New model of PIRADS and adjusted prostatespecific antigen density of peripheral zone improves the detection rate of initial prostate biopsy: a diagnostic study / 亚洲男科学杂志(英文版)

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.

Prostate Cancer Screening in Brazil: a single center experience in the public health system

ABSTRACT Purpose: Incidence and mortality of prostate cancer (PCa) are still increasing in developing countries. Limited access to the health system or more aggressive disease are potential reasons for this. Ethnic and social differences in developed countries seem to make inappropriate to extrapolate data from other centers. We aim to report the epidemiological profile of a PSA-screened population from a cancer center in Brazil. Materials and Methods: We retrospectively selected 9.692 men enrolled in a PCa prevention program, comprising total PSA level and digital rectal examination at the first appointment, associated with complementary tests when necessary. Men aged over 40 years-old were included after shared decision-making process. Prostate biopsy (TRUS) was performed when clinically suspected for PCa. After the diagnosis, patients underwent appropriate treatment. Results: TRUS was performed in 5.5% of men and PCa incidence was 2.6%. Overall ratio between number of patients who needed to be screened in order to diagnose one cancer was 38.9 patients, with 2.1 biopsies performed to diagnose a cancer. Positive predictive value (PPV) of TRUS biopsy in this strategy was 47.2%, varying from 38.5% (<50 years-old) to 60% (>80 years-old). We evidenced 70 patients (27.9%) classified as low risk tumors, 74 (29.5%) as intermediate risk, and 107 (42.6%) as high-risk disease. Conclusions: PSA-screening remains controversial in literature. In front of a huge miscegenated people and considering the big proportion of high-risk PCa, even in young men diagnosed with the disease, it is imperative to inform patients and health providers about these data particularities in Brazil.

Prior switching to a second-line nonsteroidal antiandrogen does not impact the therapeutic efficacy of abiraterone acetate in patients with metastatic castration-resistant prostate cancer: a real-world retrospective study / 亚洲男科学杂志(英文版)

Even in the era of novel targeted agents, switching to a second-line nonsteroidal antiandrogen (NSAA) is still widely used in treating metastatic castration-resistant prostate cancer (mCRPC), especially in undeveloped countries. However, whether prior treatment with a second-line NSAA would impact the efficacy of abiraterone acetate (Abi) remains uncertain. In the current study, 87 mCRPC patients treated with Abi were analyzed. Among them, 21 were treated with a second-line NSAA (from bicalutamide to flutamide) before receiving abiraterone, while the remaining 66 received Abi directly. Therapeutic efficacy of Abi was compared between those with and without prior second-line NSAA using Kaplan-Meier curves, log-rank test, and Cox regression models. The therapeutic efficacy of Abi was similar between those with or without the prior switching treatment of flutamide, in terms of either prostate-specific antigen progression-free survival (PSA-PFS, 5.5 vs 5.6 months, P = 0.967), radiographic progression-free survival (rPFS, 12.8 vs 13.4 months, P = 0.508), overall survival (OS, not reached vs 30.6 months, P = 0.606), or PSA-response rate (71.4% [15/21] vs 60.6% [40/66], P = 0.370). This is the first time that the impact of prior switching of treatment to a second-line NSAA on the efficacy of Abi in mCRPC patients has been addressed. Our data support that, use of prior sequential bicalutamide and flutamide does not seem to preclude response to abiraterone, although larger cohort studies and, ideally, a randomized controlled trial are needed. These findings will facilitate doctors' decision-making in the treatment of mCRPC patients, especially for those with previous experience of switching NSAA second-line treatments in the clinic.

