Treatment with adjuvant chemotherapy improved the overall survival of locally advanced gastroesophageal adenocarcinoma in patients treated with preoperative chemoradiotherapy and resection, according to the results of a propensity score-matched analysis of data from the National Cancer Database (NCDB).
“The findings from this study support adding chemotherapy in the adjuvant setting to improve overall survival in patients with gastroesophageal adenocarcinoma who complete preoperative chemoradiotherapy and resection,” wrote Ali A. Mokdad, MD, MS, of the University of Texas Southwestern Medical Center, and colleagues in the study published in JAMA Oncology. “These findings, while not confirmatory, provide compelling motivation to explore the potential benefit of adjuvant chemotherapy in a randomized clinical trial.”
Patients with gastroesophageal adenocarcinoma will often experience distant recurrence after undergoing preoperative chemoradiotherapy and resection. With this analysis, Mokdad and colleagues compared the outcomes in patients who underwent adjuvant chemotherapy compared with postoperative observation.
The analysis included 10,086 patients with distal esophagus or gastric cardia adenocarcinoma who received their diagnosis between 2006 and 2013 and had a clinical stage of T1N1–3M0 or T2–4N0–3M0.
Of the more than 10,000 patients enrolled, 814 received adjuvant chemotherapy. Patients who received adjuvant therapy were more likely to be young (P < .001), to have more advanced disease (P < .001), and shorter postoperative inpatient stay (P < .001).
The researchers used propensity score to match 732 patients in the adjuvant chemotherapy groups to 3,660 patients in the postoperative observation group.
Patients who received adjuvant chemotherapy had significantly improved overall survival compared with observation. The median survival after adjuvant therapy was 40 months compared with 34 months for observation (P < .001; HR, 0.79; 95% CI, 0.72–0.88).
The overall survival at 1, 3, and 5 years was 94%, 54%, and 38% for patients with adjuvant chemotherapy compared with 88%, 47%, and 34% for observation.
The researchers noted that the main limitation of the study was its retrospective nature.
“We used propensity scoring and conditional landmark analysis to mitigate selection bias and immortal time bias,” they wrote. “Another important limitation is that the NCDB lacks detailed information on certain variables, such as detailed chemotherapy regimens, that would provide more granular data for analysis.”
In an editorial that accompanied the article, Elizabeth C. Smyth, MB, BCh, MSc, and David Cunningham, MD, FMedSci, both of the Royal Marsden Hospital in London, noted that the small number of patients treated with adjuvant chemotherapy was reassuring given that this treatment is not endorsed by clinical guidelines.
“The results of Mokdad et al demonstrate a small but potentially clinically relevant absolute benefit in overall survival of 4% at 3 years for patients treated with adjuvant chemotherapy following chemoradiotherapy plus surgical resection,” they wrote. “As most recurrent gastroesophageal cancers occur within 3 years of surgery, this possibly represents an increase in the proportion of patients cured. However, these findings can only be confirmed in a randomized clinical trial.”