TY  - JOUR
A1  - D'Andrea, David
A1  - Soria, Francesco
A1  - Grotenhuis, Anne J.
A1  - Cha, Eugene K.
A1  - Malats, Nuria
A1  - Di Stasi, Savino
A1  - Joniau, Steven
A1  - Cai, Tommaso
A1  - Rhijn, Bas W. G. van
A1  - Irani, Jaques
A1  - Karnes, Jeffrey
A1  - Varkarakis, John
A1  - Baniel, Jack
A1  - Palou, Joan
A1  - Babjuk, Marek
A1  - Spahn, Martin
A1  - Ardelt, Peter
A1  - Colombo, Renzo
A1  - Serretta, Vincenzo
A1  - Dalbagni, Guido
A1  - Gontero, Paolo
A1  - Bartoletti, Riccardo
A1  - Larré, Stephane
A1  - Malmstrom, Per-Uno
A1  - Sylvester, Richard
A1  - Shariat, Shahrokh F.
T1  - Association of patients’ sex with treatment outcomes after intravesical bacillus Calmette–Guérin immunotherapy for T1G3/HG bladder cancer
JF  - World Journal of Urology
N2  - Purpose
To investigate the association of patients’ sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette–Guérin (BCG) for T1G3/HG urinary bladder cancer (UBC).

Materials and methods
We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95% confidence intervals (CI) for the association of patients’ sex with HG-recurrence and disease progression.

Results
A total of 2170 (82%) males and 465 (18%) females were available for analysis. Overall, 1090 (50%) males and 244 (52%) females experienced recurrence, and 391 (18%) males and 104 (22%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95%CI 1.01–1.56, p = 0.04) but not with recurrence (HR 1.06, 95%CI 0.92–1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients’ sex was not associated with recurrence (HR 0.99, 95%CI 0.80–1.24, p = 0.96), HG-recurrence (HR 1.00, 95%CI 0.78–1.29, p = 0.99) or disease progression (HR 1.12, 95%CI 0.78–1.60, p = 0.55).

Conclusion
Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response.
KW  - bladder cancer
KW  - BCG
KW  - response
KW  - age
KW  - progression
KW  - recurrence
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-344486
VL  - 39
IS  - 9
ER  - 
TY  - JOUR
A1  - Litovkin, Kirill
A1  - Van Eynde, Aleyde
A1  - Joniau, Steven
A1  - Lerut, Evelyne
A1  - Laenen, Annouschka
A1  - Gevaert, Thomas
A1  - Gevaert, Olivier
A1  - Spahn, Martin
A1  - Kneitz, Burkhard
A1  - Gramme, Pierre
A1  - Helleputte, Thibault
A1  - Isebaert, Sofie
A1  - Haustermans, Karin
A1  - Bollen, Mathieu
T1  - DNA Methylation-Guided Prediction of Clinical Failure in High-Risk Prostate Cancer
JF  - PLoS ONE
N2  - Background 
Prostate cancer (PCa) is a very heterogeneous disease with respect to clinical outcome. This study explored differential DNA methylation in a priori selected genes to diagnose PCa and predict clinical failure (CF) in high-risk patients. 

Methods 
A quantitative multiplex, methylation-specific PCR assay was developed to assess promoter methylation of the APC, CCND2, GSTP1, PTGS2 and RARB genes in formalin-fixed, paraffin-embedded tissue samples from 42 patients with benign prostatic hyperplasia and radical prostatectomy specimens of patients with high-risk PCa, encompassing training and validation cohorts of 147 and 71 patients, respectively. Log-rank tests, univariate and multivariate Cox models were used to investigate the prognostic value of the DNA methylation. 

Results 
Hypermethylation of APC, CCND2, GSTP1, PTGS2 and RARB was highly cancer-specific. However, only GSTP1 methylation was significantly associated with CF in both independent high-risk PCa cohorts. Importantly, trichotomization into low, moderate and high GSTP1 methylation level subgroups was highly predictive for CF. Patients with either a low or high GSTP1 methylation level, as compared to the moderate methylation groups, were at a higher risk for CF in both the training (Hazard ratio [HR], 3.65; 95% CI, 1.65 to 8.07) and validation sets (HR, 4.27; 95% CI, 1.03 to 17.72) as well as in the combined cohort ( HR, 2.74; 95% CI, 1.42 to 5.27) in multivariate analysis. 

Conclusions 
Classification of primary high-risk tumors into three subtypes based on DNA methylation can be combined with clinico-pathological parameters for a more informative risk-stratification of these PCa patients.
KW  - CpG island hypermethylation
KW  - radical prostatectomy
KW  - promoter methylation
KW  - receptor beta
KW  - gene
KW  - GSTP1
KW  - biomarkers
KW  - diagnosis
KW  - recurrence
KW  - reveals
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151705
VL  - 10
IS  - 6
ER  -