PSMA-based therapeutics for prostate cancer.

INTRODUCTION: The prostate cancer (PCa) consist the most frequently diagnosed malignancy of urogenital system in males. Traditionally, treatment of localized PCa was based on surgery or radiotherapy while hormonotherapy was used in more advanced stages. However, the implementation of radiolabels has revolutionized the landscape of prostate cancer. Specifically, prostate-specific membrane antigen (PSMA) has been investigated in different aspects of PCa therapeutic era. AREAS COVERED: A literature review is presented about the implications of PSMA radiolabels on prostate cancer treatment. PSMA tracers were initially used as an imaging technique. Afterwards, PSMA labeled with isotopes presenting cytotoxic abilities, such as lutetium-117 and actinium-225, while reports exist about the use of radioligand immunotherapy. Meanwhile, ongoing trials examine the development of novel radionuclides as well as the evolution of the PSMA-targeted ligands. EXPERT OPINION: Currently, PSMA radioligand treatment of prostate cancer is approved in the metastatic stage of the disease. Meanwhile, a variety of trials exist about its possible role in less advanced stages. However, plenty of parameters should be addressed before these implementations, such as PSMA dosage, dosimetry issues and its safety profile. A future well-designed study with proper patient selection is mandatory to further explore PSMA radioligand theranostics perspectives.

Management of urinary stones: state of the art and future perspectives by experts in stone disease.

AIM: To present state of the art on the management of urinary stones from a panel of globally recognized urolithiasis experts who met during the Experts in Stone Disease Congress in Valencia in January 2024. Options of treatment: The surgical treatment modalities of renal and ureteral stones are well defined by the guidelines of international societies, although for some index cases more alternative options are possible. For 1.5 cm renal stones, both m-PCNL and RIRS have proven to be valid treatment alternatives with comparable stone-free rates. The m-PCNL has proven to be more cost effective and requires a shorter operative time, while the RIRS has demonstrated lower morbidity in terms of blood loss and shorter recovery times. SWL has proven to be less effective at least for lower calyceal stones but has the highest safety profile. For a 6mm obstructing stone of the pelviureteric junction (PUJ) stone, SWL should be the first choice for a stone less than 1 cm, due to less invasiveness and lower risk of complications although it has a lower stone free-rate. RIRS has advantages in certain conditions such as anticoagulant treatment, obesity, or body deformity. Technical issues of the surgical procedures for stone removal: In patients receiving antithrombotic therapy, SWL, PCN and open surgery are at elevated risk of hemorrhage or perinephric hematoma. URS, is associated with less morbidity in these cases. An individualized combined evaluation of risks of bleeding and thromboembolism should determine the perioperative thromboprophylactic strategy. Pre-interventional urine culture and antibiotic therapy are mandatory although UTI treatment is becoming more challenging due to increasing resistance to routinely applied antibiotics. The use of an intrarenal urine culture and stone culture is recommended to adapt antibiotic therapy in case of postoperative infectious complications. Measurements of temperature and pressure during RIRS are vital for ensuring patient safety and optimizing surgical outcomes although techniques of measurements and methods for data analysis are still to be refined. Ureteral stents were improved by the development of new biomaterials, new coatings, and new stent designs. Topics of current research are the development of drug eluting and bioresorbable stents. Complications of endoscopic treatment: PCNL is considered the most invasive surgical option. Fever and sepsis were observed in 11 and 0.5% and need for transfusion and embolization for bleeding in 7 and 0.4%. Major complications, as colonic, splenic, liver, gall bladder and bowel injuries are quite rare but are associated with significant morbidity. Ureteroscopy causes less complications, although some of them can be severe. They depend on high pressure in the urinary tract (sepsis or renal bleeding) or application of excessive force to the urinary tract (ureteral avulsion or stricture). Diagnostic work up:  Genetic testing consents the diagnosis of monogenetic conditions causing stones. It should be carried out in children and in selected adults. In adults, monogenetic diseases can be diagnosed by systematic genetic testing in no more than 4%, when cystinuria, APRT deficiency, and xanthinuria are excluded. A reliable stone analysis by infrared spectroscopy or X-ray diffraction is mandatory and should be associated to examination of the stone under a stereomicroscope. The analysis of digital images of stones by deep convolutional neural networks in dry laboratory or during endoscopic examination could allow the classification of stones based on their color and texture. Scanning electron microscopy (SEM) in association with energy dispersive spectrometry (EDS) is another fundamental research tool for the study of kidney stones. The combination of metagenomic analysis using Next Generation Sequencing (NGS) techniques and the enhanced quantitative urine culture (EQUC) protocol can be used to evaluate the urobiome of renal stone formers. Twenty-four hour urine analysis has a place during patient evaluation together with repeated measurements of urinary pH with a digital pH meter. Urinary supersaturation is the most comprehensive physicochemical risk factor employed in urolithiasis research. Urinary macromolecules can act as both promoters or inhibitors of stone formation depending on the chemical composition of urine in which they are operating. At the moment, there are no clinical applications of macromolecules in stone management or prophylaxis. Patients should be evaluated for the association with systemic pathologies. PROPHYLAXIS: Personalized medicine and public health interventions are complementary to prevent stone recurrence. Personalized medicine addresses a small part of stone patients with a high risk of recurrence and systemic complications requiring specific dietary and pharmacological treatment to prevent stone recurrence and complications of associated systemic diseases. The more numerous subjects who form one or a few stones during their entire lifespan should be treated by modifications of diet and lifestyle. Primary prevention by public health interventions is advisable to reduce prevalence of stones in the general population. Renal stone formers at "high-risk" for recurrence need early diagnosis to start specific treatment. Stone analysis allows the identification of most "high-risk" patients forming non-calcium stones: infection stones (struvite), uric acid and urates, cystine and other rare stones (dihydroxyadenine, xanthine). Patients at "high-risk" forming calcium stones require a more difficult diagnosis by clinical and laboratory evaluation. Particularly, patients with cystinuria and primary hyperoxaluria should be actively searched. FUTURE RESEARCH: Application of Artificial Intelligence are promising for automated identification of ureteral stones on CT imaging, prediction of stone composition and 24-hour urinary risk factors by demographics and clinical parameters, assessment of stone composition by evaluation of endoscopic images and prediction of outcomes of stone treatments. The synergy between urologists, nephrologists, and scientists in basic kidney stone research will enhance the depth and breadth of investigations, leading to a more comprehensive understanding of kidney stone formation.

