Effect of 5-Alpha Reductase Inhibitors on Magnetic Resonance Imaging and Prostate Cancer Detection.

Concerns exist regarding the effects of 5-alpha reductase inhibitors (5-ARIs) on multipa-rametric magnetic resonance imaging (mpMRI) and clinically significant prostate cancer (csPCa) detection. Our objective is to analyze the effect of 5-ARI on the prostate imaging-reporting and data system (PI-RADS) distribution and csPCa and insignificant PCa (iPCa) detection. Among 2212 men with serum prostate-specific antigen levels of >3.0 ng/mL and/or suspicious digital rectal examinations who underwent mpMRI and targeted and/or systematic biopsies, 120 individuals exposed to 5-ARI treatment for over a year were identified. CsPCa was defined when the grade group (GG) was >2. The overall csPCa and iPCa detection rates were 44.6% and 18.8%, respectively. Since logistic regression revealed independent predictors of PCa, a randomized matched group of 236 individuals was selected for analysis. The PI-RADS distribution was comparable with 5-ARI exposure (p 0.685). The CsPCa detection rates in 5-ARI-naïve men and 5-ARI-exposed men were 52.6% and 47.4%, respectively (p 0.596). IPCa was detected in 37.6 and 62.5%, respectively (p 0.089). The tumor GG distribution based on 5-ARI exposure was similar (p 0.149) to the rates of csPCa and iPCa across the PI-RADS categories. We conclude that exposure to 5-ARI in suspected PCa men did not change the PI-RADS distribution and the csPCa and iPCa detection rates.

Reducing the demand for magnetic resonance imaging scans and prostate biopsies during the early detection of clinically significant prostate cancer: Applying the Barcelona risk-stratified pathway in Catalonia.

PURPOSE: To analyze the reduction in multiparametric magnetic resonance imaging (mpMRI) demand and prostate biopsies after the hypothetical implementation of the Barcelona risk-stratified pathway (BCN-RSP) in a population of the clinically significant prostate cancer (csCaP) early detection program in Catalonia. MATERIALS AND METHODS: A retrospective comparation between the hypothetical application of the BCN-RSP and the current pathway, which relied on pre-biopsy mpMRI and targeted and/or systematic biopsies, was conducted. The BCN-RSP stratify men with suspected CaP based on a prostate specific antigen (PSA) level >10 ng/ml and a suspicious rectal examination (DRE), and the Barcelona-risk calculator 1 (BCN-RC1) to avoid mpMRI scans. Subsequently, candidates for prostate biopsy following mpMRI are selected based on the BCN-RC2. This comparison involved 3,557 men with serum PSA levels > 3.0 ng/ml and/or suspicious DRE. The population was recruited prospectively in 10 centers from January 2021 and December 2022. CsCaP was defined when grade group ≥ 2. RESULTS: CsCaP was detected in 1,249 men (35.1%) and insignificant CaP was overdeteced in 498 (14%). The BCN-RSP would have avoid 705 mpMRI scans (19.8%), and 697 prostate biopsies (19.6%), while 61 csCaP (4.9%) would have been undetected. The overdetection of insignificant CaP would have decrease in 130 cases (26.1%), and the performance of prostate biopsy for csCaP detection would have increase to 41.5%. CONCLUSION: The application of the BCN-RSP would reduce the demand for mpMRI scans and prostate biopsies by one fifth while less than 5% of csCaP would remain undetected. The overdetection of insignificant CaP would decrease by more than one quarter and the performance of prostate biopsy for csCaP detection would increase to higher than 40%.

The Role of Digital Rectal Examination Prostate Volume Category in the Early Detection of Prostate Cancer: Its Correlation with the Magnetic Resonance Imaging Prostate Volume.