National Comprehensive Cancer Network (NCCN) risk classification in predicting biochemical recurrence after radical prostatectomy: a retrospective cohort study in Chinese prostate cancer patients / 亚洲男科学杂志(英文版)

This study aimed to assess the role of the National Comprehensive Cancer Network (NCCN) risk classification in predicting biochemical recurrence (BCR) after radical prostatectomy (RP) in Chinese prostate cancer patients. We included a consecutive cohort of 385 patients with prostate cancer who underwent RP at Fudan University Shanghai Cancer Center (Shanghai, China) from March 2011 to December 2014. Gleason grade groups were applied at analysis according to the 2014 International Society of Urological Pathology Consensus. Risk groups were stratified according to the NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer version 1, 2017. All 385 patients were divided into BCR and non-BCR groups. The clinicopathological characteristics were compared using an independent sample t-test, Chi-squared test, and Fisher's exact test. BCR-free survival was compared using the log-rank test and multivariable Cox proportional hazard analysis. During median follow-up of 48 months (range: 1-78 months), 31 (8.05%) patients experienced BCR. The BCR group had higher prostate-specific antigen level at diagnosis (46.54 ± 39.58 ng ml-1 vs 21.02 ± 21.06 ng ml-1, P= 0.001), more advanced pT stage (P = 0.002), and higher pN1 rate (P < 0.001). NCCN risk classification was a significant predictor of BCR (P = 0.0006) and BCR-free survival (P = 0.003) after RP. As NCCN risk level increased, there was a significant decreasing trend in BCR-free survival rate (Ptrend = 0.0002). This study confirmed and validated that NCCN risk classification was a significant predictor of BCR and BCR-free survival after RP.

The Institute of Urology, Peking University prostatectomy score: a simple preoperative classification of prostate cancer for predicting surgical difficulty and risk / 亚洲男科学杂志(英文版)

Traditional laparoscopic radical prostatectomy is a treatment choice in many developing countries and regions for most patients with localized prostate cancer; however, no system for predicting surgical difficulty and risk has been established. This study aimed to propose a simple and standard preoperative classification system of prostate cancer using preoperative data to predict surgical difficulty and risk and to evaluate the relationship between the data and postoperative complications. We collected data from 236 patients and divided them into three groups to evaluate and validate the relationships among preoperative, operative, and postoperative data. This new scoring system is based on the body mass index, ultrasonic prostate volume, preoperative prostate-specific antigen level, middle lobe protrusion, and clinical stage. In the scoring group, we classified 89 patients into two groups: the low-risk group (score of <4) and high-risk group (score of ≥4), and then compared the postoperative data between the two groups. The positive surgical margin rate was higher in the high-risk group than low-risk group. The results in validation Groups A and B were similar to those in the scoring group. The focus of our scoring system is to allow for preliminary assessment of surgical difficulty by collecting the patients' basic information. Urologists can easily use the scoring system to evaluate the surgical difficulty and predict the risks of a positive surgical margin and urinary incontinence in patients undergoing laparoscopic radical prostatectomy.

Risk of prostate cancer in men with spinal cord injury: A systematic review and meta-analysis / 亚洲男科学杂志(英文版)

A lower risk of prostate cancer has been reported in men with spinal cord injury (SCI) as compared to that observed in able-bodied subjects. As injury-related consequences can have opposite effects on prostate pathophysiology, this meta-analysis aimed to (1) establish the existence/quantify the extent of decreased prostate cancer risk following SCI and (2) find out if there is any statistically significant difference in prostate-specific antigen (PSA) levels between SCI and able-bodied subjects. MEDLINE, Cochrane Library, Scopus, CINAHL, and ScienceDirect databases were used. Only studies reporting a prostate cancer diagnosis and/or PSA levels following SCI and in able-bodied controls were included. Five studies provided information about prostate cancer on 35 293 subjects with SCI and 158 140 controls. Six studies were included in PSA analysis which reported information on 391 men with SCI and 1921 controls. Pooled estimates indicated that SCI reduced the prostate cancer risk by approximately 50% as compared to controls, whereas differences in PSA levels were not statistically significant. Funnel plots suggested the presence of publication bias only in PSA analysis. Between-study heterogeneity was established and when, according to meta-regression models, analysis was restricted to studies including men with mean age over 55 years, prostate cancer risk in SCI decreased up to 65.0% than that in controls with no heterogeneity (P = 0.33, I2 = 9%). In conclusion, in men over 55 years old, SCI decreases the prostate cancer risk up to 65.0% than that in controls. The large between-study heterogeneity on PSA confirms its poor reliability as a screening tool for prostate cancer in SCI.

