Experts Call for Increased Awareness of Existing Racial Disparities in RCC, Other Malignancies

Despite the numerous reports detailing racial differences in cancer outcomes and care over the years, the reasons underlying these disparities continue to be under deep exploration. Awareness of the factors at play is needed to improve understanding and take informed action.

An updated annual report published in March 2020 by the American Cancer Society detailing national cancer statistics showed that non-Hispanic black patients had the highest cancer mortality rate of 186.4 per 100,000, followed by American Indians and Alaskan Natives (166 per 100,000), non-Hispanic white patients (163.1 per 100,000), Hispanic patients (112.3 per 100,000), and Asian and Pacific Islanders (98.9 per 100,000).¹

However, cancer incidences were reported to be higher in white patient populations, with an incidence rate of 467.5 per 100,000, according to the report. Black patients had the second highest incidence (466.9 per 100,000), followed by American Indians and Native Alaskans (401.4 per 100,000), Hispanics (348.9 per 100,000), and Asians and Pacific Islanders (293.9 per 100,000).

“Be aware of these disparities,” Devika Das, MD, a clinical assistant professor and thoracic oncologist at the University of Alabama at Birmingham Medicine told OncLive in an interview. “Often, academic physicians who work in big [cancer] centers see a very select patient population; they’re the healthiest, they’re affluent. Of course, you’re bound by the rules of the trial to not include patients who are too sick, but we often don’t realize that we’re marginalizing a whole population.”

Survival Disparities in Pediatric Hodgkin Lymphoma

Despite recent advances made in pediatric Hodgkin lymphoma, results from population-based and single-center studies have suggested that non-Hispanic black and Hispanic patients tend to have higher relapse rates and worse overall survival (OS) than their white counterparts.² For example, results from 1 study published in 2008 demonstrated a higher incidence of late relapse and worse EFS in black patients who were receiving risk-directed combined-modality therapy compared with white patients.³ In other multivariable analyses, Hispanic ethnicity was found to be an independent predictor of poor disease-specific survival (DSS).

“What [is being] done in terms of disparities studies is [that investigators will] look at which populations—in most cases, it's non-Hispanic whites—have the healthiest [outcomes] and compare that with those who have [worse outcomes],” Moon Chen, MPH, PhD, associate director of Population Research and Cancer Disparities at University of California Davis Comprehensive Cancer Center, told OncLive. “The generalization we can make is that all populations of color are disproportionately affected [by cancer] compared with non-Hispanic whites.”

Understanding the reasons for these racial disparities in survival has been a challenge, although some investigators hypothesize that racial and ethnic differences in disease and host biology, as well as access to quality cancer care could be 2 important factors.^4-6

In a study that analyzed survival outcomes in patients with pediatric Hodgkin lymphoma by race and ethnicity, investigators noted distinct differences in how patients of different races responded to the same treatment. In order to better understand how race and ethnicity impacted patient survival, investigators examined event-free survival (EFS) and OS in Hispanic, black, and white pediatric patients who were given the same risk-stratified, response-adapted therapy for de novo Hodgkin lymphoma.

The analysis included patients with newly diagnosed Hodgkin lymphoma who were enrolled on 1 of 3 phase 3 Children’s Oncology Group trials in the United States between 2002 and 2012. Each trial had enrolled patients with newly diagnosed disease and examined dose-dense chemotherapy with augmentation of chemotherapy or radiation based on response to initial treatment. A total of 2155 patients enrolled on the trials and 1605 patients were included in the analysis.

In a pooled, secondary analysis of prospectively collected patient-level data, investigators compared baseline disease and demographic characteristics across the different racial and ethnic patient subgroups. Of the patients included in the cohort, 67% were white (n = 1083), while in the racial/ethnic minority subgroup (n = 522), 210 were non-Hispanic black patients and 312 were Hispanic patients.

Following a median follow-up of 6.9 years, investigators reported that the pooled 5-year EFS was 82%; this did not differ significantly between white (82%) and non-white patients (84%) in adjusted or non-adjusted analyses (P =.60). Additionally, the pooled 5-year OS was reported to be 97%; again, this was not found to significantly differ between white (98%) and non-white patients (96%).

However, in multivariable analyses that were done for OS, nonwhite ethnicity and an age of 15 years of age or older were factors that were found to be significantly associated with a higher risk of death. Specifically, nonwhite children were found to have a 1.88-fold increased risk of all-cause mortality (95% CI, 1.06-3.33).

Additionally, unadjusted survival estimates post-relapse was found to statistically differ by race/ethnicity. The 5-year post-relapse survival rate was 87% in white patients, 80% in Hispanic patients, and 67% in black patients. These difference in post-relapse survival continued to be statistically significant when examined in multivariable analyses. Specifically, black patients had a nearly 3.5-fold higher risk of post-relapse mortality versus white patients.