PURPOSE: To relate the prostate volume category (PVC) assessed with digital rectal examination (DRE)-small, median, and large-and the prostate volumes (PVs) assessed with magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS). To compare the clinically significant prostate cancer (csPCa) discrimination ability of two predictive models based on DRE-PVC and MRI-PV. MATERIALS AND METHODS: A prospective trial of 2,090 men with prostate-specific antigen >3 ng/mL and/or PCa suspicious DRE were prospectively recruited in 10 centers from Catalonia (Spain), between 2021 and 2022, in whom DRE-PVC was assessed. Pre-biopsy MRI, and 12-core TRUS-random biopsy was always performed after 2- to 6-core TRUS-fusion targeted biopsy of prostate imaging-report and data system >3 lesions. In 370 men (17.7%) the DRE-PVC was unconclusive. Among the 1,720 men finally analyzed the csPCa (grade group >2) detection was 42.4%. RESULTS: The median (interquartile range) of TRUS and MRI-PVs of small prostates were 33 mL (19-37 mL) and 35 mL (23-30 mL), p=0.410; in median prostates they were 51 mL (38-58 mL) and 55 mL (48-63 mL) respectively, p<0.001; in large prostates 80 mL (60-100 mL) and 95 mL (75-118 mL) respectively, p<0.001. The predictive models sharing the MRI-PV and DRE-PVC showed areas under the curves of 0.832 (95% confidence interval [CI], 0.813-0.851) and 0.828 (95% CI, 0.809-0.848) respectively, p=0.632, as well as similar net benefit and clinical utility. CONCLUSIONS: PVC was unconclusive in 17% of DREs. MRI-PV overestimated the TRUS-PV in median and large prostates. The predictive models based on MRI-PV and DRE-PVC showed similar efficacy to predict csPCa. PVC assessed with DRE is helpful to predict the csPCa risk before MRI.

A Diagnostic Accuracy Study of Targeted and Systematic Biopsies to Detect Clinically Significant Prostate Cancer, including a Model for the Partial Omission of Systematic Biopsies.

The primary objective of this study was to analyse the current accuracy of targeted and systematic prostate biopsies in detecting csPCa. A secondary objective was to determine whether there are factors predicting the finding of csPCa in targeted biopsies and, if so, to explore the utility of a predictive model for csPCa detection only in targeted biopsies. We analysed 2122 men with suspected PCa, serum PSA > 3 ng/mL, and/or a suspicious digital rectal examination (DRE), who underwent targeted and systematic biopsies between 2021 and 2022. CsPCa (grade group 2 or higher) was detected in 1026 men (48.4%). Discrepancies in csPCa detection in targeted and systematic biopsies were observed in 49.6%, with 13.9% of csPCa cases being detected only in systematic biopsies and 35.7% only in targeted biopsies. A predictive model for csPCa detection only in targeted biopsies was developed from the independent predictors age (years), prostate volume (mL), PI-RADS score (3 to 5), mpMRI Tesla (1.5 vs. 3.0), TRUS-MRI fusion image technique (cognitive vs. software), and prostate biopsy route (transrectal vs. transperineal). The csPCa discrimination ability of targeted biopsies showed an AUC of 0.741 (95% CI 0.721-0.762). The avoidance rate of systematic prostate biopsies went from 0.5% without missing csPCa to 18.3% missing 4.6% of csPCa cases. We conclude that the csPCa diagnostic accuracy of targeted biopsies is higher than that of systematic biopsies. However, a significant rate of csPCa remains detected only in systematic biopsies. A predictive model for the partial omission of systematic biopsies was developed.

Are magnetic resonance imaging and targeted biopsies needed in men with serum prostate-specific antigen over 10 ng/ml and an abnormal digital rectal examination?