Clinical impact of ERG and PTEN status in prostate cancer patients underwent radical prostatectomy.

OBJECTIVES: Phosphate and tensin homolog gene (PTEN) acts as a regulator of PI3-KAkt molecular pathway. ETS Related gene (ERG), an oncogene located in chromosome 21q22.2, is involved in prostate cancer (PCa) by serine 2 (TMPRSS2), a protein encoded by TMPRSS2 gene. The aim of this study is to evaluate the clinical impact of PTEN loss and ERG rearrangement in terms of oncologic results in patients diagnosed with localized PCa who underwent radical prostatectomy. MATERIALS AND METHODS: Prospective data were collected from a total of 74 patients who underwent open radical retropubic prostatectomy for localized PCa and immunohistochemical study was performed in tissue samples. The primary antibodies for anti-ERG antibody as well as anti-PTEN antibody were obtained from DAKO. ERG was considered positive if at least 20% of the evaluated cells were stained at least with medium intensity. PTEN protein loss was considered when the intensity of cytoplasmic and nuclear staining was mild or entirely negative across > 10% of tumor cells. RESULTS: Homogenous loss of PTEN was associated with higher clinical International Society of Urological Pathology (ISUP) grade (p = 0.018) while no statistical significant association was present regarding the presence of ERG rearrangement with either ISUPc or ISUPp. After a median follow up of 34 months, 24 patients developed biochemical recurrence. No statistical significant correlation of ERG status with biochemical recurrence was noted while PTEN was associated with biochemical recurrence development in a statistical significant way. Lastly the combination of PTEN loss with ERG rearrangement presence was detected more often in higher ISUPc and ISUPp as well as biochemical recurrence development, although in a non statistical significant way. CONCLUSIONS: Homogenous and heterogenous PTEN loss was associated with biochemical recurrence. No association of ERG and biochemical recurrence was noted. The combination of PTEN loss and ERG rearrangement presented a trend for higher ISUPc and ISUPp as well as biochemical recurrence but not in a statistical significant way.

