Efficacy of Preoperative Chemotherapy for High Risk Upper Tract Urothelial Carcinoma

Foerster, Beat; Abufaraj, Mohammad; Petros, Firas; Azizi, Mounsif; Gupta, Mohit; Schweitzer, D.G.; Margulis, Vitaly; Iwata, Takehiro; Kimura, Shoji; Shabsigh, Ahmad; Briganti, Alberto; Ku, Ja‐Lok; Muilwijk, Tim; Kassouf, Wassim; Matin, Surena F.; Spiess, Philippe E.; Pierorazio, Phillip M.; Hendricksen, Kees; Shariat, Shahrokh F.

doi:10.1097/ju.0000000000000737

Cited by 37 publications

(25 citation statements)

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“…Regarding NAC, welldesigned prospective trials are insufficient, whereas the Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network (ACRIN) 8141 trial, a Phase II trial of NAC for extirpative surgery in patients with high-grade UTUC, reported a 14% pathological complete response (pCR), although longer follow-up is required to evaluate the survival outcomes [8]. Several retrospective studies have also shown that NAC induced pathological downstaging (pDS) and pCR associated with favourable oncological outcomes in high-risk or locally advanced UTUC, supporting the consideration of NAC [9][10][11][12][13][14]. Recent metaanalyses have also shown that NAC was associated with higher rates of pDS and pCR and with better recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) in patients with locally advanced or nodepositive UTUC [15,16].…”

Section: Introductionmentioning

confidence: 99%

Two cycles of neoadjuvant chemotherapy improves survival in patients with high‐risk upper tract urothelial carcinoma

et al. 2020

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Objectives To assess the impact of two cycles of neoadjuvant chemotherapy (NAC) in patients who underwent nephroureterectomy for high‐risk cN0M0 upper tract urothelial carcinoma (UTUC), and to evaluate the efficacy of NAC in patients with localised disease (≤cT2). Patients and Methods We retrospectively analysed patients with high‐risk cN0M0 UTUC who received NAC followed by surgery, compared with a matched cohort who underwent initial surgery at Fujita Health University during 2005–2019. Baseline and tumour characteristics, overall survival (OS), cancer‐specific survival (CSS), and recurrence‐free survival (RFS) were compared between the cohorts. Cox proportional hazards models were used to identify predictors of survival. Results There were 117 and 67 patients in the study group and the control group, respectively. Significantly higher pathological downstaging (pDS) and lower lymphovascular invasion (LVI) were observed in the study group than in the control group (48% vs 22%, P = 0.008 and 29% vs 46%, P = 0.045, respectively). The NAC group had significantly better 5‐year OS (79% vs 53%, P = 0.003), 5‐year CSS (84% vs 66%, P = 0.008), and 5‐year RFS (80% vs 61%, P = 0.001) than the control group. The OS benefit of NAC was observed even in patients with localised (≤cT2) disease (P = 0.019). Patients with LVI showed significantly worse CSS both in pathologically locally advanced (≥pT3) and in localised (≤pT2) tumours (P = 0.048 and P = 0.018, respectively). Multivariate analysis identified LVI, NAC, and pDS as independent predictors of OS. Male sex and post‐NAC LVI were identified as predictors of worse survival in patients who underwent NAC. Conclusions Two cycles of NAC improved the survival of patients with high‐risk UTUC, even in patients with localised disease. Although two cycles of NAC appear to be effective in cN0M0 high‐risk UTUC including localised disease, additional larger sample size multicentre prospective studies comparing short‐course NAC regimens followed by surgery and surgery alone are required.

