Immune checkpoint inhibition in upper tract urothelial carcinoma

Califano, Gianluigi; Ouzaïd, I.; Verze, Paolo; Hermieu, Jean-François; Mirone, Vincenzo; Xylinas, Évanguelos

doi:10.1007/s00345-020-03502-7

Cited by 32 publications

(35 citation statements)

References 35 publications

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“…At the same time, in UTUC patients, as well as in those with urothelial carcinoma of the urinary bladder, chemotherapy treatment is cisplatin-based, and might have an impact on renal function and consequent survival, specifically in patients treated with RNU. 23,25 However, even after adjustment for stage, chemotherapy administration and other variables, the CSM rate of Chinese patients did not significantly or meaningful differ from other Asian ethnic subgroups. In conclusion, it might be postulated that Vietnamese patients are affected by a two-hit phenomenon that is operational at diagnosis and after treatment.…”

Section: Discussionmentioning

confidence: 84%

Stage and cancer‐specific mortality differ within specific Asian ethnic groups for upper tract urothelial carcinoma: North American population‐based study

Ruvolo

Würnschimmel

Nocera³

et al. 2021

Int J of Urology

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Objectives: To examine the effect of specific Asian ethnic subgroups on stage at presentation and cancer-specific mortality in non-metastatic upper tract urothelial carcinoma among North American upper tract urothelial carcinoma Asian patients treated with radical nephroureterectomy. Methods: We relied on the Surveillance, Epidemiology and End Results database, from 2004 to 2016. Kaplan-Meier plots and multivariable Cox regression models predicting cancer-specific mortality were used. Results: Of 584 upper tract urothelial carcinoma patients, 173 (29.6%) were Chinese versus 130 (22.3%) Japanese versus 68 (11.6%) Korean versus 64 (11.0%) Filipino versus 40 (6.8%) Vietnamese versus 109 (18.7%) other. Vietnamese and Chinese patients showed the highest rates of T 4 N 0 M 0 and/or T 1-4 N 1-2 M 0 (25.0% and 18.5%, respectively), relative to other Asian ethnic subgroups. In Kaplan-Meier plots, Vietnamese patients showed the highest cancer-specific mortality rate. In multivariable models, Vietnamese ethnicity also independently predicted higher cancer-specific mortality (hazard ratio 2.15, P = 0.02 and hazard ratio 1.96, P = 0.03), relative to Japanese and Chinese patients. All other Asian ethnic subgroups showed similar cancer-specific mortality patterns. Conclusion: Vietnamese and Chinese patients are at a stage disadvantage at upper tract urothelial carcinoma diagnosis, relative to all other Asian ethnicities. After adjustment for stage, only Vietnamese patients showed a survival disadvantage relative to all other Asian ethnic subgroups. As a result, it appears that Vietnamese patients not only present at a higher upper tract urothelial carcinoma stage, but additionally appear to harbor upper tract urothelial carcinoma that progresses at a faster rate than in other Asian ethnic subgroups.

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Section: Discussionmentioning

confidence: 84%

Stage and cancer‐specific mortality differ within specific Asian ethnic groups for upper tract urothelial carcinoma: North American population‐based study

Ruvolo

Würnschimmel

Nocera³

et al. 2021

Int J of Urology

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“…In summary, patients with UTUC represent a small portion of the patients affected by urothelial cancer studied in the main trials; nevertheless, available data are encouraging [84].…”

Section: Implications For Systemic Therapymentioning

confidence: 95%

Current Knowledge on Genomic Profiling of Upper Tract Urothelial Carcinoma

Lorenzis

Albo

Longo

et al. 2021

Genes

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Recent research in next-generation sequencing characterized the genomic landscape of urothelial cancer. However, the majority of the studies focused on bladder cancer (BC). Upper urinary tract urothelial carcinomas (UTUC) and BC share some histological characteristics, but, considering the differences in terms of embryologic precursors, epidemiology, genetics, medical and surgical management and response to therapy, UTUC and BC should be considered as two distinct diseases. Our objective is to analyze through a literature search the latest updates and the current knowledge about the genomics of UTUC. We also evaluate genetic differences between BC and UTUC and the potential implications for systemic therapy. Molecular subtyping and variant histology and their correlation with response to chemotherapy were also explored. In summary, the most frequent genomic variations in UTUC included FGFR3, chromatin remodeling genes, TP53/MDM2 and other tumor suppressors/oncogenes. The genomics of UTUC, integrated with clinical data, could drive the selection of patients who could benefit from targeted therapy or off-label treatment. Routine implementation of tumor genomic characterization in UTUC patients should therefore be contemplated and evaluated prospectively.

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“…The percentage of patients was 74.5% and 55.7%, respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; p < 0.001), for those expressing PD-L1 more than 1% [62]. Moreover, several neoadjuvant trials combining chemotherapy with ICI are actively recruiting, but available data are currently limited [63][64][65].…”

Section: Immune Checkpoint Inhibitors In the Perioperative Settingmentioning

confidence: 99%

Efficacy of Immune Checkpoint Inhibitors in Upper Tract Urothelial Carcinomas: Current Knowledge and Future Directions

Thouvenin

Chanzá

Alhalabi

et al. 2021

Cancers

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Upper tract urothelial carcinoma (UTUC) represents a rare and aggressive malignancy arising from the renal pelvis or ureter. It can develop sporadically or have a hereditary origin, such as Lynch syndrome, caused by DNA mismatch repair deficiency, leading to microsatellite instability phenotype. According to molecular characterization studies, UTUC presents different mutational profiles as compared to urinary bladder urothelial carcinomas. In particular, it has been reported that UTUC harbored a higher level of FGFR3 alterations associated with a T-cell depleted immune microenvironment. The therapeutic landscape in urothelial carcinoma is rapidly evolving, with immune checkpoint inhibitors forming part of the standard of care. A greater understanding of the molecular alterations and immune microenvironment leads to the development of new treatment combinations and targeted therapy. This review summarizes the available evidence concerning the use of immune checkpoint inhibitors and the biological rationale underlying their use in high-grade UTUC.

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Immune checkpoint inhibition in upper tract urothelial carcinoma

Cited by 32 publications

References 35 publications

Stage and cancer‐specific mortality differ within specific Asian ethnic groups for upper tract urothelial carcinoma: North American population‐based study

Stage and cancer‐specific mortality differ within specific Asian ethnic groups for upper tract urothelial carcinoma: North American population‐based study

Current Knowledge on Genomic Profiling of Upper Tract Urothelial Carcinoma

Efficacy of Immune Checkpoint Inhibitors in Upper Tract Urothelial Carcinomas: Current Knowledge and Future Directions

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