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Introduction: The combination of intravesical gemcitabine (Gem) with docetaxel (Doce) or with mitomycin C (MMC) has been used in the primary setting as an alternative to Bacillus Calmette-Guerin (BCG) to treat high-risk (HR) and intermediate-risk (IR) non-muscle invasive bladder cancer (NMIBC), as well in the rescue setting for patients in whom BCG has failed., Area Covered: Efficacy and safety of Gem/Doce and Gem/MMC to treat NMIBC in BCG-naive and failure settings., Expert Opinion: In the BCG-naive setting, Gem/Doce was the primary alternative combination therapy reported, with a weighted mean of 12- and 24-month recurrence-free survival (RFS) of 79% and 77% for HR disease and 84% and 76% for IR disease, respectively. In the HR BCG-failure setting, the weighted mean of 12- and 24-month RFS was 60% and 42% for Gem/Doce and 63% and 40% for Gem/MMC. While patients without BCG exposure and papillary disease only benefit the most from Gem/Doce, there is also reasonable efficacy in BCG refractory disease and CIS. Combination therapy is well tolerated, with grade III toxicity reported in less than 1% of patients. Unlike single-agent chemotherapy, intravesical Gem/Doce is considered effective and safe regardless of risk-stratification.

Background: To evaluate the impact of having first-degree relatives (FDR) with bladder cancer (BC) among non-muscle invasive bladder cancer (NMIBC) patients treated with Bacillus Calmette - Guérin (BCG) on their oncological outcomes., Methods: The National Phase II BCG/Interferon (IFN) trial database from 125 sites in the U.S.A. (1999-2001) and multi-institutional databases from France (FR) and Lebanon (LB) (2000-2021) were queried for NMIBC patients treated with BCG. Cox regression models were used to evaluate the effect of BC family history on tumor recurrence and progression in their relatives., Results: There were 867 patients in the U.S.A. cohort and 1232 patients in the FR/LB cohort. Almost 8% of patients in both cohorts had FDR with BC. Patients in the FR/LB cohort were more likely to have carcinoma in situ tumors (CIS) (41% vs. 24%, p  < 0.01). Having FDR with BC was not significantly associated with tumor recurrence or progression in the U.S.A. cohort. Conversely, on multivariable analysis FDR history was significantly associated with a 2.10 times increased risk of recurrence ( p  < 0.01) and a 3.01 times increased risk of progression ( p  < 0.01) in the FR/LB cohort., Conclusion: A family history of BC could have an important impact on the response to BCG.

Introduction: Failure, intolerance, or shortage of bacillus Calmette-Guerin (BCG) treatment for patients with high-risk (HR) non-muscle invasive bladder cancer (NMIBC) leave many facing the prospect of radical cystectomy (RC). However, despite the lack of large-scale randomized controlled studies with single-agent intravesical gemcitabine (Gem), it has emerged as a popular salvage agent after BCG failure or even a treatment alternative to BCG., Areas Covered: 1. Characterization of treatment regimen details pertaining to single-agent intravesical adjuvant Gem use among disease states of NMIBC characterized by risk and BCG exposure. 2. Comparison of safety and efficacy of Gem according to risk category, type of tumor (papillary vs. carcinoma in situ (CIS)), and tumor grades., Expert Opinion: Two randomized studies in early BCG failure disease demonstrate that single-agent Gem has superior efficacy versus repeated BCG therapy or mitomycin C. Studies enrolling patients with predominantly papillary disease without CIS, intermediate-risk (IR) disease, and less BCG exposure appear to derive the highest benefits from adjuvant Gem in terms of recurrence and progression. However, studies with cohorts enriched for a predominance of CIS, HR disease and/or more extensive BCG failure have poorer 2-year recurrence free survival and a somewhat higher risk of progression and RC.

