Practical implications of androgen receptor inhibitors for prostate cancer treatment.

Antiandrogens have been used for the treatment of prostate cancer as a single agent or in combination with hormone deprivation therapy. New generation antiandrogens act like androgen receptor inhibitors (ARIs). Their binding complex blocks the pathways of cellular proliferation and differentiation of the prostate. Enzalutamide, apalutamide and darolutamide are the new ARIs that demonstrated acceptable tolerability and toxicity, both active in hormone-sensitive and castration-resistant prostate cancer (CRPC). There is no evidence of superiority of one drug over the other, therefore the therapeutic choice depends on the safety profile in relation to the individual patient, their comorbidities and clinical condition. ARIs have also shown promising results in association with new drugs that are active on patients with metastatic CRPC carrying the mutated breast cancer gene (BRCA). Before undergoing new antiandrogenic therapies, patients should be evaluated for cardiological and metabolic risk and possible drug interactions.

Role of 64CuCl2 PET/CT in Detecting and Staging Muscle-Invasive Bladder Cancer: Comparison with Contrast-Enhanced CT and 18F-FDG PET/CT.

Molecular imaging of muscle-invasive bladder cancer (MBC) is restricted to its locoregional and distant metastases, since most radiopharmaceuticals have a urinary excretion that limits the visualization of the primary tumor. 64CuCl2 , a positron-emitting radiotracer with nearly exclusive biliary elimination, could be well suited to exploring urinary tract neoplasms. In this study, we evaluated the feasibility of 64CuCl2-based staging of patients with MBC; furthermore, we compared the diagnostic capability of this method with those of the current gold standards, that is, contrast-enhanced CT (ceCT) and 18F-FDG PET/CT. Methods: We prospectively enrolled patients referred to our institution for pathology-confirmed MBC staging/restaging between September 2021 and January 2023. All patients underwent ceCT, 18F-FDG, and 64CuCl2 PET/CT within 2 wk. Patient-based analysis and lesion-based analysis were performed for all of the potentially affected districts (overall, bladder wall, lymph nodes, skeleton, liver, lung, and pelvic soft tissue). Results: Forty-two patients (9 women) were enrolled. Thirty-six (86%) had evidence of disease, with a total of 353 disease sites. On patient-based analysis, ceCT and 64CuCl2 PET/CT showed higher sensitivity than 18F-FDG PET/CT in detecting the primary tumor (P < 0.001); moreover, 64CuCl2 PET/CT was slightly more sensitive than 18F-FDG PET/CT in disclosing soft-tissue lesions (P < 0.05). Both PET methods were more specific and accurate than ceCT in classifying nodal lesions (P < 0.05). On lesion-based analysis, 64CuCl2 PET/CT outperformed 18F-FDG PET/CT and ceCT in detecting disease localizations overall (P < 0.001), in the lymph nodes (P < 0.01), in the skeleton (P < 0.001), and in the soft tissue (P < 0.05). Conclusion: 64CuCl2 PET/CT appears to be a sensitive modality for staging/restaging of MBC and might represent a "one-stop shop" diagnostic method in these scenarios.

Improving Patient Outcomes in Abdominal Surgery.

Post-operative acute kidney injury (PO-AKI) is a frequent complication described in 15% of non-cardiac surgeries, 30% of cardiac surgeries, and 52% of patients requiring intensive post-operative care [...].

Analgesic Strategies for Urologic Videolaparoscopic or Robotic Surgery in the Context of an Enhanced Recovery after Surgery Protocol: A Prospective Study Comparing Erector Spinae Plane Block versus Transversus Abdominis Plane Block.

