Perioperative, Oncological, and Functional Outcomes Between Robot-Assisted Laparoscopic Prostatectomy and Open Radical Retropubic Prostatectomy: A Randomized Clinical Trial.

PURPOSE: Limited high-quality studies have compared robot-assisted laparoscopic prostatectomy (RALP) vs open retropubic radical prostatectomy. We sought to compare their postoperative outcomes in a randomized setting. MATERIALS AND METHODS: In a single center, 354 men with newly diagnosed prostate cancer were assessed for eligibility; 342 were randomized (1:1). The primary outcome was 90-day complication rates. Functional outcomes and quality of life were assessed over 18 months, and oncological outcomes, biochemical recurrence-free survival, and additional treatment over 36 months. RESULTS: From 2014 to 18, 327 patients underwent surgery (retropubic radical prostatectomy = 156, RALP = 171). Complications occurred in 27 (17.3%) vs 19 (11.1%; P = .107). Patients undergoing RALP experienced lower median bleeding (250.0 vs 719.5 mL; P < .001) and shorter hospitalization time. Urinary EPIC (Expanded Prostate Cancer Index Composite) median scores were better for RALP over 18 months, with higher continence rate at 3 months (80.5% vs 64.7%; P = .002), 6 months (90.1% vs 81.6%; P = .036) and 18 months (95.4% vs 78.8%; P < .001). Sexual EPIC and Sexual Health Inventory for Men median scores were higher with RALP up to 12 months, while the potency rate was superior at 3 months (23.9% vs 5.3%; P = .001) and 6 months (30.6% vs 6.9%; P < .001). Quality of life over the 18 months and oncological outcomes over 36 months were not significantly different between arms. CONCLUSIONS: Complications at 90 days were similar. RALP showed superior sexual outcomes at 1 year, improved urinary outcomes at 18 months, and comparable oncological outcomes at 36 months.

Honing the Hunt: A Comprehensive Review of Cell-free Tumor DNA to Predict Neoadjuvant Therapy Efficacy in Bladder Cancer.

OBJECTIVE: To provide an updated view on the role of cell-free DNA as a predictor of pathological response to neoadjuvant therapy in patients with muscle-invasive bladder cancer. METHODS: A systematic review was conducted from September 2023 to October 2023. Selected studies from the MEDLINE and clinical trial databases were critically analyzed regarding the clinical efficacy of cell-free DNA as a predictive instrument after neoadjuvant therapy in bladder cancer. The methodological quality assessment was based on the QUADAS-2 tool. RESULTS: In this systematic review, we analyzed 5 studies encompassing a cumulative patient cohort of 780 individuals diagnosed with muscle-invasive bladder cancer, with a median follow-up ranging from 6 to 23 months. Among these studies, 4 primarily focused on detecting and analyzing circulating tumor DNA in plasma, while 1 study uniquely utilized cell-free tumor DNA in urine samples. The diagnostic accuracy of cell-free DNA in plasma ranges from 79% to 100%, indicating a variable yet significant predictive capability. In contrast, the study utilizing urinary cell-free DNA demonstrated an accuracy of 81% in predicting treatment response post-neoadjuvant chemotherapy. CONCLUSION: Cell-free DNA is emerging as a valuable biomarker for predicting response to neoadjuvant chemotherapy in patients with muscle-invasive bladder tumors.

Predicting individual outcomes after radical cystectomy in urothelial variants with Cancer of the Bladder Risk Assessment (COBRA) score.

OBJECTIVE: To validate the Cancer of the Bladder Risk Assessment (COBRA) score in patients with urothelial variants. METHODS: Epidemiological, clinical, radiological, and anatomopathological data were collected from patients with urothelial carcinoma who underwent radical cystectomy at the Institute of Cancer of São Paulo between May 2008 and December 2022. Patients with the presence of at least 10% of any urothelial variants in the radical cystectomy specimens' anatomopathological exam were included in the study. The COBRA score and derivatives were applied and correlated with oncological outcomes. RESULTS: A total of 680 patients [482 men (70.9%) and 198 women (29.1%)]; 66 years (IQR 59-73) underwent radical cystectomy for bladder tumor, and of these patients, a total of 167 patients presented any type of urothelial variant. The median follow-up time was 28.77 months (IQR 12-85). The three most prevalent UV were squamous differentiation (50.8%), glandular differentiation (31.3%), and micropapillary differentiation (11.3%). The subtypes with the worst prognosis were sarcomatoid with a median survival of 8 months (HR 1.161; 95% CI 0.555-2.432) and plasmacytoid with 14 months (HR 1.466; 95% CI 0.528-4.070). The COBRA score for patients with micropapillary variants demonstrated good predictive accuracy for OS (log-rank P = 0.009; 95% IC 6.78-29.21) and CSS (log-rank P = 0.002; 95% IC 13.06-26.93). CONCLUSIONS: In our study, the COBRA score proved an effective risk stratification tool for urothelial histological variants, especially for the micropapillary urothelial variant. It may be helpful in the prognosis evaluation of UV patients after radical cystectomy.