Introduction : Currently, in prostate cancer, an increasing number of novel drugs are being used to delay its advancement to metastatic castration-resistant prostate cancer (mCRPC). Apalutamide, enzalutamide, and most recently, darolutamide (novel androgen receptor antagonists) have been approved for nonmetastatic castration-resistant prostate cancer (nmCRPC). Areas covered : The authors have evaluated darolutamide, covering all aspects of the clinical development, competence, and safety profile of the drug. Expert opinion : The unique structure of darolutamide is characterized by a high affinity for androgen receptors and detainment of antagonist activity in mutant isoforms of androgen receptors. In clinical practice, this is the main reason that makes darolutamide exceptional in terms of safety and efficacy compared to other drugs in this category. Darolutamide is considered to have the lowest probability for adverse events (AEs) compared to apalutamide and enzalutamide. Future studies, along with real-world clinical data are warranted to improve personalized treatment strategies as well as sequencing treatment between approved novel drugs.

Introduction: Treatment of recurrent Urinary tract infections (UTIs) has become challenging because of the dramatic increase in the rates of recurrent infection andof multidrug-resistant (MDR) infections., Areas Covered: The authors review recurrent UTIs(rUTI) management in women., Expert Opinion: Continuous or post-coital prophylaxis with low-dose antimicrobials or intermittent self-treatment has all been demonstrated to be effective in managing rUTIs in women. Intravaginal estrogen therapy , shows potential toward preventing rUTI. Oral vaccine Uro-Vaxom seems to reduce the number of UTIs. There is evidence that other therapies (e.g. cranberry, Methenamine hippurate, oral D-mannose) may decrease the number of symptomatic UTIs. The treatment of CRE-UTIs is focused on a colistin backbone. Carbapenems are considered first-line agents for UTIs caused by ESBL, but their use is associated with increased MDR. The usage of non-carbapenem for the treatment of ESBL UTIs is necessary. Cefepime, Piperacillin-Tazobactam, Ceftolozane-Tazobactam, and Ceftazidime-Avibactam are justified options. Oral therapy with Pivmecillinam, Fosfomycin, and Nitrofurantoin can be used against uncomplicated UTIs due to ESBL infection.

Introduction: Metastatic castration-resistant prostate cancer (CRPC) is a potentially symptomatic disease with an eventual lethal outcome. Novel pharmaceutical agents are continuously studied with encouraging results in CRPC., Areas Covered: In this perspective, the authors present established and promising pharmacotherapeutic strategies for the management of CRPC; both with and without metastases. Apart from the different treatment strategies, the authors present the relevant sequence of treatment through disease progression., Expert Opinion: Usually, docetaxel should be considered the first line treatment in mCRPC. Abiraterone acetate (AA) plus prednisone or enzalutamide (ENZ) could be alternative treatments in chemotherapy naïve patients. Sipuleucel-T has been approved for the treatment of asymptomatic or minimally symptomatic mCRPC. Ra-223 has been approved for patients with mCRPC with symptomatic bone metastases (not visceral metastases). Cabazitaxel has been approved as the second line treatment to docetaxel in mCRPC. No differences in the overall survival has been observed between sequences starting with docetaxel versus AA/ENZ. Between AA-to-ENZ and ENZ-to-AA sequence, the AA-to-ENZ sequence appeared to be more favorable than the ENZ-to-AA regarding progression-free survival but not overall survival. Carbazitaxel seemed to retain its activity regardless of the treatment sequence. Of note, ENZ and apalutamide have been approved in non-metastatic CRPC.

Introduction : Urolithiasis is a common, highly recurrent disease with increasing prevalence worldwide. There are many dietary and pharmacological measures to prevent kidney stones. Areas covered : Herein, the authors explore medical expulsive therapy as well as pharmacological therapies to prevent/treat urolithiasis. Expert opinion : All stone formers should be advised to increase their fluid intake sufficiently to achieve a urine volume of at least 2.5 L/day. In the case of hypercalciuria, a thiazide diuretic should be prescribed while in cases of hypocitraturia, potassium citrate should be given. In the case of hyperoxaluria, the treatment depends on the type of hyperoxaluria. Pyridoxine or calcium supplements with a meal can be offered. For uric acid stone formers, alkali therapy is the standard of care whereas allopurinol can be beneficial in hyperuricosuric stone formers. For cystine stone formers, increased fluid intake, restriction of sodium and animal protein ingestion, and urinary alkalinization are the standard therapies used. Cystine binding thiol drugs such as tiopronin and D-penicillamine are reserved for patients where a conservative approach fails. For struvite stone formers, optimal management is the complete stone removal. Acetohydroxamic acid may be offered only after surgical options have been exhausted, for patients with residual stones but it has many side effects.