Immunotherapy and Sonpavde score validation in advanced upper tract urothelial carcinoma: a retrospective study by the Italian Network for Research in Urologic-Oncology

Immunotherapy ◽  
2021 ◽  
Author(s):  
Melissa Bersanelli ◽  
Giulia Mazzaschi ◽  
Patrizia Giannatempo ◽  
Daniele Raggi ◽  
Elena Farè ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Treatment Decision ◽  
Progression Free Survival ◽  
Upper Tract Urothelial Carcinoma ◽  
Urologic Oncology ◽  
Upper Tract ◽  
Treatment Decision Making ◽  
Few Data

Background: Few data are available regarding the effectiveness of immune checkpoint inhibitors in advanced upper tract urothelial carcinoma (UTUC) patients. Methods: To provide a real-world experience with anti-PD-1/PD-L1-based therapy in UTUC patients, we involved an Italian network in a multicenter retrospective analysis. Results: A total of 78 UTUC patients were enrolled. The median follow-up was 25.1 months. The median progression-free survival (mPFS) was 2.2 months (95% CI 1.8–2.6), and the median OS (mOS) was 6.0 months (95% CI 3.6–8.4). The Sonpavde score (including performance status > 0, hemoglobin < 10 g/dl, liver metastases, time from prior chemotherapy ≥ 3 months) split the patients into three groups (0 vs 1 vs 2–4 factors), efficiently predicting the OS and PFS outcome at the multivariate analyses (p < 0.0001). Conclusion: The prognosis of unselected UTUC patients is still unsatisfactory. The Sonpavde score was validated for the first time in an UTUC population, as a useful tool for the treatment decision-making process.

Nivolumab demonstrates benefit over nomogram-predicted 12-month survival as salvage therapy for metastatic urothelial carcinoma.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 451-451 ◽  
Author(s):  
Gregory Russell Pond ◽  
Guru Sonpavde ◽  
Matt D. Galsky ◽  
Padmanee Sharma ◽  
Jonathan E. Rosenberg ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Urothelial Carcinoma ◽  
Salvage Therapy ◽  
Group Performance ◽  
Checkpoint Inhibitors ◽  
Statistical Significance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Metastatic Urothelial Carcinoma

451 Background: Intermediate endpoints of benefit in metastatic urothelial carcinoma (mUC) nonrandomized trials are necessary to identify promising drugs, particularly for checkpoint inhibitors, where response and progression-free survival remain suboptimal. We previously reported a nomogram (Pond GR et al, 2017 GU Cancers Symposium) using 5 prognostic factors (hemoglobin < 10 g/dL, Eastern Cooperative Oncology Group performance status ≥1, presence of liver metastasis, time from last treatment ≤3 months, and albumin < lower limit of normal) from phase 2 trials of historical agents (eg, taxanes) to estimate 12-month overall survival (OS), against which observed survival could be compared. Nivolumab was granted approval as salvage therapy for patients with mUC, based on the CheckMate (CM) 275 trial; it is thus of interest to compare the nivolumab observed survival versus nomogram-predicted survival results. Methods: Data were obtained from CM 275, including survival and all 5 prognostic factors. Nomogram points were calculated and the expected 12-month OS was estimated. Bootstrap analyses based on 2000 replications were used to estimate 95% confidence intervals (CIs) for the median expected, observed, and difference between the expected and observed 12-month OS values. All tests were 2-sided, with statistical significance defined as P≤0.05. Results: Data were available from 270 patients from CM 275. Fifteen patients did not have albumin recorded and were excluded. Among the 255 evaluable patients, 46 (18.0%) patients had 0 adverse prognostic factors, 85 (33.3%) had 1, and 124 (48.6%) had 2 or more. The observed nivolumab 12-month OS from CM 275 (43.3% [95% CI, 37.0%-50.5%]) was 19.8% higher (95% CI, 13.6%-26.4%) when compared with the nomogram-predicted 12-month OS (23.5%; [95% CI, 22.5%-25.5%]) if patients received historical chemotherapy. Across all 2000 bootstrap samples, the observed nivolumab 12-month OS exceeded the nomogram-predicted 12-month OS. Conclusions: Nivolumab was associated with a significantly improved 12-month OS compared with historical chemotherapy based on the value predicted by the validated nomogram incorporating baseline prognostic factors. Clinical trial information: NCT02387996.