Robotic-assisted approaches to urachal carcinoma: A comprehensive systematic review of the safety and efficacy outcomes.

Introduction: Surgical intervention is the treatment of choice in patients with urachal carcinoma. Due to complications and to reduce hospital stay from open surgery, minimally invasive approaches are desirable. Nowadays, robotic-assisted surgery has become increasingly popular, and robot-assisted cystectomy can be performed in patients with urachal carcinoma with low complication rates. Methods: We performed a systematic review to search for studies that evaluated patients who underwent robotic-assisted surgery for urachal carcinoma. The outcomes of interest were the type of cystectomy performed, whether there was umbilicus resection, total operative time, console time, intraoperative complications, estimated blood loss, postoperative complications, time of hospitalisation, positive surgical margins and the presence of documented tumour recurrence. Results: In this study, we evaluated three cohorts comprising a total of 21 patients. The median follow-up period ranged from 8 to 40 months. Medium age was between 51 and 54 years, with a majority (63.1%) being male. One patient (5.2%) underwent a radical cystectomy, and 19 patients (94.7%) underwent to partial cystectomy. Umbilical resections were performed in all cases, and pelvic lymphadenectomy in 14 cases (73.6%). Recurrence occurred in three patients at a median of 17 months postoperation, two cases in the trocar insertion site. Additionally, there was one death, which was attributed to postoperative cardiovascular complications. Conclusion: Robotic-assisted partial cystectomy has a low incidence of adverse outcomes in patients with urachal carcinoma. Controlled studies, ideally randomised, are warranted to establish the comparative efficacy and safety of the robotic-assisted cystectomy approach relative to open surgery.

Scoring system for prediction of overall survival in patients with renal cell carcinoma T3aN0M0.

Objective: We aim to create a new score to predict postoperative overall survival in patients with nonmetastatic T3aN0 renal cell carcinoma. Methods: We reviewed the clinical data of adult patients who underwent radical nephrectomy for renal cell carcinoma between December 2007 and January 2022 in a single tertiary oncological institution. Clinical characteristics, clinical-pathological staging and histopathological characteristics were analysed. Survival analyses were determined using the Kaplan-Meier curve. A nomogram was established using Cox proportional hazard regression to identify the prognostic factors affecting the overall survival. The area under the curve, calibration curves and decision curve analysis were used to evaluate prognostic efficacy. Results: We analyzed 362 patients classified as pT3aN0M0 stage with a median follow-up of 40 months. According to Cox univariate and multivariate analyses, weight loss greater than 5% in 6 months before surgery, stage V chronic kidney disease after radical nephrectomy, sarcomatoid pattern, and coagulative tumor necrosis were identified as predictors of overall survival. We developed a score and performed internal and external validation. The time-dependent receiver operating characteristic curve, area under the curve value and calibration curve analysis showed good prediction ability of the score. The nomogram can effectively predict and stratify overall survival after radical nephrectomy in patients with pT3aN0M0 renal cell carcinoma. Conclusion: Patients with pT3aN0MO renal cell carcinoma exhibited different characteristics, and those with unfavourable characteristics deserve greater attention during follow-up. This nomogram provides an accurate prediction of overall survival after radical nephrectomy.

Diabetes, Obesity, and Pathological Upstaging in Renal Cell Carcinoma: Results From a Large Multi-institutional Consortium.

PURPOSE: We sought to determine whether clinical risk factors and morphometric features on preoperative imaging can be utilized to identify those patients with cT1 tumors who are at higher risk of upstaging (pT3a). MATERIALS AND METHODS: We performed a retrospective international case-control study of consecutive patients treated surgically with radical or partial nephrectomy for nonmetastatic renal cell carcinoma (cT1 N0) conducted between January 2010 and December 2018. Multivariable logistic regression models were used to study associations of preoperative risk factors on pT3a pathological upstaging among all patients, as well as subsets with those with preoperative tumors ≤4 cm, renal nephrometry scores, tumors ≤4 cm with nephrometry scores, and clear cell histology. We also examined association with pT3a subsets (renal vein, sinus fat, perinephric fat). RESULTS: Among the 4,092 partial nephrectomy and 2,056 radical nephrectomy patients, pathological upstaging occurred in 4.9% and 23.3%, respectively. Among each group independent factors associated with pT3a upstaging were increasing preoperative tumor size, increasing age, and the presence of diabetes. Specifically, among partial nephrectomy subjects diabetes (OR=1.65; 95% CI 1.17, 2.29), male sex (OR=1.62; 95% CI 1.14, 2.33), and increasing BMI (OR=1.03; 95% CI 1.00, 1.05 per 1 unit BMI) were statistically associated with upstaging. Subset analyses identified hilar tumors as more likely to be upstaged (partial nephrectomy OR=1.91; 95% CI 1.12, 3.16; radical nephrectomy OR=2.16; 95% CI 1.44, 3.25). CONCLUSIONS: Diabetes and higher BMI were associated with pathological upstaging, as were preoperative tumor size, increased age, and male sex. Similarly, hilar tumors were frequently upstaged.

