Retzius-Sparing Robot-Assisted Radical Prostatectomy.

The technique of Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) and initial experience with it at a single center are provided. The technique is described step-by-step and further illustrated by a video to enhance reproducibility. Early oncological and functional results were evaluated. In total, 77 patients were included with a median follow-up of 11 months (range: 3-21 months). Fifty-one percent of patients had local high-risk or locally advanced prostate cancer. There were no intra-operative complications, and all high-grade complications (2.6%) were related to pelvic lymph node dissection performed concomitant with RS-RARP. Median operation time was 160 min (range: 122-265 min) and median hospital stay was 3 (range: 3-8) days. A positive surgical margin was reported in 42.9%. One-year biochemical recurrence-free survival was 90.1%. After 6 months, all patients were socially continent and after 1 year, 94.3% were fully continent. Of sexually active patients who underwent at least unilateral nerve-sparing, 43.3% were able to have sexual intercourse. This series underlines the surgical safety of performing RS-RARP by a standardized technique and confirms the beneficial effect on the early return of continence. The patient needs to be informed about the risk of a positive surgical margin.

Multicentre, prospective study on local treatment of metastatic prostate cancer (LoMP study).

OBJECTIVES: To investigate the role of cytoreductive radical prostatectomy in addition to standard of care for patients with newly diagnosed metastatic prostate cancer. MATERIALS AND METHODS: This multicentre, prospective study included asymptomatic patients from 2014 to 2018 (NCT02138721). Cytoreductive radical prostatectomy was offered to all fit patients with resectable tumours, resulting in 40 patients. Standard of care was administered to 40 patients who were ineligible or unwilling to undergo surgery. The primary endpoint was castration resistant cancer-free survival at the time point of ≥50% events. The secondary endpoint was local event-free survival. Kaplan-Meier and Cox regression analyses with propensity-score analysis were applied. RESULTS: After a median (quartiles) follow-up of 35 (24-47) months, 42 patients became castration-resistant or died. The median castration resistant cancer-free survival was 53 (95% confidence interval [CI] 14-92) vs 21 (95% CI 15-27) months for cytoreductive radical prostatectomy compared to standard of care (P = 0.017). The 3-year estimates for local event-free survival were 83% (95% CI 71-95) vs 59% (95% CI 51-67) for cytoreductive radical prostatectomy compared to standard of care (P = 0.012). However, treatment group showed no significance in the multivariable models for castration resistant cancer-free survival (P = 0.5) or local event-free survival (P = 0.3), adjusted for propensity-score analysis. Complications were similar to the non-metastatic setting. Patients undergoing surgery were younger, with lower baseline prostate-specific antigen levels, alkaline phosphatase levels and metastatic burden. CONCLUSION: The present LoMP study was unable to show a difference between the two inclusion groups regarding castration resistant cancer-free survival for asymptomatic patients with newly diagnosed metastatic prostate cancer. These results validate previous evidence that, in well-selected and informed patients, cytoreductive radical prostatectomy is feasible and safe, with corresponding continence rates compared to the non-metastatic, high-risk setting. Whether cytoreductive radical prostatectomy could be a valuable option to achieve good local palliation needs to be further researched. Overall, the role of cytoreductive radical prostatectomy needs to be further explored in randomized studies to correct for potential bias.

The Role of Cytoreductive Radical Prostatectomy in the Treatment of Newly Diagnosed Low-volume Metastatic Prostate Cancer. Results from the Local Treatment of Metastatic Prostate Cancer (LoMP) Registry.