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Section: Introductionmentioning

confidence: 99%

Two cycles of neoadjuvant chemotherapy improves survival in patients with high‐risk upper tract urothelial carcinoma

et al. 2020

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“…2A ). Several studies have suggested that pathological downstaging is a potential endpoint of NAC in UTUC [ 16 , 17 , 28 ]. However, difficulty in making an accurate T stage diagnosis is a strong limitation of pathological downstaging.…”

Section: Discussionmentioning

confidence: 99%

“…However, there is a lack of Level 1 evidence supporting the clinical benefit of NAC for locally advanced UTUC. Nevertheless, the use of NAC for locally advanced UTUC has slowly increased over time across the world [ 13 , 14 , 15 , 16 , 17 ]. In the present study, our aim was to evaluate the temporal trends in NAC utilisation and oncological outcomes in a representative cohort of patients with locally advanced UTUC.…”

Section: Introductionmentioning

confidence: 99%

Trends in the use of neoadjuvant chemotherapy and oncological outcomes for high‐risk upper tract urothelial carcinoma: a multicentre retrospective study

et al. 2021

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To evaluate temporal trends in neoadjuvant chemotherapy (NAC) utilisation and outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC). Patients and MethodsWe included 289 patients from seven hospitals who underwent radical nephroureterectomy (RNU) for locally advanced UTUC (≥cT3 or cN+) between 2000 and 2020. These patients received RNU alone or two to four courses of NAC with either a cisplatin-or carboplatin-based regimen. We evaluated the temporal changes in NAC use and compared the visceral recurrence-free, cancer-specific, and overall survival rates. The effect of NAC on oncological outcomes was examined using multivariate Cox regression analysis with inverse probability of treatment weighting (IPTW) models. ResultsOf 289 patients, 144 underwent NAC followed by RNU (NAC group) and 145 underwent RNU alone (Control [Ctrl] group). NAC use increased significantly from 19% (2006-2010), 58% (2011)(2012)(2013)(2014)(2015), to 79% (2016-2020). Pathological downstaging was significantly higher in the NAC group than in the Ctrl group. The IPTW-adjusted multivariable analyses showed that NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group. Moreover, carboplatin-based NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group among patients with chronic kidney disease Stage ≥3. There were no significant differences in oncological outcomes between the cisplatin-and carboplatin-based regimens. ConclusionsThe use of NAC for high-risk UTUC increased significantly after 2010. Platinum-based short-term NAC followed by immediate RNU may not impede and potentially improves oncological outcomes.

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“…Moreover, prospective data from a phase II trial showed that the use of neoadjuvant chemotherapy were associated with a 14% pathological complete response rate and a 62% downstaging rate for high-grade UTUC [39]. This result is even more encouraging given that tumor downstaging has been shown to be a strong predictor of improved survival outcomes after neoadjuvant chemotherapy and RNU [40].…”

Section: Standard Of Care According To Actual Guidelinesmentioning

confidence: 93%

Current Evidence and Future Perspectives in the Management of Nonmetastatic Upper Tract Urothelial Carcinoma

Lenfant

Breda

Xylinas

et al. 2022

European Urology Oncology

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This case-based discussion describes the management of a 66-yr-old man who presented to the emergency department with gross hematuria. His urine cytology was benign, and computed tomography (CT) with nephrographic phase revealed a 2.5 cm filling defect within the left renal pelvis and luminal narrowing in the right proximal ureter with hydronephrosis. CT showed no lymphadenopathy and no sign of metastatic disease. Cystoscopy was normal. In a progressive case-based discussion fashion, we will discuss the diagnostic and treatment options with two different perspectives: (1) guidelines-based current standard of care and (2) an outlook on future perspectives using the latest scientific advances that may soon become the standard of care. Patient summary: This presentation of a real-life clinical scenario will be useful in describing the current standard of care and future perspectives regarding the diagnosis and treatment of upper urinary tract tumors.

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Efficacy of Preoperative Chemotherapy for High Risk Upper Tract Urothelial Carcinoma

Cited by 37 publications

References 0 publications

Two cycles of neoadjuvant chemotherapy improves survival in patients with high‐risk upper tract urothelial carcinoma

Two cycles of neoadjuvant chemotherapy improves survival in patients with high‐risk upper tract urothelial carcinoma

Trends in the use of neoadjuvant chemotherapy and oncological outcomes for high‐risk upper tract urothelial carcinoma: a multicentre retrospective study

Current Evidence and Future Perspectives in the Management of Nonmetastatic Upper Tract Urothelial Carcinoma

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