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Andrea Miyahira: Hi, I'm Andrea Miyahira here at the Prostate Cancer Foundation. Please welcome Dr. Edward Chris Dee of MSKCC. He will discuss the article "Racial Disparities in Prostate Cancer in the UK and the USA: Similarities, Differences and Steps Forward" that was recently published in Nature Reviews Urology. Dr. Dee, thanks for joining us and sharing this.

Edward Christopher Dee: Good morning, everyone. I'm grateful for the opportunity to speak to UroToday about our group's work in the health equity space. I'm looking forward to highlighting some of our research on prostate cancer disparities in the US, the UK, and globally. I want to extend my gratitude to the Prostate Cancer Foundation for their support and for believing in us and for all the good work they do in support of research that ultimately changes patients' lives.

Here are my disclosures. Cancer disparities refers to the difference in cancer incidence, outcomes, and access to care that exist amongst various population groups, often influenced by intersectional factors such as race, ethnicity, socioeconomic status, geographic location, and educational access and attainment. Cancer disparities exist across a spectrum of disease, from risk factors and exposures to access to and availability of diagnostics, treatment, and treatment outcomes.

We asked whether there are disparities in rates of treatment refusal amongst patients with localized prostate cancer. This is a study done a couple of years ago, where we used the National Cancer Database, which, established in 1989, is a nationwide US hospital-based cancer registry sponsored by the American Cancer Society and the American College of Surgeons. The NCDB captures over 70% of solid tumor diagnoses in the US.

We identified patients with localized prostate cancer, who either received or refused local therapy, despite provider recommendation. As patients who refuse surgery may opt for radiation or vice versa, to best capture disparities in treatment refusal, we defined refusal of therapy as people who refuse both surgery and radiation. We developed models using multivariable logistic regressions and adjusted for multiple sociodemographic and clinical variables.

We found that in our cohort of almost 900,000 patients, 0.28% refused local therapy. However, there were significant racial disparities in rates of refusal, suggesting disparate barriers in access to care. For example, we found that amongst men with intermediate-risk or high-risk disease, Black and Asian patients were more likely to refuse local therapy than white patients. Even adjusting for insurance status, socioeconomic factors, and several other variables, these disparities continued to persist.

We also found that independent of race, insurance and socioeconomic status were also associated with rates of treatment refusal. And although only 0.28% of patients were ultimately recorded as having refused local therapy, patients who refuse local therapy may represent the tip of the iceberg in terms of the extent of disparities that people face. More common disparities could represent non-completion of treatment, shorter courses of radiation or hormone therapy due to non-completion, or delays in the initiation of treatment.

So we sought to chase this question further along a patient's disease journey. This work was led by Bhav Jain in our group, who is currently a medical student at Stanford. We explored, using the National Cancer Database, whether there are racial disparities in delays to treatment, defined as a delay of six months or greater. In this large data set, again from the National Cancer Database, we found that Black men were approximately twice as likely to experience treatment delays compared to white men.

We also conducted an interaction term analysis by age and found that this difference in treatment delays was more pronounced amongst patients under the age of 55. We then explored whether prostate cancer disparities affect Asian-American men. This work was also led by Bhav Jain. In this study exploring risk group representation using the National Cancer Database, we found that people of Chinese, Japanese, Filipino, Korean, Vietnamese, Lao, Hmong, Cambodian, Indian, Pakistani, Native Hawaiian, and Pacific Islander descent were associated with increased odds of presenting with progressively higher prostate cancer risk groups compared to white patients.

Taken together, these findings underscore that although the incidence of prostate cancer may be lower amongst Asian-American and Pacific Islander men compared to Black and white patients on average, these patients could be more likely to present with higher-risk disease at diagnosis. Again, taken together, these three findings highlight the presence of disparities across intersectional aspects of a patient's identity that can exist across the spectrum of a patient's disease journey. An important question then becomes, what mediates these disparities that we see?

A critical study from Deaths and colleagues done in 2019 asked, in men with similar stages of disease, can we clarify the contribution of biological versus non-biological differences to this observed disparity? The study included updated individual patient-level data from men from three cohorts—one from some patients from the SEER cohort, which represented real-world nationwide estimates; five equal-access regional medical centers associated with the Veterans Affairs or the VA health systems; and four pooled RTOG trials, on the assumption that people who make it to clinical trials have equitable access to care.

This study found that Black race was associated with an increased age-adjusted prostate cancer–specific mortality hazard ratio only within the SEER cohort. Black race was associated with a 0.5% increase in prostate cancer–specific mortality at 10 years. However, no significant differences in prostate cancer–specific mortality were found in the VA cohort. And in the RCT cohort, Black men had a significantly lower hazard ratio of prostate cancer–specific mortality.