Investigators concluded that future efforts to reduce racial disparities in Hodgkin lymphoma in should be dedicated to enrolling more black and Hispanic patients onto clinical cancer trials that are being done in both the relapsed and up-front settings. Other efforts should focus on understanding why nonwhite patients are more prone to experience with advanced-stage disease.

Outcomes for Black Patients with Non–Small Cell Lung Cancer

Literature over the past decade have continuously indicated that black patients with early-stage non–small cell lung cancer (NSCLC) have worse outcomes with regard to OS compared with white patients. A study that was published in 2005 in the Journal of Clinical Oncology examined the effect race has on invasive staging, surgery, and survival outcomes in NSCLC and found notable disparities directly related to racial and ethnic minorities.⁷

Investigators looked at registry and claims data from 1991 to 2001 on Medicare-eligible patients who had been diagnosed with nonmetastatic NSCLC. A total of 14,224 patients underwent invasive staging, such as bronchoscopy, mediastinoscopy, or thoracoscopy, and were included in the analysis. Of these patients, 6972 underwent surgery for their disease.

Results showed that black patients were less likely to receive staging (odds ratio [OR] = 0.75; 95% CI, 0.67-0.83). For black patients who did undergo staging, they were still less likely to go to surgery than white patients (OR = 0.55; 95% CI, 0.47-0.64). Notably, investigators noted that black patients who underwent staging were less likely to receive a recommendation for surgery when not contraindicated (67.0% vs 71.4%; P <.05); they were also less likely to agree to surgery (3.4% vs 2.0%; P <.05).

“[In this study], when they broke down their patients by [race], they saw that black patients were less likely to receive a curative surgical treatment. They found that the reasons for this were multifactorial,” explained Das. “What was very interesting was that in many of these situations, patients were declining treatment. There is some [degree] of racial tension and mistrust toward [the] healthcare [system]. Issues also exist with having [adequate] access to healthcare at the right time and having care delivered in a culturally sensitive manner. There’s a lot of complex interplay, and unless we study this further in clinical studies, we’ll never be able to bridge that gap.”

Although time has passed, and investigators and institutions alike are working toward closing these gaps, Das explained that racial disparities are still prevalent within the NSCLC space.

“If you look between 2012 and 2016, 32% of lung cancer incidence occurred in white males, while it was 82% in non-Hispanic black males,” said Das. “Similarly, in terms of mortality, non-Hispanic white males had a 51% mortality rate, while non-Hispanic black males had a 60% [rate]. Right off the bat, you can see the differences.”

A more recent study that was published in the American Journal of Clinical Oncology examined disparities in surgical recommendations for stage 1 NSCLC and demonstrated similar findings.⁸

As surgical resection is considered to be a curative standard-of-care treatment, investigators examined factors that were associated with patients not being recommended for surgery. Patients who received a diagnosis of primary stage I NSCLC between 2007 and 2016 were identified utilizing the Surveillance, Epidemiology, and End Results database (n = 56,534). Among those who were included in the analysis, 76.9% were recommended for surgery; 95% of these patients underwent surgical resection. Recommendation for surgery was found to be inversely linked with increasing age (P <.01), non-Hisplanic Black race (adjusted odds ratio [ORadj] 0.64; 95% CI, 0.59-0.70), Hispanic ethnicity (ORadj 0.75; 95% CI, 0.67-0.84), nonprivate/Medicare insurance (Medicaid: ORadj 0.55; 95% CI, 0.51-0.60), and single status (ORadj 0.66; 95% CI, 0.63-0.70). Moreover, investigators noted that those who were not recommended for surgery had increased risk of death versus those who did receive the recommendation.

Examining Contrasting Survival Rates in Renal Cell Carcinoma

Another study examined the outcomes of black and white patients with metastatic renal cell carcinoma (RCC) who were treated with first-line tyrosine kinase inhibitors (TKIs). Here, investigators found that black patients had more International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors and worse outcomes with TKIs than white patients.⁹ In the multivariable analysis, black patients with RCC were also found to have shorter median OS compared with white patients with RCC, although the difference was not determined to statistically significant.

Reports from the Surveillance, Epidemiology, and End Results Program (SEER) cancer registry and Medicare databases that were done between 1986 and 1999, the National SEER database between 1992 and 2007, and the California Cancer Registry between 1988 and 2004 all indicated that black patients with RCC had shorter OS versus white patients with the disease. Disparities in survival could be a combination of several factors, according to the study authors, including those that are socioeconomic, cultural, environmental, and biologic. The prevalence of RCC risk factors were also found to differ between black and white populations; these factors included hypertension, chronic kidney disease, obesity, smoking, and occupational/drug exposures.

