Prognostic value of PD-L1 combined positive score in patients with upper tract urothelial carcinoma

Chen, Chien-Hsu; Tsai, Mu-Yao; Chiang, Ping-Chia; Sung, Ming-Tse; Luo, Hao-Lun; Suen, Jau‐Ling; Tsai, Eing‐Mei; Chiang, Po‐Hui

doi:10.1007/s00262-021-02890-y

Cited by 11 publications

(12 citation statements)

References 32 publications

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“…Among the various biomarkers examined previously, Ki-67 appears to be the most potential biomarker with its cell proliferation characteristic [10,11,19]. In our previous study, we found that a PD-L1 combined positive score (CPS) ≥ 10 in UTUC was associated with worse CSS and overall survival (OS) [20]. However, few studies have evaluated the prognostic value of Ki-67 and PD-L1 in combination.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Prognostic Value of Ki-67 and Programmed Cell Death Ligand-1 in Patients with Upper Tract Urothelial Carcinoma

Tsai

Chiang

Chen

et al. 2021

JCM

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We retrospectively enrolled 102 patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy to examine the prognostic value of Ki-67 and programmed cell death ligand-1 (PD-L1). Then, we performed PD-L1 and Ki-67 immunohistochemical staining on whole tissue sections. The cut-off value of PD-L1 positivity was a combined positive score (CPS) ≥10 and the Ki-67 overexpression was 20%. Among the 102 patients, 16.7% and 48.0% showed positive PD-L1 expression and Ki-67 overexpression, respectively. A CPS ≥10 was significantly associated with a higher pathological T stage (p = 0.049). In addition, Ki-67 overexpression was significantly associated with a pathological T stage ≥ 2 (p = 0.027) and tumour necrosis (p = 0.016). In the multivariable analysis, a positive PD-L1 expression was significantly correlated with worse cancer-specific survival (HR = 3.66, 95% CI =1.37−9.77, p = 0.01). However, there was no predictive value using a combination of PD-L1 expression and Ki-67 overexpression as a prognostic predictor. Compared with Ki-67 overexpression, a positive PD-L1 expression with CPS ≥ 10 was a stronger independent prognostic factor for CSS in patients with UTUC.

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Section: Introductionmentioning

confidence: 99%

Comparison of the Prognostic Value of Ki-67 and Programmed Cell Death Ligand-1 in Patients with Upper Tract Urothelial Carcinoma

Tsai

Chiang

Chen

et al. 2021

JCM

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“…Finally, correlations were observed between PD-L1 positivity on tumoral cells and the worse outcomes in UTUC patients, although PD-L1 expression rate varied between 20−25% depending on the study and the cutoff used [41,42].…”

Section: The Immune Microenvironment Of Utucmentioning

confidence: 94%

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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“…11 According to the results of several current clinical trials, PD-L1 expression is a biomarker that can indicate which patients will benefit the most from PD-1/PD-L1 −targeted therapies. 12,13 Several studies have demonstrated that PD-L1 expression can be evaluated in resection specimens and tissue microarray of UTUC, and have suggested that PD-L1 expression is associated with adverse pathological features and is an independent predictor of worse cancer-specific and overall survival. 12,14,15 Some studies in other tumors have demonstrated that the expression of PD-L1 in cell blocks can represent PD-L1 expression in the entire tumor within a certain range.…”

Section: Introductionmentioning

confidence: 99%

“…12,13 Several studies have demonstrated that PD-L1 expression can be evaluated in resection specimens and tissue microarray of UTUC, and have suggested that PD-L1 expression is associated with adverse pathological features and is an independent predictor of worse cancer-specific and overall survival. 12,14,15 Some studies in other tumors have demonstrated that the expression of PD-L1 in cell blocks can represent PD-L1 expression in the entire tumor within a certain range. For example, Muggilli et al 16 found that cytological block samples are useful for evaluating PD-L1 expression based on tumor positive score because the concordance rate was 93% in pancreatic ductal adenocarcinoma.…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, as a result of an improved understanding of cancer immunobiology, systemic immunotherapies targeting immune checkpoint inhibitors (ICIs) have been explored and clinically applied for the treatment of urothelial carcinoma 11 . According to the results of several current clinical trials, PD‐L1 expression is a biomarker that can indicate which patients will benefit the most from PD‐1/PD‐L1−targeted therapies 12,13 . Several studies have demonstrated that PD‐L1 expression can be evaluated in resection specimens and tissue microarray of UTUC, and have suggested that PD‐L1 expression is associated with adverse pathological features and is an independent predictor of worse cancer‐specific and overall survival 12,14,15 .…”

Section: Introductionmentioning

confidence: 99%

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Cutoff values of PD‐L1 expression in urinary cytology samples for predicting response to immune checkpoint inhibitor therapy in upper urinary tract urothelial carcinoma

Chen

et al. 2022

Cancer Cytopathology

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Background:The objective of this study was to determine the cutoff value of PD-L1 expression that can predict response to immune checkpoint inhibitor (ICI) immunotherapy for upper tract urothelial carcinoma (UTUC). Methods:The concordance of PD-L1 expression between paired surgical resection specimens (SRSs) and urine cell blocks (UCBs) (cohort 1) was studied in a retrospective set of 58 UTUC patients to determine its suitability as a predictor of ICI immunotherapy efficacy. PD-L1 expression in UCBs obtained before neoadjuvant ICI immunotherapy was verified in a prospective set of 12 UTUC patients (cohort 2). PD-L1 (SP263 clone) expression was assessed for percentage (tumor proportional score) of tumor cell (TC) showing PD-L1 staining. Results:The authors found an overall agreement of 94.4% (51 of 54) between UCBs and SRSs in cohort 1 (positive percent agreement = 100%, negative percent agreement = 93.8%, r value = 0.63). PD-L1 expression in <10% and ≥10% of tumor cells (TCs) of UCBs were the best predictors of negative (<25%) and positive (≥25%) expression in TCs of SRSs, respectively (concordance = 98.1%, r value = 0.93). These findings were verified in cohort 2: at the 10% cutoff for PD-L1 expression, the best response predictive value was 83.3% (5 of 6) in PD-L1-positive patients, and the nonresponse predictive value was 50% (3 of 6) in PD-L1-negative patients. The sensitivity, specificity, and area under the receiver operating characteristic curve values for predicting ICI immunotherapy efficacy based on PD-L1expressing TCs in UCBs were 62.5%, 75%, and 0.688, respectively.Conclusions: Immunocytochemistry of UCBs is reliable for determining PD-L1 expression, which can predict the efficacy of ICI immunotherapy at a cutoff of 10%.

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Prognostic value of PD-L1 combined positive score in patients with upper tract urothelial carcinoma

Cited by 11 publications

References 32 publications

Comparison of the Prognostic Value of Ki-67 and Programmed Cell Death Ligand-1 in Patients with Upper Tract Urothelial Carcinoma

Comparison of the Prognostic Value of Ki-67 and Programmed Cell Death Ligand-1 in Patients with Upper Tract Urothelial Carcinoma

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

Cutoff values of PD‐L1 expression in urinary cytology samples for predicting response to immune checkpoint inhibitor therapy in upper urinary tract urothelial carcinoma

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