High cancer detection rate using cognitive fusion - targeted transperineal prostate biopsies

ABSTRACT Objective MRI of the prostate improves diagnostic accuracy of prostate cancer. Different fusion approaches with transrectal ultrasound images are employed. Objective To determine detection rate of prostate cancer in men undergoing transperineal MRI-based cognitive fusion biopsy. Materials and Methods One hundred and sixty-four consecutive men underwent a multiple-core prostate transperineal biopsy. Univariable and multivariable logistic regression analyses were used to address the relationship between clinical parameters and prostate cancer detection rate. Results One hundred and fourteen patients underwent mpMRI prior to the transperineal biopsy, 52 (45%) were diagnosed with prostate cancer, of them, 36 had Gleason score ≥7 (69%). Among these 114 patients, 82 had suspicious lesions on MRI, and 43 of them were diagnosed with cancer (52%). On multivariate analysis, the most significant independent predictive factors were PSA density (P<0.001) and suspicious MRI lesion (P=0.006). Men with a PSA density of more than 0.22 and a suspicious lesion on MRI had a detection rate of 78%. Detection rate among 50 patients with no MRI study prior to this biopsy was 26%. Conclusions This study showed that among a group of mostly multi-biopsied patients, the presence of mpMRI lesions and high PSA density values helped to detect clinically significant prostate cancer using cognitive MRI/TRUS fusion biopsies.

Metastatic prostate cancer in the modern era of PSA screening

ABSTRACT Introduction To characterize initial presentation and PSA screening status in a contemporary cohort of men treated for metastatic prostate cancer at our institution. Materials and methods We reviewed records of 160 men treated for metastatic prostate cancer between 2008-2014 and assessed initial presentation, categorizing patients into four groups. Groups 1 and 2 presented with localized disease and received treatment. These men suffered biochemical recurrence late (>1 year) or earlier (<1 year), respectively, and developed metastases. Groups 3 and 4 had asymptomatic and symptomatic metastases at the outset of their diagnosis. Patients with a first PSA at age 55 or younger were considered to have guideline-directed screening. Results Complete records were available on 157 men for initial presentation and 155 men for PSA screening. Groups 1, 2, 3 and 4 included 27 (17%), 7 (5%), 69 (44%) and 54 (34%) patients, respectively. Twenty (13%) patients received guideline-directed PSA screening, 5/155 (3%) patients presented with metastases prior to age 55 with their first PSA, and 130/155 (84%) had their first PSA after age 55, of which 122/130 (94%) had metastasis at the time of diagnosis. Conclusion Despite widespread screening, most men treated for metastatic prostate cancer at our institution presented with metastases rather than progressed after definitive treatment. Furthermore, 25 (16%) patients received guideline-directed PSA screening at or before age 55. These data highlight that, despite mass screening efforts, patients treated for incurable disease at our institution may not have been a result of a failed screening test, but a failure to be screened.

Significance of intraprostatic architecture and regrowth velocity for considering discontinuation of dutasteride after combination therapy with an alpha blocker: A prospective, pilot study

