LAUSR

PURPOSE The impact of preoperative chemotherapy (PC) in patients with upper urinary tract urothelial carcinoma (UTUC) remains poorly investigated. We assessed the rates of pathologic complete response (pCR; pT0N0/X) and downstaging (pDS; ≤pT1N0/X) at radical nephroureterectomy (RNU) after PC and evaluated their impact on survival. MATERIAL AND METHODS This was an international observational study of patients who underwent PC and RNU for high-risk UTUC between 2005 and 2017. Multiple imputation of chained equations was applied to account for missing values. Logistic regression analyses were performed to identify predictors of pathologic response. Cox proportional hazard regression models were used to estimate recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS A total of 267 patients met our inclusion criteria. Among included patients, 82 (31%) received methotrexate, vinblastine, doxorubicin and cisplatin (MVAC), 123 (46%) gemcitabine and cisplatin (GC), 25 (9%) gemcitabine and carboplatin (GCb), and 32 (12%) other regimens. The overall rates of pCR and pDS were 10.1% and 44.9%, respectively. On multivariable analysis, the use of GC and GCb was not statistically different from MVAC in achieving pCR and pDS, respectively. The number of administered cycles did not appear to have an effect on pathologic responses. Pathologic downstaging was the strongest prognostic factor for RFS (HR 0.2, p<0.001), CSS (HR 0.19, p<0.001) and OS (HR 0.40, p<0.001). CONCLUSIONS Pathologic downstaging after PC is a robust prognostic factor at RNU, and is associated with improved survival outcomes. Although PC appears to be effective, well-designed prospective studies are still needed.