Association between precystectomy epithelial tumor marker response to neoadjuvant chemotherapy and oncological outcomes in urothelial bladder cancer.

INTRODUCTION AND

objectivesWe previously reported that elevated precystectomy serum levels of epithelial tumor markers predict worse oncological outcome in patients with invasive bladder cancer (BC). Herein, we evaluated the effect of neoadjuvant chemotherapy (NAC) on elevated tumor marker levels and their association with oncological outcomes.

methodsUnder IRB approval, serum levels of Carbohydrate Antigen 125 (CA-125), Carbohydrate Antigen 19-9 (CA 19-9) and Carcinoembryonic Antigen (CEA) were prospectively measured in 480 patients with invasive BC from August 2011 through December 2016. In the subgroup undergoing NAC, markers were measured prior to the first and after the last cycle of chemotherapy (prior to cystectomy).

resultsThree hundred and thirty-seven patients were eligible for the study, with a median age was 71 years (range 34-93) and 81% (272) male. Elevated precystectomy level of any tumor markers (31% of patients) was independently associated with worse recurrence-free survival (hazard ratio [HR] = 2.81; P < 0.001) and overall survival (HR = 3.97; P < 0.001). One hundred and twenty-five (37%) patients underwent NAC, of whom 59 had a complete tumor marker profile and 30 (51%) had an elevated pre-NAC tumor marker. Following completion of chemotherapy, 10/30 (33%) patients normalized their tumor markers, while 20/30 (67%) had one or more persistently elevated markers. There was no difference in clinical or pathological stage between groups (P = 0.54 and P = 0.09, respectively). Further analysis showed a significantly lower rate and longer median time to recurrence/progression in the responder group (50% in responders vs. 90% in nonresponders at a median time of 22 vs. 4.8 months, respectively; P = 0.015). There was also significant difference in mortality rates and median overall survival between the study groups (30% in responders vs. 70% in nonresponders at a median time of 27.3 vs. 11.6 months respectively; P = 0.037). Two of the three patients that died in the normalized tumor marker group had tumor marker relapse at recurrence prior to their death.

conclusionsTo our knowledge, this is the first study showing tumor marker response to NAC. Patients with persistently elevated markers following NAC have a very poor prognosis following cystectomy, which may help identifying chemotherapy-resistant tumors. A larger, controlled study with longer follow up is needed to determine their role in predicting survival.