PURPOSE: We conducted a prospective single-center study to evaluate the possibility of discontinuation of dutasteride after combination therapy with an alpha blocker for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We prospectively treated BPH patients with an alpha blocker and dutasteride (0.5 mg/d). Patients who had been treated with alpha blockers against BPH for more than 2 months were eligible, and 20 patients were included in the study. After 6 months of combination therapy, dutasteride was discontinued. Patients were followed for 12 months after cessation. Prostate volume, intraprostatic architecture determined by transrectal ultrasound, peak urinary flow rate, postvoid residual urine volume, and the serum prostate-specific antigen level were evaluated every 6 months, and the International Prostate Symptom Score and overactive bladder symptom score (OABSS) every 3 months. Patients were allowed to restart dutasteride during the follow-up period according to their desire. RESULTS: Twelve patients (12/20, 60%) restarted the combination therapy from 6 to 12 months into the follow-up period. For patients who restarted dutasteride, the prostate volume and OABSS had increased and worsened after discontinuation, respectively. A visible transition zone with a clear border on transrectal ultrasound at baseline and regrowth of the prostate after discontinuation of dutasteride were risk factors for restarting the therapy (Mann-Whitney U test: p=0.008, p=0.017). CONCLUSIONS: Prostatic enlargement after discontinuation of dutasteride differs among patients. Rapid regrowth of the prostate leads to deterioration of storage symptoms and a tendency to restart dutasteride. Baseline intraprostatic architecture may be a predictive factor for whether the patient is a good candidate for discontinuation.

Elderly men over 65 years of age with late-onset hypogonadism benefit as much from testosterone treatment as do younger men

PURPOSE: To investigate the potential benefits of testosterone administration to elderly men (>65 years) with late-onset hypogonadism (LOH) in comparison with younger men and to assess the safety of testosterone administration to elderly men. MATERIALS AND METHODS: A total of 561 hypogonadal men from two registry studies were divided into age groups of 65 years (group O, n=111; range, 66-84 years). Following an initial 6-week interval, all men were treated with 3-month injections of parenteral testosterone undecanoate for up to 6 years. RESULTS: Over the 6 years, there was a progressive decrease of body weight and waist circumference. Beneficial effects on lipids and other metabolic factors and on psychological and sexual functioning progressed over the first 24 to 42 months and were sustained. Rather than a deterioration, there was an improvement of urinary parameters. Prostate volume and prostate-specific antigen increased moderately. Hematocrit levels increased but remained within safe margins. CONCLUSIONS: The benefits of restoring serum testosterone in men with LOH were not significantly different between men older than 65 years of age and younger men. There were no indications that side effects were more severe in elderly men. The effects on prostate and urinary function and hematocrit were within safe margins. Age itself need not be a contraindication to testosterone treatment of elderly men with LOH.

Evaluation of Serum Prostate Specific Antigens in Breast Cancer.

Serum Prostate Specific Antigen (PSA) is an established tumor marker for prostate cancer but its “specificity” for prostatic diseases was challenged after its extra prostatic sources and its presence in female serum was detected. Various studies showed the association of Total PSA (TPSA) and Free PSA (FPSA) with breast cancer in females. The present study was conducted to evaluate the status of TPSA and FPSA as a tumor marker in breast cancer patients. 54 breast cancer cases with 36 fibroadenoma patients along with 40 controls were selected for the study. Their blood samples were analyzed for estimation of serum Testosterone, TPSA and FPSA along with routine biochemical parameters. 34 breast cancer with 20 fibroadenoma cases were reevaluated for TPSA and FPSA 6 months after tumor removal by surgery. Our observations revealed high TPSA in the patient group compared to controls and raised FPSA specifically in breast cancer cases. FPSA was also found to be the predominant molecular form in breast cancer cases. A significant positive association was documented between serum Testosterone and PSA level in the study group. Both the parameters registered a significant decline after surgery. On statistical analysis TPSA and FPSA were found to possess high specificity for breast cancer cases but were deficient in the desired sensitivity to be considered as an ideal tumor marker.

Low free to total PSA ratio is not a good discriminator of chronic prostatitis and prostate cancer: An Indian experience.

