Perioperative Morbidity of Radical Prostatectomy After Intensive Neoadjuvant Androgen Blockade in Men With High-Risk Prostate Cancer: Results of Phase II Trial Compared to a Control Group.

INTRODUCTION: Recent studies about intense neoadjuvant therapy followed by Radical Prostatectomy (RP) lack standardized criteria regarding surgical complications and comparison to a group of patients who underwent RP without the use of neoadjuvant therapy. The aim of this study is to describe and compare the perioperative complication rates. MATERIALS AND METHODS: This was a prospective, single-center phase II trial in patients with high-risk prostate cancer (HRPCa). The control group included HRPCa patients who underwent RP outside the clinical trial during the same study recruitment period. The interventional group was randomized (1:1) to receive neoadjuvant androgen deprivation therapy plus abiraterone with or without apalutamide followed by RP. Complications observed up to 30 days of surgery were classified based on the Clavien-Dindo classification. Uni- and multivariate analyses were carried out to assess predictive factors associated with perioperative complications. RESULTS: In total, 124 patients with HRPCa were underwent to RP between May 27, 2019 and August 6, 2021, including 61 patients in the intervention group and 63 patients in the control group. The general and major complications in the intervention group reached 29.6% and 6.6%, respectively, and 39.7% and 7.9% in the control group, respectively. There was no significant difference between groups. We observed 4.9% of thromboembolic event in the neoadjuvant group. CONCLUSIONS: There was no significant increase in morbidity rate in RP after intense neoadjuvant therapy. The association of intense androgen deprivation neoadjuvant therapy with RP and extended pelvic lymphadenectomy may increase the risk of a perioperative thromboembolic events.

miRNA and mRNA Expression Profiles Associated with Lymph Node Metastasis and Prognosis in Penile Carcinoma.

Penile cancer (PeC) is a rare disease, and no prognostic biomarkers have been adopted in clinical practice yet. The objective of the present study was to identify differentially expressed miRNAs (DEmiRs) and genes (DEGs) as potential biomarkers for lymph node metastasis and other prognostic factors in PeC. Tumor samples were prospectively obtained from 24 patients with squamous cell carcinoma of the penis. miRNA microarray analysis was performed comparing tumors from patients with inguinal lymph node metastatic and localized disease, and the results were validated by qRT-PCR. Eighty-three gene expression levels were also compared between groups through qRT-PCR. Moreover, DEmiRs and DEGs expression levels were correlated with clinicopathological variables, cancer-specific (CSS), and overall survival (OS). TAC software, TM4 MeV 4.9 software, SPSS v.25.0, and R software v.4.0.2 were used for statistical analyses. We identified 21 DEmiRs in microarray analysis, and seven were selected for validation. miR-744-5p and miR-421 were overexpressed in tissue samples of metastatic patients, and high expression of miR-421 was also associated with lower OS. We found seven DEGs (CCND1, EGFR, ENTPD5, HOXA10, IGF1R, MYC, and SNAI2) related to metastatic disease. A significant association was found between increased MMP1 expression and tumor size, grade, pathological T stage, and perineural invasion. Other genes were also associated with clinicopathological variables, CSS and OS. Finally, we found changes in mRNA-miRNA regulation that contribute to understanding the mechanisms involved in tumor progression. Therefore, we identified miRNA and mRNA expression profiles as potential biomarkers associated with lymph node metastasis and prognosis in PeC, in addition to disruption in mRNA-miRNA regulation during disease progression.

A Prospective, Randomized Trial Comparing the Outcomes of Open vs Laparoscopic Partial Nephrectomy.

PURPOSE: Partial nephrectomy is the standard treatment for renal tumors <7 cm, and the trend toward minimally invasive surgery has increased. However, data that could support its use and benefits are still lacking. MATERIALS AND METHODS: We conducted a prospective, randomized controlled trial comparing surgical, functional and oncologic outcomes in patients undergoing open partial nephrectomy (OPN) or laparoscopic partial nephrectomy (LPN). Randomization was 1:1 to OPN or LPN for the treatment of renal tumors <7 cm. The primary endpoint was surgical complications up to 90 days after surgery. Secondary outcomes were comparison of surgical, oncologic and functional results. RESULTS: We randomized 208 patients between 2012 and 2020 (110 with OPN vs 98 with LPN). Operative data showed no differences in operative time, warm ischemia time, estimated blood loss, transfusions or length of hospital stay. Zero ischemia was more frequent in the OPN (35.4% vs 15.5%, p=0.02). OPN was associated with more abdominal wall complications (31.2% vs 13.1%, p=0.004). Regarding oncologic outcomes, no differences were noted. The LPN group had less kidney function reduction at 3 (-5.2% vs -10%, p=0.04; CI 0.09 to 9.46) and 12 months after surgery (-0.8% vs -6.3%, p=0.02; CI 1.18 to 12.95), and a lower rate of downstaging on the chronic kidney disease classification at 12 months (14.1% vs 32.6%, p=0.006). CONCLUSIONS: Surgical and oncologic outcomes of LPN were similar to OPN. Minimally invasive surgery may provide better preservation of kidney function. More studies, especially those involving robotic surgery, are necessary to confirm our findings.