Investigators conducted a retrospective 2-cohort study comprised of patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) data and the trial-database who had metastatic renal cell carcinoma (mRCC) and had been treated with frontline TKIs. To be eligible for inclusion, patients had to have a mRCC diagnosis, be of black or white race, and have received a VEGF TKI as either a frontline therapy or following cytokines.

Within the IMDC cohort (n = 3454), 73 patients were black (2%) and 3381 were white (98%), while the trial-database cohort (n = 1061) consisted of 21 black patients (2%) and 1040 white patients (98%).

A total of 2382 deaths were reported in the IMDC cohort and the median follow-up for those who were alive was 34 months. The estimated median OS was 25.8 months (95% CI, 23.1-28.8) for white patients) and 25.1 months (95% CI, 23.7-26.7) in the matched and unmatched analyses, respectively. Black patients experienced a median OS of 18.5 months (95% CI, 13.8-26.1). However, investigators noted that this difference was not statistically significant in the multivariable analyses.

The median follow-up of patients who were alive in the trial-database cohort was 24.9 months, with white patients experiencing a median OS of 25.5 months in the matched analysis and 25.6 months in the unmatched analysis. Black patients in this cohort had a median OS of 21.0 months. Again, this difference was not determined to be of statistical significance.

Additionally, the time to treatment failure (TTF) in the IMDC cohort was determined to be 4.6 months in black patients compared with 7.3 months and 7.6 months, respectively, in the matched and unmatched white cohorts. A notable difference in overall response rates (ORRs) between black and matched and unmatched white patients were also observed, at 13% versus 27% (P = .01) and 24% (P = .04), respectively. The trial-database cohort, on the other hand, saw statistically significant differences in progression-free survival, with black patients experiencing a median PFS of 5.3 months compared with 10.5 and 10.7 months in the matched and unmatched white cohorts, respectively. Moreover, the ORR reported in black patients was 11% versus 41% (P = .01) and 39% (P = .01) in the matched and unmatched white cohorts, respectively.

Although the investigators concluded that race itself does not appear to be an independent predictor of OS in patients with mRCC. Black patients tend to present with more adverse clinical features and have a shorter median survival compared with their white counterparts. Results from the analysis also suggest that VEGF TKIs may have less activity in black patients with mRCC versus white patients. Investigators conclude that there needs to be a greater representation of black patients in clinical cancer trials to determine whether study results are generalizable to all patients.

“[We] need to ensure that there is equal access to clinical trials for all patients,” Das concludes, “because that is where all the data are being generated to find the best treatment. We also need to ensure that every high-quality clinical trial is available across the country, even in rural areas, and that all patients have access, despite race or comorbidities. [It’s] important to generate real-world evidence using real-world populations, not just select patients.”

References

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2. Kahn JM, Kelly KM, Pei Q, et al. Survival by race and ethnicity in pediatric and adolescent patients with Hodgkin lymphoma: a Children’s Oncology Group study. J Clin Oncol. 2019;37(32):3009-3017. doi: 10.1200/JCO.19.00812
3. Metzger ML, Castellino SM, Hudson MM, et al. Effect of race on the outcome of pediatric patients with Hodgkin’s lymphoma. J Clin Oncol; 2008;26(8):1282-1288. doi:10.1200/JCO.2007.14.0699.
4. Albain KS, Unger JM, Crowley JJ, et al. Racial disparities in cancer survival among randomized clinical trials patients of the Southwest Oncology Group. J Natl Cancer Inst. 2009;101(14):984-992. doi:10.1093/jnci/djp175.
5. Henderson TO, Bhatia S, Pinto N, et al. Racial and ethnic disparities in risk and survival in children with neuroblastoma: A Children’s Oncology Group study. J Clin Oncol. 2011;29(1):76-82. doi:10.1200/JCO.2010.29.6103
6. Bhatia S, Sather HN, Heerema NA, et al. Racial and ethnic differences in survival of children with acute lymphoblastic leukemia. Blood. 2002;100(6):1957-1964. doi:10.1182/blood-2002-02-0395.
7. Lathan CS, Neville BA, Earle CC. The effect of race on invasive staging and surgery in non–small–cell lung cancer. J Clin Oncol. 2005;24(3)413-418. doi10.1200/JCO.2005.02.1758
8. Rapp JL, Tuminello S, Alpert N, et al. Disparities in surgical recommendation for stage I non-small cell lung cancer. Am J Clin Oncol. Published online July 21, 2020. doi:10.1097/COC.0000000000000740
9. Bossé D, Xie W, Lin X, et al. Outcomes in black and white patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors: insights from two large cohorts. JCO Global Oncol. Published online February 6, 2020. doi:10.1200/JGO.19.00380