Aims: To find out the utility of free to total PSA ratio in discriminating chronic prostatitis and prostate cancer. Setting and design: The patients visited urology clinics at Batra Hospital and Medical Research Center, New Delhi. Background: The use of serum free to total PSA as a diagnostic tool for prostate cancer has led to early detection of prostate cancer; however, the effect of inflammation on f/t PSA ratio restricts its use in early detection of cancer. Materials and Methods: The study was conducted in age related 101 patients which include 27 carcinoma patients (group I), 34 BPH patients (group II) and 40 chronic prostatitis patients (group III). Serum total PSA (tPSA) and free PSA (fPSA) were analyzed on Elecsys 2010. These were compared with histological reports of biopsy specimen. Other biochemistry tests were done on Randox Imola. P Value was calculated using one way ANOVA with posthoc Bonferroni analysis. Results: Serum total PSA levels were comparable in group I and III and were higher than group II (P < 0.049). Serum fPSA in group I was not significantly different from group II and III, However, group II has higher levels than group III (P < 0.035). Difference was significant for f/t PSA ratio in group I and II (P < 0.00) and group II and III (P < 0.000).Group I and III were with comparable levels (P < 0.807). Conclusions: f/t PSA ratio is not a good discriminator for malignancy and chronic prostatitis. This limitation of f/t PSA ratio must be taken into consideration while interpreting the results clinically.

Desenvolvimento e fabricação de filmes ultra-­finos, obtidos pela técnica layer-by-layer, para aplicações na entrega direcionada de fármacos e na captura seletiva de bio-­marcadores / Development and fabrication of ultrathin films obtained by layer­-by­-layer, aiming targeted drug delivery applications and the selective capture of biomarkers

O objetivo geral deste trabalho foi explorar a versatilidade de filmes multicamadas de polieletrólitos (PEM) e suas aplicações em sistemas de entrega de drogas e como filmes funcionais para aplicações biomédicas. Filmes PEM montados pela técnica de camada por camada (layer­-by­-layer, LbL), foram explorados em três aplicações principais. Na primeira, foi explorado o desenvolvimento de um protocolo de funcionalização em filmes de poli(alilamina)/poli (estireno sulfonato), PAH/SPS. Os parâmetros de construção do filme para biotinilação dos grupamentos amina do PAH foram otimizados e aplicados na captura e detecção do antígeno específico da próstata (PSA), na concentração de 100 a 0,1 ng/mL, usando pontos quânticos (Qdots). Em comparação com outros trabalhos, este sistema apresentou uma boa sensibilidade na detecção de PSA, dentro do limite de detecção clínica de 0,4 a 0,1 ng/mL. A segunda aplicação envolveu o desenvolvimento de filmes de sacrifício baseados nas interações naturais da mucina submandibular bovina e da lectina, jacalina (BSM/JAC). Filmes de BSM/JAC apresentaram estabilidade quando submetidos a uma ampla faixa de pH (pH 3-­-9) e em solução de alta força iônica (5 M NaCl). A dissolução dos filmes BSM/JAC pôde ser seletivamente desencadeada mediante à incubação em solução de melibiose, 37 °C, pH 7,4, sem apresentar citotoxicidade às células. Na última parte deste trabalho, a incorporação de lipossomos ecogênicos (ELIP) em mochilas celulares foi investigada. Mochilas celulares são "patches" de 7­-10 µm de diâmetro que podem ser fabricados por meio de deposição alternada de polímeros utilizando-­-se a técnica de LbL, sobre uma matriz pré­-moldada obtida por fotolitografia, a fim de criar um sistema composto por três multicamadas estratificadas: uma região de liberação, para promover o destacamento do substrato, uma região de carga de droga, e uma região adesiva às células. O uso de ELIP permitiu incorporação de até 9x mais doxorrubicina (DOX) se comparado com o fármaco livre em solução absorvido pelos dos filmes. A liberação de DOX pelos filmes foi monitorado por 25 dias. Mochilas contendo ELIP-­DOX foram então aderidos a monócitos, e sua viabilidade monitorados por 72h. Mochilas vazias mostraram diminuir a proliferação de monócitos ao longo das 72 horas, enquanto mochilas carregadas com ELIP-­DOX mostraram uma diminuição dramática na população celular, apontando uma potencialização dos efeitos da droga pela sua proximidade com as células