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.

Holmium Laser Resection of Large Bladder Tumors: Technique Description, Feasibility, and Histopathological Quality Analysis.

BACKGROUND: The HoLERBT (Holmium Laser En-bloc Resection of Bladder Tumors) has emerged as an alternative to classical TURBT (Transurethral Resection of Bladder Tumor). Recent randomized trial and meta-analysis corroborate with the benefits in pathological analysis, perioperative and long-term oncological outcomes.1-3 However, the treatment of large tumors and the technique of extraction from the bladder is a problem to be overcome.1,4 OBJECTIVE: To describe the laser resection of bladder tumors and demonstrate the feasibility of this procedure even for large tumors throughout a series of cases. It is also discussed the quality of the histopathological analysis. METHODS: A series of 8 cases randomized selected to be the pilot for a trial comparing TURBT and HoLERBT in large tumors (>3 cm) in progress was analyzed (Brazilian Registry of Clinical Trials number RBR-67npwrk). The perioperative data and 1-year outcomes were assessed and the quality of histopathological analysis after morcellation was evaluated in terms of histopathology, grade, and stage. The entire procedure of one case is shown in a step-by-step video. RESULTS: The mean follow-up was 12.6 months. The mean age was 59.6 (42-85) years, and the mean tumor size was 4.7 (4-8) cm. All the resections were En-bloc. There were 2 cases of NMIBC, 4 cases of MIBC, 1 paraganglioma, and 1 adenocarcinoma. The histopathological analysis confirmed the presence of detrusor muscle layer and accurate diagnosis and staging in all cases (100%). There were no perioperative Clavien-Dindo > 1 complications, no blood transfusion, and no bladder perforations. The histopathology analysis reveals excellent quality without artifacts of fulguration. CONCLUSION: The holmium laser resection followed by morcellation of large bladder tumors is a feasible procedure. No complications occurred in our series of cases and all cases provided excellent material for histopathological analysis.

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.

Histological Variants of Urothelial Carcinoma Predict No Response to Neoadjuvant Chemotherapy.

BACKGROUND: Platinum-based neoadjuvant chemotherapy (NAC) in muscle-invasive urothelial bladder cancer (MIBC) has been adopted as a standard of care related to better survival outcomes. However, there is a considerable number of patients who do not respond, experiencing toxicity and delay in the surgical treatment. Our aim is to find biomarkers of response that could be easily adopted in the clinical practice. METHODS: Between January 2009 and July 2016, 52 patients with MIBC were submitted to radical cystectomy after NAC. A tissue microarray containing 25 cases, who met the inclusion criteria was built for immunohistochemical analysis of Cytokeratins 5/6, 7, and 20, GATA3, Her2, EGFR, p63, p53, Carbonic-anhydrase IX (CAIX), MLH1, MSH2, MSH6, and PMS2. The surgery was performed in a mean time of 58.7 (± 21) days after the end of the NAC. Fisher's exact test was used to analyze the relationship between response (≤pT1) and histopathological and immunohistochemical results and Kaplan-Meier curves were designed for survival analysis. RESULTS: Ten (40.0%) patients presented response to NAC. Histological variants of the urothelial carcinoma characterized by squamous, sarcomatous/rhabdoid, plasmacytoid, and micropapillary was present in 36.0% and none responded to NAC (P = .002). CAIX was expressed by 53.3% and none responded to NAC (P= .005). Lymph-node metastasis, divergent differentiation, and expression of cytokeratin 5/6 were related to short cancer specific survival. CONCLUSION: Histological variants and CAIX immune-expression are biomarkers of nonresponse to NAC of MIBC, and might be easily used in the clinical practice to select patients to be submitted to surgery upfront.

Neutrophil-to-Lymphocyte Ratio Predicts Cancer Outcome in Locally Advanced Clear Renal Cell Carcinoma.

