Affiliation:
1. Department of Urology, Milan
2. Division of Oncology, Milan
3. Epidemiology Unit, Scientific Institute Ospedale San Raffaele, Milan
4. Department of Urology, Predabissi Hospital, Melegnano (Milan), Italy
Abstract
Aims and Background Neoadjuvant systemic chemotherapy in infiltrating transitional cell carcinoma of the bladder has proved to be effective and to provide a pathologic complete response in about 30% of patients. No survival benefit has yet been proved. Methods We analyzed the outcome of 75 patients with advanced bladder cancer (stages T2-T4 N+/N0 M0) treated from 1985 to 1993 at two institutions in the same geographic area with 2 or 3 cycles of neoadjuvant CMV (cisplatin, methotrexate and vinblastine) chemotherapy plus cystectomy. Transurethral resection of the tumor was expressly avoided in order to keep the tumor intact as a marker lesion to evaluate response to chemotherapy. Results At the time of analysis, the median follow-up of 67 assessable patients was 51.5±3.9 (SE) months. Forty-six patients (69%) had clinical evidence of extravesical spread of the bladder tumor and 6 of lymph node metastases at presentation. After cystectomy, a pathologic complete response (pT0, pN0) was achieved in only 6 cases (9%) and a pathologic partial response in 32 patients (48%). The overall 5-year survival rate of all patients was 61 ±6%. Those patients who had a major response to chemotherapy (pCR + pPR) had a 5-year disease-free survival rate of 74%, which was statistically higher (P=0.0021) than the 44% for the remaining nonresponding patients (pNR). Overall, 43% of the patients with stage T2-T3a disease achieved tumor downstaging (CR, 5%; PR, 38%) compared with 63% of the patients with T3b-T4 (CR, 11%; PR, 52%), although there was no significant difference in 5-year survival curves between the two groups. Conclusions A pathologic complete response was achieved in less than 10% of the cases without a preoperative tumor resection. Unfortunately, most of the responses were only partial. Even though the study appears to suggest a survival advantage for those patients who achieved a downstaging, CMV chemotherapy had a limited curative potential in most of the patients. It seems unlikely that determinant proof will be obtained that neoadjuvant chemotherapy may improve survival over a nontreatment control arm. The intrinsic chemoresistance or the suboptimal response to chemotherapy of bladder cancer remains the most adverse prognostic factor.
Subject
Cancer Research,Oncology,General Medicine