The overall goal of this thesis was to exploit the versatility of polyelectrolite multilayers (PEM) to be applied in drug delivery systems and biofunctionalizable films for biomedical applications. PEM films assembled by the layer-by­-layer technique were explored in three main applications. In the first part of this work, the development of a functionalization protocol of poly(allylamine)/poly(styrene sulfonate), PAH/SPS was explored. The optimal film parameters to the use of biotinylated multilayers were applied for the capture and detection of prostate specific antigen (PSA) protein in the range of 100 to 0.1 ng/mL, by using quantum dots. Compared to previous work, this system presented a good sensitivity for PSA detection that is within the clinical limit range of 0.4 to 0.1 ng/mL. The second application involved the creation of a novel sacrificial multilayer film. Films based in natural interactions of bovine submaxillary mucin and the lectin jacalin, BSM/JAC were assembled. BSM/JAC films showed stability when underwent a wide rage of pH (pH 3 to 9) and high ionic strength (5 M NaCl) solutions. BSM/JAC dissolution could be triggered released by incubation in melibiose at 37 °C in pH 7.4 buffer, without cytotoxicity. In the last part of this work the incorporation of echogenic liposomes (ELIP) into cell backpacks was investigated. Cell backpacks are 7-10 µm diameter patches that can be fabricated through LbL polymer deposition onto a photopatterned array to create a stacked composite of three stratified multilayer systems: a releasable region for easy detachment from the substrate, a drug payload region, and a cell adhesive region. The use of ELIP allowed up to 9x more doxorubicin (DOX) loading when compared to free drug in solution adsorbed through the films. DOX release from films was monitored for over 25 days. ELIP­-DOX backpacks were then attached to mouse monocytes and their viability monitored by 72h. Empty backpacks showed to decrease monocytes proliferation over the course of 72h, while ELIP­-DOX backpacks showed a dramatic decrease in cell population, showing that DOX effects were enhancement in drug potency by its proximity

Cancer of the Prostate Risk Assessment (CAPRA) Preoperative Score Versus Postoperative Score (CAPRA-S): Ability to Predict Cancer Progression and Decision-Making Regarding Adjuvant Therapy after Radical Prostatectomy

The University of California, San Francisco, announced in 2011 Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score which included pathologic data, but there were no results for comparing preoperative predictors with the CAPRA-S score. We evaluated the validation of the CAPRA-S score in our institution and compare the result with the preoperative progression predictor, CAPRA score. Data of 130 patients were reviewed who underwent radical prostatectomy for localized prostate cancer from 2008 to 2013. Performance of CAPRA-S score in predicting progression free probabilities was assessed through Kaplan Meier analysis and Cox proportional hazards regression test. Additionally, prediction probability was compared with preoperative CAPRA score by logistic regression analysis. Comparing CAPRA score, the CAPRA-S score showed improved prediction ability for 5 yr progression free survival (concordance index 0.80, P = 0.04). After risk group stratification, 3 group model of CAPRA-S was superior than 3 group model of CAPRA for 3-yr progression free survival and 5-yr progression free survival (concordance index 0.74 vs. 0.70, 0.77 vs. 0.71, P < 0.001). Finally the CAPRA-S score was the more ideal predictor concerned with adjuvant therapy than the CAPRA score through decision curve analysis. The CPARA-S score is a useful predictor for disease progression after radical prostatectomy.

Cancer of the Prostate Risk Assessment (CAPRA) Preoperative Score Versus Postoperative Score (CAPRA-S): Ability to Predict Cancer Progression and Decision-Making Regarding Adjuvant Therapy after Radical Prostatectomy

