The Role Of Adjuvant Systemic Chemotherapy In Management Of Patients With Invasive Transitional Cell Carcinoma Of The Upper Urinary Tract

Objects:To evaluate the effectiveness of adjuvant systemic chemotherapy after surgical operation in patients with invasive transitional cell carcinoma of the upper urinary tract.Methods : The retrospective analysis was performed in 45 patients diagnosed invasive transitional cell carcinoma of upper urinary tract whose disease stage was pT2 or worse, but not metastatic from 2001.1 to 2014.5 in The Second Affiliated Hospital of Dalian Medical University. Their mean age was 60 years(range 37 to 74). All of the 45 patients received radical nephroureterectomy(RNU) and after the surgical operation, of these 45 patients, 33 were scheduled to receive more than four courses of gemcitabine and cisplatin(GC) chemotherapy. The median follow-up period of all the evaluated patients was 31.7 months(range 5.7 to 98.6). The GC neoadjuvant chemotherapy was received: Gemcitabine(800-1000mg/m2) on days 1, 8 and 15; Cisplatin(25mg/m2) on days 1, 2 and 3. Auxiliary agents were administered before the neoadjuvant chemotherapy to reduce the toxicity. The doses were adjusted if toxicity occurred.Patients with this disease stage received three to four 28-day cycles of GC if they were tolerable. After that, there was a long-term follow-up, in which we recorded every related possible adverse reactions. The disease-free survival and overall survival times were recorded from the date of surgery to the date of documented relapse or death.According to the rule of the American National Cancer Institute to assess the side effects due to the treatment.Results : Recurrence was observed in 13 patients(39.4%) who underwent chemotherapy and 8(66.7%) who did not(P=0.273). The 1, 3, and 5-year disease-free survival rate in the nonchemotherapy group was 53.6%、35.9% and 22.6%, respectively.The corresponding rates in the chemotherapy group were 79.1%、64.8% and 42.6%.These differences were significant(P=0.0347, P=0.0278 and P=0.0428, log-rank test for trend, respectively). The actuarial disease-free survival curve is shown in Fig.1 which indicating that The disease-free survival was lower in the nonchemotherapy group than in the chemotherapy group(P=0.0428). During the follow-up period, 10 patients(30.3%)in the chemotherapy group died and 9 patients(74%) in the nonchemotherapy group died(P=0.006). The 1, 3, and 5-year overall survival rate in the nonchemotherapy group was 81.7% 、 36.6% and 36.6%, respectively. The corresponding rates in the chemotherapy group were 90.3%、82.0% and 78.6%. The difference between the 3 and5-year overall survival rates between these two groups was significant(P=0.0155 and P=0.0286, log-rank test for trend, respectively). The actuarial overall survival rate for patients in the nonchemotherapy group was significantly less than that in the chemotherapy group(Fig.2, P=0.0365). Multivariate Cox proportional hazard model analysis revealed that the use of adjuvant chemotherapy(P=0.005, relative risk=9.18)and node-positive status(P=0.007, relative risk=8.29) were strongly associated with overall survival. In the chemotherapy group, 27(81.8%) had side effects due to the treatment; however, fever and gastrointestinal symptoms were the chief adverse effects and were well tolerated.Conclusion:Our results have indicated that adjuvant systemic chemotherapy may provide therapeutic benefit in patients with invasive transitional cell carcinoma of the upper urinary tract.