Twenty-Four-Month Efficacy of Ureteroureterostomy Combined With Unilateral Nephrostomy Following Radical Cystectomy.

Introduction The purpose of this study was to evaluate the 24-month outcomes of ureteroureterostomy combined with unilateral nephrostomy following radical cystectomy in patients with muscle-invasive bladder cancer (BC). Materials and methods This single-center study with prospectively collected data with retrospective data analysis was carried out between December 2018 and November 2021 and enrolled 36 patients, who underwent radical cystectomy combined with ureteroureterostomy and unilateral nephrostomy. Regular renal function assessment was carried out using serum creatinine and estimated glomerular filtration rate (eGFR), and postoperative complications, endoscopic, ultrasound, and other radiological study findings were evaluated. The follow-up of the patients was carried out over a period of 24 months. Results After completion of the 24-month follow-up, the renal function proved to be slightly improved (mean serum creatinine and eGFR values of 1.38±0.72 mg/dL and 55.9±21.87 mL/min) compared to the first-year results (1.41±0.54 mg/dL and 52.10±19.64 mL/min). However, this improvement is statistically not significant (p=0.44, p=0.30). The 24-month follow-up imaging findings remained stable in 97.22% of patients compared to the first-year results, with preservation of bilateral ureteric dilatation and grade 1 dilatation of the non-drained kidney. No case of acute pyelonephritis was recorded after the completion of the second year of follow-up, in comparison to the eight patients (22.22%) of the 12-month follow-up, who suffered acute pyelonephritis. After completing of the 24-month follow-up, one patient was excluded from further analysis, due to the placement of a second permanent percutaneous nephrostomy in the non-drained kidney, due to ureteroureterostomy stenosis with consecutive hydronephrosis in the contralateral kidney and acute renal failure. No case of anastomotic leak was observed. Conclusions The function of the ureteroureterostomy combined with unilateral nephrostomy is proven to be a safe method of urinary diversion (UD) at 24 months, with minimal and easily manageable complications. Only one case of stenosis of the ureteroureterostomy with consecutive acute renal failure due to hydronephrosis in the non-drained kidney was observed. The renal function remained stable.

Uretero-Ureterostomy Combined With Unilateral Nephrostomy as a Method of Urinary Diversion Following Radical Cystectomy.

Introduction Uretero-ureterostomy combined with unilateral nephrostomy is a rarely performed urinary diversion following radical cystectomy for muscle-invasive bladder cancer. The aim of this study is to assess the efficacy and safety of the procedure. Materials and methods Patients with muscle-invasive bladder cancer and poor performance status were enrolled in this retrospective, observational, single-centre study, carried out between December 2018 and November 2020. The patient's renal function was regularly assessed with serum creatinine and estimated glomerular filtration rate (eGFR). Evaluation of peri- and postoperative complications was performed based on clinical, laboratory, endoscopic, ultrasound and other radiological studies findings. The patient's status was assessed for 12 months. Results Thirty-six patients with a mean age of 77.4±8.6 years were enrolled in the study. 86.11% of patients had an American Society of Anesthesiologists Score ≥3 and 91.66% had an age-adjusted Charlson comorbidity index of ≥6. Slight deterioration of renal function, although not statistically significant, was observed. 36.11% of the patients developed permanent unilateral pelvic dilatation. Acute pyelonephritis, urosepsis, pyonephrosis and anastomotic leak were observed in 22.22%, 8.33%, 5.55% and 5.55% of patients, respectively; all were treated either conservatively and/or with minimally invasive procedures (nephrostomy, JJ-stent insertion) without any need for open surgical revision. Conclusions Ureteroureterostomy combined with unilateral nephrostomy is a safe and effective method of urinary diversion following radical cystectomy for muscle-invasive bladder cancer with easily manageable complications.

Outcomes of radical cystectomy in pT4 bladder cancer frail patients: Α high-volume single center study.

