Presentation by Dr Jason Starr, Mayo Clinic and Dr Richard Kim, Moffitt Cancer Center
At the Total Health SEEK Color Virtual Workshop held in July 2023, a panel discussion on disparities in the gastrointestinal (GI) cancers was presented by Dr Jason Starr from the Mayo Clinic, and Dr Richard Kim from Moffitt Cancer Center.
Dr Starr noted that, while he does see a majority of White patients at his center (located in Jacksonville, FL), he also sees a moderate proportion of Black and Hispanic patients with stomach cancer, and among this latter population, he notes that the patients tend to have younger onset disease, and tend to have more poorly differentiated disease, or so-called “Signet cell histology”. In addition, Dr Starr noted that these minority patients tend to have more peritoneal spread of their cancer, or dissemination (metastasis) of their cancer into the abdominal cavity. Highlighting an American Association for Cancer Research (AACR) report published in 2022 (Box 1), Dr Starr emphasized that some of the biggest differences in incidence and mortality from cancer for Hispanic patients was in gastric cancer, and this was the second largest difference in incidence and mortality from cancer for Black patients.
Box 1. Some Notable Racial Disparities Across the GI Cancers
Risk Ratio (Reflects the increase in risk for Black relative to non-Hispanic White Individuals)
Stomach (Gastric Cancer)
In terms of possible biologic reasons for these disparities, Dr Starr noted that there appears to be a higher incidence of infection with a bacterium called Heliobacter pylori in Black patients, which has been associated with stomach cancer. From the basic science perspective, it is known that H. pylori hypermethylates the CDH1gene which encodes E cadherin, which could underlie the more diffuse Signet cell histology of these cancers. A limitation to our understanding, however, is that projects such as The Cancer Genome Atlas (TCGA), which is designed to characterize the molecular features of stomach and other cancer types, did not include any Hispanic patients, and only a limited number of Black patients. As such, Dr Starr emphasized that our molecular understanding of disease in minority patients is limited, despite clinical evidence that stomach cancers display distinct features in these populations. For example, he noted that Signet cell or poorly differentiated cancers are largely human epidermal growth factor receptor 2 (HER2) negative, programmed death 1 ligand (PD-L1) negative, and are generally proficient in mismatch repair (MMR), and the absence of these biomarkers and features precludes the use of most targeted therapies. Dr Starr also noted the increasing incidence of so-called early onset gastric and colorectal cancers (defined in both cases by diagnosis at age under 50) and the higher proportion of Black and Hispanic patients who present with early onset disease.
Dr Starr noted that factors such as social inequities, structural racism, lack of education, and access to care could underlie some of these differences in incidence, and he also highlighted the lower minority enrollment across the majority of cancer clinical trials, as well as studies like the TCGA. Owing to this underrepresentation, the molecular understanding, and the applicability of many cancer therapies is limited, as trials fail to consider the possible biologic differences in cancer across racial groups. He noted that institutions such as the National Cancer Institute (NCI) have recognized this underrepresentation in clinical research, and now require that cancer centers be more inclusive and representative of the populations that they serve in order to become NCI-designated cancer centers.
Dr Kim agreed, acknowledging that, like Dr Starr, he also sees predominantly White populations of patients at his center (located in Tampa, FL), with a lower proportion of Black and Hispanic. He noted both the higher incidence and mortality for Black patients with colorectal cancer that has been observed across studies, and agreed that multiple factors are likely to underlie these differences, including environmental factors such as diet, obesity, and smoking. Dr Kim also noted that colorectal cancer (CRC) is preventable through screening such as colonoscopy, but that if patients don’t have proper access to care (e.g., living far away from a center), or are unaware of the current screening guidelines recommending screening at age 45, they will not undergo CRC screening. He also noted other non-modifiable factors such as family history and potential genetic differences between Black and non-Hispanic White populations that remain poorly understood. For example, he notes that Black patients tend to have more proximal, right sided tumors, more KRAS mutations, and some data show that there is a higher incidence of microsatellite instability high status (MSI-high) which is associated with a more aggressive tumor phenotype. Dr Kim also agreed with the issue of minority underrepresentation in clinical trials and the possibility that current therapies may not be as effective across racial groups. He added that the reverse may also be true, that some therapies might actually be better suited for Black patients, and as such, this remains an area that must be further studied.