Tranexamic acid in patients with complex stones undergoing percutaneous nephrolithotomy: a randomised, double-blinded, placebo-controlled trial.

OBJECTIVES: To assess the efficacy and safety of single-dose tranexamic acid on the blood transfusion rate and outcomes of patients with complex kidney stones undergoing percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: In a randomised, double-blinded, placebo-controlled trial, 192 patients with complex kidney stone (Guy's Stone Scores III-IV) were prospectively enrolled and randomised (1:1 ratio) to receive either one dose of tranexamic acid (1 g) or a placebo at the time of anaesthetic induction for PCNL. The primary outcome measure was the occurrence rate of perioperative blood transfusion. The secondary outcome measures included blood loss, operative time, stone-free rate (SFR), and complications. ClinicalTrials.gov identifier: NCT02966236. RESULTS: The overall risk of receiving a blood transfusion was reduced in the tranexamic acid group (2.2% vs 10.4%; relative risk, 0.21, 95% confidence interval [CI] 0.03-0.76, P = 0.033; number-needed-to-treat: 12). Patients randomised to the tranexamic acid group had a higher immediate and 3-month SFR compared with those in the placebo group (29% vs 14.7%, odds ratio [OR] 2.37, 95% CI 1.15-4.87, P = 0.019, and 46.2% vs 28.1%, OR 2.20, 95% CI 1.20-4.02, P = 0.011, respectively). Faster haemoglobin recovery occurred in patients in the tranexamic acid group (mean, 21.3 days; P = 0.001). No statistical differences were found in operative time and complications between groups. CONCLUSIONS: Tranexamic acid administration is safe and reduces the need for blood transfusion by five-times in patients with complex kidney stones undergoing PCNL. Moreover, tranexamic acid may contribute to better stone clearance rate and faster haemoglobin recovery without increasing complications. A single dose of tranexamic acid at the time of anaesthetic induction could be considered standard clinical practice for patients with complex kidney stones undergoing PCNL.

Robot-assisted simple prostatectomy: the evolution of a surgical technique

ABSTRACT Purpose: Enucleation of a large prostate is the best surgical choice for patients refractory to clinical treatment (1,2). Since the first robot-assisted simple prostatectomy (RASP) was described (3,4), some technical modifications (5-7) and different approaches to reach the adenoma have been proposed (8,9). The aim of this video is to demonstrate three different techniques of RASP. Materials and Methods: The first procedure begins with a transversal incision over the bladder neck, the second is a transvesical approach and the last one is a Retzius-sparing RASP. All techniques were performed with a vesico-urethral anastomosis. Results: Three patients underwent RASP, each one with a different approach. Patients presented mean age of 66±4.4 years, PSA baseline level of 7.8±3ng/mL, IPSS score of 17.7±4.5, maximum urine flow of 8.3±1.5mL/seg and 122.3±11.2cm3 of prostate volume. The mean operative time was 63±8 minutes, estimated blood loss of 106.7±11.5mL, prostate weight of the surgical specimen of 106.3±8 grams and 1 day of length of stay. No continuous bladder irrigation was required and there was no complication. The mean postoperative PSA and IPSS were 0.7±0.3ng/mL, 4.7±1.5. The maximum urine flow raised to 20±4.4mL/seg. Conclusions: RASP with vesico-urethral anastomosis allowed minimal blood loss, short length of stay and great functional outcomes. All the three approaches allowed to perform this technique in a safe way, while showing different alternatives to reach the adenoma.

Opioids and premature biochemical recurrence of prostate cancer: a randomised prospective clinical trial.