The European Association of Urology currently recommends the use of risk-organized models to decrease the demand of prebiopsy magnetic resonance imaging (MRI) and unnecessary prostate biopsies in men with suspected prostate cancer (CaP). Low evidence suggests that men with prostate-specific antigen >10 ng/ml and an abnormal digital rectal examination (DRE) do not benefit from prebiopsy MRI and targeted biopsies. We aim to validate this low evidence in a sizable cohort and knowing how many clinically significant CaP (csCaP) would go undetected if only random biopsies were performed in these cases. We analyze a subset of 545 men with PSA >10 ng/ml and an abnormal DRE who met the previous criteria among 5,329 participants in a prospective trial in whom random biopsy was always performed and targeted biopsies of PI-RADS ≥3 lesions (10.2%). CsCaP (grade group ≥2) was detected in 370 men (67.9%), with 11 of 49 with negative MRI (22.5%) and 359 of 496 (72.4%) having PI-RADS ≥3. CsCaP was identified in random and targeted biopsies in 317 (88.7%) men, in targeted biopsies only in 23 (6.4%), and in random biopsies only in 19 (5.3%). If only random biopsies were performed in these men, 23 of overall 1,914 csCaP (1.2%) would go undetected in this population. Prebiopsy MRI can be saved in men with serum PSA >10 ng/ml and an abnormal DRE and only random biopsy performed. However, a close follow-up of men with negative random biopsy seems appropriate due to the high-risk of csCaP in these men.

Treatment of non-metastatic castration-resistant prostate cancer: facing age-related comorbidities and drug-drug interactions.

INTRODUCTION: Patients with non-metastatic castration-resistant prostate cancer (nmCRPC) are frequently poly-medicated due to age-related and androgen deprivation therapy (ADT)-derived comorbidities. In high-risk patients, androgen receptor inhibitors (ARIs) have shown to delay disease progression; however, drug-drug interactions (DDIs) with preexisting medications may impact the therapeutic effect and safety of these and of the ARIs themselves. AREAS COVERED: We review the potential comorbidity burden of nmCRPC patients on the basis of epidemiologic studies on age-related comorbidities, the impact of ADT and specific studies analyzing this topic. Using the DDIs compendia Lexicomp® and Drugs.com®, we provide a scenario of the potential DDIs between common mediations used to treat these comorbidities and the three currently available ARIs: apalutamide, enzalutamide and darolutamide. EXPERT OPINION: In high-risk nmCRPC patients to be treated with an ARI, careful multidisciplinary evaluation of potential DDIs is a fundamental component in the clinical-decision making. The lower potential for DDIs, the lower need for dose adjustment or change of current comedications and of patient monitoring, and safer introduction of new comedications. To optimize this step, an effort is still needed to determine the clinical relevance of DDIs and to harmonize their definition and classification among the different compendia.

Prostate cancer is one of the most common cancers in men. It is normally diagnosed at age 60 or above, so these men are usually taking medications to treat age-related conditions (e.g. hypertension, diabetes, high cholesterol, etc.).One of the main treatments for prostate cancer is 'androgen deprivation therapy' (ADT), a hormone treatment that reduces androgens level. This is because the growth of prostate cancer cells is dependent on male sex hormones called androgens. Despite ADT helping keep the cancer controlled for a time, it increases the risk for adverse events that may need new medications. Consequently, men with prostate cancer usually take multiple medications.After some years, ADT may not be enough to control the prostate cancer. A type of medication called 'androgen receptor inhibitors' (ARIs), which prevent the androgen entering the cell, are helpful at this stage, especially the second-generation ones: apalutamide, enzalutamide, and darolutamide. The problem is that these ARIs usually interact with other medications already taken by patients, an effect called 'drug­drug interaction.' When this happens, the ARI (the interaction 'perpetrator') may modify the effectiveness of other medications (the 'victims') and/or cause unexpected effects. Consequently, the conditions being treated by these medications may not be properly controlled, which may pose a risk to the patient's health. Thus, when starting treatment with a second-generation ARI, it is crucial to consider all possible interactions with the medications taken. The fewer potential interactions the ARI has, the easier it is to properly control other common conditions in prostate cancer patients.

Multidisciplinary Consensus on the Prevention and Treatment of Osteoporosis and Fragility Fractures in Patients with Prostate Cancer Receiving Androgen-Deprivation Therapy.

