Teramukai S et al. (2006) Evaluation for surrogacy of end points by using data from observational studies: tumor downstaging for evaluating neoadjuvant chemotherapy in invasive bladder cancer. Clin Cancer Res 12: 139–143

Researchers from Kyoto, Japan, have shown that tumor downstaging is an appropriate SURROGATE ENDPOINT for overall survival when evaluating the effectiveness of neoadjuvant chemotherapy in phase II trials of invasive bladder cancer.

Teramukai and co-workers used data from a follow-up observational study. Of 586 patients, aged <80 years, with clinical stage T2–4, N0, M0, transitional cell carcinoma, 183 were assigned to neoadjuvant chemotherapy followed by radical cystectomy and 403 to cystectomy alone. The authors developed a new criterion for tumor downstaging effect (the difference between clinical stage at diagnosis and pathological stage at the time of cystectomy); this criterion classified patients according to their good, intermediate or poor response to treatment. Overall comparison between patients in whom treatment was most effective and those showing intermediate and poor response produced HRs for overall survival of 1.9 (95% CI 1.0–3.7) and 5.0 (95% CI 2.6–9.8), respectively, following adjustment for prognostic factors.

The relationship between tumor downstaging, effectiveness of neoadjuvant chemotherapy, and overall survival was assessed in accordance with PRENTICE'S CRITERION; tumor downstaging satisfied three of the four conditions of surrogacy. Neoadjuvant chemotherapy had a statistically significant effect on tumor downstaging (P = 0.001), but the treatment did not affect survival. These results, however, require validation in randomized clinical trials and are therefore inconclusive. The authors conclude that tumor downstaging could be an appropriate endpoint for evaluating efficacy of neoadjuvant chemotherapy in invasive bladder cancer patients.