Role of Ki-67, MRE11, and PD-L1 As Predictive Biomarkers for Recurrence Pattern in Muscle Invasive Bladder Cancer Following Radical Cystectomy

2021 ◽  
Author(s):  
Croix C. Fossum ◽  
Yin Xiong ◽  
Anthony Magliocco ◽  
Siamak Daneshmand ◽  
Manju Aron ◽  
...  
Keyword(s):  
Local Recurrence ◽  
Radical Cystectomy ◽  
Univariate Analysis ◽  
Predictive Biomarkers ◽  
Molecular Signature ◽  
Recurrence Pattern ◽  
Ki 67 ◽  
Normal Bladder ◽  
Muscle Invasive

Abstract Background Muscle invasive bladder (MIBC) cancer is an aggressive disease with high rates of local recurrence following radical cystectomy (RC). Currently, there are no clinically validated biomarkers to predict local only recurrence (LOR) and guide adjuvant treatment decisions. This pilot study evaluated the role of Ki-67, MRE11 and PD-L1 as predictive biomarkers for recurrence patterns in patients undergoing RC for MIBC. Methods: Our institutional cystectomy database containing cases of urothelial MIBC from 1992–2014 was queried for patients with LOR and case-matched with patients who had distant recurrence (DR) and no recurrence (NR). Clinical and histopathological data were collected from selected patients and a tissue microarray was built and analyzed for presence of Ki-67, MRE11 and PD-L1 using immunofluorescence (IF) and immunohistochemistry (IHC). Univariate, multivariate, and principal component analyses (PCA) were performed to evaluate association of these biomarkers with recurrence pattern. Results: Pathologic specimens from 42 patients (18 NR, 16 LOR and 8 DR) were reviewed. Compared to adjacent normal bladder tissue, tumors had increased expression of PD-L1 on both IHC and IF (p < 0.05) and higher Ki-67 H-score on IHC (33 vs 0, p < 0.01). A high Ki-67 was associated with recurrence pattern (local vs distant) on univariate analysis (p < 0.05) and on multivariate regression, having positive surgical margins was associated with local recurrence (p = 0.04). Ki-67 cell density varied by recurrence type: LR (1354 cells/mm2), DR (557 cells/mm2) and NR (1111 cells/mm2) p = 0.034. Several PCAs were unable to identify a signature associated with recurrence pattern. Conclusion: The biomarkers used in this study were helpful in distinguishing tumor from normal tissue and high Ki-67 may be associated with LOR, however, a useful molecular signature for recurrence pattern could not be identified.

scholarly journals Role of Ki-67, MRE11, and PD-L1 as Predictive Biomarkers for Recurrence Pattern in Muscle-invasive Bladder Cancer

2021 ◽  
Vol 41 (8) ◽  
pp. 3851-3857
Author(s):  
CROIX C. FOSSUM ◽  
YIN XIONG ◽  
ANTHONY MAGLIOCCO ◽  
SIAMAK DANESHMAND ◽  
MANJU ARON ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Predictive Biomarkers ◽  
Invasive Bladder Cancer ◽  
Recurrence Pattern ◽  
Muscle Invasive Bladder Cancer ◽  
Ki 67 ◽  
Muscle Invasive

Patterns of local recurrence after radical cystectomy in a contemporary series of patients with muscle-invasive bladder cancer

2012 ◽  
Vol 30 (6) ◽  
pp. 821-826 ◽  
Author(s):  
Jean-Nicolas Cornu ◽  
Yann Neuzillet ◽  
Jean-Marie Hervé ◽  
Laurent Yonneau ◽  
Henry Botto ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Local Recurrence ◽  
Radical Cystectomy ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

480 The staging role of 18FDG PET-CT in patients with muscle-invasive bladder cancer selected for radical cystectomy

2013 ◽  
Vol 12 (1) ◽  
pp. e480
Author(s):  
M.C. Ferriero ◽  
G. Simone ◽  
R. Papalia ◽  
S. Guaglianone ◽  
R. Sciuto ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
18Fdg Pet ◽  
Pet Ct ◽  
Muscle Invasive

scholarly journals Role of FGF Receptors and Their Pathways in Adrenocortical Tumors and Possible Therapeutic Implications

