Association of patients’ sex with treatment outcomes after intravesical bacillus Calmette–Guérin immunotherapy for T1G3/HG bladder cancer

D’Andrea, David; Soria, Francesco; Grotenhuis, Anne J.; Eugene, K.; Malats, Núria; Stasi, S. Di; Joniau, Steven; Cai, Tommaso; Irani, J.; Karnes, Jeffrey; Varkarakis, John; Baniel, Jack; Palou, Joan; Babjuk, Marek; Spahn, Martin; Ardelt, Peter; Colombo, Renzo; Serretta, Vincenzo; Dalbagni, Guido; Bartoletti, Riccardo; Larré, S.; Malmström, Per Uno; Sylvester, Richard; Shariat, Shahrokh F.

doi:10.1007/s00345-021-03653-1

Cited by 10 publications

(3 citation statements)

References 32 publications

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“…Meta-analysis of 31 studies by Mori et al revealed that there is no gender-specific difference in the overall survival, recurrence-free survival, and progression-free survival in NMIBC patients after surgical removal of tumor and BCG treatment [ 51 , 52 ]. However, the meta-analysis of 63 studies of MIBC patients showed a gender-specific difference in overall survival, recurrence-free survival, and progression-free survival [ 51 ].…”

Section: Clinical Aspects Of Sex and Gender Differences In Bladder Ca...mentioning

confidence: 99%

Biological differences underlying sex and gender disparities in bladder cancer: current synopsis and future directions

Doshi,

Athans,

Woloszynska

2023

Oncogenesis

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Sex and gender disparities in bladder cancer have long been a subject of interest to the cancer research community, wherein men have a 4 times higher incidence rate than women, and female patients often present with higher-grade disease and experience worse outcomes. Despite the known differences in disease incidence and clinical outcomes between male and female bladder cancer patients, clinical management remains the same. In this review, we critically analyze studies that report on the biological differences between men and women and evaluate how these differences contribute to sex and gender disparities in bladder cancer. Distinct characteristics of the male and female immune systems, differences in circulating hormone levels and hormone receptor expression, and different genetic and epigenetic alterations are major biological factors that all likely contribute to disparate incidence rates and outcomes for male and female bladder cancer patients. Future preclinical and clinical studies in this area should employ experimental approaches that account for and consider sex and gender disparities in bladder cancer, thereby facilitating the development of precision medicine for the effective treatment of bladder cancer in all patients.

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Section: Clinical Aspects Of Sex and Gender Differences In Bladder Ca...mentioning

confidence: 99%

Biological differences underlying sex and gender disparities in bladder cancer: current synopsis and future directions

Doshi,

Athans,

Woloszynska

2023

Oncogenesis

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“…Similarly, Palou et al [9], in their single-center retrospective series of 146 primary T1G3 patients, reported an independent association between female sex and RFS, PFS, and CSS. More recently, D’Andrea et al [10] analyzed the data of 2635 T1 patients treated with BCG; after adjusting for differences in baseline patients’ and tumor's characteristics, female sex was associated with disease progression (HR 1.25) but not with recurrence. However, this association was no longer present when the analysis was restricted to patients treated with adequate BCG therapy.…”

Section: Evidence Synthesismentioning

confidence: 99%

Clinical and biological markers for risk-stratification of T1 high-grade non-muscle invasive bladder cancer

Soria

Dutto²

2022

Current Opinion in Urology

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Purpose of reviewTo summarize the prognostic and predictive role of current clinical and biological markers in patients with T1 high-grade (T1HG) nonmuscle invasive bladder cancer (NMIBC).Recent findingsClassical clinico-pathologic markers such as age, tumor size, focality, and location as well as the presence of concomitant carcinoma in situ, lymphovascular invasion, and histological variants at the time of transurethral resection (TUR) should be used in the risk-stratification of T1HG to improve patients’ selection for early aggressive treatment. pathological T1 substaging has shown to predict disease progression and response to intravesical therapy, and should therefore be reported in the pathological assessment to improve clinical decision-making. Urinary inducible cytokines measured at different time points during Bacillus Calmette-Guerin therapy may be used to predict response to treatment, while urinary mRNA-based biomarkers may be of value to select patients for repeated TUR (reTUR). The advent of genomic classification in NMIBC and that of immune markers may improve current risk-stratification tools and pave the way toward personalized treatment.SummaryThe role of clinico-pathologic variables in the risk-stratification of T1HG NMIBC remains unaltered, despite insufficient. Urinary biomarkers and tissue-based immune markers hold the promise to revolutionize the paradigm of risk-stratification due to their potential role in predicting response to intravesical and systemic immunotherapy. However, to date, none of the investigated biomarkers is used in clinical practice to risk-stratify T1HG patients due to the lack of external and/or prospective validations.

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“…However, the standard HRBC management involves thorough transurethral resection of the bladder tumor (TURBT) supplemented with a second restaging TUR (reTUR) and adjuvant intravesical instillations of Bacillus Calmette–Guérin (BCG). Given this complexity of HRBC management, the evidence concerning disparate outcomes between males and females remains inconclusive [ 8 ]. The aim of the study is to determine sex diversities in the treatment and oncologic outcomes of primary non-muscle-invasive high-risk bladder cancer in comprehensive, high-volume centers.…”

Section: Introductionmentioning

confidence: 99%

Sex Remains Negative Prognostic Factor in Contemporary Cohort of High-Risk Non-Muscle-Invasive Bladder Cancer

Bilski¹,

Kozikowski²,

Skrzypczyk³

et al. 2022

Cancers

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Sex-specific differences in outcomes of patients diagnosed with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) have been reported with controversial findings. This study aims to investigate sex-specific diversities in the treatment and oncologic outcomes of primary HR-NMIBC in a multicenter setting. A multicenter retrospective analysis of 519 patients (388 men and 131 women) treated with transurethral resection (TUR) for primary HR-NMIBC was performed. Univariable and multivariable Cox regression models were used to investigate the association of clinico-pathologic features and generate hazard ratios (HRs). Second-look TUR (reTUR) was performed in 406 (78%) patients. A total of 218 (42%) of patients were subjected to an induction course of intravesical BCG (Bacillus Calmette–Guérin) plus maintenance therapy. The median follow-up was 44 months. Among the entire cohort, 238 (46%) and 86 patients (17%) had recurred and progressed to muscle-invasive disease (MIBC), respectively. Female sex was associated with increased risk of disease recurrence in the entire cohort: HR = 1.94, 95% CI = 1.48–2.55, p < 0.001 and HR = 1.91, 95% CI = 1.39–2.60, p < 0.001 in univariate and multivariate analysis, respectively. In patients subjected to reTUR and treated additionally with BCG, female sex was associated with increased risk of disease recurrence in univariate analysis (HR 1.81, 95% CI 1.07–3.06, p = 0.03), but not in multivariate analysis (HR 1.99, 95% CI 0.98–4.02, p = 0.06). There was no difference between sexes with regard to disease progression. HR-NMIBC diagnosed in females is associated with higher risk of disease recurrence when compared to males.

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Association of patients’ sex with treatment outcomes after intravesical bacillus Calmette–Guérin immunotherapy for T1G3/HG bladder cancer

Cited by 10 publications

References 32 publications

Biological differences underlying sex and gender disparities in bladder cancer: current synopsis and future directions

Biological differences underlying sex and gender disparities in bladder cancer: current synopsis and future directions

Clinical and biological markers for risk-stratification of T1 high-grade non-muscle invasive bladder cancer

Sex Remains Negative Prognostic Factor in Contemporary Cohort of High-Risk Non-Muscle-Invasive Bladder Cancer

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