BACKGROUND: Radiotherapy to the prostate (RTp) prolongs survival for patients with low-volume, newly diagnosed metastatic prostate cancer (ndmPC). OBJECTIVE: to evaluate whether cytoreductive radical prostatectomy (cRP) is equally beneficial as RTp in low-volume ndmPC. DESIGN SETTING AND PARTICIPANTS: A multicenter prospective registry was established in 2014 to observe patients with ndmPC. Eligible patients were offered cRP or RTp. For this study we selected only patients with low-volume ndmPC (n = 109). Of these, 48, 26, and 35 patients underwent cRP, RTp, and no local therapy (NLT), respectively. Median follow-up was 32 mo (interquartile range 16-49). INTERVENTION: cRP was compared with RTp and NLT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS), cancer-specific survival (CSS), and local event-free survival (LEFS) were calculated using the Kaplan-Meier method. Factors prognostic for OS were identified using univariate and multivariate Cox regression analysis. RESULTS AND LIMITATIONS: The 2-yr OS was 93%, 100%, and 69%, and 2-yr CSS was 93%, 100%, and 75% for cRP, RTp, and NLT, respectively. The cRP and RTp groups had better OS compared to NLT and there was no significant difference between cRP and RTp. The 2-yr LEFS was 92%, 77%, and 60% for cRP, RTp, and NLT, respectively. The cRP group had better LEFS compared to RTp and NLT, and there was no significant difference between RTp and NLT. Advanced tumor stage, Eastern Cooperative Oncology Group performance status ≥2, and NLT were negative prognostic factors for OS. The main limitation is selection of fitter patients with less advanced tumors for cRP and the small sample size. CONCLUSIONS: For selected patients with low-volume ndmPC, cRP is able to achieve similar OS and CSS to RTp. cRP is effective in preventing local events due to disease progression. PATIENT SUMMARY: Patients with a low volume of newly diagnosed prostate cancer that has spread beyond the prostate gland might benefit from removal of the prostate, which we found was as effective as radiotherapy to the prostate in prolonging survival. Removal of the prostate is effective in preventing urinary problems caused by cancer progression.

Robot-assisted Boari flap and psoas hitch ureteric reimplantation: technique insight and outcomes of a case series with ≥1 year of follow-up.

OBJECTIVE: To describe step-by-step surgical techniques and report outcomes of the largest single-centre series of patients with distal ureteric disease exclusively treated with robot-assisted ureteric reimplantation with Boari flap (RABFUR) and psoas hitch (RAPHUR), with a minimum follow-up of 1 year and complete postoperative data. PATIENTS AND METHODS: A total of 37 patients with distal ureteric disease were treated between 2010 and 2018. Of these, 81% and 19% underwent RAPHUR and RABFUR, respectively. Intra-, peri- and postoperative outcomes were assessed. The 90-day postoperative complications were reported according to the standardised methodology proposed by the European Association of Urology Ad Hoc Panel. Functional outcomes (creatinine, estimated glomerular filtration rate [eGFR]) and postoperative symptoms (visual analogue pain scale) were assessed. RESULTS: The median operating time and blood loss were 180 min and 100 mL, respectively. There were no conversions to open surgery and no intraoperative transfusions. The median length of stay, bladder catheter indwelling time and stent removal were 4, 7 and 30 days, respectively. The median follow-up was 24 months. Overall, 10 patients (27%) had postoperative complications and of these, eight (22%) and two (5.4%) were Clavien-Dindo Grade I-II and III, respectively. At the last follow-up, the median postoperative creatinine level and eGFR were 0.9 mg/dL and 73.5 mL/min/1.73 m2 , respectively. At the last follow-up, five (13.5%) and three (8%) patients had Grade 1 hydronephrosis and mild urinary symptoms, respectively. The study limitations include its retrospective nature. CONCLUSION: In the present study, we present our RABFUR and RAPHUR techniques. We confirm the feasibility and safety profile of both approaches in patients with distal ureteric disease relying on the largest single-centre series with ≥1 year of follow-up.

The Effect of Surgical Experience on Perioperative and Oncological Outcomes After Robot-assisted Radical Cystectomy with Intracorporeal Urinary Diversion: Evidence from a Referral Centre with Extensive Experience in Robotic Surgery.