Regional anesthesia in postoperative pain management has developed in recent years, especially with the advent of fascial plane blocks. This study aims to compare the ultrasound-guided bilateral erector spinae plane block (ESPB) versus the ultrasound-guided bilateral transversus abdominis plane block (TAPB) on postoperative analgesia after laparoscopic or robotic urologic surgery. This was a prospective observational study; 97 patients (ESPB-group) received bilateral ultrasound-guided ESPB with 20 mL of ropivacaine 0.375% plus 0.5 mcg/kg of dexmedetomidine in each side at the level of T7-T9 and 93 patients (TAPB-group) received bilateral ultrasound-guided TAPB with 20 mL ropivacaine 0.375% or 0.25%. The primary outcome was the postoperative numeric rating scale (NRS) pain score, which was significantly lower in the ESPB group on postoperative days 0, 1, 2, and 3 (p < 0.001) and, consequently, the number of patients requiring postoperative supplemental analgesic rescue therapies was significantly lower (p < 0.001). Concerning the secondary outcomes, consumption of ropivacaine was significantly lower in the group (p < 0.001) and the total amount of analgesic rescue doses was significantly lower in the ESPB-group than the TAPB-group in postoperative days from 2 to 4 (1 vs. 3, p > 0.001). Incidence of postoperative nausea and vomiting was higher in the TAPB group and no block-related complications were observed. Our data indicate that ESPB provides postoperative pain control at least as good as TAPB plus morphine, with less local anesthetic needed.

Perioperative Intravenous Amino Acid Infusion in Major Urologic Surgery.

Post-operative acute kidney injury (PO-AKI) is a serious complication that may occur after major abdominal surgery. The administration of intravenous perioperative amino acids (AAs) has been proven to increase kidney function and has some beneficial effects to prevent PO-AKI. The aim of this study was to establish if the perioperative infusion of AAs may reduce the incidence of PO-AKI in patients undergoing major urological minimally invasive surgery. From a total of 331 patients, the first 169 received perioperative crystalloid fluids and the following 162 received perioperative AA infusions. PO-AKIs were much higher in the crystalloid group compared to the AA group (34 vs. 17, p = 0.022) due to a lower incidence of KDIGO I and II in the AA group (14 vs. 30 p = 0.016). The AA group patients who developed a PO-AKI presented more risk factors compared to those who did not (2 (2-4) vs. 1 (1-2), p = 0.031) with a cut-off of 3 risk factors in the ROC curve (p = 0.007, sensitivity 47%, specificity 83%). The hospital length of stay was higher in the crystalloid group (p < 0.05) with a consequent saving in hospital costs. Perioperative AA infusion may help reduce the incidence of PO-AKI after major urological minimally invasive surgery.

Perioperative Renal Ultrasonography of Arterio-to-Venous Coupling Predicts Postoperative Complications after Major Laparoscopic Urologic Surgery.

Point-of-care ultrasonography (POCUS) with concomitant venous and arterial Doppler assessment enables clinicians to assess organ-specific blood supply. To date, no studies have investigated the usefulness of including a comprehensive perioperative POCUS assessment of patients undergoing major laparoscopic surgery. The primary aim of the present study was to evaluate whether the combined venous and arterial renal flow evaluation, measured at different time points of perioperative period, may represent a clinically useful non-invasive method to predict postoperative acute kidney injury (AKI) after major laparoscopic urologic surgery. The secondary outcome was represented by the development of any postoperative complication at day 7. We included 173 patients, subsequently divided for analysis depending on whether they did (n = 55) or did not (n = 118) develop postoperative AKI or any complications within the first 7 days. The main results of the present study were that: (1) the combination of arterial hypoperfusion and moderate-to-severe venous congestion inferred by POCUS were associated with worst outcomes (respectively, HR: 2.993, 95% CI: 1.522-5.884 and HR: 8.124, 95% CI: 3.542-18, p < 0.001); (2) high intra-operative abdominal pressure represents the only independent determinant of postoperative severe venous congestion (OR: 1.354, 95% CI: 1.017-1.804, p = 0.038); (3) the overall number of complications relies on the balance between arterial inflow and venous outflow in order to ensure the adequacy of peripheral perfusion; and (4) the overall reliability of splanchnic perfusion assessment by Doppler is high with a strong inter-rater reliability (ICC: 0.844, 95% CI: 0.792-0.844). The concomitant assessment of arterial and venous Doppler patterns predicts postoperative complications after major laparoscopic urologic surgery and may be considered a useful ultrasonographic biomarker to stratify vulnerable patients at risk for development of postoperative complications.

Application of a protocol for enhanced recovery after radical cystectomy: a before-and-after cohort study.

