Abstract
The United States has seen a decrease in the incidence of bladder cancer and a decline in mortality rates over the past 20 years. However, not all groups have benefited equally from this trend. The American Association of Community Cancer Centers (ACCC) has issued ten strategies to improve cancer care delivery for underserved patient populations. Unfortunately, the evidence supporting the best methods for reducing disparities in different patient groups and care delivery settings remains severely limited. In this short communication, using a personalized narrative woven into a clinical case, we highlight the need for more research on bladder cancer care delivery to ensure that significant investments in precision oncology translate into genuine improvements for all patients diagnosed with bladder cancer.
Introduction
As reported in this journal, 1 bladder cancer mortality rates have declined in the United States over the past two decades, yet significant survival disparities remain. Women, Black men, and especially Black women face lower survival rates. Data from 18 SEER sites from 2000 to 2017 show that White males have the highest incidence rates of bladder cancer but experience lower mortality rates compared to other race and gender groups. 2 These results align with earlier trends showing gradual shifts toward earlier-stage diagnoses in both Black and White patients, but Black individuals still present with more advanced-stage disease. 3
Historical sex-specific analyses reveal that Black women consistently have the highest proportions of regional and distant tumors. A recent study using the National Cancer Database, 4 which included bladder cancer cases from 2004 to 2016, identified Black race, female gender, and uninsured status as strong independent predictors of advanced-stage diagnosis. Additional factors linked to delayed diagnosis included older age, treatment at non-academic centers, Medicaid insurance, and living in lower-income, less-educated, and more rural areas. These demographic factors, along with being Hispanic or Black, were also associated with a lower likelihood of receiving treatment for early-stage disease. Additionally, women, older patients, and Black patients were less likely to receive treatment for muscle-invasive, locally advanced, and metastatic disease. Among all factors, Black race emerged as the strongest independent predictor of both delayed diagnosis and substandard treatment for bladder cancer.
Addressing disparities in bladder cancer care
In May 2022, the American Association of Community Cancer Centers (ACCC) shared information on health equity in bladder cancer care with the cancer center community. The Education Program published their findings online in “Understanding and Mitigating Disparities in Bladder Cancer Care.” 5 Analyzing Medicare claims data from 2016 to 2019, the ACCC's Multi-disciplinary Bladder Cancer Care Education Program ACCC identified several factors associated with bladder cancer health disparities and inequities. The study found that the type of hospital, provider density, travel burden, and demographic characteristics such as being female, black, Hispanic or Latino, or having a low socioeconomic status or educational level are associated with worse outcomes, findings supported in other studies.4,6
As a response, the ACCC proposed ten strategies to improve bladder cancer care to mitigate these disparities. These strategies included expanding diagnostic considerations and screening recommendations, advocating for a multidisciplinary care model, and increasing patient and care team involvement in decision-making. However, the lack of evidence supporting the most effective methods for addressing disparities in different patient groups and care settings remains a major obstacle. For changes in clinical practice to be widely adopted, there must be strong evidence that the proposed interventions are effective. This evidence is needed to inform practice guidelines and ensure that the services provided can be billed, thus facilitating their widespread implementation. The limited research on what works best in improving outcomes for diverse populations hinders the equitable translation of research advances to real-world patient settings.
Clinical case: personalizing the impact
To emphasize these points and personalize their impacts, we share the story of co-author Dr Yelba Castellon Lopez and her father, who was diagnosed with muscle-invasive bladder cancer (MIBC).
Early symptoms and initial diagnosis
Dad, a Nicaraguan native, and late-arriving immigrant to the U.S., began experiencing recurring urinary infections, urinary frequency, microscopic hematuria in 2021, resulting in multiple visits to the emergency department (ED). Despite persistent symptoms and increased risk factors, he was repeatedly discharged from the ED at the local county hospital without a referral for further evaluation. This clinical experience highlights a significant gap in the implementation of evidence-based guidelines.
