Undertreatment in patients with advanced urothelial cancer: systematic literature review and meta-analysis

<b>Aim:</b> To assess rates of no systemic treatment (NST), attrition across lines of therapy, and factors influencing treatment selection in patients with locally advanced or metastatic urothelial cancer (la/mUC). <b>Methods:</b> Systematic literature review to identify real-world studies reporting NST or attrition rates in la/mUC from 2017–2022 (including data reported since 2015). <b>Results:</b> Of 2439 publications screened, 29 reported NST rates, ranging from 40–74% in eight European-based studies, 14–60% in 12 US-based studies, and 9–63% in nine studies in other locations (meta-analysis estimate, 39%). Factors associated with NST or no second-line therapy included older age, female sex, poor performance status, poor renal function and distant metastases. <b>Conclusion:</b> A substantial proportion of patients with la/mUC do not receive guideline-recommended treatment. <b>A review of how patients with bladder cancer are treated or not treated with anti-cancer drugs</b> People with advanced bladder cancer have a short survival. Bladder cancer is called advanced when it has spread outside of the urinary tract. Several drug treatments are available for people with advanced bladder cancer. However, sometimes people do not receive any drug treatment. We looked at published studies to see how many people with advanced bladder cancer did not receive any drug treatment and the reasons why. We also looked at how long people lived with or without drug treatment. We found that many people with advanced bladder cancer did not receive drug treatment. The number of people who received no drug treatment varied in studies from different countries. People who were older, were female, had poor health or kidney problems, or had cancer that had spread to other parts of the body were less likely to receive drug treatment. People who did not receive drug treatment lived for an average of 2 to 7 months, compared with 9 to 35 months for people who received drug treatment. More studies are needed to investigate the reasons why drug treatment is sometimes not used in people with advanced bladder cancer who could receive treatment, so that more people can benefit from available treatments. This systematic literature review assessed real-world evidence for undertreatment rates, attrition rates and factors influencing treatment selection in patients with locally advanced or metastatic urothelial carcinoma (la/mUC). Of 2439 studies reporting real-world evidence in la/mUC or bladder cancer that were screened, 29 reported the proportion of patients receiving no systemic treatment (NST), 47 reported the proportion of patients receiving no subsequent treatment after first-line (1L) treatment (ie, attrition rate) and six reported treatment rates after the approval of immunotherapy; in total, 66 studies reported either NST rates or attrition rates. Several regions and countries were represented, including the USA, the European Union, Asia, the Middle East, the UK and Russia. NST rates ranges from 40–74% in eight European-based studies, 14–60% in 12 US-based studies, and 9–63% in nine studies from other locations. Rates of receipt of second-line treatment were lower in cisplatin-ineligible versus -eligible patients, and in those who received 1L immunotherapy versus chemotherapy. Factors associated with NST or no subsequent treatment after 1L treatment included older age, female sex, poor performance status, poor renal function and distant metastases. Median overall survival for patients with NST ranged from 2.0 to 6.9 months, compared with 9.2 to 34.5 months for patients who received systemic treatment. Overall, our findings indicate that a substantial proportion of patients with la/mUC do not receive treatment according to guidelines, or at all. Additional studies are needed to explore the factors influencing treatment selection to support optimal treatment sequencing in the era of 1L maintenance and targeted therapies in later lines, and allow most patients to benefit from available treatments.