Adenocarcinoma of the urinary bladder is a rare malignancy with a poor prognosis. Patient survival is similar to that of muscle-invasive urothelial carcinoma. Unlike other cancers, there is currently no consensus regarding a standard chemotherapy regime for adenocarcinoma of the urinary bladder. In the present study, we used GC plus S-1 for neoadjuvant chemotherapy. Johnson et al. reported that adenocarcinomas of the urinary bladder have a clinical behavior similar to that of urothelial (transitional) cell carcinoma of the bladder, and GC as first-line chemotherapy for urothelial cell carcinoma has fewer side effects and similar overall survival compared with MVAC. 5-FU is widely used in the treatment of adenocarcinomas (such as stomach cancer), and Logothetis et al. reported using 5-FU to treat urachal cancers, but continuous 5-FU infusion has recently been replaced by S-1, to avoid some of the inconveniences and adverse effects of 5-FU[12, 13]. S-1 is a novel oral Xuoropyrimidine derivative that consists of tegafur, 5-chloro-2, 4-dihydropyrimidine (CDHP), and potassium oxonate.
All the 6 patients of the present study received GC plus S-1 for 3 cycles, and no patient failed to complete the cycles because of side effects. The most severe side effect was grade 2 myelosuppression such as leucopenia and thrombocytopenia. This was resolved within 2 to7 days after symptomatic treatment with granulopoietin. More severe side effects can be treated by blood transfusion. No patient suffered renal function impairment because of chemotherapy. Three patients experienced transient elevated serum creatinine (averaging 1.5-fold normal). However, this also returned to normal after the end of treatment. Thus, the safety of this chemotherapy regime was acceptable.
In the present study, we applied GC plus S-1. Two patients had a partial response, and 2, 1, and 1 patient had complete response, stable disease, and progressive disease, respectively. In contrast, a study conducted by the MD Anderson Cancer Center (MDACC) used combinations of 5-FU and cisplatin and reported a 33% response rate. Thus, our results are encouraging. Several factors may contribute to the difference in response rate. Firstly, the composition of patients is different. The patients in MDACC report are pure with urachal cancers, while in our study, NU adenocarcinoma patients are included. Secondly, the differences in the predominant ethnicities of the study populations (Houston, TX cf. Nanjing, China) may have influenced the response rate to chemotherapy. Many studies report that genetic polymorphisms exist in different races, especially in drug-metabolizing enzymes, drug targets, and drug receptors[14, 15]. These genetic polymorphisms may have contribution to the response rate. Compared with western populations, the patients in China have more attention from their family. Better food and family care may encourage the nutrients and psychological healthy of patients. More importantly, adenocarcinomas of the urinary bladder are rare and all studies are limited in the small cases. The choice of chemotherapy regimens has been based largely on case reports and single institution experiences and the statistical power is limited.
After 3 cycles of neoadjuvant chemotherapy, 5 patients received surgery. The surgeries were straightforward and uneventful. Considering neoadjuvant chemotherapy may lead to increased edema and adhesion of the bladder to the surrounding tissue, increasing the difficulty of the operation. However, no unusual bleeding or postoperative infection was observed in our cases. Patient 1 rejected surgery because he had no medical insurance and could not bear any further financial burden. This patient had complete response after 3 cycles of chemotherapy, but after 3 months, the tumor recurred.
The majority of relevant studies have indicated that tumor stage is a highly significant predictor of outcome[16, 17]. The shorter follow-up time, small case number, and the heterogeneity of patient 1 (who refused surgery and even other treatments) handicapped our analysis in this study. However, our results are enough to warrant further clinical studies with a larger number of patients with primary adenocarcinomas of the urinary bladder, to evaluate the efficacy of GC plus S-1 combination chemotherapy for neoadjuvant chemotherapy, and even for adjuvant chemotherapy.
Despite the limitations, the preliminary results of this study show that chemotherapy with GC plus S-1 for primary adenocarcinomas of the urinary bladder is effective. For patients at a locally advanced stage, this regimen effectively downstaged the tumor and may eradicate potential micrometastases, without increasing the difficulty of surgery.