Objectives: This study aims to evaluate the effect of frailty in patients undergoing radical cystectomy (RC) for locally advanced bladder cancer. Methods: In this retrospective, single center study we evaluated 51 patients with pT4 bladder cancer treated with radical cystectomy between 2016-2020. Patient frailty was assessed with the Clinical Frailty Scale (CFS). Furthermore, six separate parameters (early mortality index within 30 days after surgery, death after one year, length of stay, respiratory complications, readmission index, total hospital charges) were also evaluated. The patients were categorized on three groups (Group 1, 2, 3) based on the CFS. Results: A total of 51 pT4 RC patients were included in the study. Mean age was 75.6 years. Early mortality rate at 30 days after surgery was low all the groups. One year mortality rate was higher in Group 2 (22%) and 3 (69%). The length of stay and the number of patients with respiratory complications were also higher in the frailer groups. 30 days readmission rate was 22% in Group 2 and 38% in Group 3. Conclusions: Preoperative frailty is associated with worse postoperative results after RC. CFS is an objective tool for patient risk stratification and can predict postoperative complications and mortality.

Risk for Arterial Thromboembolic Events (ATEs) in Patients with Advanced Urinary Tract Cancer (aUTC) Treated with First-Line Chemotherapy: Single-Center, Observational Study.

Arterial thromboembolism has been associated with cancer or its treatment. Unlike venous thromboembolism, the incidence and risk factors have not been extensively studied. Here, we investigated the incidence of arterial thromboembolic events (ATEs) in an institutional series of advanced urinary tract cancer (aUTC) treated with cytotoxic chemotherapy. The ATE definition included peripheral arterial embolism/thrombosis, ischemic stroke and coronary events. A total of 354 aUTC patients were analyzed. Most patients (95.2%) received platinum-based chemotherapy. A total of 12 patients (3.4%) suffered an ATE within a median time of 3.6 months from the start of chemotherapy. The most frequent ATE was ischemic stroke (n = 7). Two ATEs were fatal. The 6-month and 24-month incidence were 2.1% (95% confidence interval [CI]: 0.9-4.1) and 3.6% (95% CI: 1.9-6.2), respectively. Perioperative chemotherapy increased the risk for ATE by 5.55-fold. Tumors other than UTC and pure non-transitional cell carcinoma histology were also independent risk factors. No association with the type of chemotherapy was found. Overall, ATEs occur in 4.6% of aUTC patients treated with chemotherapy and represent a clinically relevant manifestation. Perioperative chemotherapy significantly increases the risk for ATE. The role of prophylaxis in high-risk groups should be prospectively studied.

Perspectives on the urological care in Parkinson's disease patients.

Parkinson's disease (PD) is recognized as the most common neurodegenerative disorder after Alzheimer's disease. Lower urinary tract symptoms are common in patients with PD, either storage symptoms (overactive bladder symptoms or OAB) or voiding symptoms. The most important diagnostic clues for urinary disturbances are provided by the patient's medical history. Urodynamic evaluation allows the determination of the underlying bladder disorder and may help in the treatment selection. Pharmacologic interventions especially anticholinergic medications are the first-line option for treating OAB in patients with PD. However, it is important to balance the therapeutic benefits of these drugs with their potential adverse effects. Intra-detrusor Botulinum toxin injections, electrical stimulation were also used to treat OAB in those patients with variable efficacy. Mirabegron is a ß3-agonist that can also be used for OAB with superior tolerability to anticholinergics. Desmopressin is effective for the management of nocturnal polyuria which has been reported to be common in PD. Deep brain stimulation (DBS) surgery is effective in improving urinary functions in PD patients. Sexual dysfunction is also common in PD. Phosphodiesterase type 5 inhibitors are first-line therapies for PD-associated erectile dysfunction (ED). Treatment with apomorphine sublingually is another therapeutic option for PD patients with ED. Pathologic hypersexuality has occasionally been reported in patients with PD, linked to dopaminergic agonists. The first step of treatment of hypersexuality consists of reducing the dose of dopaminergic medication. This review summarizes the epidemiology, pathogenesis, risk factors, genetic, clinical manifestations, diagnostic test, and management of PD. Lastly, the urologic outcomes and therapies are reviewed.

Atypical small acinar proliferation and its significance in pathological reports in modern urological times.

