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.
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.
Authors: Homayoun Zargar; Patrick N Espiritu; Adrian S Fairey; Laura S Mertens; Colin P Dinney; Maria C Mir; Laura-Maria Krabbe; Michael S Cookson; Niels-Erik Jacobsen; Nilay M Gandhi; Joshua Griffin; Jeffrey S Montgomery; Nikhil Vasdev; Evan Y Yu; David Youssef; Evanguelos Xylinas; Nicholas J Campain; Wassim Kassouf; Marc A Dall'Era; Jo-An Seah; Cesar E Ercole; Simon Horenblas; Srikala S Sridhar; John S McGrath; Jonathan Aning; Shahrokh F Shariat; Jonathan L Wright; Andrew C Thorpe; Todd M Morgan; Jeff M Holzbeierlein; Trinity J Bivalacqua; Scott North; Daniel A Barocas; Yair Lotan; Jorge A Garcia; Andrew J Stephenson; Jay B Shah; Bas W van Rhijn; Siamak Daneshmand; Philippe E Spiess; Peter C Black Journal: Eur Urol Date: 2014-09-23 Impact factor: 20.096