Introduction: There was no useful serum marker to predict the survival in patients with bladder cancer (BCa). BCa with squamous cell carcinoma or adenocarcinoma have worse prognosis compared to that with only urothelial cancer. On the other hand, prognostic roles of serum levels of these non-urothelial carcinoma-related markers in BCa patients are still unclear
Methods: We measured serum levels of squamous cell carcinoma associated antigen (SCC antigen), carcinoembryonic antigen (CEA), and carbohydrate antigen (CA)19-9 in 161 BCa patients. In this study, BCa patients with SCC or adenocarcinoma were excluded. Our study population has 84 patients with muscle invasive disease (MIBC) and 24 patients with metastasis. In addition, fifty-nine patients were treated with platinum-based chemotherapies and there was no patient treated with immune-checkpoint inhibitors.
Results: Median serum levels of SCC antigen, CEA, and CA19-9 were 1.2 ng/ml, 2.8 ng/ml, and 18.8 U/ml, respectively. Finally, 59 (36.6%), 27 (16.7%), and 12 (7.5%) were judged as higher in SCC antigen, CEA, and CA19-9, respectively. Serum SCC antigen levels were positively associated with grade, muscle invasion, and metastasis (P <0.001, <0.001, and 0.001, respectively). In addition, such significant relationship on grade was found in MIBC (P=0.013), but not in non-MIBC. Serum CA19-9 levels were associated with only metastasis (P=0.031). Serum CEA level was not associated with all pathological features. Kaplan-Meier survival curves showed that high serum levels of SCC antigen and CA19-9 were associated with worse overall survival (OS) in entire and MIBC patients. In addition, these two markers were identified as worse predictors for OS in patients with chemotherapy. These findings were confirmed in multivariate analysis models including pathological features. Moreover, such significant prognostic roles were detected in patients with non-curative transurethral resection, but not in those with curative one. On the other hand, all our serum marker has no significant predictive value for recurrence in non-MIBC.
Conclusions: Serum levels of SCC antigen and CA19-9 were useful predictive markers for outcome in urothelial carcinoma of the urinary bladder, especially in MIBC. As reasons of such findings, we speculated that these markers were produced from deep muscle layer and/or metastatic tumors. We also think serum SCC levels is more useful in clinical setting because higher ratio of CA19-9 level was under 10%.