On the topic of enhancing colorectal cancer screening and uptake, Dr Starr noted an initiative from the Kaiser Permanente Care Consortium, which mailed at-home colorectal cancer screening tests to patients between the years 2006 and 2008. The initiative resulted in an increase in CRC screening among Black patients and a marked reduction in the difference in CRC mortality between White and Black populations (Box 2).
Box 2. Narrowing Mortality Disparities in Colorectal Cancer (CRC): An Example
Intervention and Outcome
Dr Starr and Dr Kim noted the continued mistrust of medical research and the healthcare system among minority populations as a result of past injustices such as the Tuskegee Syphilis Study, in which Black patients were treated inferiorly, as test subjects. Dr Starr suggested that overcoming this mistrust is difficult, and will require continued educational initiatives and community outreach, and he noted ongoing efforts at both Mayo Clinic and Moffit Cancer Center in this regard. He further noted the standardized screening efforts across Asian countries (which show a higher incidence of gastric cancer) that have helped to reduce cancer rates. “We know prevention is always the best treatment” Dr Starr said, noting that, if enough data on the higher incidence of gastric and other GI cancer is presented, guidelines for more appropriate and/or enhanced screening in these populations could be developed and enacted at a population level.
Dr Kim agreed that the disparity in CRC outcomes could certainly be narrowed with better screening initiatives, and he noted the importance of having “champions” for engagement, meaning leaders who can go out into the community and connect with them, to encourage things like screening, and promote an atmosphere of greater trust and collaboration. With respect to the topic of clinical trials, Dr Kim noted that often times patients will ask if they are being used as a “guinea pig”, but that some these barriers and biases can be overcome simply by taking the time to explain the trial and its purpose to the patient. Dr Starr agreed, and noted that placebo use (which can also generate some level of distrust) is, overall, less common in trials today, and that if patients are adequately informed about how a trial works and that the purpose is in their best interest, patients will often be receptive and agreeable to participation. He further noted the importance for clinicians to not make assumptions that minority patients will not be interested in trial participation, and to be aware of their own inherent biases in that regard. For other barriers, such as healthcare literacy gaps and/or language barriers for consent forms, etc., it is also incumbent upon the treating clinician to help close that gap for the patient, as a means to facilitate participation.
With regard to what, specifically oncologists, can do to help eliminate disparities, Dr Starr stressed the importance of “checking our own implicit biases at the door”, and approaching the patient in a non-judgmental way, and from a place of compassion. It is also important to ensure that, when offering a clinical trial, that it really is the best option for that patient. Dr Starr noted that sometimes patients are simply not ready to consider a trial, for whatever reason, and that a consent form should never be completed on the same day; patients should always be given time to review with their families and come back with questions. He further stressed that patients should never be made to feel “like they’re being sold something” when suggesting a clinical trial.
Both Dr Starr and Dr Kim lauded current efforts by the NCI, as well as the National Institutes of Health (NIH), which now recognize the issue of racial disparities in cancer as a national problem and have brought greater attention and focus to possible solutions. Dr Kim noted the importance of continued community outreach for education and disease awareness, and to recognize that other socioeconomic barriers may exist, such as transportation, which can limit patient access to care. For example, he noted that often patients drive 3 or 4 hours to get to his center, and that simply may not be possible for many underserved populations and for those in more suburban or rural areas. One possible solution he suggested is to develop and invest funding in clinical trial centers that are closer to the populations that are most in need.
Summarizing, Dr Kim suggested that by encouraging and enabling more diversity in clinical trials, and with further research, it may be possible to better define which therapies are more effective, or more appropriate for Black and Hispanic populations. Dr Starr agreed, noting that currently, many federal agencies, including the NCI are “very willing to support that type of research… the funding is ripe for studying healthcare disparities…”. He suggested this should be the motivation and inspiration for a new era and focus of cancer research, now that the etiology and treatment approach for many cancers is better understood: “Once you get the foundation… how can we apply this to a greater patient population?” Dr Kim agreed, and re-emphasized the example of gastric cancer across Asian countries, which have reduced rates now as a result of expanded screening and consequently, earlier detection and better outcomes, for this higher risk population.
You can see the full GI cancers discussion from the SEEK Color Virtual Workshop here: