INTRODUCTION: Platinum-based chemotherapy followed by the immune checkpoint inhibitor avelumab represents an intensified upfront therapy regimen that may result in significant downstaging and, subsequently, potentially radical robotic nephroureterectomy with a lymph node dissection, an uncommon approach with an unexpectedly favorable outcome. CASE PRESENTATION: We report a case of a 70-year-old female presented with a sizeable cN2+ tumor of the left renal pelvis and achieved deep partial radiologic response after systemic therapy with four cycles of gemcitabine-cisplatin chemotherapy followed by avelumab maintenance therapy and subsequent robotic resection of the tumor. The patient continued with adjuvant nivolumab therapy once recovered after surgery and remained tumor-free on the subsequent follow-up. The systemic treatment was without any severe adverse reaction. CONCLUSION: We highlight the feasibility of the upfront systemic therapy with four cycles of gemcitabine-cisplatin chemotherapy followed by avelumab maintenance, robotic-assisted removal of the tumor, and adjuvant immunotherapy with nivolumab. This intensification of the upfront systemic therapy, and the actual treatment sequence significantly increase the chances of prolonged survival or even a cure. This type of personalized therapeutic approach can accelerate future advanced immunotherapeutic strategies.

• Klíčová slova
• UTUC, cancer-specific survival, immune checkpoint inhibitors, immunotherapy, neoadjuvant chemotherapy, radical nephroureterectomy, upper urinary tract carcinoma,
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Urothelial cancer (UC) is most commonly found in the urinary bladder, but can also appear in the upper urinary tract, where it is associated with several disease-specific challenges affecting its diagnosis, clinical staging, surgical management, and systemic therapy. A significant number of patients experience extra-vesical disease recurrence despite radical nephroureterectomy (RNU), leading to inevitable demise. Over the last years, the therapeutic armamentarium of UC has expanded with several systemic treatment options entering clinical care and deliver the potential to support a more individualized treatment in the near future. Currently, novel targeted therapies are emerging, accompanied with extensive biomarker research, which leads to a better understanding of the disease and therefore, reshaping the treatment landscape continuously and decisively. Though, systemic treatment of UTUC comes along with certain challenges that are specific to the disease, e.g., loss of renal function after RNU, which might result in ineligibility for a cisplatin-based chemotherapy. In this narrative review, the current standard of systemic treatment of UC in the perioperative and metastatic treatment setting are reported, with focus on UTUC. In addition, molecular aspects of UTUC, as well as future directions and specific implications for treatment of patients diagnosed with UTUC are discussed.

• Klíčová slova
• Systemic therapy, chemotherapy, immune-checkpoint inhibitor, upper tract urothelial carcinoma (UTUC), urothelial cancer,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• Publikační typ
• časopisecké články MeSH

The objectives of this study are to evaluate the available literature regarding the oncologic effect of neoadjuvant and adjuvant chemotherapy in the treatment of patients with clinically non-metastatic upper tract urothelial carcinoma (UTUC) and locally advanced UTUC. We searched PubMed, Cochrane Library, and Scopus databases in November 2019, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We included studies that compared patients with non-metastatic UTUC who received either neoadjuvant or adjuvant chemotherapy with patients who underwent surgery alone. Subgroup meta-analyses were also performed for studies that investigated only locally advanced UTUC. Overall, 36 studies were included in the review of which 22 studies and 15,378 patients were eligible for the meta-analysis. Neoadjuvant chemotherapy (NAC) was associated with higher rates of pathological downstaging (pDS) (RR 6.48, 95% CI 2.05-20.44, p = 0.001) and pathological complete response (RR 18.46, 95% CI 3.34-99.24, p = 0.001); and this was also proven in a subgroup analysis of studies that evaluated pDS in locally advanced UTUC (RR 3.18, 95% CI 2.0-5.07, p < 0.001). The association of NAC with overall survival (OS) and cancer-specific survival (CSS) was also statistically significant in all patients and in patients with locally advanced UTUC. Adjuvant chemotherapy (AC) was associated with improved metastasis-free survival (HR 0.65, 95% CI 0.55-0.76, p < 0.001) and CSS (HR 0.66, 95% CI 0.57-0.77, p < 0.001), which continued to be true for the patients with locally advanced UTUC. The association of AC with OS was only significant in patients with locally advanced UTUC. Perioperative chemotherapy might provide better survival outcomes in patients with clinically non-metastatic UTUC treated with radical nephroureterectomy. Neoadjuvant chemotherapy seems to have promising results, although high level of evidence is still lacking. Despite the low level, the body of evidence suggests a need for multimodal therapy of invasive UTUC.

• Klíčová slova
• Adjuvant, Chemotherapy, Neoadjuvant, Nephroureterectomy, Upper urinary tract urothelial carcinoma,
• MeSH
• adjuvantní chemoterapie MeSH
• karcinom z přechodných buněk farmakoterapie   patologie   chirurgie   MeSH
• lidé MeSH
• nefroureterektomie MeSH
• neoadjuvantní terapie MeSH
• urologické nádory farmakoterapie   patologie   chirurgie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• srovnávací studie MeSH
• systematický přehled MeSH