Disease-free survival as a surrogate for overall survival in upper tract urothelial carcinoma

作者：Fajkovic Harun; Cha Eugene K; Xylinas Evanguelos^*; Rink Michael; Pycha Armin; Seitz Christian; Bolenz Christian; Dunning Allison; Novara Giacomo; Quoc Dien Trinh; Karakiewicz Pierre I; Margulis Vitaly; Raman Jay D; Walton Thomas J; Baba Shiro; Carballido Joaquin; Otto Wolfgang; Montorsi Francesco; Lotan Yair; Kassouf Wassim; Fritsche Hans Martin; Bensalah Karim; Zigeuner Richard; Scherr Douglas S; Sonpavde Guru; Roupret Morgan; Shariat Shahrokh F

来源：World Journal of Urology, 2013, 31(1): 5-11.

DOI：10.1007/s00345-012-0939-5

• Upper tract urothelial carcinoma
• Disease-free survival
• Overall survival
• Recurrence
• Surrogacy

The primary endpoint in trials of perioperative systemic therapy for urothelial carcinoma is 5-year overall survival (OS). A shorter-term endpoint could significantly speed the translation of advances into practice. We hypothesized that disease-free survival (DFS) could be a surrogate endpoint for OS in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU). %26lt;br%26gt;The study included 2,492 patients treated with RNU with curative intent for UTUC. %26lt;br%26gt;2/3-year DFS estimates were 78/73 %, and the 5-year OS estimate was 64 %. The overall agreements between 2- and 3-year DFS with 5-year OS were 85 and 87 %, respectively. Agreements were similar when analyzed in subgroups stratified by pathological stages, lymph node status, and adjuvant chemotherapy. The kappa statistic was 0.59 (95 % CI 0.55-0.63) for 2-year DFS/5-year OS and 0.64 (95 % CI 0.61-0.68) for 3-year DFS/5-year OS, indicating moderate reliability. The hazard ratio for DFS as a time-dependent variable for predicting OS was 11.5 (95 % CI 9.1-14.4), indicating a strong relationship between DFS and OS. %26lt;br%26gt;In patients treated with RNU for UTUC, DFS and OS are highly correlated, regardless of tumor stage and adjuvant chemotherapy. While significant differences in DFS, assessed at 2 and 3 years, are highly likely to persist in OS at 5 years, marginal DFS advantages may not translate into OS benefit. External validation is necessary before accepting DFS as an appropriate surrogate endpoint for clinical trials investigating advanced UTUC patients.

• 出版日期2013-2