BACKGROUND: Evidence on the learning curve for robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is limited. OBJECTIVE: To assess the effect of surgical experience (SE) on perioperative and intermediate-term oncological outcomes in a large contemporary cohort of RARC patients after accounting for the impact of intersurgeon variability. DESIGN, SETTING, AND PARTICIPANTS: The study cohort included 164 patients treated with RARC and ICUD by two surgeons between 2004 and 2017 at a single European referral centre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: For each patient, SE was defined as the total number of RARCs performed by each surgeon before the patient's operation. The relationship between SE and operative time (OT), lymph node yield (LNY), positive surgical margins (PSMs), Clavien-Dindo grade ≥2 30-d postoperative complication (CD≥2), and oncological outcomes (18-mo recurrence rate) was evaluated in multivariable linear and logistic regression models, clustering at a single-surgeon level. RESULTS AND LIMITATIONS: After adjusting for case mix, SE was associated with shorter OT (p= 0.003), lower probability of postoperative CD≥2 rates (p= 0.01), and lower 18-mo recurrence rates (p= 0.002). Conversely, SE did not predict lower PSM rates (p= 0.3) and higher LNY (p= 0.4). The relationship between SE and OT was nonlinear, with a plateau observed after 50 cases. Conversely, the relationship between SE and CD≥2 and 18-mo recurrence was linear without reaching a plateau after 88 procedures. CONCLUSIONS: SE affects perioperative and oncological outcomes after RARC with ICUD in a linear fashion, and its beneficial effect does not reach a plateau. Conversely, after 50 cases, no further improvement was observed for OT. PATIENT SUMMARY: Robot-assisted radical cystectomy with intracorporeal urinary diversion is a complex surgical procedure with a relatively long learning curve.

Time to Move On: The Impending Need for a New Disease-specific Comorbidity Index for Bladder Cancer Patients Undergoing Robot-assisted Radical Cystectomy.

The Charlson comorbidity index is an outdated comorbidity assessment tool which is not disease specific and is not applicable to contemporary BCa patients.

Current Management of pT3b Prostate Cancer After Robot-assisted Laparoscopic Prostatectomy.

BACKGROUND: Robot-assisted radical prostatectomy (RALP) in high-risk and locally advanced prostate cancer (PCa) is gaining increasing traction. The optimal use of additional treatments for PCa with seminal vesicle invasion (pT3b) after RALP remains ill explored. OBJECTIVE: To evaluate the management of pT3b PCa after RALP in current clinical practice. DESIGN, SETTING, AND PARTICIPANTS: As part of the prospective Belgian RALP Consortium project (October 2009-March 2016), 796 patients with pT3b disease were evaluated. INTERVENTION: Robot-assisted radical prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Population and perioperative characteristics were described to assess surgical outcome. Multivariable regression analyses were used to identify independent predictors of lymph node invasion (pN1), positive surgical margins (R+), postoperative morbidity, and additional treatments. RESULTS AND LIMITATIONS: In this prospective population-based registry, 85% of patients with clinical high-risk locally advanced PCa received pelvic lymph node dissection (PLND). Early postoperative complications (0-30 d) were observed in 68 patients (8.5%). During oncologic follow-up (median 12 mo), 63% of pN1 patients and 56% of R+ patients received additional therapy. Performing PLND (necessary for assessing pN1 status) was a specific predictor for androgen deprivation therapy only, whereas R+ and younger age were independent predictors for radiotherapy only. Limitations include the nonstandardized policy on additional treatments among hospitals. CONCLUSIONS: In current practice, RALP is performed with acceptable morbidity for PCa with seminal vesicle invasion and the use of postoperative additional treatments is influenced by different patient, tumor, and surgical variables. Despite the recommendations, 15-21% of patients do not receive adequate pelvic lymph node staging and adjuvant therapy is given in 38% of patients. Full and correct staging of the real disease extent remains important in the management of these patients. PATIENT SUMMARY: This study on prostate cancer with seminal vesicle invasion after robot-assisted prostatectomy evaluates the use of additional treatments in current clinical practice. Additional treatments for advanced prostate cancer should be patient-adjusted according to the disease extent.

Pelvic lymph node dissection in prostate cancer staging: evaluation of morbidity and oncological outcomes.