Marker of lipid peroxidation TBARS predicts survival in patients with metastaticurothelial carcinoma (MUC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17023-e17023
Author(s):  
Jan Slopovsky ◽  
Jarmila Kucharska ◽  
Jana Obertova ◽  
Michal Mego ◽  
Katarina Kalavska ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Performance Status ◽  
Treatment Decision ◽  
Progression Free Survival ◽  
High Plasma ◽  
Rank Test ◽  
Treatment Decision Making ◽  
Kaplan Meier ◽  
Platinum Based Chemotherapy ◽  
Chemotherapy Initiation

e17023 Background: Oxidative stress plays a significant role in cancer development and progression. A marker of lipid peroxidation TBARS is upregulated in various diseases. The objective of this prospective study was to explore predictive and prognostic values of TBARS in MUC patients (pts.) before the first-line platinum-based chemotherapy. Methods: Seventy-two consecutive pts. (57 men) with MUC (58 bladder, 14 upper GU tract) were enrolled into this study. Performance status ECOG ≥ 2 had 11 pts., visceral metastases were present in 34 pts. Most common type of treatment regimen was gemcitabine and cisplatin (65 pts.), gemcitabine and carboplatin received 7 pts. Based upon TBARS mean of 6,06 μmol/L, pts. were dichotomized into low and high groups. Progression-free survival (PFS), overall survival (OS) and their 95% CI were estimated by Kaplan-Meier method and compared with log-rank test. Results: At median follow-up of 9.6 months, 65 pts. experienced progression and 64 pts. died. Pts. with low TBARS had significantly better survival opposed to pts. with high TBARS (HR 0.44, 95% CI 0.27-0.74; P = 0,0009 for OS and HR 0.51; 95% CI 0.31-0.84; P = 0,006 for PFS, respectively). Pts. with ECOG ≤ 1 had significantly better both, OS and PFS in comparison to pts. with ECOG > 2. Conclusions: In this study, high plasma TBARS levels in patients with MUC before chemotherapy initiation were associated with poor survival. Therefore, this biomarker could be used for identification of patients with worse prognosis and could lead to better patient stratification and treatment decision making. The study was supported by VEGA 1/0614/12. Key Words: Metastatic Urothelial Carcinoma. Platinum-Based Chemotherapy. Lipid Peroxidation. TBARS. Survival.

scholarly journals Validation of Hyponatremia as a Prognostic Predictor in Multiregional Upper Tract Urothelial Carcinoma

2020 ◽  
Vol 9 (4) ◽  
pp. 1218
Author(s):  
Hsin-Chih Yeh ◽  
Ching-Chia Li ◽  
Sheng-Chen Wen ◽  
Nirmish Singla ◽  
Solomon L. Woldu ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Cox Regression ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Upper Tract Urothelial Carcinoma ◽  
Clinicopathologic Characteristics ◽  
General Applicability ◽  
Upper Tract ◽  
The Impact ◽  
The U.S

Hyponatremia has been shown to be associated with prognosis in various cancers, but its role in upper tract urothelial carcinoma (UTUC) is largely unidentified. We created an international multiregional cohort of UTUC, consisting of 524 and 213 patients from Taiwan and the U.S., to validate the significance of hyponatremia. Clinicopathologic characteristics were compared according to the presence of hyponatremia. Univariate and multivariate Cox regression models were used to investigate the association of hyponatremia with disease progression and survival. The impact of hyponatremia in patients from distinct regions was also analyzed. Hyponatremia was found in 143 (19.4%) patients. Hyponatremic patients had significantly worse Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.00001) and higher pT stage (p = 0.002). In multivariate analysis, hyponatremia was an independent prognostic factor for progression (HR 1.585, 95% CI 1.115–2.253, p = 0.010), cancer-specific death (HR 2.225, 95% CI 1.457–3.397, p = 0.0002), and overall mortality (HR 1.819, 95% CI 1.299–2.545, p = 0.0005). Kaplan–Meier analysis showed the consistent adverse effect of hyponatremia on all outcomes in patients from Taiwan and the U.S. (all p < 0.05). Hyponatremia is commonly accessible and can serve as a negative marker for both the general health condition and disease severity of UTUC patients. A similar implication of hyponatremia in progression and survival despite patients’ region of presentation suggests its general applicability across different ethnicities.

