Adjutant Chemoradiation with Gemcitabine/Cisplatin Versus Adjutant Chemotherapy in High-Risk Patients with Transitional Cell Carcinoma of the Urinary Bladder

Purpose: A phase III study to compare the effect of adjuvant chemotherapy versus adjuvant chemoradition in high risk post-cystectomy patients on disease free survival, overall survival and local control.Patients and Methods: Between June 2003 and January 2007, seventy patients with one or more risk factors (T3/T4a lesions, grade III, positive surgical margins, lymphovascular invasion, positive pelvic nodes) were randomized into two groups; Group (1) included 35 patients and received 4 cycles of gemcitabine 1 gm/m2 on day 1, 8 and cisplatin 70 mg/m2 on day 1 (GC) every 21 days. Group (2), included 35 patients and received adjuvant chemoradiation with 2 cycles of GC, followed by postoperative radiotherapy (50 Gy/2 Gy / 5 weeks) and followed by 2 cycles of the same chemotherapy.Results: In group (1), 91.4% of the patients received the 4 cycles of chemotherapy while in group (2), 85.7% of the patients received the full treatment. The most common acute toxicity was the hematologic toxicity with grade 3/4 neutro¬penia, thrombocytopenia and anemia in 22.9%, 17.2% and 8.6% respectively in group (1) patients, while in group (2), 22.9% of the patients had grade 3/4 neutropenia. 14.3% of patients had grade3/4 thrombocytopenia and 11.5% of patients had grade 3/4 anemia. Grade 3/4 diarrhea and tenesmus were recorded in 8.6% and 11.5% respectively in group (2). As regards the late toxicity four patients (11.5%) had grade II small bowel toxicity in group (2). With a median follow-up of 43 month, the 3-year disease free survivals were 60% and 74.3% for group (1) and (2) respectively (p=0.01). The 3- year overall survival was 65.7% for patients in group (1) versus 80% for group (2) (p=0.08). The disease free survival was significantly better for patients with grade I/II than those with grade III lesions (84.6% versus 64.5%, p-0.03) and also for patients with negative lymph nodes than those with positive lymph nodes (65.3% versus 33.3%, p 0.0001). The local recurrence free survival was 85.7% and 65.7% for group 2 and group 1 respectively (p=0.04). There was no statically significant difference in the distant failure rate between the two groups (22.9% and 17.1% for group 1 and 2 respectively p=0.14).Conclusion: Adjuvant chemoradiation compared with adjuvant chemotherapy only was associated with statistically significant improvement in the local recurrence free survival, with no statistically significant benefits in the disease free survival, overall survival or distant metastasis rates. Further studies are necessary to allow clear conclusions on the benefits of this treatment.