Patients with prostate cancer (PCa) on androgen-deprivation therapy (ADT) are at high risk of osteoporosis and fragility fractures. We aimed to provide some practical insights into the delivery of optimal bone health care for PCa patients, particularly those on ADT. An interdisciplinary group of experts, including urologists and rheumatologists developed recommendations based on their expertise, current evidence and guidelines. The multidisciplinary group's main recommendations are: fragility fracture risk should be assessed in all PCa patient, especially, in those under ADT. FRAX® tool may be incorporated into clinical practice to identify patients at high risk of fracture. Bone mineral density (BMD) should be measured routinely by dual energy X-ray absorptiometry in all patients scheduled for or on ADT. Thoracic and lumbar spine X-ray may be performed at the initial evaluation of patients with the diagnosis of osteoporosis and in case of suspected clinical vertebral fracture. Basic laboratory tests are recommended to exclude secondary osteoporosis. Treatment with bisphosphonates or denosumab should be considered in patients on ADT with fragility fracture, osteoporosis (BMD T-score ≤-2.5), or high risk of fracture according to FRAX®. Referral to a bone metabolism specialist should be contemplated in some cases. The recommendations provided in this document, tailored for clinicians treating PCa patients, may be of help to identify and treat patients at high risk of fracture.

[Posterior Retroperitoneoscopic adrenalectomy in the prone position. Initial experience.] / Suprarrenalectomía retroperitoneoscópica en decúbito prono. Experiencia inicial.

OBJECTIVE: Transperitoneal laparoscopic adrenalectomy (TLA) is considered the treatment of choice for small and benign adrenal tumors. In the recent years, posterior retroperitoneoscopic adrenalectomy (PRA) has gained popularity due to its advantages over TLA, presenting a shorter surgical time and a faster recovery without increasing complications. Conversely, a greater learning curve is considered because the use of a different and unusual surgical field. MATERIAL AND METHODS: Our objective is to describe the PRA technique to ass our initial experience evaluating its feasibility, safety and effectiveness in a prospective series of patients. A total of 11 (9 left and 2 right) PRA performed between March 2017 and February 2020 were analyzed. RESULTS: Median age was 55 (36-65) years with a median BMI of 25.69 (20.8-34.5) Kg/m2. 54.55% had ASA≥3. 63.37% of adrenal tumors were hormonally functional. The tumor mean size was 4 cm (0.6-8) and cortical adenoma was the predominant pathological anatomy (72.72%). No pheochromocytoma was operated. Median operative time was 87 minutes (35-125) with an intraoperative bleeding of 50 (0-300) mL. No patient presented intraoperative complications or reconversion. Median length of stay was 1 (1-6) days. Only one patient presented postoperative complications. CONCLUSION: The PRA is feasible, reproducible and safe, even during the initial learning curve, presenting a clear early recovery with a shorter surgical time.

OBJETIVO: La suprarrenalectomía laparoscópica transperitoneal (SLT) se considera el tratamiento de elección de los tumores suprarrenales benignos y de pequeño tamaño. En los últimos años el acceso retroperitoneoscópico en decúbito prono (SRP) ha ganado popularidad por las ventajas que ofrece con respecto a la SLT, al emplear un menor tiempo quirúrgico y obtener una recuperación más rápida sin aumentar las complicaciones, a expensas de una curva de aprendizaje dificultada por emplear un campo quirúrgico diferente al habitual.MATERIAL Y MÉTODOS: Nuestro objetivo es describir la técnica quirúrgica de SRP y nuestra experiencia inicial evaluando su factibilidad, seguridad y efectividad en una serie prospectiva de pacientes. Se analizaron un total de 11 SRP (9 izquierdas y 2 derechas) realizadas entre marzo de 2017 y febrero de 2020. RESULTADOS: La mediana de edad fue de 55 (36-65) años con un IMC de 25,69 Kg/m2 (20,8-34,5). El 54,55% tenía un ASA≥3. El 63,37% de los tumores suprarrenales fueron hormonalmente funcionantes. El tamaño medio fue de 4 cm (0,6-8), siendo el adenoma cortical la anatomía patológica predominante (72,72%). No se realizó ningún feocromocitoma. La mediana de tiempo quirúrgico fue de 87 minutos (35-125) con un sangrado intraoperatorio de 50mL (0-300). Ningún paciente presentó complicaciones intraoperatorias o reconversión. La mediana de días de ingreso fue de1 (1-6) día. Sólo un paciente presentó complicaciones postoperatorias. CONCLUSIONES: La SRP es factible, reproducible y segura, incluso durante la curva de aprendizaje inicial, presentando una clara recuperación temprana con un tiempo quirúrgico corto.