BACKGROUND: Prostate cancer is one of the most prevalent neoplasms in male patients, and surgery is the main treatment. Opioids can have immune modulating effects, but their relation to cancer recurrence is unclear. We evaluated whether opioids used during prostatectomy can affect biochemical recurrence-free survival. METHODS: We randomised 146 patients with prostate cancer scheduled for prostatectomy into opioid-free anaesthesia or opioid-based anaesthesia groups. Baseline characteristics, perioperative data, and level of prostate-specific antigen every 6 months for 2 yr after surgery were recorded. Prostate-specific antigen >0.2 ng ml-1 was considered biochemical recurrence. A survival analysis compared time with biochemical recurrence between the groups, and a Cox regression was modelled to evaluate which variables affect biochemical recurrence-free survival. RESULTS: We observed 31 biochemical recurrence events: 17 in the opioid-free anaesthesia group and 14 in the opioid-based anaesthesia group. Biochemical recurrence-free survival was not statistically different between groups (P=0.54). Cox regression revealed that biochemical recurrence-free survival was shorter in cases of obesity (hazard ratio [HR] 1.63, confidence interval [CI] 0.16-3.10; p=0.03), high D'Amico risk (HR 1.58, CI 0.35-2.81; P=0.012), laparoscopic surgery (HR 1.6, CI 0.38-2.84; P=0.01), stage 3 tumour pathology (HR 1.60, CI 0.20-299) and N1 status (HR 1.34, CI 0.28-2.41), and positive surgical margins (HR 1.37, CI 0.50-2.24; P=0.002). The anaesthesia technique did not affect time to biochemical recurrence (HR -1.03, CI -2.65-0.49; P=0.18). CONCLUSIONS: Intraoperative opioid use did not modify biochemical recurrence rates and biochemical recurrence-free survival in patients with intermediate and high D'Amico risk prostate cancer undergoing radical prostatectomy. CLINICAL TRIAL REGISTRATION: NCT03212456.

Robot-assisted retroperitoneal lymphadenectomy: The state of art.

OBJECTIVE: To perform a narrative review about the role of robot-assisted retroperitoneal lymphadenectomy (R-RPLND) in the management of testicular cancer. METHODS: A PubMed search for all relevant publications regarding the R-RPLND series up until August 2019 was performed. The largest series were identified, and weighted means calculated for outcomes using the number of patients included in each study as the weighting factor. RESULTS: Fifty-six articles of R-RPLND were identified and eight series with more than 10 patients in each were included. The weighted mean age was 31.12 years; primary and post chemotherapy R-RPLND were performed in 50.59% and 49.41% of patients. The clinical stage was I, II and III in 47.20%, 39.57% and 13.23% of patients. A modified R-RPLND template was used in 78.02% of patients, while 21.98% underwent bilateral full template. The weighted mean node yield, operative time and estimated blood loss were, respectively, 22.15 nodes, 277.35 min and 131.94 mL. The weighted mean length of hospital stay was 2 days and antegrade ejaculation was preserved in 92.12% of patients. Major post-operative complications (Clavien III or IV) occurred in 5.34%. Positive pathological nodes were detected in 24.54%, while the recurrence free survival was 95.77% with a follow-up of 21.81 months. CONCLUSION: R-RPLND has proven to be a reproducible and safe approach in experienced centers; short-term oncologic outcomes are similar to the open approach with less morbidity and shorter convalescence related to its minimal invasiveness. However, longer follow-up and new trials comparing head-to-head both techniques are expected.

Extended Versus Limited Pelvic Lymph Node Dissection During Radical Prostatectomy for Intermediate- and High-risk Prostate Cancer: Early Oncological Outcomes from a Randomized Phase 3 Trial.

BACKGROUND: The role of extended pelvic lymph node dissection (EPLND) in the surgical management of prostate cancer (PCa) patients remains controversial, mainly because of a lack of randomized controlled trials (RCTs). OBJECTIVE: To determine whether EPLND has better oncological outcomes than limited PLND (LPLND. DESIGN, SETTING AND PARTICIPANTS: This was a prospective, single-center phase 3 trial in patients with intermediate- or high-risk clinically localized PCa. INTERVENTION: Randomization (1:1) to LPLND (obturator nodes) or EPLND (obturator, external iliac, internal iliac, common iliac, and presacral nodes) bilaterally. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was biochemical recurrence-free survival (BRFS). Secondary outcomes were metastasis-free survival (MFS), cancer-specific survival (CSS), and histopathological findings. The trial was designed to show a minimal 15% advantage in 5-yr BRFS by EPLND. RESULTS AND LIMITATIONS: In total, 300 patients were randomized from May 2012 to December 2016 (150 LPLND and 150 EPLND). The median BRFS was 61.4 mo in the LPLND group and not reached in the EPLND group (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.63-1.32; p = 0.6). Median MFS was not reached in either group (HR 0.57, 95% CI 0.17-1.8; p = 0.3). CSS data were not available because no patient died from PCa before the cutoff date. In exploratory subgroup analysis, patients with preoperative biopsy International Society of Urological Pathology (ISUP) grade groups 3-5 who were allocated to EPLND had better BRFS (HR 0.33, 95% CI 0.14-0.74, interaction p = 0.007). The short follow-up and surgeon heterogeneity are limitations to this study. CONCLUSION: This RCT confirms that EPLND provides better pathological staging, while differences in early oncological outcomes were not demonstrated. Our subgroup analysis suggests a potential BCRFS benefit in patients diagnosed with ISUP grade groups 3-5; however, these findings should be considered hypothesis-generating and further RCTs with larger cohorts and longer follow up are necessary to better define the role of EPLND during RP. PATIENT SUMMARY: In this study, we investigated early outcomes in prostate cancer patients undergoing prostatectomy according to the anatomic extent of lymph node resection. We found that extended removal of lymph nodes did not reduce biochemical recurrence of prostate cancer in the expected range.

