Racial, ethnic disparities emerge after neoadjuvant therapy for gastric cancer
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Key takeaways:
- Asians and Hispanics with stage II/III gastric cancer have lower mortality risk compared with Black or white patients.
- Black patients receiving neoadjuvant therapy have improved OS compared with white patients.
There are significant differences in response to treatment and survival outcomes for certain racial and ethnic groups among patients with resected stage II or stage III gastric cancer, study findings published in JAMA Network Open showed.
Most notably, researchers observed that patients who identify as Asian or Black responded favorably to neoadjuvant therapy, whereas Asian and Hispanic patients appeared independently associated with improved OS compared with Black and white patients.
“To our knowledge, this is the first large nationwide retrospective cohort study evaluating the association of neoadjuvant therapy with different racial and ethnic groups with clinical stage II and III gastric cancer,” S. Peter Wu, MD, a radiation oncologist at City of Hope, and colleagues wrote. “Asian and Black patient groups had higher proportions of patients responding favorably to neoadjuvant therapy with downstaging or pathological complete response, which may contribute to Black patients having higher OS compared with white patients among those who received neoadjuvant therapy.”
Background and methodology
Neoadjuvant therapy is recommended for patients with locally advanced gastric cancer throughout the United States. Nevertheless, researchers are unsure about the association of neoadjuvant therapy treatment and outcomes according to race and ethnicity.
Wu and colleagues sought to evaluate the potential differences in outcomes by race and ethnicity among patients with noncardia gastric cancer undergoing surgical procedures with and without neoadjuvant therapy.
The investigators conducted a retrospective cohort study examining the National Cancer Database from the American College of Surgeons. The analysis included 6,938 patients (mean age, 65.9 years; 61.4% men) with clinical stage II or III gastric adenocarcinoma and excluded patients with gastric cardia tumors that underwent surgical resection procedures from Jan. 2006 to Dec. 2019.
Researchers stratified patients by race and ethnicity and analyzed outcomes for those who did and did not receive neoadjuvant therapy.
Results
A racial and ethnic breakdown of the study population showed 3,540 (53.6%) patients who identified as white, 1,606 (24.3%) as Black, 1,175 (17.8%) as Hispanic and 1,046 (15.8%) as Asian.
The white patient cohort had the highest proportion of individuals aged 65 years or older with more comorbidities compared with other races and ethnicities in the study group. Additionally, white patients underwent surgical resection procedures without neoadjuvant therapy or adjuvant therapy more frequently than patients of other racial or ethnic groups.
Researchers observed that Asian and Black patients had the highest proportion of study participants being downstaged or achieving pathological complete response following neoadjuvant therapy.
Study investigators also noted an association between perioperative chemotherapy and improved OS (HR = 0.79; 95% CI, 0.69-0.90). Meanwhile, the analysis also revealed that the largest decreases in OS to be associated with the number of positive lymph nodes and surgical margins.
Patients identifying as Asian (HR = 0.64; 95% CI, 0.58-0.72) or Hispanic (HR = 0.77; 95% CI, 0.69-0.85) had significantly improved OS compared with patients who identify as Black or white.
Study findings also showed Black patients who received neoadjuvant therapy had improved OS compared with white patients (HR = 0.78; 95% CI, 0.67-0.90).
The researchers acknowledged several study limitations, including available data through the National Cancer Database accounting for approximately 70% of cancer diagnoses, thus potentially hurting its generalizability.
Additionally, some patients in the study may belong to two or more different racial and/or ethnic groups, or may be misclassified altogether, thus potentially altering the impact of the associations the researchers observed.
Next steps
In this specific population of patients with gastric cancer, the study results suggest significantly improved outcomes associated with the use of neoadjuvant therapy for those who identify as Hispanic, Asian or Black compared with white patients.
“Our findings suggest the importance of future research toward investigating the biological differences in tumor behavior across races that have yet to be elucidated, including consideration of clinical trial design in gastric cancer as well as genomic studies to include stratification on factors of race and ethnicity,” the researchers wrote.
Perspective
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Suneel Kamath, MD
Stage II/stage III gastric cancer is challenging because there are many conflicting trials of perioperative, neoadjuvant and adjuvant therapies using chemotherapy alone or chemoradiation. Although these paradigms are supposedly done with curative intent, 5-year survival is only 34.6% in this population and treatment toxicities are substantial.This study by Wu and colleagues was robust because it analyzed stage II/stage III gastric cancer outcomes in the National Cancer Database, which encompasses 70% of all cancer care in the United States and over a long period of time (2006-2019).
The main findings were interesting because they showed Black patients had equivalent OS compared with White patients, and that Asian and Hispanic patients had improved outcomes compared with both Black and White patients. In the subset of patients who received neoadjuvant therapy, Asian, Hispanic and Black patients actually had better outcomes than White patients. This is most likely due to older age and more comorbidities among White patients in the study, but it does raise the question: Are there actual racial differences in treatment response due to tumor molecular differences or pharmacogenomic differences in chemotherapy metabolism?
Overall, the study highlights the importance of neoadjuvant therapy in stage II/stage III gastric cancer. In particular, patients who received perioperative chemotherapy had the best outcomes compared to with those who received other treatment paradigms. This affirms perioperative FLOT as the gold standard in this setting. Only 8.6% of patients had surgery only in 2019, the final year included in this analysis, compared with 34% to 40% of patients treated between 2006 and 2010. This is an encouraging trend.
The study also confirms prior studies showing an increasing incidence of early-onset gastric cancer, especially in Hispanic patients.
More work is needed to understand the etiology for the rising incidence of early-onset gastric cancer and also to further explore racial differences in treatment and outcomes.
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