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

OBJECTIVE: To assess the differential response to neoadjuvant chemotherapy (NAC) in patients with urothelial carcinoma of the bladder (UCB) compared to upper tract urothelial carcioma (UTUC) treated with radical surgery. PATIENTS AND METHODS: Data from 1299 patients with UCB and 276 with UTUC were obtained from multicentric collaborations. The association of disease location (UCB vs UTUC) with pathological complete response (pCR, defined as a post-treatment pathological stage ypT0N0) and pathological objective response (pOR, defined as ypT0-Ta-Tis-T1N0) after NAC was evaluated using logistic regression analyses. The association with overall (OS) and cancer-specific survival (CSS) was evaluated using Cox regression analyses. RESULTS: A pCR was found in 250 (19.2%) patients with UCB and in 23 (8.3%) with UTUC (P < 0.01). A pOR was found in 523 (40.3%) patients with UCB and in 133 (48.2%) with UTUC (P = 0.02). On multivariable logistic regression analysis, patients with UTUC were less likely to have a pCR (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.27-0.70; P < 0.01) and more likely to have a pOR (OR 1.57, 95% CI 1.89-2.08; P < 0.01). On univariable Cox regression analyses, UTUC was associated with better OS (hazard ratio [HR] 0.80, 95% CI 0.64-0.99, P = 0.04) and CSS (HR 0.63, 95% CI 0.49-0.83; P < 0.01). On multivariable Cox regression analyses, UTUC remained associated with CSS (HR 0.61, 95% CI 0.45-0.82; P < 0.01), but not with OS. CONCLUSIONS: Our present findings suggest that the benefit of NAC in UTUC is similar to that found in UCB. These data can be used as a benchmark to contextualise survival outcomes and plan future trial design with NAC in urothelial cancer.

• Klíčová slova
• #BladderCancer, #blcsm, #uroonc, #utuc, bladder cancer, neoadjuvant chemotherapy, response, survival, upper tract urothelial carcinoma,
• MeSH
• cisplatina terapeutické užití   MeSH
• cystektomie MeSH
• deoxycytidin aplikace a dávkování   analogy a deriváty   MeSH
• doxorubicin terapeutické užití   MeSH
• gemcitabin MeSH
• karcinom z přechodných buněk patologie   terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• methotrexát terapeutické užití   MeSH
• míra přežití MeSH
• nádory ledvin patologie   terapie   MeSH
• nádory močového měchýře patologie   terapie   MeSH
• nádory močovodu patologie   terapie   MeSH
• nefroureterektomie MeSH
• neoadjuvantní terapie MeSH
• proporcionální rizikové modely MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• srovnávací výzkum účinnosti MeSH
• staging nádorů MeSH
• vinblastin terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cisplatina MeSH
• deoxycytidin MeSH
• doxorubicin MeSH
• gemcitabin MeSH
• methotrexát MeSH
• vinblastin 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