Tumor budding outperforms ypT and ypN classification in predicting outcome of rectal cancer after neoadjuvant chemoradiotherapy

Abstract

Background: Budding is a complementary prognostic factor for colorectal cancer. In this study, we aimed to clarify the role of tumor budding in rectal cancer patients after preoperative chemoradiotherapy. Methods: A total of 124 patients with rectal cancer treated with neoadjuvant chemoradiotherapy and consecutive surgery were included. Surgical specimens were evaluated for budding and routine clinicopathological features. Budding was evaluated on hematoxylin and eosin (H&E)-stained slides and by cytokeratin immunohistochemical (IHC) staining. Results: A budding rate of 36.9% (n = 38) by H&E and 55.6% (n = 55) by IHC was observed. Budding was significantly associated with a high ypT and ypN status, poor differentiation, and low degrees of tumor regression. Moreover, budding was strongly predictive of a worse patient outcome, as measured by tumor recurrence or death. In multivariate analyses, budding remained the only significant parameter for overall survival and was even superior to the ypT and ypN status (budding in H&E: hazard ratio (HR) 2.72, 95% confidence interval (95% CI) 1.15-6.44, p = 0.023; budding in IHC: HR 5.19, 95% CI 1.62-16.61, p = 0.006). Conclusion: Budding is a strong prognostic predictor of survival in rectal cancer patients after neoadjuvant therapy. A standardized evaluation of tumor budding after neoadjuvant therapy may thus aid in risk stratification and guide the clinical management of patients with rectal cancer. Immunostaining can help to enhance the diagnostic accuracy and prognostic significance.

Post‐neoadjuvant assessment of tumour budding according to ITBCC subgroups delivers stage‐ and regression‐grade independent prognostic information in intestinal‐type gastric adenocarcinoma

“…This assumption is also supported by the observation that the distribution of budding groups in our neoadjuvant cohort is generally in line with those described for primary resected GCs [16]. Our data almost perfectly recapitulate post-neoadjuvant studies from rectal or oesophageal carcinomas, where TB remains a stage-independent prognostic parameter that even outperformed conventional ypTNM staging [18][19][20][21]. Therefore, we believe that the assessment of TB can serve as a very strong additional histopathological parameter that should be included in the pathology reports of GCs after neoadjuvant treatment.…”

“…TB has been identified as a highly valuable histopathological parameter in a plethora of carcinoma entities throughout the body [ 8 , 12 , 13 , 14 , 15 , 38 , 39 , 40 , 41 ] and recent studies on other gastrointestinal carcinomas were able to demonstrate that, as opposed to conventional grading systems, TB remains a reliable prognosticator even after neoadjuvant therapy [ 18 , 19 , 20 , 21 ]. For GC, several previous studies have already demonstrated the high prognostic relevance of TB in therapy‐naïve tumours [ 16 , 22 , 23 , 42 ].…”

“…Numerous studies across various carcinoma entities throughout the body have identified TB as an independent predictor of poor survival in therapy‐naïve tumours [ 7 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. Results from recent post‐neoadjuvant studies investigating TB in oesophageal squamous cell carcinoma and rectal adenocarcinoma suggest that even after neoadjuvant treatment, where conventional histopathological grading is usually omitted, the prognostic power of TB is retained [ 18 , 19 , 20 , 21 ].…”

A Novel Combined Tumor Budding-Poorly Differentiated Clusters Grading System Predicts Recurrence and Survival in Stage I-III Colorectal Cancer

“…At present, most guidelines do not recommend evaluating TB postneoadjuvant therapy owing to insufficient data supporting its prognostic significance in this setting and concerns regarding the distinction of true TB from treatment effect 5. A growing number of studies, however, suggest that TB may retain prognostic significance in the postneoadjuvant setting 30–32. We found TB, PDC, and CS to all be significantly associated with RFS, DSS, and OS in the neoadjuvant treated group, further supporting the prognostic utility of these features in this setting.…”

Establishment and Clinical Application of an Artificial Intelligence Diagnostic Platform for Identifying Rectal Cancer Tumor Budding

“…In recent years, it was found that tumor budding has important diagnostic value in the clinicopathology and prognosis of gastrointestinal tumors ( 3 , 4 ). The incidence of tumor budding in rectal cancer cases with lymph node metastasis and lymphatic invasion is significantly higher than in those without lymph node metastasis, while local recurrence and liver metastasis are also more common in those with tumor budding ( 5 ). The incidences of tumor budding and lymph node metastasis among rectal cancer patients are closely related to TNM stage.…”