Now, looking towards metastatic disease, I want to point out the study by my friend and colleague, Dr. Kenrick Ng, a medical oncologist in the UK. In this study, Dr. Ng and his team looked at race-based outcomes for 425 patients with metastatic castrate-resistant disease in a single-center retrospective study. Note that this study was conducted at Saint Bartholomew's, or Bart's, in East London, which is amongst the most racially diverse parts of the UK. So the proportion of patients who identify as Black is relatively higher compared to many British studies.

Between 1997 and 2016, this study found that Black men demonstrated survival outcomes comparable with white men. Specifically, median overall survival in the 103 Black men in the study was 25.5 months compared to 21.8 months amongst the 322 white British men. Survival amongst Black patients was also improved compared to white patients in the cohort that only received hormone-based treatment. Thus, in the metastatic setting, equitable access to quality care—as evidenced in the VA cohort and the clinical trial cohort in the Deaths paper, as well as the equal-access setting in the metastatic study led by Dr. Ng—equal access to treatment can mitigate and potentially even reverse cancer disparities.

This work led us to our paper in Nature Reviews Urology, where we sought to outline what is known about prostate cancer disparities in the UK and the US across both localized and metastatic disease. We felt that in comparing and contrasting findings in these settings, including integrating the papers that we discussed in earlier slides, we might be able to shed light on how these disparities may be mitigated. What was really striking to us was the abundance of evidence from both localized and metastatic disease in the UK and the US that suggests that equal access to treatment reduces disparities in prostate cancer–specific mortality amongst people who actually are able to get treatment. There was some evidence for a tumor biology component to this as well.

In a study of over 92,000 patients in the VA system in the US, led by Dr. Yamoah, they explored patients who underwent radiation or surgery for localized prostate cancer. This study found—and we include this in the review—that the rate of distant metastasis was lower amongst Black men than amongst white men in the cohort that received radiation. By contrast, amongst those treated with radical prostatectomy, no significant differences in rate of metastatic disease was observed.

These findings, which could be related to differences in the nature of tumor mutations that exist that are associated with patients' ancestral makeup, are hypothesis-generating, but these are also exciting findings. Because these findings suggest that there are ways in which we could actually use what we know about tumor biology and leverage this to promote equity in everyday care.

I also want to share that this review article forms the basis of the TRANSFORM study, a large undertaking led by Dr. Ng and team in the UK, as well as Rebecca Todd, who's a behavioral scientist, Dr. Gloryanne Aidoo-Micah, who is a medical oncologist, and Dr. Zoe Moon, also a behavioral scientist. This study seeks to explore questions of treatment adherence amongst Black British men, again based off of our findings in the Nature Reviews article.

The present ongoing study will have qualitative interview components, treatment perception questionnaires, population-based retrospective studies, and patient advisory group interviews. Altogether, the goal of this work is to find ways to assess underlying drivers of the differences in treatment adherence, which could be a mediating factor in the population-level disparities that they observe in the UK, and to use this as a basis to design culturally tailored interventions.

I also want to point out some ongoing work in our group led by Dr. Rod Carlo Columbres. We're using the Global Burden of Disease data from the IHME to explore trends in prostate cancer epidemiology in Southeast Asia, where I am from. The region is home to over 690 million people, who are immensely diverse in culture, history, and social determinants of health. This work is forthcoming, but we hope for this study to represent the most updated estimates of GU cancers in the region and for these data to inform cancer policy. Taken together, prostate cancer is a truly global issue that will require global collaboration.

In sum, evidence from both localized and metastatic disease in the UK and the US suggests that equal access to treatment can eliminate disparities in prostate cancer mortality amongst patients who can actually access this treatment. Therefore, actively engaging patients and communities in research and intervention may enable the translation of research findings into truly equitable care for patients globally. I want to thank the many friends and mentors that I continue to have the privilege of working with, collaborating with, and learning from. These people span the globe, span multiple areas of expertise. It’s my honor to be part of this team. Thank you all.

Andrea Miyahira: Well, thank you so much for sharing all of this, Dr. Dee. So what are the most tangible and immediate steps that can be taken to improve health access equity in the United States?

Edward Christopher Dee: That's a really important question. I think so much of the research needs to find its translation. And directly, how can we help patients every day? I'll be honest, I think one of the biggest factors that plays a role in patients' access to care and uptake is the question of financial toxicity. We talk a bit about that in the review.

But there are actually ways that are cost-effective and implementable to assess financial toxicity and to act upon financial toxicity. I suspect that—number one is really the recognition that financial toxicity is multifaceted. And in addition to the direct costs of care, there are also the indirect costs of care, as well as the family-level aspects of care.

