Survival Outcomes Associated with First and Second-Line Palliative Systemic Therapies in Patients with Metastatic Bladder Cancer

Background: Real-world data on palliative systemic therapies (PST) in treating metastatic bladder cancer (mBC) is limited. This study investigates current trends in treating mBC with first- (1L) and second-line (2L) chemotherapy (CT) and immunotherapy (IT). Methods: A chart review was conducted on patients diagnosed with stage II-IV bladder cancer in 2014–2016. Survival outcomes were compared between chemotherapy, immunotherapy, and supportive care. Results: out of 297 patients, 77% were male. 44% had stage IV disease at diagnosis. Median age at metastasis was 73 years. 40% of patients received 1L PST and 34% received 2L PST. Median overall survival (mOS) was longer in those receiving PST versus no treatment (p < 0.001). Patients receiving CT and IT sequentially had the longest mOS (18.99 months). First-line IT and CT mOS from treatment start dates were 5.03 and 9.13 months, respectively (p = 0.81). Gemcitabine with cisplatin (8.88 months) or carboplatin (9.13 months) were the most utilized 1L chemotherapy regimens (p = 0.85). 2L IT and CT mOS from treatment start dates were 6.72 and 3.78 months, respectively (p = 0.15). Conclusion: real-world mOS of >1.5 years in mBC is unprecedented and supports using multiple lines of PST. Furthermore, immunotherapy may be a comparable alternative to chemotherapy in both 1L and 2L settings

Survival Outcomes Associated with First and Second-Line Palliative Systemic Therapies in Patients with Metastatic Bladder Cancer

Background: Real-world data on palliative systemic therapies (PST) in treating metastatic bladder cancer (mBC) is limited. This study investigates current trends in treating mBC with first- (1L) and second-line (2L) chemotherapy (CT) and immunotherapy (IT). Methods: A chart review was conducted on patients diagnosed with stage II-IV bladder cancer in 2014–2016. Survival outcomes were compared between chemotherapy, immunotherapy, and supportive care. Results: out of 297 patients, 77% were male. 44% had stage IV disease at diagnosis. Median age at metastasis was 73 years. 40% of patients received 1L PST and 34% received 2L PST. Median overall survival (mOS) was longer in those receiving PST versus no treatment (p 1.5 years in mBC is unprecedented and supports using multiple lines of PST. Furthermore, immunotherapy may be a comparable alternative to chemotherapy in both 1L and 2L settings.Medicine, Faculty ofNon UBCMedicine, Department ofMedical Oncology, Division ofReviewedFacult

MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis.

Low temperatures delay aging and promote longevity in many organisms. However, the metabolic and homeostatic aspects of low-temperature-induced longevity remain poorly understood. Here, we show that lipid homeostasis regulated by Caenorhabditis elegans Mediator 15 (MDT-15 or MED15), a transcriptional coregulator, is essential for low-temperature-induced longevity and proteostasis. We find that inhibition of mdt-15 prevents animals from living long at low temperatures. We show that MDT-15 up-regulates fat-7, a fatty acid desaturase that converts saturated fatty acids (SFAs) to unsaturated fatty acids (UFAs), at low temperatures. We then demonstrate that maintaining a high UFA/SFA ratio is essential for proteostasis at low temperatures. We show that dietary supplementation with a monounsaturated fatty acid, oleic acid (OA), substantially mitigates the short life span and proteotoxicity in mdt-15(-) animals at low temperatures. Thus, lipidostasis regulated by MDT-15 appears to be a limiting factor for proteostasis and longevity at low temperatures. Our findings highlight the crucial roles of lipid regulation in maintaining normal organismal physiology under different environmental conditions