The prognostic value of adjuvant and neoadjuvant chemotherapy in total cystectomy for locally advanced bladder cancer

PURPOSE: Adjuvant chemotherapy and neoadjuvant chemotherapy have been widely used as adjuvant treatment in patients requiring total cystectomy for locally advanced transitional cell carcinoma of the bladder. However, there has been no conclusive evidence that the adjunctive chemotherapy improves survival and no agreement exists concerning what subsets of such patients receive significant benefits from the adjunctive chemotherapy. The study retrospectively sought to clarify these points. PATIENTS AND METHODS: We retrospectively analyzed clinical and pathological records of the 229 patients with transitional cell carcinoma of the bladder who underwent total cystectomy with or without lymph node dissection in our University Hospital from January 1975 to December 1997. Forty-two patients received 1-4 cycles (mean = 1.7) of adjuvant chemotherapy with VPMisCF (n = 19), CisCA (n = 4), MVAC (n = 8), or MEC (Methotrexate, Epirubicin and Cisplatin) (n = 11). Twenty-three patients received 1-4 cycles (mean = 2.1) of neoadjuvant chemotherapy with CisCA (n = 2), MVAC (n = 5), or MEC (n = 16). Using the Kaplan-Meier method, disease-specific survival rate was assessed according to various clinical and pathological factors as well as the administration of adjuvant or neoadjuvant chemotherapy. The generalized-Wilcoxon test was used to evaluate statistical significance (p < 0.05) of survival curves for two or more groups. In addition, a multivariate analysis using the Cox proportional hazards model was performed with respect to multiple clinical and pathological parameters, and treatment modalities. RESULTS: In patients who received neither adjuvant chemotherapy nor radiotherapy, the disease-specific survival rate was significantly lower in those with pT3a and/or more advanced tumors compared with those with pT2 or less advanced tumors. The survival rate in patients with positive lymph node metastasis was significantly lower than that in patients without lymph node metastasis. No apparent survival benefit was noted for those patients who received adjuvant chemotherapy when compared with patients who had pT3a or more advanced tumor and were followed without any adjunctive therapy. In patients with pN2 or more advanced lymph node metastasis, the survival rate of those who received adjuvant CisCA/MVAC/MEC chemotherapy was significantly higher than that those without any adjunctive therapy. Although no apparent survival benefit was observed in patients who received neoadjuvant chemotherapy, the survival rate in patients whose tumor was considered to be down-staged to pT1 or lower was significantly higher than patients who did not receive neoadjuvant chemotherapy and had pT3a or higher pT-stage tumor. The survival rate in patients whose tumor showed clinical partial or complete response by neoadjuvant chemotherapy was also significantly higher than the same control patients. However, the multivariate analysis revealed no significant survival benefit after adjuvant chemotherapy or after neoadjuvant chemotherapy. CONCLUSIONS: Adjuvant chemotherapy after total cystectomy is an acceptable approach in patients with pN2 or higher pN-stage bladder cancer. The significant survival benefit may be obtained who acquired pathological downstaging or partial to complete clinical response after neoadjuvant chemotherapy. To get maximum survival benefit from the present chemotherapeutic regimens and exclude administration of toxic chemotherapeutic agents to unresponsive patients, there should be more reliable markers that give clear information to differentiate tumors that will respond fairly to present chemotherapeutic regimens from tumors that will respond poorly.