PURPOSE: Radical cystectomy with urinary diversion is a major urological surgery burdened both by a high rate of short- and long-term complications and by a high emotional and psychological impact. Post-operative recovery is extremely important and the application of ERAS protocols can facilitate the return to functional autonomy. The aim of the present study was to verify the efficacy of our ERAS programme on outcomes of recovery after surgery of patients undergoing radical cystectomy with various urinary diversions. METHODS: This is a before-after study comparing the historical group (n. 77) of radical cystectomies following a peri-operative standard of care with the prospective observational group (n. 83) following our ERAS programme. Recovery after surgery outcomes evaluated were length of stay, re-admission rate at 30-90/days and post-operative complications. RESULTS: Patients treated following the ERAS protocol presented less intra-operative blood loss (p < 0.001) and less intra-operative fluid infusions (p < 0.001). Time of first flatus was shorter in the ERAS group, though no difference was found in timing of nasogastric tube removal and defecation. Removal of drainage was done significantly earlier in the ERAS group. The median length of stay decreased from 12 to 9 days (p = 0.003) with a significant reduction also in re-admission rates at 30 and long-term complications at 90 days from surgery. CONCLUSION: The application of an opioid-free ERAS protocol to patients undergoing open radical cystectomy was associated, as compared with prior traditional care, with significant reductions of recovery time and length of stay, number of total in-hospital complications, in particular functional ileus and re-admissions by 30 and 90 days after surgery.

Low Intra-Abdominal Pressure with Complete Neuromuscular Blockage Reduces Post-Operative Complications in Major Laparoscopic Urologic Surgery: A before-after Study.

Most urological interventions are now performed with minimally invasive surgery techniques such as laparoscopic surgery. Combining ERAS protocols with minimally invasive surgery techniques may be the best option to reduce hospital length-of-stay and post-operative complications. We designed this study to test the hypothesis that using low intra-abdominal pressures (IAP) during laparoscopy may reduce post-operative complications, especially those related to reduced intra-operative splanchnic perfusion or increased splanchnic congestion. We applied a complete neuromuscular blockade (NMB) to maintain an optimal space and surgical view. We compared 115 patients treated with standard IAP and moderate NMB with 148 patients treated with low IAP and complete NMB undergoing major urologic surgery. Low IAP in combination with complete NMB was associated with fewer total post-operative complications than standard IAP with moderate NMB (22.3% vs. 41.2%, p < 0.001), with a reduction in all medical post-operative complications (17 vs. 34, p < 0.001). The post-operative complications mostly reduced were acute kidney injury (15.5% vs. 30.4%, p = 0.004), anemia (6.8% vs. 16.5%, p = 0.049) and reoperation (2% vs. 7.8%, p = 0.035). The intra-operative management of laparoscopic interventions for major urologic surgeries with low IAP and complete NMB is feasible without hindering surgical conditions and might reduce most medical post-operative complications.

Are Urologists Ready for Interpretation of Multiparametric MRI Findings? A Prospective Multicentric Evaluation.

Aim: To assess urologists' proficiency in the interpretation of multiparametric magnetic resonance imaging (mpMRI). Materials and Methods: Twelve mpMRIs were shown to 73 urologists from seven Italian institutions. Responders were asked to identify the site of the suspicious nodule (SN) but not to assign a PIRADS score. We set an a priori cut-off of 75% correct identification of SN as a threshold for proficiency in mpMRI reading. Data were analyzed according to urologists' hierarchy (UH; resident vs. consultant) and previous experience in fusion prostate biopsies (E-fPB, defined as <125 vs. ≥125). Additionally, we tested for differences between non-proficient vs. proficient mpMRI readers. Multivariable logistic regression analyses (MVLRA) tested potential predictors of proficiency in mpMRI reading. Results: The median (IQR) number of correct identifications was 8 (6−8). Anterior nodules (number 3, 4 and 6) represented the most likely prone to misinterpretation. Overall, 34 (47%) participants achieved the 75% cut-off. When comparing consultants vs. residents, we found no differences in terms of E-fPB (p = 0.9) or in correct identification rates (p = 0.6). We recorded higher identification rates in urologists with E-fBP vs. their no E-fBP counterparts (75% vs. 67%, p = 0.004). At MVLRA, only E- fPB reached the status of independent predictor of proficiency in mpMRI reading (OR: 3.4, 95% CI 1.2−9.9, p = 0.02) after adjusting for UH and type of institution. Conclusions: Despite urologists becoming more familiar with interpretation of mpMRI, their results are still far from proficient. E-fPB enhances the proficiency in mpMRI interpretation.

