San Diego, CA USA (UroToday.com) In this session, Dr. Milowsky addressed the role of adjuvant chemotherapy and novel targeted agents after surgery for bladder urothelial carcinoma. As we know, muscle-invasive bladder cancer is a lethal disease with a median survival of approximately 2 years if left untreated.
There is level 1 evidence of a survival benefit supporting neoadjuvant cisplatin-based chemotherapy (NAC) in the management of this disease. Trends in the use of perioperative chemotherapy demonstrate an increase in the use of NAC from 2006 to 2010; unfortunately, this regimen remains underused with rates as low as 20% in some reports. The unquestioned benefit of NAC naturally leads to the question of where systemic therapy fits in the post-surgery space.
There have been 6 historical trials (mostly in patients with T3 and/or N+ disease). Two were positive and 4 were negative. All were small, underpowered studies. More modern trials by both an Italian and Spanish groups failed to accrue and therefore were underpowered and did not detect a difference. EORTC 30994 accrued 284 patients and demonstrated a promising progression free survival with a HR of 0.54. A metaanalysis of 945 patients also favored use of adjuvant chemotherapy and an analysis of the NCDB favored the use of adjuvant chemotherapy (HR 0.72). Therefore, Dr. Milowsky argued that it’s likely time to recommend adjuvant chemotherapy in appropriately selected patients and particularly in those who have not received NAC.
The comprehensive molecular characterization of urothelial bladder carcinoma by the Cancer Genome Atlas found several potential therapeutic targets (mTor, FGFR3, TSC1), and these new pathways are currently in clinical development. Checkpoint inhibition as reported in the IMvigor 210 trial has generated considerable excitement and multiple PD-1 and PD-L1 pathway agents in currently being developed. An intriguing notion is that such agents can be used in the adjuvant setting even with patients who have received NAC.
Presented By: Michael S. Cookson , MD