Histologic grading of the extent of residual carcinoma following neoadjuvant chemoradiation in pancreatic ductal adenocarcinoma: a predictor for patient outcome

Abstract

Background: Several grading schemes for the extent of residual tumor in posttreatment pancreaticoduodenectomy (PD) specimens have been proposed. However, the prognostic significance of these grading schemes is unknown.

Methods: Histopathologic slides of 223 cases who received neoadjuvant chemoradiation and PD were reviewed. The extent of residual tumor was graded using both the College of American Pathologists (CAP) and the Evans grading systems. The grading results were correlated with clinicopathological parameters and survival.

Results: Among the 223 patients, 6 patients (2.7%) showed pathologic complete response (pCR; CAP grade 0 or Evans grade IV), 36 cases (16.1%) had minimal residual tumor (CAP grade 1 or Evans grade III), 124 cases (55.6%) had moderate response (CAP grade 2 or Evans grade IIb), and 57 cases (25.6%) had poor response (CAP grade 3, where 18 had Evans grade I and 39 had Evans grade IIa response). Patients with pCR or minimal residual tumor (response group 1) had better survival rates than those with moderate and poor response (response group 2). Response group 1 patients had lower posttherapy tumor and American Joint Committee on Cancer stages and lower rates of lymph node metastasis, positive resection margin, and recurrence and/or metastasis. Grading the extent of residual tumor is an independent prognostic factor for overall survival in multivariate analysis.

Conclusions: pCR or minimal residual tumor in posttreatment PD specimens correlate with better survival in patients with pancreatic ductal adenocarcinoma who received neoadjuvant therapy and PD. Histologic grading of the extent of residual tumor in PD specimen is an important prognostic factor in patients with pancreatic ductal adenocarcinoma who received neoadjuvant therapies.

Figure 1

Panel a, representative micrographs show the post-treatment scar with fibrosis, but no residual carcinoma cells (pathologic complete response, CAP grade 0 and Evans grade IV); panel b, post-treatment scar with fibrosis and individual tumor cells (arrows mark the tumor cell, CAP grade 1 and Evans grade III), which is positive for pan-cytokeratin (insert); panel c, post-treatment scar with fibrosis and microscopic focus of residual tumor cells (arrows mark the tumor cells, CAP grade 1 and Evans grade III); panel d, post-treatment tumor bed with residual tumor cells outgrown by stroma and mucin pools (approximately 20% of viable residual tumor cells, CAP grade 2 and Evans grade IIb); panel e, post-treatment tumor bed with residual tumor cells outgrow the stroma (approximately 70% of viable residual tumor cells, CAP grade 3 and Evans grade IIa); panel f, poorly differentiated adenocarcinoma with minimal treatment effect, more than 90% of the tumor cells are viable (CAP grade 3 and Evans grade I).

Figure 2

Kaplan-Meier estimates of disease-free survival (Panels a and c) and overall survival (Panels b and d) in patients with pancreatic ductal adenocarcinoma treated with neoadjuvant chemoradiation followed by pancreaticoduodenectomy. The CAP grading (a and b) and the Evans grading (c and d) of the extent of residual tumor correlate with disease-free and overall survival.

Figure 3

Kaplan-Meier estimates of disease-free survival (a) and overall survival (b) in response group 1 patients who had pathologic complete response or minimal residual tumor (<5% of residual tumor cells) and response group 2 patients which had moderate to poor response (≥5% residual tumor).