Correlation Between Long-Term Acetylsalicylic Acid Use and Prostate Cancer Screening with PSA. Should We Reduce the PSA Cut-off for Patients in Chronic Therapy? A Multicenter Study.

Purpose: To evaluate the prostate cancer (PCa) detection rate in men with chronic use of Aspirin and to compare it with the detection rate of non-users. Patients and Methods: Prospectively maintained database regarding patients undergoing prostate biopsy over the last 10 years in five institutions. Patients were divided into two groups according to their exposure to Aspirin. We relied on multivariable linear and logistic regression models to test whether Aspirin administration was associated with lower PSA values at prostate biopsy, higher PCa diagnosis, and higher Gleason Grade Grouping (GGG) at biopsy. Results: Were identified 1059 patients, of whom 803 (76%) did not take Aspirin vs 256 (24%) were taking it. In multivariable log-linear regression analysis, Aspirin administration was associated with lower PSA levels (OR 0.83, 95% CI 0.71-0.97, p = 0.01), after controlling for age, prostate volume, smoking history, associated inflammation at prostate biopsy, presence of PCa at biopsy, and GGG. In multivariable logistic regression analysis, Aspirin administration was not found to be a predictor of PCa at prostate biopsy (OR 1.40, 95% CI 0.82-2.40, p = 0.21) after controlling for age, PSA, smoking history, prostate volume, findings at digital rectal examination and the number of biopsy cores. In patients with PCa at prostate biopsy (n = 516), Aspirin administration was found to predict higher GGG (OR 2.24, 95% CI 1.01-4.87, p = 0.04). Conclusion: Aspirin administration was found to be a predictor of more aggressive GGG. These findings suggest that a lower PSA threshold should be considered in patients taking Aspirin, as, despite low PSA levels, they might harbour aggressive PCa.

Robot-Assisted, Laparoscopic, and Open Radical Cystectomy: Pre-Operative Data of 1400 Patients From The Italian Radical Cystectomy Registry.

Introduction: The Italian Radical Cystectomy Registry (RIC) is an observational prospective study aiming to understand clinical variables and patient characteristics associated with short- and long-term outcomes among bladder cancer (BC) patients undergoing radical cystectomy (RC). Moreover, it compares the effectiveness of three RC techniques - open, robotic, and laparoscopic. Methods: From 2017 to 2020, 1400 patients were enrolled at one of the 28 centers across Italy. Patient characteristics, as well as preoperative, postoperative, and follow-up (3, 6, 12, and 24 months) clinical variables and outcomes were collected. Results: Preoperatively, it was found that patients undergoing robotic procedures were younger (p<.001) and more likely to have undergone preoperative neoadjuvant chemotherapy (p<.001) and BCG instillation (p<.001). Hypertension was the most common comorbidity among all patients (55%), and overall, patients undergoing open and laparoscopic RC had a higher Charlson Comorbidities Index (CCI) compared to robotic RC (p<.001). Finally, laparoscopic patients had a lower G-stage classification (p=.003) and open patients had a higher ASA score (p<.001). Conclusion: The present study summarizes the characteristic of patients included in the RIC. Future results will provide invaluable information about outcomes among BC patients undergoing RC. This will inform physicians about the best techniques and course of care based on patient clinical factors and characteristics.

Two-stage functional and aesthetic reconstructive surgery in melanoma in situ of the glans penis and urethra.

Melanoma in situ including glans penis and fossa navicularis is unique and represents a challenging dilemma since surgery should not be very aggressive. We present a case of melanoma in situ treated with a two-stage penile and urethral reconstructive surgery, with emphasis on functional and aesthetic results. At the first-stage surgery an anatomic glansectomy was perfomed, and combined preputial and full-thickness skin grafts were used to prepare the urethral plate and restore the aesthetic aspect of the corpora cavernosa. After 6 months, the distal urethra was repaired including the configuration of an orthotopic meatus and a neo-glans.