scholarly journals Expression of Nectin-4 and PD-L1 in Upper Tract Urothelial Carcinoma

2020 ◽  
Vol 21 (15) ◽  
pp. 5390
Author(s):  
Eisuke Tomiyama ◽  
Kazutoshi Fujita ◽  
Maria Del Carmen Rodriguez Pena ◽  
Diana Taheri ◽  
Eri Banno ◽  
...  
Keyword(s):  
High Risk ◽  
Urothelial Carcinoma ◽  
Progression Free Survival ◽  
Immunohistochemical Analysis ◽  
High Risk Group ◽  
Upper Tract Urothelial Carcinoma ◽  
Antibody Drug Conjugate ◽  
Upper Tract ◽  
Risk Of Progression ◽  
Expression Rate

Enfortumab vedotin is a novel antibody–drug conjugate targeting Nectin-4, which is highly expressed in urothelial carcinoma. However, the expression status of Nectin-4 in upper tract urothelial carcinoma (UTUC) remains unclear. The relationship between Nectin-4 and Programmed Death Ligand 1 (PD-L1) in UTUC is also ambiguous. We performed immunohistochemical analysis of 99 UTUC tissue microarray to assess the expression of Nectin-4 and PD-L1 in UTUC. Nectin-4-positivity was detected in 65 (65.7%) samples, and PD-L1 was detected in 24 (24.2%) samples. There was no correlation between the expression of Nectin-4 and PD-L1. Patients with strong Nectin-4-expressing tumors had a significantly higher risk of progression (p = 0.031) and cancer-specific mortality (p = 0.036). Strong Nectin-4 expression was also an independent predictor of disease progression in the high-risk group (pT3 ≤ or presence of lymphovascular invasion or lymph node metastasis) (Hazard ratio, 3.32 [95% confidence interval, 1.20–7.98; p = 0.027]). In conclusion, we demonstrated that Nectin-4 expression rate in UTUC was 65.7% and independent of PD-L1 expression. Strong Nectin-4 expression was associated with worse progression-free survival in high-risk UTUC. These findings suggested that enfortumab vedotin may be effective in a broad range of patients with UTUC, regardless of PD-L1 expression.

scholarly journals The interplay of cell cycle and DNA repair gene alterations in upper tract urothelial carcinoma: predictive and prognostic implications

2020 ◽  
Vol 3 (3) ◽  
pp. 153-160
Author(s):  
Panagiotis J Vlachostergios
Keyword(s):  
Cell Cycle ◽  
Urothelial Carcinoma ◽  
Checkpoint Inhibitors ◽  
Clinical Importance ◽  
Upper Tract Urothelial Carcinoma ◽  
Cell Cycle Gene ◽  
Repair Gene ◽  
Upper Tract ◽  
Dna Repair Gene ◽  
Gene Alterations

Abstract Upper tract urothelial carcinoma (UTUC) is rare but can occur sporadically outside the context of Lynch syndrome. In these cases, knowing whether non-mismatch repair (MMR), DNA damage response and repair (DDR), and cell cycle gene alterations may predict responses to chemotherapy or immunotherapy and survival is of clinical importance. This study examined the germline and somatic mutational landscape of two UTUC patients with differential responses to programmed death 1 (PD-1)/PD-ligand 1 (PD-L1) immune checkpoint inhibitors and queried three independent UTUC cohort studies for co-occurrence of key cell cycle and DDR genes, as well as for their associations with overall survival (OS). TP53 and RB1 emerged as potential determinants of shorter OS in UTUC cohort patients, regardless of concurrent DDR alterations, and if prospectively assessed in larger studies they might also explain resistance to PD-1/PD-L1 blockade despite PD-L1 expression.

