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Is Infiltrating Tumor Border Configuration Linked to Poor Survival in Colon Adenocarcinoma?


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Findings from a retrospective cohort study could fuel the debate over the use of adjuvant chemotherapy in stage II colon cancer, according to data presented during the virtual edition of the 2020 Society of Surgical Oncology (SSO) International Conference on Surgical Cancer Care.1 Results of the study showed worse overall and disease-free survival in patients with -“infiltrating” tumor border configurations (ie, loss of a clear tumor-host interface, which is associated with aggressive disease) vs “pushing” tumor border configurations (ie, well-demarcated borders associated with lower-risk disease). What’s more, the hazard ratio in patients with stage II infiltrating borders did not significantly differ from that in patients with stage III pushing borders once adjustments for all factors were made.

In addition, these data suggest that tumor border configuration may carry a similar prognostic value to lymph node positivity in patients with colon cancer after accounting for adjuvant chemotherapy, the study authors reported.


“Based on these data, patients with node-negative disease and infiltrating tumor border configuration should be considered for adjuvant chemotherapy.”
— Yasmeen Qwaider, MD

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“Infiltrating tumor border configuration is a high-risk feature in patients with stage II and III colon adenocarcinoma, possibly comparable to or worse than node positivity,” said lead study author Yasmeen Qwaider, MD, a surgical research fellow at Massachusetts General Hospital, Boston. “Based on these data, patients with node-negative disease and infiltrating tumor border configuration should be considered for adjuvant chemotherapy.”

Background and Study Methods

According to a number of studies, the 5-year overall survival after surgical resection alone is approximately 80% in patients with stage II colon cancer.2 Although some of these patients may benefit from adjuvant chemotherapy, said Dr. Qwaider, chemotherapy is not routinely offered to patients with stage II colon cancer after surgery in the absence of high-risk features (poorly differentiated histology, presence of lymphovascular invasion, presence of perineural invasion, report of  up to 12 lymph nodes, bowel obstruction, localized perforation, or positive margins). Moreover, tumor border configuration is a prognostic factor in colorectal adenocarcinoma, but its significance is not well documented in colon adenocarcinoma alone, Dr. Qwaider reported.

For this single-institution, retrospective cohort study, Dr. Qwaider and colleagues included patients with pathologic stage II and III colon adenocarcinomas who were surgically treated at a tertiary medical center between 2004 and 2015 to ensure long-term follow-up. The researchers stratified patients into four groups based on tumor stage and tumor border configuration status. Patients who had received neoadjuvant chemotherapy were excluded from the analysis.

The study’s primary endpoints were overall survival and disease-free survival. A Cox regression model was used to control for confounders, including group, histologic grade, American Society of Anesthesiologists score, age, adjuvant therapy, and extramural vascular invasion.

Infiltrating Tumor Border Configuration: Poor Prognostic Factor

As Dr. Qwaider reported, the final cohort consisted of 725 patients (376 with stage II disease and 349 with stage III disease). The mean age of patients was 68 years.

Infiltrating tumor border configuration was evident in 222 of the stage II cases (45%) and 268 of the stage III cases (55%), said Dr. Qwaider. She noted that patients with infiltrating tumor border configuration were more likely to present with stage III disease and extramural vascular invasion and were more likely to experience disease progress to metastasis.

In general, patients with infiltrating tumor border configurations also had worse overall and worse disease-free survival than patients with pushing tumor border configurations. Compared with pushing tumor borders, the presence of infiltrating tumor border configurations increased the hazard of death by a factor of 1.6 (P = .01) and 1.6 (P = .002) in patients with stage II and III disease, respectively. A Cox regression model showed no significant difference in the risk of death or disease recurrence between patients with stage II infiltrating borders and those with stage III pushing borders after adjustment was made for all factors.

KEY POINTS

  • Infiltrating tumor border configuration increased the hazard of death by a factor of 1.6 (P = .01) and 1.6 (P = .002) in patients with stage II and III disease, respectively, vs pushing tumor border configuration.
  • The hazard of death in patients with stage II infiltrating tumor borders and in patients with stage III pushing tumor borders was not significantly different.

According to Dr. Qwaider, these data suggest that tumor border configuration carries a similar prognostic value to node positivity in patients with colon cancer, although the impact of adjuvant chemotherapy should be considered in future analyses.

“Only 16% of patients with stage II disease in this cohort received chemotherapy, so we were unable to analyze the impact of adjuvant chemotherapy on overall or disease-free survival,” commented Dr. Qwaider. She reported no increase in chemotherapy usage over time for patients with stage II disease. “Hopefully, we will continue our database and answer questions about adjuvant chemotherapy in the future.” 

DISCLOSURE: Dr. Qwaider reported no conflicts of interest.

REFERENCES

1. Qwaider YZ, Sell NM, Stafford CE, et al: Infiltrating tumor border configuration is a poor prognostic factor in stage II and III colon adenocarcinoma. 2020 SSO International Conference on Surgical Cancer Care. Abstract 40.

2. Gray R, Barnwell J, McConkey C, et al; Quasar Collaborative Group: Adjuvant chemotherapy versus observation in patients with colorectal cancer: A randomised study. Lancet 370:2020-2029, 2007.


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