Oncological cases and complications in Urology.

This collection of cases describes some unusual urological tumors and complications related to urological tumors and their treatment. Case 1: A case of left hydronephrosis referred four years after a right radical mastectomy for lobular breast carcinoma was described. Computed tomography scan revealed a left hydronephrosis with dilated ureter up to the proximal third. An exploratory laparoscopy was performed and the definitive histopathology examination showed a recurrence of the carcinoma with a right tubal metastasis and peritoneal carcinosis. Case 2: A rare case of an extensive penile squamous cell carcinoma in a young man. The patient was treated with radical surgery and modified inguinal lymphadenectomy. No recurrence was noticed so far. Case 3: A rare case of left sided Inferior Vena Cava (IVC) in a patient diagnosed with renal cell cancer who underwent open left partial nephrectomy. Case 4: A case of urethrorrhagia, caused by a recent trauma from an urinary catheter placed in a patient submitted to gastric resection due to a neoplastic pathology. Urethrorrhagia only temporarily responded to conservative treatment and ultimately resolved by coagulation with an endoscopic approach.

Protocol of the Italian Radical Cystectomy Registry (RIC): a non-randomized, 24-month, multicenter study comparing robotic-assisted, laparoscopic, and open surgery for radical cystectomy in bladder cancer.

BACKGROUND: Bladder cancer is the ninth most common type of cancer worldwide. In the past, radical cystectomy via open surgery has been considered the gold-standard treatment for muscle invasive bladder cancer. However, in recent years there has been a progressive increase in the use of robot-assisted laparoscopic radical cystectomy. The aim of the current project is to investigate the surgical, oncological, and functional outcomes of patients with bladder cancer who undergo radical cystectomy comparing three different surgical techniques (robotic-assisted, laparoscopic, and open surgery). Pre-, peri- and post-operative factors will be examined, and participants will be followed for a period of up to 24 months to identify risks of mortality, oncological outcomes, hospital readmission, sexual performance, and continence. METHODS: We describe a protocol for an observational, prospective, multicenter, cohort study to assess patients affected by bladder neoplasms undergoing radical cystectomy and urinary diversion. The Italian Radical Cystectomy Registry is an electronic registry to prospectively collect the data of patients undergoing radical cystectomy conducted with any technique (open, laparoscopic, robotic-assisted). Twenty-eight urology departments across Italy will provide data for the study, with the recruitment phase between 1st January 2017-31st October 2020. Information is collected from the patients at the moment of surgical intervention and during follow-up (3, 6, 12, and 24 months after radical cystectomy). Peri-operative variables include surgery time, type of urinary diversion, conversion to open surgery, bleeding, nerve sparing and lymphadenectomy. Follow-up data collection includes histological information (e.g., post-op staging, grading, and tumor histology), short- and long-term outcomes (e.g., mortality, post-op complications, hospital readmission, sexual potency, continence etc). DISCUSSION: The current protocol aims to contribute additional data to the field concerning the short- and long-term outcomes of three different radical cystectomy surgical techniques for patients with bladder cancer, including open, laparoscopic, and robot-assisted. This is a comparative-effectiveness trial that takes into account a complex range of factors and decision making by both physicians and patients that affect their choice of surgical technique. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04228198 . Registered 14th January 2020- Retrospectively registered.

Management of Prostate Cancer with Systemic Therapy: A Prostate Cancer Unit Perspective.

The scenario of systemic therapy for prostate cancer is rapidly evolving, with new drugs and new treatment options. To update the background knowledge of shared uro-oncologic practice, we reviewed current statements and landmarks in systemic therapy. A number of new agents are under investigation in non-metastatic and metastatic disease. Similarly, new target imaging technologies are under development to improve the detection rate of true non-metastatic and true metastatic patient. Five new drugs have shown to be effective on progression-free and overall survival in metastatìc prostate cancer. However, the optimal sequencing of these treatments requires further investigation. The tolerability and side effects of the new drugs are also crucial issues to be discussed, as well as their activity against the disease. The uro-oncologic team has to stay updated about new medical therapies in order to be confident in debating with other professionals involved in prostate cancer decision making. Different points of view and nuances should be shared during multidisciplinary group discussions to achieve a balanced decision in disease management.