BACKGROUND: To evaluate the morbidity of different surgical approaches for pelvic lymph node dissection (PLND), to evaluate the influence of morbidity on radiotherapy (RT) planning and to evaluate a possible therapeutic effect of a more extensive yield of PLND. METHODS: From 2000-2016, 228 patients received staging PLND before primary RT in a single tertiary care center. Nine patients were excluded for the evaluation of morbidity. Fifty patients were operated in an open approach, 96 laparoscopic and 73 robot-assisted (RA). Clavien-Dindo classification was used for evaluating complications. Predictors of biochemical recurrence (BCR), clinical relapse (CR), cancer-specific survival (CSS) and overall survival (OS) were evaluated by regression analyses to determine a possible therapeutic effect. RESULTS: Minimal invasive surgery (laparoscopic or RA) caused five times less major complications (22% vs. 4.3%, p = .001) and a median 3 days shorter hospital stay (5 days versus 2 days, p < .001). Major complications resulted in a delayed (23 days, p < .001) RT start but no oncological effect was seen. Independent oncological predictors were the number of positive nodes (BCR, CR, CSS, OS), a lower age (CR), a higher level of initial prostate-specific antigen (PSA) (BCR) and post-RT PSA (BCR). CONCLUSION: Minimal invasive surgery can diminish major complications which delay RT start. Nodal staging proved to be of importance for prognosis but no therapeutic effect was seen of performing PLND as such.

Persisting Complaints after Carpal Tunnel Release: Nerve Compression by the Palmaris Profundus Muscle.

We present the case of a 66-year-old man who had persisting complaints after initial classical open carpal tunnel release. During revision a reversed palmaris profundus muscle was identified as being the cause of residual compression of the median nerve. Neurolysis with release of the palmaris profundus muscle was performed without resection of this anatomical variant and resulted in full resolution of the complaints.

Validated uroflowmetry-based predictive model for the primary diagnosis of urethral stricture disease in men.

OBJECTIVES: To define a uroflowmetry-based non-invasive predictive tool for the primary diagnosis of urethral stricture disease. METHODS: A total of 300 male patients (150 with urethral stricture disease and 150 with benign prostatic obstruction), treated surgically between 2005 and 2015, and 75 healthy males were included in this study. Patients were randomly assigned to one of two groups (75 benign prostatic obstruction patients and 75 urethral stricture disease patients in each group). A model, able to objectively differentiate between benign prostatic obstruction and urethral stricture disease, was created by use of original and hybrid uroflowmetry variables in logistic regression in group A (test group). Receiver operating characteristics curve analysis was used for validation in group B (validation group) and to calculate cut-off values to distinguish healthy individuals from benign prostatic obstruction as a result of urethral stricture disease. RESULTS: Receiver operating characteristics area under the curve values of the created model were 0.841 (0.777-0.905) and 0.807 (0.735-0.879) in groups A and B, respectively. Optimal cut-off values were 2.2847 and 0.1182 to distinguish healthy individuals versus benign prostatic obstruction and benign prostatic obstruction versus urethral stricture disease. CONCLUSIONS: A triphasic uroflowmetry-based model is able to objectively distinguish voiding patterns of healthy individuals, benign prostatic obstruction and urethral stricture disease. The probability of urethral stricture disease can be objectively calculated for each individual patient based on a non-invasive uroflowmetry test. Uroflowmetry pattern interpretation by use of statistical models could become a new standard.

Prospective Randomized Controlled Trial Exploring the Effect of TachoSil on Lymphocele Formation After Extended Pelvic Lymph Node Dissection in Prostate Cancer.

OBJECTIVE: To explore whether TachoSil, a hemostatic patch, can reduce the incidence of lymphocele formation. Development of a lymphocele is a frequent complication after pelvic lymph node dissection (PLND) for nodal staging in prostate cancer. MATERIALS AND METHODS: From 2013 to 2017, 100 patients with prostate cancer who were set to undergo a staging PLND before external beam radiotherapy (n = 50) or PLND concomitant with radical prostatectomy (RP) (n = 50) were prospectively randomized 1:1 between bilateral TachoSil placement or nonplacement. Primary end points were radiographic lymphocele development, lymphocele volume (1 week and 1 month postoperatively), and the duration and volume of postoperative catheter drainage. RESULTS: Patient, tumor, and surgical characteristics of the TachoSil and the control groups did not differ significantly. In total, 65 patients (65%) experienced a radiographic lymphocele up to 3 months after surgery: 29 (58%) in the TachoSil group and 36 (72%) in the control group (P = .34). Significantly less radiographic lymphoceles were observed 1 week postoperatively for patients who underwent sole PLND and 1 month postoperatively for patients who underwent PLND with RP in the TachoSil group compared with the control group (16% vs 48%, P = .024, and 24% vs 52%, P = .047, respectively). The other postoperative characteristics presented no significant differences between the 2 groups, neither for patients undergoing sole PLND nor for patients undergoing PLND with RP. CONCLUSION: Patients undergoing bilateral TachoSil placement after PLND seem less likely to develop a radiographic lymphocele early postoperatively. Nevertheless, the clinical relevance of the use of TachoSil remains highly debatable.