2021 ◽  
Vol 12 ◽  
Author(s):  
Iuliu Sbiera ◽  
Stefan Kircher ◽  
Barbara Altieri ◽  
Kerstin Lenz ◽  
Constanze Hantel ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Kinase Inhibitors ◽  
Univariate Analysis ◽  
Tumor Stage ◽  
Adrenal Tumors ◽  
Ki 67 ◽  
Fgf Receptor ◽  
Therapeutic Implications ◽  
Adrenocortical Tumors

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy and treatment of advanced disease is challenging. Clinical trials with multi-tyrosine kinase inhibitors in the past have yielded disappointing results. Here, we investigated fibroblast growth factor (FGF) receptors and their pathways in adrenocortical tumors as potential treatment targets. We performed real-time RT-PCR of 93 FGF pathway related genes in a cohort of 39 fresh frozen benign and malignant adrenocortical, 9 non-adrenal tissues and 4 cell lines. The expression of FGF receptors was validated in 166 formalin-fixed paraffin embedded (FFPE) tissues using RNA in situ hybridization (RNAscope) and correlated with clinical data. In malignant compared to benign adrenal tumors, we found significant differences in the expression of 16/94 FGF receptor pathway related genes. Genes involved in tissue differentiation and metastatic spread through epithelial to mesechymal transition were most strongly altered. The therapeutically targetable FGF receptors 1 and 4 were upregulated 4.6- and 6-fold, respectively, in malignant compared to benign adrenocortical tumors, which was confirmed by RNAscope in FFPE samples. High expression of FGFR1 and 4 was significantly associated with worse patient prognosis in univariate analysis. After multivariate adjustment for the known prognostic factors Ki-67 and ENSAT tumor stage, FGFR1 remained significantly associated with recurrence-free survival (HR=6.10, 95%CI: 1.78 – 20.86, p=0.004) and FGFR4 with overall survival (HR=3.23, 95%CI: 1.52 – 6.88, p=0.002). Collectively, our study supports a role of FGF pathways in malignant adrenocortical tumors. Quantification of FGF receptors may enable a stratification of ACC for the use of FGFR inhibitors in future clinical trials.

scholarly journals Complications and Discharge after Radical Cystectomy for Older Patients with Muscle-Invasive Bladder Cancer: The ELCAPA-27 Cohort Study

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6010
Author(s):  
Romain Geiss ◽  
Lucrezia Sebaste ◽  
Rémi Valter ◽  
Johanne Poisson ◽  
Soraya Mebarki ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Geriatric Assessment ◽  
Complication Rate ◽  
Older Patients ◽  
Univariate Analysis ◽  
Invasive Bladder Cancer ◽  
High Morbidity ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Radical cystectomy is the standard of care for localized bladder cancer but is associated with high morbidity and mortality rates—especially among older patients with comorbidities. The association between geriatric assessment parameters on post-operative complications and discharge has not previously been investigated. The present analysis of the Elderly Cancer Patient (ELCAPA) prospective cohort included all patients aged ≥70 having undergone a geriatric assessment and then radical cystectomy for localized muscle-invasive bladder cancer between 2007 and 2018. The primary endpoint was the proportion of patients with one or more complications in the first 30 days after cystectomy. The secondary endpoints were the length of hospital stay (LOS), the 30-day mortality, and discharge rates. Sixty-two patients (median age: 81; range: 79–83.8) were included. The 30-day complication rate was 73%, and 49% of the patients had experienced a major complication, according to the Clavien-Dindo classification. The 30-day mortality rate was 4%. None of the geriatric, oncological, or laboratory parameters were significantly associated with the occurrence or severity of complications. The median (interquartile range) LOS was 18 days (15–23) overall and was longer in patients with complications (19 days vs. 15 days in those without complications; p = 0.013). Thirty days after cystectomy, 25 patients (53%) had been discharged to home and 22 (47%) were still in a rehabilitation unit. In a univariate analysis, a Geriatric-8 score ≤14, a loss of one point on the Activities of Daily Living Scale, anemia, at least one grade ≥3 comorbidity on the Cumulative Illness Rating Scale-Geriatric, and an inpatient geriatric assessment were associated with a risk of not being discharged to home. In older patients having undergone a geriatric assessment, radical cystectomy is associated with a high complication rate, a longer LOS, and functional decline at 30 days.

