Prostate cancer (PCa) is the second leading cause of cancer death in men. Despite initial responses, almost all patients progress to castration-resistant prostate cancer (CRPC). Over the past decade, increased underst...Prostate cancer (PCa) is the second leading cause of cancer death in men. Despite initial responses, almost all patients progress to castration-resistant prostate cancer (CRPC). Over the past decade, increased understanding of the mechanisms that drive resistance to castration has led to the development of next-generation androgen receptor targeting agents such as abiraterone acetate and enzalutamide. Moreover in the last few years, results from large Phase III trials led to the approval of an α-emitter (radium-223), the bone resorption-targeting drug denosumab and an immunotherapy (sipuleucel-T) that showed improvements in terms of overall survival. In the field of metastatic CRPC, other novel therapeutics have recently been proven to extend survival via distinct mechanisms of action such as the new and more potent classes of androgen inhibitors, ortonel, ARN-509 and galeterone, the endothelin A receptor antagonist zibotentan, the Src inhibitor dasatinib, the c-MET inhibitor cabozantinib and the immune checkpoint inhibitor ipilimumab. This review aims to revisit the evolution of androgen receptor targeting therapeutics and to discuss other important alternative biologic pathways that have given rise to new agents in metastatic prostate cancer.展开更多
Background The coronavirus disease(COVID-19)pandemic has posed challenges to the global health care community,affecting the management of upper urinary tract stones.Materials and methods This retrospective study invol...Background The coronavirus disease(COVID-19)pandemic has posed challenges to the global health care community,affecting the management of upper urinary tract stones.Materials and methods This retrospective study involved 9 Italian centers.We compared the 12-month period prior to COVID-19(March 1,2019,to February 28,2020;Period A)with the COVID-19 period(March 1,2020,to February 28,2021,Period B).This study aimed to compare outcomes during Periods A and B,specifically focusing on the overall number of treatments,rate of urgent/elective cases,and operational complexity.Results A total of 4018 procedures were collected,comprising 2176 procedures during Period A and 1842 during Period B,indicating a loss of 15.35%(p<0.001).In the elective cases,1622 procedures were conducted in Period A,compared with 1280 in Period B,representing a 21.09%reduction in cases(p=0.001).All types of stone treatments were affected:extracorporeal shock wave lithotripsy(−29.37%,p=0.001),percutaneous nephrolithotomy(−26.47%,p=0.008),retrograde surgeries for renal stones(−10.63%,p=0.008),and semirigid ureterolithotripsy(−24.86%,p=0.008).Waiting lists experienced significant delays during Period B.The waiting time(WT)for elective procedures increased during Period B(p<0.001).For ureteral stones,the mean WT in Period A was 61.44 days compared with 86.56 days in Period B(p=0.008).The WT for renal stones increased from 64.96 days in Period A to 85.66 days in Period B for retrograde intrarenal surgery(p=0.008)and from 96.9 days to 1103.9 days(p=0.035)for percutaneous nephrolithotomy procedures.Conclusions Our study demonstrates that COVID-19 significantly disrupted endourological services across the country.Our data underline how patients received treatment over a prolonged period,potentially increasing the risk of stone-related complications and patient discomfort.展开更多
文摘Prostate cancer (PCa) is the second leading cause of cancer death in men. Despite initial responses, almost all patients progress to castration-resistant prostate cancer (CRPC). Over the past decade, increased understanding of the mechanisms that drive resistance to castration has led to the development of next-generation androgen receptor targeting agents such as abiraterone acetate and enzalutamide. Moreover in the last few years, results from large Phase III trials led to the approval of an α-emitter (radium-223), the bone resorption-targeting drug denosumab and an immunotherapy (sipuleucel-T) that showed improvements in terms of overall survival. In the field of metastatic CRPC, other novel therapeutics have recently been proven to extend survival via distinct mechanisms of action such as the new and more potent classes of androgen inhibitors, ortonel, ARN-509 and galeterone, the endothelin A receptor antagonist zibotentan, the Src inhibitor dasatinib, the c-MET inhibitor cabozantinib and the immune checkpoint inhibitor ipilimumab. This review aims to revisit the evolution of androgen receptor targeting therapeutics and to discuss other important alternative biologic pathways that have given rise to new agents in metastatic prostate cancer.
文摘Background The coronavirus disease(COVID-19)pandemic has posed challenges to the global health care community,affecting the management of upper urinary tract stones.Materials and methods This retrospective study involved 9 Italian centers.We compared the 12-month period prior to COVID-19(March 1,2019,to February 28,2020;Period A)with the COVID-19 period(March 1,2020,to February 28,2021,Period B).This study aimed to compare outcomes during Periods A and B,specifically focusing on the overall number of treatments,rate of urgent/elective cases,and operational complexity.Results A total of 4018 procedures were collected,comprising 2176 procedures during Period A and 1842 during Period B,indicating a loss of 15.35%(p<0.001).In the elective cases,1622 procedures were conducted in Period A,compared with 1280 in Period B,representing a 21.09%reduction in cases(p=0.001).All types of stone treatments were affected:extracorporeal shock wave lithotripsy(−29.37%,p=0.001),percutaneous nephrolithotomy(−26.47%,p=0.008),retrograde surgeries for renal stones(−10.63%,p=0.008),and semirigid ureterolithotripsy(−24.86%,p=0.008).Waiting lists experienced significant delays during Period B.The waiting time(WT)for elective procedures increased during Period B(p<0.001).For ureteral stones,the mean WT in Period A was 61.44 days compared with 86.56 days in Period B(p=0.008).The WT for renal stones increased from 64.96 days in Period A to 85.66 days in Period B for retrograde intrarenal surgery(p=0.008)and from 96.9 days to 1103.9 days(p=0.035)for percutaneous nephrolithotomy procedures.Conclusions Our study demonstrates that COVID-19 significantly disrupted endourological services across the country.Our data underline how patients received treatment over a prolonged period,potentially increasing the risk of stone-related complications and patient discomfort.