Atypical small acinar proliferation is a histopathological diagnosis of unspecified importance in prostate needle-biopsy reports, suggestive but not definitive for cancer. The terminology corresponds to some uncertainty in the biopsy report, as the finding might represent an underlying non-cancerous pathology mimicking cancer or an under-sampled prostate cancer site. Therefore, traditional practice favors an immediate repeat biopsy. However, in modern urological times, the need of urgent repeat biopsy is being challenged by some authors as in the majority of cases, the grade of cancer found in subsequent biopsy is reported to be low or the disease to be non-significant. On the other hand, high risk disease cannot be excluded, whereas no clinical or pathological factors can predict the final outcome. In this review, we discuss the significance of the diagnosis of atypical small acinar proliferation in the biopsy report, commenting on its importance in modern urological practice.

Prostate cancer immunotherapy.

INTRODUCTION: Medical treatment for prostate cancer (PC) targets hormonal pathways used by malignant cells. Research advances aided in gaining knowledge about implicated molecular pathways and opened the way for establishment of new types of therapies by modifying immunological mechanisms. The aim of this review is to present completed and ongoing research projects regarding PC immunotherapy. AREAS COVERED: A literature search was conducted in PubMed/MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, and https://www.clinicaltrials.gov/ from inception until 07/2021, to identify completed or ongoing Phase III trials regarding several immunotherapies against PC. Studies on vaccine therapies, CTLA-4 inhibitors, PD-1/PD-L1 inhibitors, PARP inhibitors, PSMA-targeted therapies, and tyrosine kinase inhibitors were considered eligible. EXPERT OPINION: Although many molecules are being tested against PC cells, only sipuleucel-T has gain approval in the USA. The main reason for this delay in establishing immunotherapy as a standard option for managing PC is the heterogeneity and tumor immune microenvironment complexities. Ipilimumab and olaparib were proved to prolong overall survival significantly against placebo, but a lot of research is going on to identify which patients and at what stage of disease will benefit the most before incorporating them in clinical practice. More recent options such as PSMA-targeted treatments are currently evaluated. ARTICLE HIGHLIGHTS: Intense research performed on immunotherapy for prostate cancer.Vaccine therapy with sipuleucel-T, the only approved immunotherapy for prostate cancer.Ipilimumab shows survival benefits.Olaparib shows survival benefits.Findings should be confirmed on further trials to identify target population characteristics and proper disease stage.Immunotherapy is not yet a standard due to tumor environment complex interaction between immune system and malignant cells.

ERCC1 19007 Polymorphism in Greek Patients with Advanced Urothelial Cancer Treated with Platinum-Based Chemotherapy: Effect of the Changing Treatment Paradigm: A Cohort Study by the Hellenic GU Cancer Group.

We previously showed that ERCC1 19007 C>T polymorphism was associated with cancer-specific survival (CSS) after platinum-based chemotherapy in patients with advanced urothelial cancer (aUC). We aimed to confirm this association in a different cohort of patients. Genotyping of the 19007C>T polymorphism was carried out by polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP) in 98 aUC patients, treated with platinum-based chemotherapy. Median age of the patients was 68.8, 13.3% of them were female, 90.8% had ECOG PS of 0 or 1, and 48% received cisplatin-based chemotherapy. In addition to chemotherapy, 32.7% of the patients received immunotherapy, and 19.4% vinflunine. Eighty-one patients (82.7%) were carriers of the 19007T polymorphic allele: 46 (46.9%) were heterozygotes, and 35 (35.7%) were homozygotes. The ERCC1 polymorphism was not associated with CSS, progression-free (PFS), or overall (OS) survival in the total population. Nevertheless, there was a significant interaction between the prognostic significance of ERCC1 polymorphism and the use of modern immunotherapy: the T allele was associated with worse outcome in patients who received chemotherapy only, while this association was lost in patients who received both chemotherapy and immune checkpoint inhibitors. Our study suggests that novel therapies may influence the significance of ERCC1 polymorphism in patients with aUC. Its determination may be useful in the changing treatment landscape of the disease.

Relugolix: A new kid on the block among gonadotrophin-releasing hormone antagonists.

