clinical stage and Gleason score for the prediction of pathological features only in patients with clinical stage T1c and serum PSA between 4.1 and 10 ng/mL.

Objectives Determination of free testosterone (FT) serum level is an efficient method to evaluate bioavailable testosterone. We analyzed the behavior of serum FT in patients with prostate cancer receiving androgen deprivation therapy (ADT) and correlated FT with total testosterone (TT). We also analyzed the efficiency of both isoforms in the evaluation of the ADT. Methods Serum levels of TT and FT were determined in 191 patients with prostate cancer in a cross-sectional study. A subset of 56 patients submitted only to radical prostatectomy served as control group. The remaining 135 patients with advanced prostate cancer on three-month LHRH agonist treatment comprised the study group. The median age of the population was 73 years (range, 53–86 years) and the median time on ADT was 42 months (6–198). Results A significant correlation and linear regression between TT and FT was observed (r2 0.948). The efficiency of TT and FT to discriminate patients with and without ADT was similar (AUC: 0.993 and 0.995, respectively, p>0.05). A castration level of serum FT established at 1.7 pg/mL had a sensitivity of 85.9% and a specificity of 100%, which are similar to the sensitivity and specificity of 50 ng/dL of TT. All patients without ADT had levels of serum TT and FT above the castration level. In 19 of the 135 (14.1%) patients on ADT serum TT was above 50 ng/dL. In 12 of these 19 patients (63.2%) serum FT was below 1.7 pg/mL while in seven patients (5.2%) FT was also above the castration level. Conclusions The castration level of FT was established at 1.7 pg/mL. Serum TT and TF correlated very well; however, they seemed to provide complementary information in the evaluation of ADT efficiency. 14.1% of the patients on ADT failed to reach the castration level of serum TT; determination of serum FT in these patients would reduce this rate to 5.2%.

The objective of this study was to evaluate the usefulness of serum determination of bone alkaline phosphatase (BAP) in the diagnosis of osteoporosis in men with prostate cancer under androgen ablation. Serum levels of BAP and bone mineral density (BMD) were assessed in 110 patients with non-metastatic, treated prostate cancer. Fifty-eight patients were under androgen deprivation during a period between two and 96 months and 52 had been submitted only to radical prostatectomy. Mean serum BAP was 11.8 ng/mL in patients with normal BMD, 16.7 ng/mL in patients with osteopenia (p. 0.058), and 19.3 ng/mL in patients with osteoporosis (p=0.044). The correlation between serum BAP and BMD was significant (p. 0.006) but with an index of only 0.26. Receiver operating characteristic analysis for the diagnosis of osteoporosis showed an area under the curve of 0.608. None of the cutoff points that provided specificities of 75%, 90% and 95% gave significant distributions. The positive and negative predictive values as well as the odds ratios were not of any clinical usefulness. We conclude that serum BAP should not be considered a good marker for the diagnosis of osteoporosis in men with prostate cancer. Therefore, BAP serum determination cannot replace bone densitometry as a diagnostic tool.