A systematic review and meta-analysis of adjuvant and neoadjuvant chemotherapy for upper tract urothelial carcinoma
School of Medicine; Senior Scholars Program
Joaquim Bellmunt (Dana Farber)
Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Humans; Kidney Neoplasms; Neoadjuvant Therapy; Paclitaxel; Survival Rate; Ureteral Neoplasms; Urothelium
Neoplasms | Therapeutics | Urology
CONTEXT: The role of adjuvant chemotherapy (AC) or neoadjuvant chemotherapy (NC) remains poorly defined for the management of upper tract urothelial carcinoma (UTUC), although some studies suggest a benefit.
OBJECTIVE: To update the current evidence on the role of NC and AC for UTUC patients.
EVIDENCE ACQUISITION: We searched for all studies investigating NC or AC for UTUC in Medline, Embase, the Cochrane Central Register of Controlled Trials, and abstracts from the American Society of Clinical Oncology meetings prior to February 2014. A systematic review and meta-analysis were performed.
EVIDENCE SYNTHESIS: No randomized trials investigated the role of AC for UTUC. There was one prospective study (n=36) investigating adjuvant carboplatin-paclitaxel and nine retrospective studies, with a total of 482 patients receiving cisplatin-based or non-cisplatin-based AC after nephroureterectomy (NU) and 1300 patients receiving NU alone. Across three cisplatin-based studies, the pooled hazard ratio (HR) for overall survival (OS) was 0.43 (95% confidence interval [CI], 0.21-0.89; p=0.023) compared with those who received surgery alone. For disease-free survival (DFS), the pooled HR across two studies was 0.49 (95% CI, 0.24-0.99; p=0.048). Benefit was not seen for non-cisplatin-based regimens. For NC, two phase 2 trials demonstrated favorable pathologic downstaging rates, with 3-yr OS and disease-specific survival (DSS) < /= 93%. Across two retrospective studies investigating NC, there was a DSS benefit, with a pooled HR of 0.41 (95% CI, 0.22-0.76; p=0.005).
CONCLUSIONS: There appears to be an OS and DFS benefit for cisplatin-based AC in UTUC. This evidence is limited by the retrospective nature of studies and their relatively small sample size. NC appears to be promising, but more trials are needed to confirm its utility.
PATIENT SUMMARY: After a comprehensive search of studies examining the role of chemotherapy for upper tract urothelial cancer, the pooled evidence shows that cisplatin-based adjuvant chemotherapy was beneficial for prolonging survival.
Adjuvant, Chemotherapy, Kidney neoplasms, Neoadjuvant, Nephroureterectomy, Renal pelvic tumors, Upper tract urothelial carcinoma, Ureteral neoplasms, Urothelial carcinoma
DOI of Published Version
Eur Urol. 2014 Sep;66(3):529-41. doi: 10.1016/j.eururo.2014.03.003. Epub 2014 Mar 16. Link to article on publisher's site
Leow, Jeffrey J.; Martin-Doyle, William; Fay, Andre P.; Choueiri, Toni K.; Chang, Steven L.; and Bellmunt, Joaquim, "A systematic review and meta-analysis of adjuvant and neoadjuvant chemotherapy for upper tract urothelial carcinoma" (2014). University of Massachusetts Medical School. Senior Scholars Program. Paper 217.