Androgen deprivation therapy improves the in vitro capacity of high-density lipoprotein (HDL) to receive cholesterol and other lipids in patients with prostate carcinoma.

BACKGROUND: Androgen deprivation therapy (ADT) is widely used in the treatment of testosterone-dependent prostate carcinomas. ADT often increases plasma LDL and HDL cholesterol and triglycerides. The aim was to test whether ADT changes the transfer of lipids to HDL, an important aspect of this metabolism and HDL protective functions, and related parameters. METHODS: Sixteen volunteers with advanced prostate carcinoma submitted to pharmacological ADT or orchiectomy had plasma collected shortly before and after 6 months of ADT. In vitro transfer of lipids to HDL was performed by incubating plasma with donor emulsion containing radioactive lipids by 1 h at 37 °C. After chemical precipitation of apolipoprotein B-containing lipoprotein, the radioactivity of HDL fraction was counted. RESULTS: ADT reduced testosterone to nearly undetectable levels and markedly diminished PSA. ADT increased the body weight but glycemia, triglycerides, LDL and HDL cholesterol, HDL lipid composition and CETP concentration were unchanged. However, ADT increased the plasma unesterified cholesterol concentration (48 ± 12 vs 56 ± 12 mg/dL, p = 0.019) and LCAT concentration (7.15 ± 1.81 vs 8.01 ± 1.55µg/mL, p = 0.020). Transfer of unesterified (7.32 ± 1.09 vs 8.18 ± 1.52%, p < 0.05) and esterified cholesterol (6.15 ± 0.69 vs 6.94 ± 1.29%, p < 0.01) and of triglycerides (6.37 ± 0.43 vs 7.18 ± 0.91%, p < 0.001) to HDL were increased after ADT. Phospholipid transfer was unchanged. CONCLUSION: Increase in transfer of unesterified and esterified cholesterol protects against cardiovascular disease, as shown previously, and increased LCAT favors cholesterol esterification and facilitates the reverse cholesterol transport. Thus, our results suggest that ADT may offer anti-atherosclerosis protection by improving HDL functional properties. This could counteract, at least partially, the eventual worse effects on plasma lipids.

COVID-19 and urology: a comprehensive review of the literature.

OBJECTIVE: To discuss the impact of COVID-19 on global health, particularly on urological practice and to review some of the available recommendations reported in the literature. MATERIAL AND METHODS: In the current narrative review the PubMed database was searched to identify all the related reports discussing the impact of COVID-19 on the urological field. RESULTS: The COVID-19 pandemic is the latest and biggest global health threat. Medical and surgical priorities have changed dramatically to cope with the current challenge. These changes include postponements of all elective outpatient visits and surgical procedures to save facilities and resources for urgent cases and patients with COVID-19 patients. This review discuss some of the related changes in urology. CONCLUSIONS: Over the coming weeks, healthcare workers including urologists will be facing increasingly difficult challenges, and consequently, they should adopt triage strategy to avoid wasting of medical resources and they should endorse sufficient protection policies to guard against infection when dealing with COVID-19 patients.

Oncologic Outcomes in Young Adults With Kidney Cancer Treated During the Targeted Therapy Era.