Think about a working parent who has to deal with daily radiation for anywhere from one to eight weeks, depending on the nature of treatment. How does that affect their families, their ability to work, their ability to put food on the table? All of these are really important things to explore, and I think are truly important aspects that are often overlooked in the day-to-day care of patients.

How do we actually manage this? I think the first method beyond recognition is to screen. There are tools such as the COST-FACIT questionnaire that allow clinicians to pretty effectively and efficiently screen patients for financial toxicity. There's work by one of my mentors, Dr. Fumiko Chino, looking at actual ways to turn this question into just two questions, akin to the depression screen in primary care, to improve uptake by facilitating more efficient data gathering.

But I think the second piece is linking patients with support systems that exist within health systems. There's a growing body of work that financial navigators—who are often social workers—can really help to mitigate the barriers that patients face in accessing financial support for their cancer treatment. I think that's a really tangible way to improve equity and access. I think the second piece that is, again, extremely tangible for patients and for researchers is for clinicians to be more mindful of clinical trial enrollment.

There's a vast body of literature that we also include in the review that calls into question the equity with which clinical trial enrollment is carried out. We know that only a minority of patients who identify as Black end up on clinical trials. If I'm not mistaken, the numbers from the early 1990s into the early 2000s show that in the country of the US, with approximately 12% to 13% of the population identifying as Black—and approximately 2x incidence of prostate cancer in Black patients—Black individuals only account for approximately 5% of people on clinical trials.

And that's something that I think we can do every day. When we have a patient who is part of a minority group in front of us, what clinical trials could we potentially offer that could really benefit them? And how can we support them on these trials? I think a lot goes into improving diversity within trials and, in so doing, improving the generalizability of clinical trial findings for the vast majority of the population.

Andrea Miyahira: OK, thank you. And are there models of community engagement that you recommend?

Edward Christopher Dee: Absolutely. One of the most exciting—and, again, cost-effective—models of community engagement is led by one of my mentors, Dr. Brandon Mahal, who's also a PCF awardee from several years ago. He is one of the leaders who supports these support vans—this is out of the University of Miami—that actually go out into the community and provide education, screening, and connections with providers, really going into the communities that are most affected by prostate cancer.

There are enclaves in different cities and different societies where the incidence of prostate cancer can be much higher. And actually getting into those communities, building trust, spending time with people are ways that are cost-effective and truly patient-centric. I think getting vans, putting clinicians in cars, and going to churches, going to community events, going to spaces that are there for people who are part of these minoritized groups, can really make a big difference.

And especially in the context of Miami, where different populations who identify as members of minoritized groups speak different languages, including Spanish and the different Caribbean Creole languages, having people who can speak those languages can really break down barriers and improve the partnership with communities that ultimately should drive how we deliver care.

Andrea Miyahira: OK, thanks. And are there any other actions that the prostate cancer research and oncology community can take to help address disparities?

Edward Christopher Dee: I think number one, for clinicians, is trying to get a sense of who is the patient in front of me? What kind of barriers might they face every day? If you're offering radiation to someone—I'm biased, I'm a radiation oncologist—what are the things that may help or hinder their completion of treatment, or the initiation of treatment on time? For our medical oncology colleagues, especially in the context of ADT, which is so commonplace in the treatment of patients with prostate cancer, how can we partner with patients and help them on this journey? What can we do to lower barriers to completing treatment?

I think from the research standpoint, step number one is to be mindful of how disparities affect our patients every day. I think it's easy to get lost in the weeds and think, OK, I'm studying the biologic underpinnings of how cell transport leads to drug resistance. But step back and see, who are the people that we're doing this for? And how can we apply an equity lens to the research that we do every day?

And I think, pragmatically, that can be as simple as ensuring that there's representation in the kind of biological samples that we get for our research. But I think another also actionable way is: can we partner with patients in the authorships? Can we partner with patients in how we write papers that are ultimately about them?

One of the most meaningful papers that we've done, which is forthcoming in Lancet Oncology, is a short piece on patient advocate–led survivorship groups in the Philippines, with a focus on breast cancer. Breast cancer is the most common cancer amongst women in the Philippines. And one of my colleagues and friends, Kara Magsanoc-Alikpala, is the founder of a now 20-year-old patient advocacy group in the Philippines, and Lancet Oncology is featuring them. And she's first author.

I think having folks who have the lived experience of cancer in all its different forms can really be meaningful for guiding how we do research—and not just what we say in paper one, paper two, paper three, but also in guiding the trajectory of how we ask, of the questions that we ask.

Andrea Miyahira: OK, well, thank you for coming on today and sharing all of this really meaningful research and excellent ideas for calls to action.

Edward Christopher Dee: Absolutely. Thank you for your time, and thank you for the opportunity. And to both the PCF team and the UroToday team, thank you for all the work that you do for our patients. It means a lot.