Hormone receptors intertwined with bladder structure symbolizing activity

Decoding Bladder Cancer: How Hormones Hold the Key to Better Outcomes

Theo Raines in Health & Wellness November 2025 • 4 min read.

"New Research Reveals the Impact of Sex Hormones on Bladder Cancer Treatment and Survival"

Bladder cancer, particularly muscle-invasive urothelial carcinoma (UCB), is a formidable challenge, often recurring even after radical cystectomy (RC). For decades, treatment options have remained limited, and recurrence rates stubbornly high. However, emerging research is shedding light on a new frontier: the critical role of sex hormones and their receptors in bladder cancer progression and treatment outcomes.

A groundbreaking study analyzes the expression of sex-steroid hormone receptors—androgen receptor (AR), estrogen receptor 1 (ESR1), and progesterone receptor (PGR)—in patients undergoing RC. By measuring mRNA levels of these receptors, scientists are uncovering how these hormones influence the course of the disease, offering potential new avenues for targeted therapies.

With a keen focus on how these hormonal signals affect recurrence-free survival (RFS) and disease-specific survival (DSS), this research opens doors to more personalized and effective treatment strategies. Understanding these hormonal dynamics is the first step toward transforming bladder cancer care and improving patient outcomes.

The Hormonal Connection: What the Research Reveals

Hormone receptors intertwined with bladder structure symbolizing activity

The study assessed mRNA expression of AR, ESR1, and PGR in 87 patients with muscle-invasive UCB. The findings highlight a significant imbalance: AR mRNA expression was markedly lower compared to ESR1 and PGR expression. This disparity is critical, as it directly correlates with patient survival outcomes.

High expression levels of AR were associated with reduced recurrence-free survival (RFS) and disease-specific survival (DSS). Patients with high AR mRNA levels experienced poorer outcomes, underscoring AR’s complex role in bladder cancer progression. Specifically, high AR mRNA expression, combined with lymph node involvement, emerged as an independent predictor of reduced RFS and DSS.

Key findings from the study include:

AR mRNA expression is lower compared to ESR1 and PGR expression.
High AR expression levels are associated with reduced RFS and DSS.
Lymph node status is an independent predictor of reduced RFS and DSS.
ESR1 and PGR expression status can further stratify patients with low AR expression into subgroups with significantly reduced RFS and DSS.

Intriguingly, the research also revealed that in patients with low AR mRNA expression, increased ESR1 and PGR mRNA expression were associated with reduced RFS and DSS. This suggests that the interplay between these hormone receptors is crucial in determining disease progression. This stratification allows for a more nuanced understanding of patient subgroups, potentially paving the way for tailored treatment strategies. These insights suggest that therapeutic targeting of AR, either alone or in combination with therapies targeting ESR1 and PGR, could significantly influence outcomes in UCB.

The Future of Bladder Cancer Treatment: A Personalized Approach

These findings mark a significant step forward in understanding the complex interplay between sex hormones and bladder cancer. By identifying specific hormonal profiles and their impact on survival, researchers are paving the way for personalized treatment strategies. Future research will likely focus on developing targeted therapies that modulate hormone receptor activity, offering new hope for patients with muscle-invasive UCB. The ability to stratify patients based on their AR, ESR1, and PGR expression levels will enable clinicians to tailor treatment plans, potentially leading to improved outcomes and a better quality of life for those affected by this challenging disease.

About this Article -

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This article is based on research published under:

DOI-LINK: 10.1007/s00428-018-2496-9, Alternate LINK

Title: Analysis Of The Prognostic Relevance Of Sex-Steroid Hormonal Receptor Mrna Expression In Muscle-Invasive Urothelial Carcinoma Of The Urinary Bladder

Subject: Cell Biology

Journal: Virchows Archiv

Publisher: Springer Science and Business Media LLC

Authors: Philipp Erben, Danijel Sikic, Ralph M. Wirtz, Thomas Martini, Cleo-Aron Weis, Johannes Breyer, Wolfgang Otto, Bastian Keck, Arndt Hartmann, Christian Bolenz

Published: 2018-11-27

Everything You Need To Know

Why is there a need to study the role of sex hormones in bladder cancer?

Emerging research indicates that sex hormones and their receptors play a critical role in the progression and treatment outcomes of bladder cancer, specifically muscle-invasive urothelial carcinoma (UCB). A study analyzing the expression of sex-steroid hormone receptors like androgen receptor (AR), estrogen receptor 1 (ESR1), and progesterone receptor (PGR) has revealed how these hormones influence the course of the disease, opening potential new avenues for targeted therapies. This is important because, traditionally, treatment options for bladder cancer have been limited with stubbornly high recurrence rates.

What did the study reveal about the expression levels of AR, ESR1, and PGR and their impact on survival?

The study found a significant imbalance in the expression of sex hormone receptors. AR mRNA expression was markedly lower compared to ESR1 and PGR expression. High expression levels of AR were associated with reduced recurrence-free survival (RFS) and disease-specific survival (DSS). Specifically, high AR mRNA expression, combined with lymph node involvement, emerged as an independent predictor of reduced RFS and DSS. Also, intriguingly, the research revealed that in patients with low AR mRNA expression, increased ESR1 and PGR mRNA expression were associated with reduced RFS and DSS, suggesting that the interplay between these hormone receptors is crucial in determining disease progression.

How might understanding the roles of androgen receptor (AR), estrogen receptor 1 (ESR1) and progesterone receptor (PGR) impact future bladder cancer treatment strategies?

The research suggests that therapeutic targeting of AR, either alone or in combination with therapies targeting ESR1 and PGR, could significantly influence outcomes in UCB. By understanding specific hormonal profiles (AR, ESR1, and PGR expression levels) and their impact on survival, clinicians can tailor treatment plans, potentially leading to improved outcomes. This approach allows for a more nuanced understanding of patient subgroups, potentially paving the way for tailored treatment strategies. Future research will likely focus on developing targeted therapies that modulate hormone receptor activity.

What do recurrence-free survival (RFS) and disease-specific survival (DSS) measure, and why are they significant in bladder cancer research?

Recurrence-free survival (RFS) refers to the length of time after primary treatment for bladder cancer that a patient survives without any signs or symptoms of the cancer recurring. Disease-specific survival (DSS) measures the length of time after treatment that a patient lives before dying specifically from bladder cancer, excluding deaths from other causes. These metrics are important because they provide insights into the effectiveness of treatment strategies and the aggressiveness of the disease.

How does the interplay between androgen receptor (AR), estrogen receptor 1 (ESR1) and progesterone receptor (PGR) influence bladder cancer progression?

The interplay between androgen receptor (AR), estrogen receptor 1 (ESR1), and progesterone receptor (PGR) is crucial in determining bladder cancer progression. The research revealed that in patients with low AR mRNA expression, increased ESR1 and PGR mRNA expression were associated with reduced recurrence-free survival (RFS) and disease-specific survival (DSS). This suggests that the combined effect of these hormone receptors can influence disease progression. Understanding this interplay could allow for more precise stratification of patients and the development of combined therapies targeting multiple hormone receptors, potentially leading to improved outcomes.