Metastatic burden in newly diagnosed hormone-naive metastatic prostate cancer: Comparing definitions of CHAARTED and LATITUDE trial.

OBJECTIVES: No uniformity exists in the definition of metastatic burden in metastatic hormone-naive prostate cancer (mHNPC) across clinical trials making their comparison challenging. We explored definition agreement and prognostic significance of bulky mHNPC according to the CHAARTED and LATITUDE trial. MATERIALS AND METHODS: Since 2014, 95 patients with newly diagnosed mHNPC were prospectively registered. For this study, they were categorized as having high-volume (HVD) vs. low-volume (LVD) and high-risk (HRD) vs. low-risk disease (LRD) according to the definition of CHAARTED and LATITUDE, respectively. Agreement was tested using Cohen's κ coefficient. The Kaplan-Meier method was used to compare castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS). Prognostic significance was analyzed using Cox regression models. RESULTS: In total, 44 (46%) and 46 (48%) patients showed HVD and HRD, respectively. Cohen's κ coefficient was 0.83 indicating "almost perfect" agreement (P<0.001). Median CRPC-FS was 40 (95% CI: 25-55) vs. 11 months (95% CI: 8-14) for LVD and HVD (P = 0.001); 40 (95% CI: 27-53) vs. 11 months (95% CI: 8-14) for LRD and HRD (P<0.001), respectively. Median OS was not reached vs. 51 months (95% CI: 0-102) for LVD and HVD (P = 0.001); not reached vs. 51 months (95% CI: 2-100) for LRD and HRD (P = 0.003), respectively. The prognostic significance of both definitions remained significant in the multivariate model for CRPC-FS (P = 0.012 and P = 0.003). CONCLUSIONS: There is an excellent agreement between the definitions of bulky mHNPC in the CHAARTED and LATITUDE trial. Both definitions have significant prognostic value for predicting worse CRPC-FS and OS.

Prognostic and Therapeutic Implications of Circulating Androgen Receptor Gene Copy Number in Prostate Cancer Patients Using Droplet Digital Polymerase Chain Reaction.

BACKGROUND: Resistance mechanisms in the androgen receptor (AR) signaling pathway remain key drivers in the progression to castration-resistant prostate cancer (CRPC) and relapse under antihormonal therapy. MATERIALS AND METHODS: We evaluated the circulating AR gene copy number (CN) gain using droplet digital polymerase chain reaction in 21 control and 91 prostate cancer serum samples and its prognostic and therapeutic implications in prostate cancer. RESULTS: In CRPC, AR CN gain was associated with faster progression to CRPC (P = .026), a greater number of previous treatments (P = .045), and previous chemotherapy (P = .016). Comparing patients with and without CN gain, the median progression-free survival (PFS) in the abiraterone subgroup was 1.7 months versus not reached (P = .004), and the median overall survival (OS) was 7 months versus 20.9 months (P = .020). In the enzalutamide subgroup, PFS was 1.7 versus 10.8 months (P = .006), and OS was 6.1 versus 16.5 months (P = .042). In the taxane subgroup, PFS was 3.2 versus 6.5 months (P = .093), and OS was 3.9 months versus not reached (P = .026). The presence of more AR copies correlated with shorter androgen deprivation (P = .002), abiraterone (P = .022), enzalutamide (P = .008), and taxane (P = .039) therapy. CONCLUSION: Circulating AR CN gain predicts for a poor prognosis in CRPC. It is a promising biomarker predetermining rapid CRPC progression and predicting worse abiraterone and enzalutamide outcomes. Furthermore, it is associated with multiple previous treatments and previous chemotherapy.

Cytoreductive Prostatectomy for Metastatic Prostate Cancer: First Lessons Learned From the Multicentric Prospective Local Treatment of Metastatic Prostate Cancer (LoMP) Trial.