Bladder cancer is more common in men and older individuals, with an average age of diagnosis between 70 and 84 years. 7 Hematuria, including microscopic hematuria, is a common early symptom frequently encountered in clinical practice. In 2020, the American Urological Association updated its guidelines for bladder cancer screening, recommending a risk-stratified approach for patients with hematuria based on known risk factors such as older age, male gender, non-Hispanic white ethnicity, and smoking history. These revised guidelines aim to reduce the use of ‘low value’ CT programs for incremental cancer detection by advocating for a personalized, risk-stratified approach to hematuria.
In Dad's case, his repeated discharges without proper referral demonstrate a disconnect between clinical practice and the guidelines that advocate for a risk-based approach. While retrospective analyses categorize hematuria patients based on the likelihood of a cancer diagnosis, this algorithm's real-world uptake and efficacy are currently unknown.8,9
Navigating the healthcare system
Eventually, Dad was referred to primary care for an outpatient workup and evaluation of a suspected enlarged prostate. Predominantly Spanish-speaking, he became frustrated with his experiences of “not being offered any treatment” and persistent urinary symptoms and engaged his daughter, a primary care doctor. He refused to see his assigned primary care provider, who is female, does not speak Spanish, and “had been dismissive,” exhibiting perceived microaggressions on prior visits. Working at a large academic medical center, his daughter urged him to consult a male primary care physician at a different safety-net clinic to establish care, undergo more testing, and apply for Medicare to access care closer to her so she could accompany him to visits. To this point, Dad had refused enrollment in Medicare despite eligibility due to cost concerns.
Access to care remains a significant barrier in the United States, especially for minoritized groups. Bladder cancer is among the costliest cancer diagnoses, 10 and immigrant and non-native language bias in the healthcare setting are predictors of worse health outcomes. Further, perceived discrimination and provider bias within the healthcare system are associated with screening behaviors and contribute to disparities in early cancer detection.11,12 Gender and masculine identity also influence patient decision-making, often leading to significant delays in seeking or accepting necessary care. 13
Advanced disease and treatment delays
Suspected of having an enlarged prostate, Dad was prescribed finasteride and tamsulosin for benign prostatic hypertrophy and referred to urology for follow-up for persistent hematuria. However, securing a urology appointment within the county medical system left him waiting 6 to 12 months for further evaluation. This delay reflects a broader issue highlighted by a survey from the World Bladder Cancer Patient Coalition, which found that 57% of respondents reported being misdiagnosed with another condition before their bladder cancer diagnosis, with urinary tract infection (28%) and prostate problems (15%) being the most common misdiagnosed. 14 Such delays in diagnosis and lack of access to specialty care for underserved populations significantly impact mortality as patients diagnosed with bladder cancer after a delay are more likely to die from the disease compared to those diagnosed within three months, independent of stage and tumor grade. 15
Shortly after enrolling in Medicare, Dad presented to the ED at a large academic medical center with Stage 3 acute kidney failure due to obstruction. Subsequent CT imaging showed asymmetric thickening of the bladder and some prostate enlargement. Nephrostomies and urine cytology were performed, and a urology consultation was scheduled for outpatient cystoscopy. With four weeks of repeated cystoscopy imaging and clinic visits due to complications like the kinking of the nephrostomy tube, Dad was diagnosed with stage 2b bladder cancer. This triggered intensive caregiving as he began to manage the subacute to chronic complications requiring medical attention with percutaneous nephrostomy tubes. These complications include infection, catheter malfunction, dislodgement, and kinking, which are reported to affect up to 45% of patients. 16
Clinical trial and treatment options
Dad was deemed an excellent candidate for a randomized controlled clinical trial involving standard-of-care platinum-based neoadjuvant chemotherapy alone or in combination with a PD-1 immune checkpoint inhibitor therapy. Response rates to PD-1 blockade are around 20%, but predictive biomarkers of response remain unclear. 17 Excited to participate, Dad was placed in the standard-of-care group (ultimately, the tumor was later found to be PD-1 negative).
