Although men are over 3 times more likely to be diagnosed with bladder cancer than women, women are more likely to die from the disease.1 A retrospective analysis recently published in Cancer examined the disparities in treatment and outcomes among men and women, and concluded that these disparities may partially be caused by varying access to systemic chemotherapy. Even when adjusting for treatment with systemic chemotherapy, the survival gap persisted.2

Lauren Harshman, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, wrote an accompanying editorial to the study.3 In it she considered the limitations of retrospective analyses and explored potential causal factors for the disparity.

“Randomized, blinded prospective studies are the gold standard and the best method to control for confounding variables, but are not always feasible,” said Dr Harshman in an email to Cancer Therapy Advisor.

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“Retrospective database studies…are important and can highlight issues such as the sex disparity in survival among bladder cancer patients,” she said. “[The authors’] work allowed them to tease out that while a survival disparity existed, it could not be blamed solely on less chemotherapy utilization.”

In the editorial, Dr Harshman called the study authors’ measure of chemotherapy “a relatively blunt instrument” that could not account for the quality or quantity of chemotherapy the patients received.

She identified a number of possible confounding variables, including the potential use of carboplatin-based regimens in lieu of cisplatin, lower rates of second-line therapies, death from comorbidities, less informed care, and physician biases. She also noted that the study’s findings emphasize the roles socioeconomic and demographic factors play in access to treatment and overall survival.

The study’s findings may also have been influenced by tumor biology. Dr Harshman wrote that certain subtypes of bladder cancer, notably nonurothelial subtypes, are “notoriously less sensitive” to treatment. These subtypes were disproportionately represented in the female cohort the study examined, and affect African American women at higher rates than their counterparts. Basal subtypes, a more aggressive form of bladder cancer, also seem to disproportionately affect women and African Americans.

In both cases, Dr Harshman observed that even with “equal and optimal” treatment with current therapies, differences in tumor biology could induce differences in treatment response and subsequent survival outcomes.

According to Dr Harshman, because of the “generally lackluster accrual and completion rates” of previous prospective bladder cancer studies, it is imperative to make the most of ongoing collaborative projects. She highlighted Coexpression Extrapolation (COXEN) and the National Cancer Institute’s Molecular Analysis for Therapy Choice (MATCH) trial.

RELATED: Gender Differences Found in Bladder Cancer Treatment, Survival

These trials may allow researchers to determine whether outcome disparities persist even in prospective, more controlled studies. “If found,” she said, “differences in tumor biology, gene signatures, immune profiles, and a variety of biomarker analyses should be evaluated to see if they can explain the worse outcomes.”

She recommended increasing awareness to minimize disparities in this and other cancers while the causal factors are investigated.

“By increasing awareness among physicians, care teams, and the public that this survival disparity among the sexes exists, we can make a dent in identifying and correcting any modifiable societal factors, ageism, or other physician biases that may be at play,” she said. “Ideally, it will also foster interest in further prospective study of the inciting biologic factors driving the gap.”


  1. Bladder Cancer – Statistics. American Society of Clinical Oncology. Updated June 2015.  
  2. Rose TL, Deal AM, Nielsen ME, Smith AB, Milowsky MI. Sex disparities in use of chemotherapy and survival in patients with advanced bladder cancer. 1 Jul 2016. Cancer. doi: 10.1002/cncr.30029 [Epub ahead of print]
  3. Harshman LC. Mind the Gap: What is driving the survival disparity between the sexes in bladder cancer? 25 May 2016. Cancer. doi: 0.1002/cncr.30027 [Epub ahead of print]