Adjuvant chemotherapy for high-risk upper tract urothelial carcinoma: Results from the Upper Tract Urothelial Carcinoma Collaboration

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5075-5075
Author(s):  
N. Hellenthal ◽  
S. F. Shariat ◽  
V. Margulis ◽  
P. I. Karakiewicz ◽  
M. Roscigno ◽  
...  
Keyword(s):  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Urothelial Carcinoma ◽  
Performance Status ◽  
Tumor Grade ◽  
Upper Tract Urothelial Carcinoma ◽  
Cancer Specific Survival ◽  
Upper Tract ◽  
High Risk Patients ◽  
Risk Patients

5075 Background: There is relatively little literature regarding the use of adjuvant chemotherapy following radical nephroureterectomy in the management of patients with upper tract urothelial carcinoma (UTUC). Our goal was to determine the incidence of receipt of adjuvant chemotherapy in high-risk patients and the ensuing effect on overall- and cancer-specific survival. Methods: Using an international collaborative database, we identified 1390 patients who underwent nephroureterectomy for non-metastatic UTUC between the years of 1992 and 2006. Of these, 542 (39%) patients were classified as high-risk (pT3N0, pT4N0, and/or lymph node positive). These patients were separated into two groups—those who did and did not receive adjuvant chemotherapy—and were stratified by gender, age group, performance status, tumor grade and stage. Cox proportional hazard modeling and Kaplan-Meier analyses were used to determine overall- and cancer-specific survival amongst the cohorts. Results: Of the high-risk patients, 121 (22%) received adjuvant chemotherapy. Adjuvant chemotherapy was more commonly administered in the context of increased tumor grade and stage (p < 0.001). Median survival in the entire cohort was 24 months (range 0–231 months). There was no significant difference in overall- or cancer-specific survival between those who did and did not receive adjuvant chemotherapy; however age, performance status, tumor grade, and tumor stage were significant predictors of both overall and cancer-specific survival. Conclusions: Adjuvant chemotherapy is infrequently utilized in the treatment of patients with high-risk UTUC after nephroureterectomy. Despite this, it appears that adjuvant chemotherapy confers minimal impact on overall- or cancer-specific survival in this group. No significant financial relationships to disclose.

Developing a nomogram for predicting intravesical recurrence after radical nephroureterectomy: a retrospective cohort study of mainland Chinese patients

2021 ◽  
Author(s):  
Shicong Lai ◽  
Xingbo Long ◽  
Pengjie Wu ◽  
Jianyong Liu ◽  
Samuel Seery ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Cox Regression ◽  
Upper Tract Urothelial Carcinoma ◽  
Chinese Patients ◽  
Clinicopathological Parameters ◽  
Radical Nephroureterectomy ◽  
Ki 67 ◽  
Data Set ◽  
Mainland Chinese ◽  
Upper Tract

Abstract Objective To evaluate the role of Ki-67 in predicting subsequent intravesical recurrence following radical nephroureterectomy and to develop a predictive nomogram for upper tract urothelial carcinoma patients. Methods This retrospective analysis involved 489 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision. The data set was randomly split into a training cohort of 293 patients and a validation cohort of 196 patients. Immunohistochemical analysis was used to assess the immunoreactivity of the biomarker Ki-67 in the tumor tissues. A multivariable Cox regression model was utilized to identify independent intravesical recurrence predictors after radical nephroureterectomy before constructing a nomographic model. Predictive accuracy was quantified using time-dependent receiver operating characteristic curve. Decision curve analysis was performed to evaluate the clinical benefit of models. Results With a median follow-up of 54 months, intravesical recurrence developed in 28.2% of this sample (n = 137). Tumor location, multifocality, pathological T stage, surgical approach, bladder cancer history and Ki-67 expression levels were independently associated with intravesical recurrence (all P &lt; 0.05). The full model, which intercalated Ki-67 with traditional clinicopathological parameters, outperformed both the basic model and Xylinas’ model in terms of discriminative capacity (all P &lt; 0.05). Decision-making analysis suggests that the more comprehensive model can also improve patients’ net benefit. Conclusions This new model, which intercalates the Ki-67 biomarker with traditional clinicopathological factors, appears to be more sensitive than nomograms previously tested across mainland Chinese populations. The findings suggest that Ki-67 could be useful for determining risk-stratified surveillance protocols following radical nephroureterectomy and in generating an individualized strategy based around intravesical recurrence predictions.

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