Prognostic Value of Tumor Deposits for Disease-Free Survival in Patients With Stage III Colon Cancer: A Post Hoc Analysis of the IDEA France Phase III Trial (PRODIGE-GERCOR)

Abstract

PURPOSE Tumor deposits (TDs) seem to affect the prognosis of patients with colon cancer (CC). In the seventh edition of the American Joint Committee on Cancer TNM staging system for CC, the presence of TDs is only considered in the absence of lymph node metastases (LNMs). In the era of personalized duration of histopathologic criteria-based adjuvant therapy, this could potentially lead to a decrease in the prognostic prediction accuracy. PATIENTS AND METHODS A post hoc analysis of all pathologic reports from patients with stage III CC included in the IDEA France phase III study (ClinicalTrials.gov identifier: NCT00958737 ) investigating the duration of adjuvant fluorouracil, leucovorin, and oxaliplatin or capecitabine and oxaliplatin therapy (3 v 6 months) was performed. The primary objective was to determine the prognostic impact of TD on disease-free survival (DFS). The effect of the addition of TD to LNM count on pN restaging was also evaluated. A multivariable analysis was performed to establish the association between TD and DFS. RESULTS Of 1,942 patients, 184 (9.5%) had TDs. The pN1a/b and pN1c populations showed similar DFS. TD-positive patients had worse prognosis compared with TD-negative patients, with 3-year DFS rates of 65.6% (95% CI, 58.0% to 72.1%) and 74.7% (95% CI, 72.6% to 76.7%; P = .0079), respectively. On multivariable analysis, TDs were associated with a higher risk of recurrence or death (hazard ratio [HR], 1.36; P = .0201). Other adverse factors included pT4 and/or pN2 disease (HR, 2.21; P < .001), the 3 months of adjuvant treatment (HR, 1.29; P = .0029), tumor obstruction (HR, 1.28; P = .0233), and male sex (HR, 1.24; P = .0151). Patients restaged as having pN2 disease (n = 35, 2.3%) had similar DFS as patients initially classified as pN2. CONCLUSION The presence of TDs is an independent prognostic factor for DFS in patients with stage III CC. The addition of TD to LNM may help to better define the duration of adjuvant therapy.

Combining tumor deposits with the number of lymph node metastases to improve the prognostic accuracy in stage III colon cancer: a post hoc analysis of the CALGB/SWOG 80702 phase III study (Alliance)☆

“…Previous publications have suggested a potential pathophysiologic relationship between TD and lymphovascular or perineural invasion, which are high-risk features of stage II colon cancer. 10,12,19 The IDEA France analysis observed a significant interaction between TD and these features, but the relatively high amount of missing data did not permit firm conclusions to be drawn. 12 Here, the presence or absence of lymphovascular and perineural invasion was reported for 94.9% of patients.…”

“…10,12,19 The IDEA France analysis observed a significant interaction between TD and these features, but the relatively high amount of missing data did not permit firm conclusions to be drawn. 12 Here, the presence or absence of lymphovascular and perineural invasion was reported for 94.9% of patients. The negative prognostic impact of TD remained significant whether the tumor exhibited lymphovascular or perineural invasion or not.…”

“…A post hoc analysis of the IDEA France study reported a negative impact of TD on DFS. 12 The observed frequency of TD was 9.5%, but may have been artificially low because only 36.7% of pathology reports were standardized to include this information. In our study, the observed frequency of TD in stage III colon cancer was higher (26%) and more in accordance with the incidence reported in other publications.…”

“…2 The potentially practice-changing results of the IDEA France study require validation, particularly as most pathology reports in this study lacked standardization. 12 In the Cancer and Leukemia Group B/Southwest Oncology Group (CALGB/SWOG) 80702 phase III study (NCT01150045), 2526 stage III colon cancer patients were randomized to 3 versus 6 months of adjuvant FOLFOX plus 3 years of celecoxib or placebo. The primary objective was to compare DFS of patients treated with standard chemotherapy with or without celecoxib.…”

N1c colon cancer and the use of adjuvant chemotherapy: a current audit of the National Cancer Database

“…Stage III staging [5][6][7][8][9]; to this end, adjuvant chemotherapy (AC) has been recommended by the National Comprehensive Cancer Network (NCCN) and supported by others as the standard of care to improve disease-free survival and overall survival (OS) in N1c disease [3,7,[9][10][11][12][13]. The increased risks posed by TD remain incompletely addressed [14].…”