OBJECTIVE: To prospectively evaluate patients with newly diagnosed metastatic prostate cancer in the context of the LoMP trial (which investigates the role of cytoreductive radical prostatectomy [cRP] in addition to standard of care [SoC]) and to provide a preliminary analysis of patient's characteristics, safety of cRP, and early local symptoms. PATIENTS AND METHODS: cRP was performed in asymptomatic patients with a resectable tumor and who were fit to undergo surgery (group A, n = 17). Only SoC was administered to patients with metastatic prostate cancer ineligible or unwilling to undergo cRP (group B, n = 29). At 3 months, surgical complications related to cRP and local symptoms for both groups were evaluated. RESULTS: Median operation time, blood loss, and hospital stay for cRP were 215 minutes (150-290), 250 mL (100-900), and 4 days (2-7), respectively. Respectively 5 (29.4%) and 2 (11.8%) patients suffered grades 1 and 2 complications within 3 months postoperatively. When compared with Group B, patients in group A were younger (64 vs 72 years, P = .005), had lower initial prostate-specific antigen (15.9 vs 156 µg/L, P = .002), and less high-volume metastatic disease (5.9% vs 69%, P <.001). At 3 months, 5 (29.4%) patients in group A reported stress urinary incontinence without any further local symptoms. In group B, respectively 2 (6.8%), 11 (37.9%), and 2 (6.8%) patients suffered urge incontinence, obstructive voiding needing medical intervention, and ureteric obstruction. CONCLUSION: In a group of well-selected patients, cRP is safe. These patients have more favorable characteristics compared with patients treated with only SoC. If only SoC can be offered, patients are at risk to suffer from local symptoms.

Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile.

AIM: Nowadays, extracellular vesicles are of great interest in prostate cancer (PCa) research. Asparagine (N)-linked glycosylation could play a significant role in the pathological mechanism of these vesicles. We investigated if prostatic protein N-glycosylation profiles were related to urinary vesicle-associated prostate-specific antigen (PSA) extractability and if this parameter showed diagnostic potential for PCa. METHODS: Urinary extracellular vesicles were visualised using transmission electron microscopy. Urinary extracellular vesicles extraction by means of n-butanol allowed determination of urinary vesicle-associated PSA extractability. Diagnostic value was assessed between benign prostate hyperplasia (BPH; n=122) and patients with PCa (n=85). Additionally, correlation with urine N-glycosylation was assessed. RESULTS: Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). Next, vesicle-associated PSA extraction ratio was correlated to biantennary core-fucosylation (p=0.003). Finally, vesicle-associated PSA extraction ratio proved beneficial in PCa diagnosis, next to serum PSA and the urinary glycosylation marker (p=0.021). CONCLUSIONS: The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. The urinary vesicle-associated PSA extraction ratio was associated with changes in N-glycoforms and showed diagnostic potential. Further research is warranted to unravel the pathological link between N-glycosylation and extracellular vesicles in cancer, as well as to assess the prognostic value of this biomarker.

Androgen Receptor Gene Copy Number and Protein Expression in Treatment-Naïve Prostate Cancer.

OBJECTIVES: To evaluate the androgen receptor (AR) gene copy number in androgen deprivation therapy (ADT) treatment-naïve prostate cancer (PCa) patients and to evaluate the corresponding AR protein expression and assess the association between these features and prognostic factors. MATERIALS AND METHODS: Chromosome X and AR gene copy number, using fluorescence-in-situ-hybridization, and epithelial-stromal AR expression, using AR immunohistochemistry, were analyzed in 62 ADT treatment-naïve PCa patients and 8 castration-refractory patients. RESULTS: In ADT treatment-naïve PCa patients, the AR expression was higher in tumor epithelial cells versus surrounding stromal cells (p < 0.001) and versus normal epithelium in the same patient (p = 0.043). The difference between tumoral AR expression and expression in normal epithelium was higher in patients with ≥15% of tumor cells with increased AR copy number (p = 0.019). Peritumoral stroma had lower AR expression in patients with lymph-node or distant metastases compared to those without metastases (p = 0.038). CONCLUSIONS: This research evaluates the link between AR gene status, expression profile, and possible prognostic factors. Furthermore, it highlights the importance of the peritumoral environment in PCa. Additional research is needed to further clarify the role of stromal AR in PCa dissemination and identify possible therapeutic strategies to target this mechanism.