Contemporary best practice in the management of urothelial carcinomas of the renal pelvis and ureter

Maristella Bianconi, Alessia Cimadamore, Luca Faloppi, Mario Scartozzi, Matteo Santoni, Antonio Lopez-Beltran, Liang Cheng, Marina Scarpelli, Rodolfo Montironi

Research output: Contribution to journalReview article

Abstract

Upper tract urothelial carcinoma (UTUC) accounts for 5% of urothelial carcinomas (UCs), the estimated annual incidence being 1–2 cases per 100,000 inhabitants. Similarly to bladder UC, divergent differentiations and histologic variants confer an adverse risk factor in comparison with pure UTUC. Molecular and genomic characterization studies on UTUC have shown changes occurring at differing frequencies from bladder cancer, with unique molecular and clinical subtypes, potentially with different responses to treatment. Systemic chemotherapy is the standard approach for patients with inoperable locally advanced or metastatic UCs. Although initial response rates are high, the median survival with combination chemotherapy is about 15 months. In first-line chemotherapy several cisplatin-based regimens have been proposed. For patients with advanced UC who progress to first-line treatment, the only product licensed in Europe is vinflunine, a third-generation, semisynthetic, vinca alkaloid. Better response rates (15–60%), with higher toxicity rates and no overall survival (OS) benefit, are generally achieved in multidrug combinations, which often include taxanes and gemcitabine. The US FDA has recently approved five agents targeting the programmed death-1 and programmed death ligand-1 pathway as a second-line therapy in patients with locally advanced or metastatic UC with disease progression during or following platinum-containing chemotherapy. Potential therapeutic targets are present in 69% of tumours analyzed. Specific molecular alterations include those involved in the RTK/Ras/PI(3)K, cell-cycle regulation and chromatin-remodeling pathways, many of them have either targeted therapies approved or under investigation. Angiogenic agents, anti-epidermal growth factor receptor therapy, phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) pathway inhibitors and immunotherapeutic drugs are being successfully investigated.

Original languageEnglish (US)
JournalTherapeutic Advances in Urology
Volume11
DOIs
StatePublished - Jan 1 2019

Fingerprint

Kidney Pelvis
Practice Management
Ureter
Practice Guidelines
Carcinoma
gemcitabine
Drug Therapy
Therapeutics
Vinca Alkaloids
Taxoids
Chromatin Assembly and Disassembly
1-Phosphatidylinositol 4-Kinase
Survival
Sirolimus
Combination Drug Therapy
Platinum
Epidermal Growth Factor Receptor
Urinary Bladder Neoplasms
Cisplatin
Disease Progression

Keywords

  • antiangiogenic agents
  • chemotherapy
  • gene expression profiling
  • immunotherapy
  • target therapies
  • upper urinary tract
  • urothelial carcinoma

ASJC Scopus subject areas

  • Urology

Cite this

Bianconi, M., Cimadamore, A., Faloppi, L., Scartozzi, M., Santoni, M., Lopez-Beltran, A., ... Montironi, R. (2019). Contemporary best practice in the management of urothelial carcinomas of the renal pelvis and ureter. Therapeutic Advances in Urology, 11. https://doi.org/10.1177/1756287218815372

Contemporary best practice in the management of urothelial carcinomas of the renal pelvis and ureter. / Bianconi, Maristella; Cimadamore, Alessia; Faloppi, Luca; Scartozzi, Mario; Santoni, Matteo; Lopez-Beltran, Antonio; Cheng, Liang; Scarpelli, Marina; Montironi, Rodolfo.

In: Therapeutic Advances in Urology, Vol. 11, 01.01.2019.

Research output: Contribution to journalReview article

Bianconi, M, Cimadamore, A, Faloppi, L, Scartozzi, M, Santoni, M, Lopez-Beltran, A, Cheng, L, Scarpelli, M & Montironi, R 2019, 'Contemporary best practice in the management of urothelial carcinomas of the renal pelvis and ureter', Therapeutic Advances in Urology, vol. 11. https://doi.org/10.1177/1756287218815372
Bianconi, Maristella ; Cimadamore, Alessia ; Faloppi, Luca ; Scartozzi, Mario ; Santoni, Matteo ; Lopez-Beltran, Antonio ; Cheng, Liang ; Scarpelli, Marina ; Montironi, Rodolfo. / Contemporary best practice in the management of urothelial carcinomas of the renal pelvis and ureter. In: Therapeutic Advances in Urology. 2019 ; Vol. 11.
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abstract = "Upper tract urothelial carcinoma (UTUC) accounts for 5{\%} of urothelial carcinomas (UCs), the estimated annual incidence being 1–2 cases per 100,000 inhabitants. Similarly to bladder UC, divergent differentiations and histologic variants confer an adverse risk factor in comparison with pure UTUC. Molecular and genomic characterization studies on UTUC have shown changes occurring at differing frequencies from bladder cancer, with unique molecular and clinical subtypes, potentially with different responses to treatment. Systemic chemotherapy is the standard approach for patients with inoperable locally advanced or metastatic UCs. Although initial response rates are high, the median survival with combination chemotherapy is about 15 months. In first-line chemotherapy several cisplatin-based regimens have been proposed. For patients with advanced UC who progress to first-line treatment, the only product licensed in Europe is vinflunine, a third-generation, semisynthetic, vinca alkaloid. Better response rates (15–60{\%}), with higher toxicity rates and no overall survival (OS) benefit, are generally achieved in multidrug combinations, which often include taxanes and gemcitabine. The US FDA has recently approved five agents targeting the programmed death-1 and programmed death ligand-1 pathway as a second-line therapy in patients with locally advanced or metastatic UC with disease progression during or following platinum-containing chemotherapy. Potential therapeutic targets are present in 69{\%} of tumours analyzed. Specific molecular alterations include those involved in the RTK/Ras/PI(3)K, cell-cycle regulation and chromatin-remodeling pathways, many of them have either targeted therapies approved or under investigation. Angiogenic agents, anti-epidermal growth factor receptor therapy, phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) pathway inhibitors and immunotherapeutic drugs are being successfully investigated.",
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