Androgen-deprivation therapy (ADT) is the cornerstone of metastatic prostate cancer treatment. ADT can be achieved through surgical castration, or it may be induced either by gonadotrophin-releasing hormone (GnRH) agonists or GnRH antagonists. GnRH antagonists provide a more rapid castration alongside with a safer profile regarding adverse events. Degarelix is the sole GnRH antagonist used in clinical practice. Injection site reactions are the commonest adverse events related to the use of degarelix. Relugolix, a novel molecule, represents the first orally administered United States Food and Drug Administration approved GnRH antagonist, with clinical efficacy equal to that of the established ADT regimens. The main advantages of relugolix are the avoidance of the injection site reactions of GnRH antagonists such as degarelix alongside its patient-friendly oral administration. The aim of the present review article is to present novel data regarding the role of relugolix as ADT for the treatment of prostate cancer. Abbreviations: ADT: androgen-deprivation therapy; FDA: United States Food and Drug Administration.

Association of metabolic syndrome with prostate cancer diagnosis and aggressiveness in patients undergoing transrectal prostate biopsy.

INTRODUCTION AND OBJECTIVE: Even though the only established risk factors for prostate cancer (PCa) are age, ethnic origin and family history, there are data suggesting that environmental factors, such as the presence of metabolic syndrome (MetS), may also play a role in the etiology of the disease. The aim of this study is to correlate MetS with PCa diagnosis and Gleason score (GS) in patients undergoing transrectal ultrasound guided prostate biopsy. MATERIALS AND METHODS: This is a prospective, single-center study including 378 patients who underwent transrectal ultrasound guided prostate biopsy in our department during the years from 2018 to 2019. Patients were divided into two groups according to the presence of PCa. Group A included 197 patients diagnosed with PCa while Group B consisted of 181 patients without PCa in their biopsy result. Multiple variables such as the presence of MetS and its components were evaluated in correlation to the presence of PCa and PCa characteristics. Statistical analysis was performed using the IBM SPSS Statistics v.23 program. RESULTS: Mean PSA value was 8.7 ng/dl in the PCa group and 7.1 ng/dl in the non PCa group, respectively. MetS was diagnosed in 108 patients (54.8%) with PCa and 80 patients (44.2%) without PCa and the difference was statistically significant. Hypertriglyceridemia was the MetS component with statistically higher frequency in PCa patients. Furthermore, the prevalence of MetS was higher in higher Gleason score PCa (GS ≥ 4+3) patients vs lower Gleason score PCa (GS ≤ 3+4) patients. More specifically, MetS, hypertriglyceridemia, and low HDL levels were independent factors associated with higher Gleason score PCa (GS ≥ 4+3). CONCLUSIONS: Patients suffering from MetS who undergo prostate biopsy present with higher rates of PCa diagnosis and higher GS in comparison with patients with a normal metabolic profile.

Referral for "Neoadjuvant Chemotherapy" for Muscle-Invasive Bladder Cancer to a Multidisciplinary Board: Patterns, Management and Outcomes.

BACKGROUND: Utilization of neoadjuvant chemotherapy for the treatment of muscle invasive bladder cancer in everyday practice differs from that of clinical trials. We describe the patterns of referral for "neoadjuvant chemotherapy", treatment and outcomes in a multidisciplinary tumor board. METHODS: This was an observational study. Patients referred for neoadjuvant chemotherapy received 4 cycles of dose-dense gemcitabine/cisplatin and were then assessed for definitive local therapy. Patients had a minimum follow-up of 2 years. Primary objective was a 3-year disease-free survival rate. RESULTS: Forty-six patients (clinical stages II: 28, IIIA: 9, IIIB: 4, IVA: 3, missing: 2) were included. Following chemotherapy, 30 underwent radical cystectomy, 8 radiotherapy and 8 no further therapy. Pathological downstaging was observed in 14 (46.6%) of the 30 patients who underwent radical cystectomy; clinical TNM staging was correlated with disease-free survival in the whole population, while clinical and pathological stages, as well as pathological downstaging, were correlated with disease-free survival in patients undergoing radical cystectomy. Three-year disease-free survival rates for the whole cohort and for patients undergoing radical cystectomy were 67.3% (95% confidence interval [CI]: 51-79.2) and 65.2 (95% CI: 44.9-79.6), respectively. CONCLUSION: Real-world muscle invasive bladder cancer patients who receive neoadjuvant chemotherapy are characterized by more advanced diseases and less frequent radical surgery than those included in clinical trials. Nevertheless, outcomes were comparable and, therefore, offering patients with stage II-IVA muscle invasive bladder cancer neoadjuvant chemotherapy after assessment by multidisciplinary tumor boards should be strongly encouraged.

