Comparison of Pathological Stage in Patients Treated with and without Neoadjuvant Chemotherapy for High Risk Upper Tract Urothelial Carcinoma

Liao, Ross; Gupta, Mohit; Schwen, Zeyad; Patel, Hiten D.; Kates, Max; Johnson, Michael H.; Hahn, Noah M.; McConkey, David J.; Bivalacqua, Trinity J.; Pierorazio, Phillip M.

doi:10.1016/j.juro.2017.12.054

Cited by 52 publications

(25 citation statements)

References 24 publications

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“…Of the 20 patients with UTUC who received NAC before RNU, two were MSI-H (one of which was UCC17), one was MSI-indeterminant (MSIsensor scores 3-10), and 17 were microsatellite stable (MSS, MSIsensor scores <3). Defining pathologic response as ≤pT1N0 34,35 , we observed pathologic response in 10 of 17 MSS patients (59%) and in neither of the two MSI-H patients.…”

Section: Establishment and Characterization Of Utuc Pdx And Pdcmentioning

confidence: 84%

Modeling biological and genetic diversity in upper tract urothelial carcinoma with patient derived xenografts

Kim

Audenet

et al. 2020

Nat Commun

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Treatment paradigms for patients with upper tract urothelial carcinoma (UTUC) are typically extrapolated from studies of bladder cancer despite their distinct clinical and molecular characteristics. The advancement of UTUC research is hampered by the lack of diseasespecific models. Here, we report the establishment of patient derived xenograft (PDX) and cell line models that reflect the genomic and biological heterogeneity of the human disease. Models demonstrate high genomic concordance with the corresponding patient tumors, with invasive tumors more likely to successfully engraft. Treatment of PDX models with chemotherapy recapitulates responses observed in patients. Analysis of a HER2 S310F-mutant PDX suggests that an antibody drug conjugate targeting HER2 would have superior efficacy versus selective HER2 kinase inhibitors. In sum, the biological and phenotypic concordance between patient and PDXs suggest that these models could facilitate studies of intrinsic and acquired resistance and the development of personalized medicine strategies for UTUC patients.

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Section: Establishment and Characterization Of Utuc Pdx And Pdcmentioning

confidence: 84%

Modeling biological and genetic diversity in upper tract urothelial carcinoma with patient derived xenografts

Kim

Audenet

et al. 2020

Nat Commun

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“…Although the pure adjuvant approach has been the general strategy for Phase III studies in RCC, a compelling argument can be made for incorporating neoadjuvant therapy, which has been utilized for other urological malignancies including urothelial carcinoma of the bladder and the upper urinary tracts [21][22][23][24]. Early data suggest the addition of neoadjuvant pembrolizumab to standard chemotherapy for high-risk breast cancer may triple the rate of pathologic complete response [25].…”

Section: Background and Rationalementioning

confidence: 99%

The Future of Perioperative Therapy in Advanced Renal Cell Carcinoma: How Can We Prosper?

et al. 2019

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Patients with high-risk renal cell carcinoma (RCC) experience high rates of recurrence despite definitive surgical resection. Recent trials of adjuvant tyrosine kinase inhibitor therapy have provided conflicting efficacy results at the cost of significant adverse events. PD-1 blockade via monoclonal antibodies has emerged as an effective disease-modifying treatment for metastatic RCC. There is emerging data across other solid tumors of the potential efficacy of neoadjuvant PD-1 blockade, and preclinical evidence supporting a neoadjuvant over adjuvant approach. PROSPER RCC is a Phase III, randomized trial evaluating whether perioperative nivolumab increases recurrence-free survival in patients with high-risk RCC undergoing nephrectomy. The neoadjuvant component, intended to prime the immune system for enhanced efficacy, distinguishes PROSPER from other purely adjuvant studies and permits highly clinically relevant translational studies.

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“…High tumor grade, increasing pathologic stage, lymph node metastases, sessile architecture, and lymphovascular invasion were independently associated with CSS. Prognosis of muscle invasive UTUC remains poor with 5-year CSS < 50% in pT2/T3 disease and less than 10% in pT4 disease [15]. With a mean follow-up of 51 months, 28% of patients had a disease recurrence [14].…”

Section: Prevalence and Prognosis Of Pt0mentioning

confidence: 99%

“…The reported rate of pT0 in patients undergoing radical nephroureterectomy (RNU) is between 0% and 0.7% [14,15,16,17,18]. This small number in comparison to UCB is likely due to the inability to completely resect or endoscopically ablate upper tract tumors due to the limitations of instrumentation and access through the ureter.…”

Section: Prevalence and Prognosis Of Pt0mentioning

confidence: 99%

Molecular Predictors of Complete Response Following Neoadjuvant Chemotherapy in Urothelial Carcinoma of the Bladder and Upper Tracts

Tse

Ghandour

Singla

et al. 2019

IJMS

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Urothelial carcinoma of the bladder (UCB) and upper tracts (UTUC) is often regarded as one entity and is managed generally with similar principles. While neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is an established standard of care in UCB, strong evidence for a similar approach is lacking in UTUC. The longest survival is seen in patients with complete response (pT0) on pathological examination of the RC specimen, but impact of delayed RC in nonresponders may be detrimental. The rate of pT0 following NAC in UTUC is considerably lower than that in UCB due to differences in access and instrumentation. Molecular markers have been evaluated to try to predict response to chemotherapy to reduce unnecessary treatment and expedite different treatment for nonresponders. A variety of potential biomarkers have been evaluated to predict response to cisplatin based chemotherapy including DNA repair genes (ATM, RB1, FANCC, ERCC2, BRCA1, and ERCC1), regulators of apoptosis (survivin, Bcl-xL, and emmprin), receptor tyrosine kinases (EGFR and erbB2), genes involved in cellular efflux (MDR1 and CTR1), in addition to molecular subtypes (Basal, luminal, and p53-like). The current state of the literature on the prediction of response to NAC based on the presence of these biomarkers is discussed in this review.

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Comparison of Pathological Stage in Patients Treated with and without Neoadjuvant Chemotherapy for High Risk Upper Tract Urothelial Carcinoma

Abstract: Patients with high risk upper tract urothelial carcinoma treated with neoadjuvant chemotherapy were noted to have a lower pathological stage distribution than patients treated with radical nephroureterectomy alone.

Cited by 52 publications

References 24 publications

Modeling biological and genetic diversity in upper tract urothelial carcinoma with patient derived xenografts

Modeling biological and genetic diversity in upper tract urothelial carcinoma with patient derived xenografts

The Future of Perioperative Therapy in Advanced Renal Cell Carcinoma: How Can We Prosper?

Molecular Predictors of Complete Response Following Neoadjuvant Chemotherapy in Urothelial Carcinoma of the Bladder and Upper Tracts

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