Dad initiated standard-of-care neoadjuvant platinum-based chemotherapy, tolerated it relatively well, and planned for post-neoadjuvant surgery. The options included radical cystoprostatectomy (RCP) with bilateral pelvic lymphadenectomy and urinary diversion or cystectomy plus radiation. RCP following neoadjuvant chemotherapy is the ‘gold standard therapy’ for MIBC. 18 However, this procedure carries significant risks of urinary and sexual dysfunction, significantly reducing the quality of life. 19 After extensive discussions and seeking multiple opinions, Dad, with deep concern over sexual function and quality of life with a urostomy, elected to undergo RCP. Research indicates that patient education and active participation in decision-making can lower decisional conflict in cancer patients, highlighting the importance of informed patient choices in such critical situations. 20 Despite being well-informed, Dad faced the reality of post-surgery life when his then partner left, stating that his caregiving needs were too much.
Dad's journey underscores the complexities and challenges in the current practice setting on what is most effective surgically at the patient level. A subset of patients with MIBC gain reasonable cancer control with radiation therapy, but its effectiveness remains debated. There is also ongoing research into whether trimodality therapy, which includes maximal transurethral resection, chemotherapy, and radiation therapy, can preserve the bladder and quality of life while achieving oncologic benefits equivalent to radical cystectomy in a subset of patients. 21
Second-Line therapy and care coordination
Post-surgery, Dad initiated second-line therapy with a PD-1/L1 inhibitor, achieving stable disease. However, a change in insurance contracting with the health system resulted in Dad being misassigned to a primary care provider in another health system, leading to delays in his infusions, highlighting the real-world impacts of navigating the complexities of insurance changes and high treatment costs. The cost per dose of immune checkpoint inhibitors can range between $8000 and $12,000 monthly, depending on the drug and dosage. For second-line treatment of advanced bladder cancer, pembrolizumab has been found to generate a gain of 0.36–0.37 quality-adjusted life-years (QALY) compared to chemotherapy, with an estimated incremental cost-effectiveness ratio of $122,557 per QALY. 22 After incessant attempts to get treatment approved by Dad, his daughter, and the oncology care team, treatments finally resumed.
As Dad's care needs escalated, his oncology care team became the primary point of contact, managing medication and cancer-related side effects as he moved in with his daughter. Months later, with disease progression, Dad discontinued PD-1/L1 therapy. With access to an academic medical center, Dad started enfortumab vedotin, an antibody-drug conjugate directed against nectin-4. Dad remained on enfortumab vedotin, navigating medication and cancer-related side effects, including occasional urinary infections and anemia requiring iron infusions and multiple blood transfusions with support from his oncology care team. Most patients with locally advanced/metastatic urinary cancer who discontinue PD-1/L1 inhibitors have been reported to face high symptom and caregiver burdens. Outcomes in this patient group are poor. 23 Unlike Dad, who was fortunate to receive care at an academic center, few in this group receive subsequent therapy. This highlights a significant gap in care patterns that requires further investigation.
End-of-life care
As Dad's disease progressed, care coordination for doctor and infusion visits became increasingly important. Running out of insurance-provided transport services, Dad filed a grievance with the insurance carrier. His four adult children arranged transportation and accompanied him to visits. Despite abdominal obstruction symptoms, Dad remained independent and functional. However, he was hospitalized for an acute infection and experienced a rapid decline. Reversible causes were treated, and he was discharged home to his daughter's care, requiring daily assistance with transferring, feeding, and all activities of daily living.
Tyrosine kinase inhibitors were initiated based on FGFR tumor marker status. Erdafitinib, a pan-FGFR inhibitor, is used to treat advanced urothelial carcinoma patients with specific mutations. Erdafitinib is prescribed to patients who have failed chemotherapy and immunotherapy. Clinical trials showed a 42% response rate, but only a partial response was observed in 40% of responsive patients. Ongoing investigation of FGFR inhibitors in combination with other drugs or immune checkpoint inhibitors may further improve treatment outcomes for bladder cancer patients with FGFR3 mutations. 24
Due to Dad's rapid acute decline in overall function, the family required home physical therapy, occupational therapy, pressure ulcer prevention care, and nursing visits. In-home care support was requested, and the case manager initiated the process. The family was connected to the extensivist program for close monitoring and high-needs care coordination. With this support, Dad regained the strength to ambulate on his own. Extensivist care models aim to provide a medical home tailored to high-needs, high-cost patients, leveraging multidisciplinary teams to deliver close follow-up care focused on seamless care transitions and reducing hospital readmissions. 25 However, evidence of the cost and benefit effectiveness of extensivist and similar programs remains limited, and data on advanced oncology patient-centered outcomes in diverse care settings are needed.