Overview of Olaparib as a treatment option for metastatic castration-resistant prostate cancer.

Introduction: Men with prostate cancer undergoing castration will eventually progress. In addition to androgen receptor pathway inhibitors (like abiraterone and enzalutamide) or chemotherapy (like docetaxel), exists olaparib, a relatively new drug that interferes with the base excision repair (BER) pathway mainly due to selective inhibition of Poly ADP-ribose polymerase (PARP) 1 and 2.Areas covered: Herein, the authors evaluate the basic characteristics of olaparib, including its pharmacokinetics, mechanism of action, efficacy, and safety profile. The authors also provide their expert opinion and future perspectives for the place of this drug in the current treatment armamentarium.Expert opinion: Olaparib is the first drug to prove that genetic sequencing and precise medicine is a viable and important option for prostate cancer patients. In patients with deletions in preselected genes, its efficacy renders it as a viable option for second- or third-line management of metastatic castrate resistance prostate cancer (mCRPC). This fact, along with its acceptable toxicity profile, provide physicians with a new weapon in their armamentarium against this extremely difficult to treat disease.

The Impact of COVID-19 Disease on Urology Practice.

The diagnosis and timely treatment of cancer patients should not be compromised during an infectious disease pandemic. The pandemic of coronavirus disease 2019 (COVID-19) has serious implications on urology practice and raises particular questions for urologists about the management of different conditions. It was recommended to cancel most of the elective urological surgeries. Urological cancers surgeries that should be prioritized are radical cystectomy for selective tumors, orchiectomy for suspected testicular tumors, nephrectomy for c T3 + , nephroureterectomy for high-grade disease, and radical adrenalectomy for tumors >6 cm or adrenal carcinoma. Most prostatectomies can be delayed without compromising the survival rate of patients. Urological emergencies should be treated adequately even during this pandemic. There is a potential risk of coronavirus diffusion during minimally invasive procedures performed. It is crucial to use specific precautions when urologists performed those type of surgeries. It was also recommended to suspend the kidney transplantation program during the COVID-19 pandemic except for specific cases. In this review, we discussed the triage of urological surgeries, the risk of minimally invasive urological procedure, the kidney transplantation challenges, the systemic therapies, intravesical instillation of Bacillus Calmette-Guérin (BCG), endourology, teleconferencing, and telemedicine application in urology during the COVID-19 pandemic.

A pharmacoeconomic evaluation of pharmaceutical treatment options for prostate cancer.

INTRODUCTION: Prostate cancer is one of the most common neoplasms in men. For many years the mainstay of treatment was androgen deprivation therapy, but during last decade many novel agents have emerged, accompanied by increased costs for healthcare systems. AREAS COVERED: In this literature review, the authors provide a pharmacoeconomic review of several pharmaceutical agents used in several disease stages, by summarizing evidence from cost-analysis, cost-effectiveness, cost-utility, cost-saving, cost-benefit and budgetary impact analysis studies. EXPERT OPINION: The rapid development of therapeutic agents for prostate cancer has put a great budgetary burden on healthcare systems, since these drugs are prolonging survival and improving quality of life . Since existing data are now mature enough from a number of clinical trials with long-term follow-up, policy makers should propose not only the most clinically effective but also the most cost-effective agents, in order for every patient to gain access at least to some of these therapies. Docetaxel addition seems to be a cost-effective option, when compared to both abiraterone and enzalutamide (due to costs related to acquisition and side effects). Cabazitaxel is a strong candidate after docetaxel failure, while both denosumab and bisphosphonates are cost-effective for reducing skeletal-related events in metastatic disease.

The role of 18F-FDG PET/CT scan compared to CT-scan alone for lymph node staging before radical cystectomy in patients with bladder cancer.

