A sequential treatment approach to myoinvasive urothelial cancer: a phase II Southwest Oncology Group trial (S0219).
OBJECTIVE
We conducted a phase II trial of neoadjuvant paclitaxel, carboplatin and gemcitabine as well as transurethral resection of bladder tumor to evaluate the clinical T0 (cT0) rate with paclitaxel, carboplatin and gemcitabine, and to study cystoscopic surveillance or immediate cystectomy for patients with cT0 status following chemotherapy.


METHODS
Patients with T2-T4a chemotherapy and radiation naive urothelial cancer were eligible. T2+ tumor had to be diagnosed by transurethral bladder tumor resection followed by a second transurethral bladder tumor resection to confirm persistent disease within 16 weeks of the first resection. Three cycles of paclitaxel, carboplatin and gemcitabine were administered within 8 weeks of the second transurethral bladder tumor resection. Patients with cT0 status after paclitaxel, carboplatin and gemcitabine therapy could elect immediate cystectomy or cystoscopic surveillance, and those with greater than cT0 status were to undergo immediate cystectomy.


RESULTS
Of 77 patients 74 were assessable, and cT0 status after paclitaxel, carboplatin and gemcitabine was achieved in 34 of 74 patients (46%). Of the 34 patients with cT0 status 10 underwent immediate cystectomy, 6 of whom had persistent cancer. Persistent tumor at transurethral bladder tumor resection was seen in 28 patients (38%) and 21 underwent cystectomy. Thus, 35 of 74 patients underwent cystectomy. With a median followup of 22 months 2-year overall survival was 59% (95% CI 45, 72) and among cT0 cases it was 75% (95% CI 57, 93).


CONCLUSIONS
Although neoadjuvant paclitaxel, carboplatin and gemcitabine had a promising 46% cT0 rate, the study failed to meet the primary objective as there was an unacceptably high rate (60%) of persistent cancer at cystectomy in patients presumed to have pT0 status. Patients completing neoadjuvant chemotherapy should strongly consider definitive local therapy rather than cystoscopic surveillance regardless of post-chemotherapy cT0 status.
University of California at Davis, Sacramento, California 95817, USA. rwdeverewhite@ucdavis.edu
Ralph W
RW
deVere White
Primo N
PN
Lara
Bryan
B
Goldman
Cathy M
CM
Tangen
David C
DC
Smith
David P
DP
Wood
Maha H A
MH
Hussain
E David
ED
Crawford
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002295:Carcinoma, Transitional Cell / Q000473:pathology* / Q000628:therapy*; D015653:Cystectomy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D017239:Paclitaxel / Q000008:administration & dosage; D001749:Urinary Bladder Neoplasms / Q000473:pathology* / Q000628:therapy*; D000093542:Gemcitabine
D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine