Gender-specific Differences in Recurrence of Non–muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis

Uhlig, Annemarie; Strauß, Arne; Hosseini, Ali; Lotz, Joachim; Trojan, Lutz; Schmid, Marianne; Uhlig, Johannes

doi:10.1016/j.euf.2017.08.007

Cited by 51 publications

(40 citation statements)

References 53 publications

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“…Epidemiologic data strongly supports the idea that men are at an increased risk of developing bladder cancer compared to women, although women are more likely to present with advanced disease [2][3][4]. While environmental or lifestyle factors, such as industrial chemicals and cigarette smoke exposure may contribute to these differences, recent studies demonstrate that even after adjusting for these factors, sex-related differences in incidence persist [5].…”

Section: Introductionmentioning

confidence: 91%

Does 5-alpha Reductase Inhibitor Use Improve The Efficacy of Intravesical Bacille Calmette-Guérin (BCG) for Non-muscle Invasive Bladder Cancer?

Alhogbani

Gilbert

Lodde

et al. 2020

BLC

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BACKGROUND: Prior research implicates the androgen receptor pathway as important in bladder cancer progression and recurrence. In particular, use of 5-alpha reductase inhibitors (5-ARIs) appears to improve bladder cancer outcomes. This study aims to determine if concomitant use of 5-ARIs with intravesical Bacille Calmette-Guérin (BCG) decreases recurrences in patients with non-muscle invasive bladder cancer (NMIBC). MATERIALS & METHODS: This retrospective analysis included male patients diagnosed with NMIBC who were treated with induction intravesical BCG at our institution from 2013 to 2018. Patients were excluded who received prior induction BCG. Recurrence and progression-free survival were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox proportional hazards and Poisson events models. RESULTS: We identified 206 male patients, of whom 39 received 5-ARIs and 167 did not. Most patients (72.8%) received >6 instillations of BCG, with 20.4% completing all induction and maintenance treatments during a median follow up of 3.31 years. There were no significant differences in recurrence or progression-free survival between 5-ARI users or non-users (59% vs 55.7%; p = 0.72 and 97.4% vs 98.2%; p = 1.00, respectively). Similarly, no differences in the number of recurrences between groups was observed (p = 0.78). However, the proportion of patients who completed all prescribed BCG installations was higher among 5-ARI users (39.7% vs 17.9 %, p = 0.07). CONCLUSIONS: In contrast to prior reports, our study does not suggest that 5-ARI use decreases the recurrence rate in men receiving induction BCG for NMIBC. However, our results suggest 5-ARI use may improve patient tolerance to BCG.

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Section: Introductionmentioning

confidence: 91%

Does 5-alpha Reductase Inhibitor Use Improve The Efficacy of Intravesical Bacille Calmette-Guérin (BCG) for Non-muscle Invasive Bladder Cancer?

Alhogbani

Gilbert

Lodde

et al. 2020

BLC

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“…According to a meta-analysis, female patients have a higher risk than males for intravesical recurrence after local treatment of NMIBC. 19 Both factors were related to this result. Further study of bladder carcinoma recurrence and female residual urine analysis is warranted.…”

Section: Discussionmentioning

confidence: 54%

Relationship between post‐void residual urine volume, preoperative pyuria and intravesical recurrence after transurethral resection of bladder carcinoma

et al. 2020

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Abbreviations & Acronyms BCG = bacillus Calmette-Gu erin BPH = benign prostatic hyperplasia CI = confidence interval CIS = carcinoma in situ EORTC = European Organization for Research and Treatment of Cancer HR = hazard ratio LUTS = lower urinary tract symptoms MMC = mitomycin C NMIBC = non-muscleinvasive bladder cancer PSM = propensity score matching RFS = recurrence-free survival TUR = transurethral resection TUR-Bt = transurethral resection of bladder tumor TUR-P = transurethral resection of the prostate UUTUC = upper urinary tract urothelial carcinoma

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“…While these cell types robustly infiltrated bladders of BBN-treated mice, the only sex-specific difference that we measured was a greater number of tumor antigen-specific CD8 + OT1 T cells in male mice compare to female mice. This observation may provide a first clue as to why men experience fewer tumor recurrences compared to women (Uhlig et al, 2018). Certainly, additional sex-based immune-mediated differences are likely involved, such as cytokine expression or T cell polarization, and the BBN URO-OVA model will be useful to explore these possibilities in future studies.…”

Section: Discussionmentioning

confidence: 92%

“…We did recapitulate historical findings that BBN induces tumor growth at a faster rate in male mice compared to female mice (Bertram and Craig, 1972;Kaneko and Li, 2018) in the URO-OVA transgenic mouse, permitting use of this model to specifically explore sex differences in the immune response to immunotherapy in the BBN model. Greater understanding of the influence of sex and gender are needed in bladder cancer as men make up the majority of bladder cancer patients, although women are often diagnosed with more advanced disease and have poorer outcomes (Marks et al, 2016;Uhlig et al, 2018). Sex hormone receptors play a role in bladder cancer, as transgenic androgen receptor expression in the bladder increases tumor development in male and female mice, whereas mice deficient for the androgen receptor, specifically in the urothelium, are protected from BBN-induced tumorigenesis (Hsu et al, 2013;Johnson et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Identification of sex differences in tumor-specific T cell infiltration in bladder tumor-bearing mice treated with BCG immunotherapy

Rousseau

O'Brien

Antequera

et al. 2020

Preprint

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Bladder cancer is the fourth most common cancer for men. However, women are often diagnosed with later stage disease and have poorer outcomes. Whether immune-based sex differences contribute to this discrepancy is unclear. In addition, models to investigate tumorspecific immunity in bladder cancer, in the context of tumor development or response to therapy, are lacking. To address this specific unmet need, we incorporated a commonly used model antigen, ovalbumin, into two well-established models of bladder cancer; the orthotopic MB49 cell line model and the carcinogenic BBN bladder cancer model. We tested the utility of these models to investigate tumor-specific immunity in the context of immunotherapy in both sexes. We found that BCG vaccination, prior to weekly BCG instillation does not impart an immune-specific benefit to tumor-bearing mice in the context of multiple BCG instillations.Furthermore, tumors developed in the testes in male mice, precluding the use of the MB49 model to directly investigate sex-based immune differences. In the BBN model, we observed that more tumor antigen-specific CD8 + T cells infiltrated male bladders compared to female bladders in the context of BCG immunotherapy and that these cells had the highest levels of the exhaustion marker PD-1. We propose our modified BBN model will contribute to our understanding of how tumor-specific immunity arises in bladder cancer. Additionally, the BBN bladder cancer model may help to uncover sex differences in tumor-specific immunity, which would provide valuable information for the development of new treatments or combination therapies for bladder cancer in women and men.

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Gender-specific Differences in Recurrence of Non–muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis

Cited by 51 publications

References 53 publications

Does 5-alpha Reductase Inhibitor Use Improve The Efficacy of Intravesical Bacille Calmette-Guérin (BCG) for Non-muscle Invasive Bladder Cancer?

Does 5-alpha Reductase Inhibitor Use Improve The Efficacy of Intravesical Bacille Calmette-Guérin (BCG) for Non-muscle Invasive Bladder Cancer?

Relationship between post‐void residual urine volume, preoperative pyuria and intravesical recurrence after transurethral resection of bladder carcinoma

Identification of sex differences in tumor-specific T cell infiltration in bladder tumor-bearing mice treated with BCG immunotherapy

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