The University of California, San Francisco, announced in 2011 Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score which included pathologic data, but there were no results for comparing preoperative predictors with the CAPRA-S score. We evaluated the validation of the CAPRA-S score in our institution and compare the result with the preoperative progression predictor, CAPRA score. Data of 130 patients were reviewed who underwent radical prostatectomy for localized prostate cancer from 2008 to 2013. Performance of CAPRA-S score in predicting progression free probabilities was assessed through Kaplan Meier analysis and Cox proportional hazards regression test. Additionally, prediction probability was compared with preoperative CAPRA score by logistic regression analysis. Comparing CAPRA score, the CAPRA-S score showed improved prediction ability for 5 yr progression free survival (concordance index 0.80, P = 0.04). After risk group stratification, 3 group model of CAPRA-S was superior than 3 group model of CAPRA for 3-yr progression free survival and 5-yr progression free survival (concordance index 0.74 vs. 0.70, 0.77 vs. 0.71, P < 0.001). Finally the CAPRA-S score was the more ideal predictor concerned with adjuvant therapy than the CAPRA score through decision curve analysis. The CPARA-S score is a useful predictor for disease progression after radical prostatectomy.

Avaliação de alterações histopatológicas da próstata e séricas do PSA em ratos tratados com N-Metil-N-Nitrosureia e testosterona / Evaluation of histopathological changes in the prostate and serum PSA in mice treated with N-Methyl-N-Nitrosourea and testosterone

A testosterona tem sido cada vez mais usada em homens na fase do envelhecimento como prevenção e tratamento de doenças metabólicas, melhora do desempenho sexual, proteção cardiovascular e manutenção da cognição. Porém ainda há conflito sobre seus efeitos na próstata com relação às doenças benignas e malignas. O presente estudo avaliou o efeito do tratamento com duas formas de testosterona sobre carcinoma de próstata induzido por N-Metil-N-Nitrosureia (NMU) a partir de análises histopatológicas e séricas do antígeno prostático específico (PSA). Para tal foram utilizados 80 ratos Wistar jovens, sadios, divididos em dois grupos (40 animais cada) tratados ou não com NMU intraperitoneal. Cada grupo foi dividido em quatro subgrupos iguais e tratados durante 16 semanas: 1) tratado com cipionato de testosterona a cada sete dias via intramuscular; 2) tratado com cipionato de testosterona a cada 14 dias via intramuscular; 3) tratado com undecanoato de testosterona oral diariamente; 4) tratado com óleo mineral. Após 16 semanas e tratamento, os níveis do PSA não alteraram em nenhum grupo ou subgrupo e não houve desenvolvimento de tumores em nenhum deles. Portanto, as duas formas distintas de testosterona associada ao uso de NMU em curto espaço de tempo por via intraperitoneal não alteraram as dosagens séricas do PSA e não induziram a formação de tumores na próstata em ratos Wistar jovens e saudáveis. As alterações histopatológicas acinares encontradas nas próstatas foram projeção, secreção, congestão e inflamação, e as epiteliais foram: epitélio normal, redução do epitélio e redução na altura do mesmo. Tais achados colaboram para que outros estudos sejam realizados de maneira a orientar o uso de testosterona na prática clinica diária sem receio de indução do câncer na próstata.

Testosterone has been increasingly used in men during the aging process as prevention and treatment of metabolic diseases, improving sexual performance, cardiovascular protection and maintenance of cognition. But there are still conflicted about its effects in the prostate with respect to benign and malignant diseases. The present study evaluated the effect of treatment with two forms of testosterone on prostate carcinoma induced by N-methyl-N-nitrosourea (NMU) from pathological examinations and serum prostate-specific antigen (PSA). For this we used 80 young Wistar rats, healthy, divides into two groups (40 animals each) or not treated with intraperitoneal NMU. Each group was divided into four equal subgroups and treated for 16 weeks: 1) treated with testosterone cypionate every seven days intramuscularly, 2) treated with testosterone cypionate every 14 days intramuscularly, 3) treated with oral testosterone undecanoate daily, 4) treated with mineral oil. After 16 semanas and treatment, PSA levels did not change in either group or sub-group and no tumor development in any of them. Therefore, two different forms of testosterone associated with the use of NMU in short time intraperitoneally did not affect the serum PSA and did not induce tumor formation in prostate in young healthy rats. Acinar histopathological changes were found in the prostates projection, secretion, congestion and inflammation, epithelial and were normal epithelium, epithelial reduction and reduction in height thereof. These findings collaborate to further studies are performed in order to guide the use of testosterone in daily clinical practice without fear of inducing prostate cancer.