Two months later, abdominal symptoms recurred, and the oncologist recommended a new clinical trial. With appetite declining and a required washout from current medications for new trial eligibility, Dad experienced complications with treatment withdrawal, was hospitalized, and succumbed to his disease. At the end of life, Dad was placed in comfort care and died peacefully, surrounded by his loving children and with the support of his exceptional oncology and extended care team. After a three-month waiting period, long-term in-home support services (IHSS) provided to Medi-Cal patients were approved – the day before he was hospitalized for the last time. Near simultaneously, a PD-1/L1 inhibitor with enfortumab vedotin was approved for use, with significant gains in progression-free survival and overall survival in patients with previously untreated locally advanced or metastatic urothelial cancer over platinum-based chemotherapy alone. 26
Conclusions
To fully realize the societal benefits of significant investments in precision oncology and bladder cancer care advances, it is crucial to address existing disparities, as exemplified by Dad's journey. These disparities underscore the need for research funding from government agencies, the private sector, cancer organizations, and private philanthropy to develop evidence-based strategies that close care gaps and lead to more cost-effective, patient-centered care models.
Dad's journey highlights several critical obstacles that fall under the broader umbrella of cancer care delivery research: delayed diagnosis due to repeated discharges without proper referral, access to care issues stemming from language barriers and perceived discrimination, significant delays in diagnosis and treatment due to healthcare navigation challenges, the economic burden of high treatment costs and uninsured status, treatment disparities in securing specialist appointments, care coordination difficulties due to insurance complexities, and the need for intensive caregiving and in-home support services which were not readily accessible.
Addressing these real-world challenges of bladder cancer care requires collaboration among pharmaceutical companies, clinical trialists, care delivery scientists, health economists, patients, caregivers, community advocates, and other experts. These collaborations are essential for developing effective care delivery models, creating solutions when delivery falls short, and evaluating treatment efficacy across diverse patient populations and settings. By addressing gaps and shortcomings in care delivery, we can fully realize the benefits of investments in new drugs, tests, and procedures. When care delivery fails, these advancements are compromised, highlighting the need for unified efforts to enhance and equitably distribute bladder cancer care.
Recommended research areas
To address these obstacles and improve bladder cancer care delivery for all patients, we advocate for a greater and more balanced prioritization of funding for health delivery research that encompasses the structural drivers of health disparities and social determinants of health. This approach will promote evidence-based best practices in care delivery, ensuring more equitable bladder cancer care. This includes supporting more research that informs real-world treatment guidelines and provides evidence-based countermeasures eligible for payer reimbursement. This research will enhance the educational efforts of organizations like the ACCC, BCAN, and others working to improve bladder cancer care at community and academic centers.
Given that bladder cancer care carries the highest cost per patient life year, developing effective strategies that reduce disparities in patient outcomes, including more cost-effective delivery models and improved access to care, presents an opportunity to inform best practices for other cancers where disparities are also a challenge. In Box 1, we outline nine priority areas for research to support efforts to reduce bladder cancer-related disparities. By focusing on these priority research areas, we aim to reduce bladder cancer-related disparities and ensure equitable care for all patients.
Priority research areas for bladder cancer health equity.
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Footnotes
Acknowledgements
The authors have no acknowledgments.
Author contributions
Both authors contributed to the conception, writing, and approval of the article and agreed to be accountable for the accuracy of the content and integrity of the work.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data availability
There are no data to share with the submitted commentary.