Durvalumab as neoadjuvant therapy for muscle-invasive bladder cancer: Preliminary results from the Bladder Cancer Signal Seeking Trial (BLASST)-2.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 507-507 ◽  
Author(s):  
Xiao X. Wei ◽  
Bradley Alexander McGregor ◽  
Richard J. Lee ◽  
Xin Gao ◽  
Kerry L. Kilbridge ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Therapy ◽  
Radical Cystectomy ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Predictive Biomarkers ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Platinum Based Chemotherapy ◽  
Muscle Invasive

507 Background: There is no established neoadjuvant therapy (NAT) for patients (pt) with muscle invasive bladder cancer (MIBC) ineligible for cisplatin-based chemotherapy preceding radical cystectomy. Encouraging prospective data indicate PD-1/PD-L1 inhibitors, including pembrolizumab and atezolizumab, are safe and active as NAT for MIBC. Durvalumab (D), a PD-L1 inhibitor, is FDA approved for treating locally advanced or metastatic urothelial carcinoma following platinum-based chemotherapy. The safety and activity of D as NAT in MIBC have not been reported. Methods: We are conducting a single-center sequential multicohort trial (NCT03773666) of D alone (Cohort 1, N=10) and D plus the CD73 inhibitor oleclumab (Cohort 2, N=10) in cT2-T4aN0M0 MIBC pts who are RC candidates and are ineligible for or declined cisplatin-based chemotherapy. The primary endpoint is feasibility, defined as ≥7 of 10 pts receiving at least 1 dose of D followed by radical cystectomy without dose limiting toxicity (DLT) up to 12 wks post-RC. In Cohort 1, D is administered at 750mg IV Q2W for 3 cycles followed by RC 2-4 weeks after the last dose. Baseline and RC tissue and baseline and on-study blood are collected for correlative studies, including immunohistochemistry, genomics, transcriptomics, and metabolomics. Results: Cohort 1 has completed enrollment; ten pts were enrolled between Feb 2019 to Sept 2019. Median age was 67 (Range: 53-85) and 8 (80%) were men. All 10 pts completed 3 durvalumab doses. Eight pts completed planned RC with at least 12wk follow-up post-op to date. No DLTs were observed. One Grade 3 treatment-related adverse event (trAE) was reported (anemia), with no Grade 4 or higher trAE. Pathologic response (<pT2N0) was seen in 2 of 8 (25%) pts with pathologic complete response (pT0) in 1 (12.5%) pts. Updated safety and efficacy data from Cohort 1 will be presented. Conclusions: D appears to be feasible as NAT in MIBC with preliminary evidence for antitumor activity. Toxicities are consistent with data from other PD-1/PD-L1 inhibitor trials. Future cohorts will examine D-containing combination NAT strategies. Analysis of tissue and blood-based predictive biomarkers are ongoing. Clinical trial information: NCT03773666.

scholarly journals Evaluation of different p16 immunostaining methods and the prognostic role of p16/Ki-67 combined expression in non-muscle invasive bladder cancers

2015 ◽  
Vol 1 ◽  
pp. 57-66 ◽  
Author(s):  
Gülzade Özyalvaçli ◽  
Mehmet E. Özyalvaçli ◽  
Hesna M. Astarci ◽  
Çetin Boran ◽  
Cemile Yeşil ◽  
...  
Keyword(s):  
Prognostic Role ◽  
Ki 67 ◽  
Muscle Invasive
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