Prognostic value of lymphocyte-to-monocyte ratio previously determined to surgery in patients with non-metastatic renal cell carcinoma: A systematic review and a prisma-compliant meta-analysis.

BACKGROUND: The prognostic value of pretreatment lymphocyte to monocyte ratio in patients with renal cell carcinoma and, especially, in non-metastatic patients remains controversial. METHODS: We conducted a PRISMA-compliant meta-analysis to systematically assess the prognostic value of LMR in patients with non-metastatic RCC. Overall survival, cancer-specific survival, and disease-free survival were analyzed. Pooled hazard ratios and 95% confidence intervals were calculated. RESULTS: Seven studies comprising 4666 patients were included in the analysis. Unlike those observed in a previous meta-analysis, a lower lymphocyte to monocyte ratio was associated with poorer cancer-specific survival (fix-effect model, hazard ratio 3.04, 95% confidence intervals 2.05-4.51, P < .05). Heterogeneity Chi-squared value Q exp = 0. (P = .82) (I2 = 0%). However, the association between a low lymphocyte to monocyte ratio and overall survival or disease-free survival did not obtain significance. CONCLUSION: A lower lymphocyte to monocyte ratio implied poor cancer-specific survival in patients with non-metastatic renal cell carcinoma. Prospective studies are required to confirm our findings. REGISTRATION NUMBER: ClinicalTrials.gov (identifier: NCT04213664).

Effect of muscle density in patients with metastatic prostate cancer administered androgen deprivation therapy. / Efecto de la densidad muscular en pacientes con cáncer de próstata metastásico tratados con terapia de privación androgénica.

INTRODUCTION: Sarcopenia is a syndrome characterized by the loss of muscle mass and strength. The study objective was to determine the association between muscle density and overall survival (OS) in patients with metastatic onset prostate cancer (MPCa). MATERIALS AND METHODS: This was a retrospective study of patients diagnosed with MPCa between 2009 and 2015 who received androgen deprivation therapy alone as initial treatment. Muscle density was calculated using the Hounsfield Unit Average Calculation (HUAC) in both psoas muscles in the computed tomography (CT) scan performed for diagnosis. RESULTS: A total of 59 patients diagnosed with MPCa, with a mean age of 57.5±72.47 years, were found. Median prostate-specific antigen (PSA) level at diagnosis was 68.25 ng/dL (IQR 37.26-290). Gleason scores≥8 were recorded in 90.75% of the patients, bone metastases in 88.13%, and visceral metastases in 10.16%. Median HUAC was 20.32 HU (IQR 15.46-22.83). In a univariate analysis, the number of bone metastases, the presence of visceral metastases, and testosterone levels≥50 ng/dL at follow-up were associated with poorer OS, while high HUAC levels were associated with better OS. In a multivariate analysis, the number of bone metastases [hazard ratio (HR)=1.573, 95% confidence interval (CI)=1.103-2.243, p=0.012], the presence of visceral metastases (HR=7.404, CI=2.233-24.549, p=0.001), and the Gleason score (HR=2.001, CI=1.02-3.923, p=0.044) were associated with greater overall mortality, and HUAC (HR=0.902, CI=0.835-0.973, p=0.008) was associated with better OS. CONCLUSIONS: In our series, increased HUAC values in the psoas muscles, as a reflection of muscle density, when MPCa was diagnosed had a protective effect on OS in these patients.

Dissection of the inferior mesenteric vein versus of the inferior mesenteric artery for the genitourinary function after laparoscopic approach of rectal cancer surgery: a randomized controlled trial.

