Neoadjuvant cisplatin-methotrexate chemotherapy for invasive bladder cancer -- Nordic cystectomy trial 2.
BACKGROUND
In the first Nordic cystectomy trial (1986-1989) a chemotherapy combination of cisplatin-doxorubicin and external radiation seemed to improve the long-term survival after cystectomy in patients with stage T3-T4a bladder carcinomas. The aim of this study was to investigate if solely neoadjuvant chemotherapy could influence survival in patients with advanced urothelial bladder cancer undergoing cystectomy.


METHODS
The study (1991-1997) recruited 317 patients with T2-T4aNXM0 urothelial bladder tumours. The patients were randomly allocated to three courses of cisplatin-methotrexate or no pretreatment before cystectomy, eight were subsequently excluded due to protocol violation.


RESULTS
Chemotherapy according to protocol was administered to 74% (115/155) of the patients in the experimental arm. No chemotherapy related mortality was observed. Of remaining patients in the experimental arm, 14 did not receive any chemotherapy, nine discontinued after one course and 14 after two courses due to side effects. Median follow-up time among censored patients was 5.3 years. Estimated 5-year overall survival was 53% in the experimental arm and 46% in the control arm (n.s. log-rank test). The proportion of patients with pathological stage pT0 was 26.4% in the experimental arm and 11.5% in the control arm (p = 0.001). Risk of locoregional relapse and distant metastases was similar in the study arms.


CONCLUSIONS
The chemotherapy regimen was well tolerated. Despite substantial downstaging no statistically significant survival benefit with the neoadjuvant therapy could be seen after 5 years of follow-up.
Sherif
Amir
A
Department of Urology, Akademiska University Hospital, Uppsala, Sweden.
Rintala
Erkki
E
Mestad
Oddvar
O
Nilsson
Jonas
J
Holmberg
Lars
L
Nilsson
Sten
S
Malmström
Per-Uno
PU
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D015653:Cystectomy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery
D002945:Cisplatin; D008727:Methotrexate