BACKGROUND: The objective of this study was to determine the outcomes of young adults with kidney cancer treated during the targeted therapy era and evaluate the impact of young age on survival. MATERIALS AND METHODS: We reviewed the records from 445 patients younger than 55 years with kidney cancer at a single institution from 2006 to 2017. Overall survival (OS) and recurrence-free survival were estimated with the Kaplan-Meier method and log-rank test. Cox proportional hazards regression was used to determine the impact of clinical and pathologic variables on all-cause mortality. RESULTS: Overall, 104 (23%) patients 40 years or younger were compared with 341 (77%) patients who were 41 to 55 years old. Younger patients presented with more advanced stages of the disease, including metastasis at diagnosis, positive lymph nodes, venous tumor thrombus and had more non-clear cell tumors (54% vs. 30%; P < .001). Young adults had significantly worse OS at 2 and 5 years (67% vs. 82% and 53% vs. 69%, respectively). Younger patients with metastatic disease received targeted agents less often compared with the older group (64% vs. 75%). There was no difference in recurrence-free survival across patients with localized disease. Independent prognostic factors associated with increased mortality were metastasis at diagnosis, pT2 or greater, and age younger than 40 years (hazard ratio, 1.65; 95% confidence interval, 1.0-2.6; P = .03). CONCLUSION: Patients younger than 40 years with kidney tumors treated during the targeted therapy era have worse OS compared with older adults. Young age is an independent predictor of mortality.

Robot-assisted extended pelvic lymph node dissection in prostate cancer. When and how?

OBJECTIVE: To review the literature evaluating the role of the extended pelvic lymph node dissectione PLND during robot assisted radical prostatectomy (RARP) in the management of PCa patients, as well as the preoperative clinic pathologic factors that predict lymph node metastases (LNM). The technique and current outcomes of robotic ePLND will be presented. METHODS: Medline®/Pubmed® were searched up to august 2018 to find comparative studies of different anatomic limits of pelvic lymph node dissection (PLND) during RARP, open or pure laparoscopic surgery that reported number of nodes retrieved, oncologic outcomes and complications. The search was complemented to identify studies that evaluated diagnostic images and factors that predict LNM. Overall, 44 articles were included for full text review. RESULTS: There is not an imaging technique with an acceptable performance to select patients for PLND, the decision to perform a PLND is based on clinical characteristics described on validated nomograms. Median lymph node yield at RARP range from 5 to 21 depending on the extent of PLND, positivity rate of LN as high as 37% depending on the risk stratification of patients. Robot-assisted can be carried out to any extent with lymph node yields and safety concerns comparable to the open approach. CONCLUSION: Extended pelvic lymph node dissection is recommended to be performed at the time of RARP in intermediate and high-risk patients and cannot be replaced by other modalities. A benefit in terms of oncologic outcomes remains to be established. The robot assisted approach offers shorter length of hospital stay, lower transfusion rates and comparable outcomes compared to other surgical approaches.

ARTICULO SOLO EN INGLES.OBJETIVO: Revisar la literatura que evalúa  el papel de la linfadenectomía pélvica extendida  (LPe) durante la prostatectomía radical asistida por robot  (PRAR) en el manejo de pacientes con cáncer de próstata,  así como los factores clínico-patológicos preoperatorios  que predicen las metástasis ganglionares. Presentamos la técnica de LPe y sus resultados actuales.MÉTODOS: Se realizó una búsqueda bibliográfica en Medline®/Pubmed® hasta agosto 2018 para encontrar estudios comparativos de los diferentes límites anatómicos de la linfadenectomía pélvica duranteprostatectomía radical asistida por robot, abierta olaparoscópica que comunicaran número de ganglios,resultados oncológicos y complicaciones. La búsquedafue complementada para identificar estudios que evaluaran imágenes diagnósticas y factores predictivos demetástasis ganglionares. Finalmente, se incluyeron 44artículos. RESULTADOS: No hay una técnica de imagen que tengauna resolución aceptable para seleccionar pacientespara linfadenectomía. La decisión de practicar linfadenectomíase basa en las características clínicas descritasen nomogramas validados. La mediana del númerode ganglios obtenidos oscila entre 5 y 21 dependiendode la extensión de la linfadenectomía, y la tasa de gangliospositivos es tan alta como el 37% dependiendo dela estratificación del riesgo de los pacientes. La cirugíaasistida por robot puede realizarse con cualquier extensióncon un número de ganglios obtenidos y aspectosde seguridad comparables con el abordaje abierto. CONCLUSION: Se recomienda realizar la linfadenectomíapélvica extendida en el momento de la PRAR enpacientes de riesgo intermedio y alto y no puede reemplazarsepor otras modalidades. Sigue por establecerseun beneficio en términos de resultados oncológicos. Elabordaje asistido por robot ofrece estancias hospitalariasmás cortas, menores tasas de transfusión y resultadoscomparables en comparación con otros abordajesquirúrgicos.