Relación de PSA libre sobre PSA total en pacientes con diagnóstico de cáncer de próstata mediante biopsia de próstata transrectal ecodirigida (2008-2012) / Relationship of free PSA on total PSA in patients with a diagnosis of prostate cancer by ultrasound-guided transrectal prostate biopsy (2008-2012)

Objetivos: Determinar el punto de corte de sensibilidad óptima del cociente PSAL/PSAt, para detectar CaP en pacientes tratados en el Hospital Nacional PNP Luis N. Sáenz en el periodo entre el 2008 al 2012. Material y métodos: Estudio de tipo retrospectivo y metodología observacional, comparativa (no concurrente), analítico y descriptivo en 398 pacientes con sospecha de Cáncer de próstata quienes se les realizó biopsia de próstata transrectal eco-dirigidas en el Servicio de Urología del Hospital Nacional PNP Luis N. Sáenz, post criterios de inclusión. La ficha de datos, fue el instrumento principal de la investigación. Resultados: La edad promedio fue de 61.4 años, donde la edad más frecuente fue entre 66-70 años (55.75 por ciento). Se diagnosticaron 61 adenocarcinoma de Próstata (15.35 por ciento), con un valor de corte por debajo de 15 por ciento de PSAL/PSAt, en 55 pacientes con CaP y menos del 10 por ciento de CaP presentaron índices de PSAL/PSAt > 20 por ciento. La curva de ROC señala decidir entre 14 y 15 como valor de corte. Se observaron 269 casos con complicaciones post biopsia 178 leves (44.70 por ciento) y 91 no leves (22.90 por ciento). Conclusiones: El cociente PSAL/PSAt o porcentaje de PSAL incrementa la especificidad del PSA en pacientes asintomáticos y con un valor de PSAt entre 4 y 10 ng/ml. Con un punto de corte del 15 por ciento, la sensibilidad de CaP fue de 90.15 por ciento, pero con una especificidad de 22 por ciento (decreciente). El índice PSAL/PSAt, es un método útil para optimizar la indicación de biopsia y mejorar así la tasa de productividad de la misma, evitando así biopsias innecesarias. Las complicaciones del método diagnóstico por biopsia prostática transrectal ecodirigida fueron frecuentes en esta serie (67.60 por ciento), con un aumento de costo hospitalario adicional.

Is Prostate-Specific Antigen Effective for Population Screening of Prostate Cancer? A Systematic Review

BACKGROUND: The effectiveness of prostate-specific antigen (PSA) for population screening has presented controversial results in large trials and prior reviews. We investigated the effectiveness of PSA population screening in a systematic review. METHODS: The study was conducted using existing systematic reviews. We searched Ovid MEDLINE, Embase, Cochrane library, and the major Korean databases. The quality of the systematic reviews was assessed by two reviewers independently using AMSTAR. Randomized controlled trials were assessed using the risk of bias tool in the Cochrane group. Meta-analyses were conducted using Review Manager. The level of evidence of each outcome was assessed using GRADE. RESULTS: Prostate-cancer-specific mortality was not reduced based on similar prior reviews (relative risk [RR] 0.93; 95% confidence interval [CI], 0.81-1.07, P=0.31). The detection rate of stage 1 prostate cancer was not greater, with a RR of 1.67 (95% CI, 0.95-2.94) and high heterogeneity. The detection rate of all cancer stages in the screening group was high, with a RR of 1.45 (95% CI, 1.13-1.85). No difference in all-cause mortality was observed between the screening and control groups (RR, 0.99; 95% CI, 0.98-1.01, P=0.50). Prostate-cancer-specific mortality, all-cause mortality, and diagnosis of prostate cancer at stages 3-4 showed moderate levels of evidence. CONCLUSIONS: Differently from prior studies, our review included updated Norrkoping data and assessed the sole effect of PSA testing for prostate cancer screening. PSA screening alone did not increase early stage prostate cancer detection and did not lower mortality.