Quantified pathologic response assessed as residual tumor burden is a predictor of recurrence-free survival in patients with rectal cancer who undergo resection after neoadjuvant chemoradiotherapy

Abstract

Background: The current study was conducted to determine whether quantified pathologic response assessed as a percentage of residual tumor cells is predictive of recurrence-free survival (RFS) in patients with rectal cancer.

Methods: The authors studied 251 patients with rectal adenocarcinoma who were treated with neoadjuvant chemoradiation and radical resection. Quantified pathologic response was defined as an estimated percentage of residual cancer cells in relation to the tumor bed: complete, no residual cancer cells; near-complete, ≤ 5% residual cancer cells; major, > 5%, and < 50% residual cancer cells; and minor, ≥ 50% residual cancer cells. The reproducibility of quantified pathologic response between 2 pathologists was assessed using tumors from 55 randomly selected patients who did not demonstrate a complete response.

Results: Pathologic response was complete in 21% of patients, near-complete in 20% of patients, major in 37% of patients, and minor in 22% of patients. Nineteen percent of patients had ypT0N0 disease, 27% had ypT1-2N0 disease, 21% had ypT3-4N0 disease, and 33% had N+ disease. The 5-year RFS rates by category of quantified pathologic response were as follows: complete, 95%; near-complete, 88%; major, 69%; and minor, 61% (P < .001). Major and minor response, high histologic grade, and perineural invasion were found to be significant predictors of decreased RFS on multivariate analysis. The 5-year RFS rates for patients with ypT3-4 or N+ disease were better for those with a near-complete response (94%) compared with those with a major (64%) or minor (61%) response (P < .02). Moderate to substantial agreement was observed between the 2 pathologists (κ = 0.72).

Conclusions: Quantified pathologic response is a predictor of RFS in patients with rectal adenocarcinoma and stratifies patients with high pathologic stage disease.

Keywords: adenocarcinoma; cancer; chemoradiation; complete; near-complete; neoadjuvant therapy; pathologic response; preoperative; rectum; recurrence-free survival.

FIGURE 1

Photomicrographs showing representative examples of complete (A), near complete (B), major (C), and minor pathologic response (D). (Hematoxylin and eosin, magnification ×100.)

FIGURE 2

Recurrence-free survival curves (2A) and (2B) for categories of quantified pathologic response.

FIGURE 3

Recurrence-free survival curves (3A) and (3B) for categories of quantified pathologic response for patients with ypT3-4 or ypN+ disease.

FIGURE 4

Scatter plot showing the correlation between measurements of quantified pathologic response between 2 pathologists.