BACKGROUND: Total Mesorectal Excision (TME) is the standard surgical technique for the treatment of rectal cancer. However, rates of sexual dysfunction ofup to 50% have been described after TME, and rates of urinary dysfunction of up to 30%. Although other factors are involved, the main cause of postoperative genitourinary dysfunction is intraoperative injury to the pelvic autonomic nerves. The risk is particularly high in the inferior mesenteric artery (IMA). The aim of this study is to compare pre- and post-TME sexual dysfunction, depending on the surgical approach usedin the inferior mesenteric vessels: either directly on the IMA, or from the inferior mesenteric vein (IMV) to the IMA. METHODS: Prospective, randomized,controlled study of patients with rectal adenocarcinoma with neoadjuvant chemoradiotherapy, who will be randomly assigned to one of two groups depending on the surgical approach to the inferior mesenteric vessels. The main variable is pre- and postoperative sexual dysfunction; secondary variables are visualization and preservation of the pelvic autonomic nerves, pre- and postoperative urinary dysfunction, and pre- and postoperative quality of life. The sample will comprise 90 patients, 45 per group. DISCUSSION: The aim is to demonstrate that the dissection route from the IMV towards the IMA favors the preservation of the pelvic autonomic nerves and thus reducesrates of sexual dysfunction post-surgery. TRIAL REGISTRATION: Ethical and Clinical Research Committee, Parc Taulí University Hospital: ID 017/315. ClinicalTrials.gov TAU-RECTALNERV-PRESERV-2018 (TRN: NCT03520088 ) (Date of registration 04/03/2018).

The Place of Transanal Endoscopic Surgery in the Treatment of Rectourethral Fistula.

OBJECTIVE: To assess the role of transanal endoscopic operation (TEO) or transanal endoscopic microsurgery (TEM) in rectourethral fistulas (RUF). RUF may appear after radical prostatectomy. Their treatment represents a challenge; many therapies have been proposed, from conservative to aggressive surgical approaches. Transanal endoscopic surgery (TEO or TEM) is a minimally invasive technique to access the site of the RUF to perform repair. MATERIALS AND METHODS: This is an observational study with prospective data collection, conducted between September 2006 and December 2015. All patients were diagnosed with RUF following management of prostate cancer. Conservative treatment was administered in the form of urinary and fecal diversion with cystotomy and terminal colostomy, to achieve total urinary and fecal exclusion. If the fistula persisted, it was treated by TEO or TEM, with or without biological mesh interposition. If this failed, gracilis muscle was applied as salvage therapy. RESULTS: Ten patients were diagnosed with RUF. In 1 patient (1 of 10), the fistula healed with bladder catheterization alone. In another patient (1 of 9), it resolved after total urinary and fecal exclusion. Eight patients underwent repair by TEO or TEM, 4 with biological mesh interposition; all 4 presented recurrence. In the other 4 patients treated via TEO or TEM, 2 had early recurrence, whereas the others had healed at follow-up visits after 4-6 months (2 of 8)-a success rate of 25%. The 6 patients who recurred were treated with gracilis muscle interposition via a transperineal approach. CONCLUSION: The low rate of positive results obtained by TEO or TEM argues against its use as technique of choice in RUF, and against the use of biological meshes.

Giant Prostatic Hyperplasia: Case Report of 3987 mL.

We present herein a 72-year-old male with a long history of mild lower urinary tract symptoms, with a serum prostate-specific antigen level value of 87.9 ng/mL and an estimated prostate size of 3987 mL, according to magnetic resonance imaging. Prostatic biopsies showed benign prostatic hyperplasia. Prostatic surgery has not been required. To the best of our knowledge, this is the highest prostate volume reported in the medical literature.

Repeated spurious elevation of serum prostate-specific antigen values solved by chemiluminescence analysis: A possible interference by heterophilic antibodies.

Heterophilic antibodies are human immunoglobulins directed against various animal antigens. They can produce false-positive results in the analysis of different tumor markers, including prostate-specific antigen. This interference can lead to misdiagnosis, unnecessary tests, and overtreatment in some cases. We present herein the case of a 52-year-old man with repeated spurious elevation of prostate-specific antigen, reaching levels of 108.7 ng/mL, that were suspected to be caused by heterophilic antibodies. The interference was solved by changing the analysis technique. Real values of prostate-specific antigen were less than 1 ng/mL.