BACKGROUND: To evaluate the association of neutrophil-to-lymphocyte ratio (NLR) with recurrence-free survival (RFS) and overall survival (OS) in patients with locally advanced nonmetastatic clear cell renal cell carcinoma (ccRCC) undergoing radical nephrectomy. MATERIAL AND METHODS: We retrospectively identified 880 nephrectomies performed between January 2009 and December 2016 in a single center, reviewed data from 478 radical nephrectomies for kidney tumors and identified 187 patients with locally advanced nonmetastatic ccRCC (pT3-T4 N0M0). NLR was obtained preoperatively and calculated by dividing absolute neutrophil count by absolute lymphocyte count. OS and RFS were evaluated by the Kaplan-Meier method. Cox proportional-hazards regression models were used to evaluate predictors of RFS and OS. RESULTS: Among 187 patients with ccRCC (mean age 63.4 ± 11.5 years; 118 [63.1%] male), the median follow-up was 48.7 months. On univariate analysis, in patients with Fuhrman nuclear grade of differentiation 3-4, the median time to recurrence was significantly shorter with NLR ≥ 4 than < 4 (24 vs. 55 months, P = .045). On multivariable analysis adjusted for NLR ≥ 4, among all variables analyzed (NLR, microvascular invasion, sarcomatoid differentiation, tumor size and body mass index), only nuclear grade of differentiation was an independent predictor of recurrence (hazard ratio 2.18; 95% confidence interval 1.07-4.92, P = .03). The 3-year OS had no statistically significant difference between patients with NLR ≥ 4 or < 4. CONCLUSION: For patients with locally advanced, nonmetastatic ccRCC, RFS was reduced with high nuclear grade of differentiation and high preoperative NLR. These findings suggest an association between higher NLR and worse outcomes in locally advanced ccRCC.

Disruption of miRNA-mRNA Networks Defines Novel Molecular Signatures for Penile Carcinogenesis.

Penile cancer (PeC) carcinogenesis is not fully understood, and no biomarkers are reported in clinical practice. We aimed to investigate molecular signatures based on miRNA and mRNA and perform an integrative analysis to identify molecular drivers and pathways for PeC development. Affymetrix miRNA microarray was used to identify differentially expressed miRNAs (DEmiRs) comparing 11 tumoral tissues (TT) paired with non-neoplastic tissues (NNT) with further validation in an independent cohort (n = 13). We also investigated the mRNA expression of 83 genes in the total sample. Experimentally validated targets of DEmiRs, miRNA-mRNA networks, and enriched pathways were evaluated in silico. Eight out of 69 DEmiRs identified by microarray analysis were validated by qRT-PCR (miR-145-5p, miR-432-5p, miR-487b-3p, miR-30a-5p, miR-200a-5p, miR-224-5p, miR-31-3p and miR-31-5p). Furthermore, 37 differentially expressed genes (DEGs) were identified when comparing TT and NNT. We identified four downregulated DEmiRs (miR-30a-5p, miR-432-5p, miR-487b-3p, and miR-145-5p) and six upregulated DEGs (IL1A, MCM2, MMP1, MMP12, SFN and VEGFA) as potential biomarkers in PeC by their capacity of discriminating TT and NNT with accuracy. The integration analysis showed eight dysregulated miRNA-mRNA pairs in penile carcinogenesis. Taken together, our findings contribute to a better understanding of the regulatory roles of miRNAs and altered transcripts levels in penile carcinogenesis.

MCT1 expression is independently related to shorter cancer-specific survival in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) has been considered a metabolic disease, with loss of von Hippel-Lindau (VHL) gene and consequent overexpression of hypoxia-inducible factor 1 alpha (HIF-1α), which is central for tumor development and progression. Among other effects, HIF-1α is involved in the metabolic reprogramming of cancer cells towards the Warburg effect involved in tumor cell proliferation, migration and survival. In this context, several proteins are expressed by cancer cells, including glucose and lactate transporters as well as different pH regulators. Among them, monocarboxylate transporters (MCTs) can be highlighted. Our aim is to comprehensively analyze the immunoexpression of MCT1, MCT2, MCT4, CD147, CD44, HIF-1α, GLUT1 and CAIX in ccRCC surgical specimens correlating with classical prognostic factors and survival of patients with long follow-up. Surgical specimens from 207 patients with ccRCC who underwent radical or partial nephrectomy were used to build a tissue microarray. Immunostaining was categorized into absent/weak or moderate/strong and related to all classic ccRCC prognostic parameters. Kaplan-Meier curves were generated to assess overall and cancer-specific survival, and multivariate analysis was performed to identify independent prognostic factors of survival. Multivariate analysis showed that MCT1 together with tumor size and TNM staging, were independently related to cancer-specific survival. MCT1, CD147, CD44 and GLUT1 expression were significantly associated with poor prognostic factors. We show that MCT1 is an independent prognostic factor for cancer-specific survival in ccRCC justifying the use of new target therapies already being tested in clinical trials.

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.