BACKGROUND: Accurate Lymph node (LN) staging before radical cystectomy (RC) in patients with bladder cancer (BC) is crucial to improve patient's management. 18F-fluorodeoxyglucose positron-emission tomography-computed tomography (FDG-PET-CT) become widely used in the loco-regional staging of BC. The diagnostic performance of PET-CT in preoperative LN staging of BC is still unknown due to lacking large trials. OBJECTIVES: We aim to evaluate the diagnostic value of PET-CT scan, compared with CT scan alone for preoperative LN staging of BC. PATIENTS AND METHODS: From January 2010 to November 2020, we retrospectively reviewed the records of 300 patients undergoing RC for muscle-invasive BC and high-risk non-muscle-invasive BC. All patients had PET-CT and CT of abdomen and pelvis to assess for pelvic LN metastases before RC. Patients were excluded from analysis if they had neoadjuvant chemotherapy (NAC). Sensitivity, specificity, and accuracy for detecting pelvic LN metastases were determined by comparing the results of the FDG PET-CT and CT alone to the final histopathology reports obtained after RC. RESULTS: LN metastasis was confirmed histology in 134 patients (44.7%). On a patient-based analysis, PET-CT, and CT showed a sensitivity of 40.3% and 13.4 %, respectively, a specificity of 79.5% and 86.7 %, respectively, positive predictive value (PPV) of 61.4% and 45%, respectively, and negative predictive value (NPV) of 62.3% and 55.4%, respectively. The diagnostic accuracy of PET-CT scan depends on multiple preoperative and postoperative factors. CONCLUSION: PET-CT is more accurate than CT-scan alone for preoperative LN staging in patients with BC.

Current and emerging gonadotropin-releasing hormone (GnRH) antagonists for the treatment of prostate cancer.

Introduction:Androgen deprivation therapy (ADT) is currently the backbone treatment of metastatic prostate cancer and is also used in combination with external beam radiotherapy (EBRT). Castration may be achieved either by bilateral orchiectomy or by administration of LHRH agonists or GnRH antagonists.Areas covered: In this article, the authors assess the current and emerging role of GnRH antagonists for the treatment of prostate cancer focusing on oncological results and safety (i.e. cardiovascular risk). In addition, updated data regarding the first orally administered GnRH antagonist, relugolix, is presented.Expert opinion: Studies demonstrate that GnRH antagonists are at least equal with LHRH agonists in terms of testosterone suppression and PSA progression free survival with a major advantage being rapid testosterone suppression. Thus, the optimal group of patients included symptomatic metastatic prostate cancer patients especially if cardiovascular comorbidities or LUTS are also present. Emerging data regarding benefit of the use of GnRH antagonists in patients with concomitant cardiovascular disease are of great interest. Relugolix has emerged as the first orally administered GnRH antagonist able to achieve and maintain testosterone castration levels and it is associated with a profound reduction of major cardiovascular events.

Erectile dysfunction post radical cystectomy. The role of early rehabilitation with pharmacotherapy in nerve sparing and non-nerve sparing group: A randomized, clinical trial.

OBJECTIVES: No clinical studies testing erectile function (EF) post radical cystectomy (RC) were done. Our objective was to assess the effect of early pharmacologic therapy after RC using intracorporeal injection (ICI), phosphodiesterase inhibitor (PDE5i) and PDE5i+ICI. MATERIALS AND METHODS: In our randomized, double-blinded study, we prospectively enrolled 160 potent male patients with invasive bladder cancer. Patients were operated by RC using the nerve-sparing (NS) or non-nerve sparing (NNS) technique. They were treated since 1 month postoperatively by different regimens (PDE5i vs. ICI vs. ICI+PDE5i). Patients were evaluated using the international index of erectile function questionnaire and were followed up regularly at 1, 3, 6, and 12 months using the same parameters. RESULTS: One month after therapy, the mean of EF domain improved in both NS and NNS group. In the NNS group, in patients treated with ICI alone and ICI+PDE5i, the EF domain at 12 months moved to the moderate and to the mild category respectively. In patients treated by the NS approach, the mean value remained in the mild category with or without therapy. CONCLUSIONS: Early pharmacotherapy since one-month post RC using ICI and a combination of ICI+PDE5i can improve the erectile function of patients operated with a NNS approach.