Neoadjuvant Chemotherapy before Nephroureterectomy in High-Risk Upper Tract Urothelial Cancer: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: In muscle-invasive bladder cancer, platinum-based neoadjuvant chemotherapy is a well-established concept, since it contributes to pathological downstaging and improves overall survival. Immunotherapy has become increasingly important in adjuvant and palliative treatment for metastatic urothelial carcinoma, and phase II studies have shown assuring data in neoadjuvant treatment before cystectomy. Although upper urinary tract urothelial cancer usually presents as more invasive at diagnosis than bladder cancer, there is no recommendation for neoadjuvant therapy before nephroureterectomy. This meta-analysis comprises eleven comparative trials on neoadjuvant chemotherapy in this setting and analyzes pathological downstaging as well as oncological outcomes. However, no comparative studies investigating immunotherapy in upper tract urothelial cancer were found. The pathological downstaging and complete response were significantly improved in patients who received neoadjuvant chemotherapy. The data also suggested a benefit in overall survival and progression-free survival in these patients. Prospective studies are needed to confirm these findings and assess the role of immunotherapy in this setting. ABSTRACT: Neoadjuvant chemotherapy is a well-established concept in muscle-invasive bladder cancer with known advantages in overall survival. Phase II trials show encouraging response rates for neoadjuvant immunotherapy before radical surgery in urothelial cancer. There is no recommendation for neoadjuvant therapy in upper tract urothelial carcinoma before nephroureterectomy. Our aim was to assess the available data on neoadjuvant chemotherapy and immunotherapy before nephroureterectomy in patients with high-risk upper tract urothelial carcinoma in terms of pathological downstaging and oncological outcomes. Two investigators screened PubMed/Medline for comparative trials in the English language. We identified 368 studies and included eleven investigations in a systematic review and meta-analysis for neoadjuvant chemotherapy and control groups. There were no comparative trials investigating immunotherapy in this setting. All 11 studies reported on overall pathological downstaging with a significant effect in favor of neoadjuvant chemotherapy (OR 5.17; 95%CI 3.82; 7.00). Pathological complete response and non-muscle invasive disease were significantly higher in patients receiving neoadjuvant chemotherapy (OR 12.07; 95%CI 4.16; 35.03 and OR 1.62; 95%CI 1.05; 2.49). Overall survival and progression-free survival data analysis showed a slight benefit for neoadjuvant chemotherapy. Our results show that neoadjuvant chemotherapy is effective in downstaging in upper urinary tract urothelial carcinoma. The selection of patients and chemotherapy regimens are unclear.