The dilemma of neoadjuvant and adjuvant therapy in urothelial carcinoma: will immunotherapy solve the problem?

TPS600 Background: Radical surgery ± cisplatin‐based (neo)adjuvant therapy (NAT) is the mainstay of treatment for invasive urothelial carcinoma of the upper urinary tract (UTUC) or bladder (UBC), but recurrence rates are high. Furthermore, many patients (pts) are unable to receive NAT because of cisplatin ineligibility. Fibroblast growth factor receptor 3 (FGFR3) genetic alterations occur in up to 70% of UTUC and up to 20% of UBC, and may constitute a potential candidate for targeted therapy. Infigratinib (BGJ398), a selective FGFR1–3 inhibitor, has shown promising clinical activity and tolerability in pts with advanced urothelial carcinoma having FGFR3 alterations [Pal et al. Cancer Discov 2018]. PROOF 302 has been designed to investigate the efficacy and safety of infigratinib versus placebo as adjuvant therapy in pts with high-risk invasive urothelial carcinoma and FGFR3 alterations. Methods: PROOF 302 is a randomized, double-blind, placebo-controlled, phase III study of approx. 218 pts. Adults with high-risk invasive UTUC or UBC with FGFR3 genetic alterations (i.e. mutations, gene fusions or translocations) who are ≤120 days following surgical resection and ineligible for cisplatin-based adjuvant chemotherapy or with residual disease after cisplatin- based NAT are eligible. Those who received non cisplatin-based NAT are eligible if they have residual disease and are ineligible for adjuvant cisplatin. Pts receive oral infigratinib 125 mg or placebo (1:1 ratio) once daily on days 1–21 every 28 days for up to 52 weeks or until disease recurrence, unacceptable toxicity or death. Primary endpoint: centrally reviewed disease-free survival (DFS). Secondary endpoints: DFS including intraluminal low-risk recurrence; metastasis-free survival; overall survival; DFS (per investigator); safety and tolerability. Exploratory endpoints include: quality of life; pharmacokinetics; cell-free DNA (cfDNA) and/or RNA for resistance mechanisms. The study will involve approximately 120 centers worldwide. Enrollment is expected to begin in January 2020. Trial registration: EudraCT 2019-003248-63. Clinical trial information: EudraCT 2019-003248-63.

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Selection, Administration and Description of Neoadjuvant versus Adjuvant Therapy for Upper Tract Urothelial Carcinoma

Bladder Cancer ◽

10.1007/978-3-030-70646-3_39 ◽

2021 ◽

pp. 447-456

Author(s):

Rohan Shotton ◽

Alison Birtle

Keyword(s):

Adjuvant Therapy ◽

Urothelial Carcinoma ◽

Upper Tract Urothelial Carcinoma ◽

Upper Tract

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Multifocal Synchronous Upper Urinary Tract Carcinosarcoma (Sarcomatoid Carcinoma) With Rhabdomyoblastic Differentiation

International Journal of Surgical Pathology ◽

10.1177/1066896919828111 ◽

2019 ◽

Vol 27 (5) ◽

pp. 547-552 ◽

Cited By ~ 1

Author(s):

Kosuke Takemura ◽

Toru Motoi ◽

Akiko Tonooka ◽

Nobuaki Funata ◽

Yasukazu Nakanishi ◽

...

Keyword(s):

Stem Cells ◽

Urinary Tract ◽

Adjuvant Therapy ◽

Urothelial Carcinoma ◽

Renal Pelvis ◽

Sarcomatoid Carcinoma ◽

Upper Urinary Tract ◽

Radical Nephroureterectomy ◽

Visceral Metastases ◽

Neoplastic Stem Cells

Carcinosarcoma of the upper urinary tract is very rare. In this article, we report a case of upper urinary tract carcinosarcoma with rhabdomyoblastic differentiation showing distinct transition between the epithelial and mesenchymal components confirmed by morphology and immunohistochemistry. An 81-year-old female underwent radical nephroureterectomy under the diagnosis of left ureteral urothelial carcinoma (UC). Multiple invasive tumors showed combined histology with UC and rhabdomyosarcomatous elements (pT2-ureter and pT3-renal pelvis, pN0, u-lt0, ly0, v0, RM0). Each element demonstrated typical epithelial or mesenchymal staining patterns (positive for AE1/AE3 in the former and positive for vimentin and myogenin in the latter). Notably, immunohistochemical transition patterns of GATA-3, p63, SOX2, and myogenin between UC and rhabdomyosarcomatous elements were observed, implying possible involvement of neoplastic stem cells in the process of carcinosarcoma formation. The patient did not receive any adjuvant therapy and eventually succumbed to multiple visceral metastases (lungs and liver) at 11 months postoperatively. No autopsy was performed.

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