Actual status of distribution and prognostic impact of extramural discontinuous cancer spread in colorectal cancer.

Abstract

To clarify the prognostic impact of tumor nodules without residual lymph node (LN) structure (ND) in colorectal cancer and to determine optimal categorization of ND in tumor staging. A multicenter, retrospective pathologic review was performed for 1716 patients with stages I to III curatively resected colorectal cancer treated at 11 institutions between 1994 and 1998. An additional 2242 patients from nine institutions were enrolled between 1999 and 2003 as a second cohort to validate the results. LN metastasis (LNM) and ND were observed in 33.7% and 16.0% (smooth-contour nodule [S-ND], 8.2%; irregular-contour nodule [I-ND], 10.7%) of patients in the first cohort. S-ND and I-ND were similarly distributed in the regional area. There was no considerable difference in the impact on survival between S-ND (hazard ratio [HR], 2.7; 95% CI, 1.9 to 3.8) and I-ND (HR, 4.3; 95% CI, 3.3 to 5.8) or between LNM (HR, 4.5; 95% CI, 3.4 to 6.0) and ND (HR, 4.0; 95% CI, 3.1 to 5.3). LNM and ND were similarly associated with the mode of recurrence. Tumor nodules ≥ 5 mm growing with venous/perineural invasion (ND [v/pni+]), judged with 0.61 κ value among 11 observers, had an independent prognostic value for 5-year survival of 42%; similar results were observed in the second cohort. These results do not support the TNM system in which S-ND is treated differently from I-ND in tumor staging; LNM and ND should be considered together in the same category. The presence of ND (v/pni+) has a considerable adverse prognostic effect.