Prognostic and Predictive Value of the Tumor-Stroma Ratio in STAGE II Colon Cancer

Abstract

Background: Tumor-stroma ratio (TSR) is an independent prognosticator in colon cancer. Objective: We set out to investigate the predictive power, as well as to validate the prognostic power of TSR in stage II colon cancer patients. Better identification of patients who could benefit from adjuvant chemotherapy remains an important issue in stage II disease. Methods: TSR was microscopically determined on haematoxylin and eosin-stained primary tumor tissue slides of 212 patients who received either adjuvant chemotherapy or surveillance after curative resection in a prospective randomized clinical trial (ABCSG-91). Results: Stroma-high tumors were associated with significantly more cancer-related death ((CaDeath) HR 2.30, 95% CI 1.05−5.03; p=0.037) and significantly shorter distant recurrence-free survival ((DRFS) HR 2.32, 95% CI 1.10−4.87; p=0.027) compared to stroma-low tumors. Backward multivariate Cox-regression analysis demonstrated TSR as an independent prognosticator for DRFS (p=0.027) and CaDeath (p=0.031). TSR did not validate as a predictive biomarker; CaDeath (HR 0.87, 95% CI 0.18−4.17; p=0.87), DRFS (HR 0.76, 95% CI 0.17−3.36; p=0.71) and OS (HR 0.96, 95% CI 0.29−3.21; p=0.95) for the type of chemotherapy given in ABCSG-91. Conclusions: TSR, an easily applicable and inexpensive observer-based method, is an independent predictor of poor prognosis in stage II colon cancer. Predictive value for adjuvant 5-FU/leucovorin could not be demonstrated.

Impact of Tumor–Stroma Ratio on the Prognosis of Colorectal Cancer: A Systematic Review

“…On the other hand, a study published by Roseweir et al, which had a total of 14% low TSR in study population, noted statistically significantly worse outcome for DFS among low TSR subjects. The other three studies (5,26,28) have showed significant association of low TSR with worse prognosis for outcome DFS in stage II CRC. In the stage III CRC, two studies (5,19) showed that low TSR is associated with worse outcome for DFS and OS.…”

“…Nine studies reported on the use of chemotherapy for treatment, with five ( 18 , 19 , 25 , 28 , 30 ) describing adjuvant chemotherapy, two ( 17 , 26 ) describing surgery combined with chemotherapy, one describing chemotherapy and rofecoxib ( 5 ), and one describing only chemotherapy ( 16 ). One study ( 20 ) documented radiotherapy in conjunction with chemoradiotherapy ( 27 ), while another study ( 24 ) recommended neo-adjuvant radiotherapy in conjunction with radiotherapy as a treatment option.…”

“…Two studies had a high risk of bias in the “study participation domain”, as they did not mention the inclusion and exclusion criteria for the study participants. These studies ( 16 , 22 ) had a high risk of bias, as they did not adequately account for study participant selection, and six studies were rated as having a moderate risk of bias in study participation due to incomplete information regarding inclusion criteria of study ( 17 , 19 , 21 , 23 , 26 , 28 ). Overall, we judged five studies ( 16 , 17 , 19 , 22 , 28 ) to have a moderate risk of bias.…”

“…All the studies we included had reported the data using a cutoff value of 0.5 (50%) or more for classifying the high stroma or low TSR value. One study was reported from China (16), one from Turkey (17), three from the United Kingdom (5,18,19), seven from the Netherlands (20)(21)(22)(23)(24)(25)(26), one from Poland (27), and two from Denmark (28). Five studies used the retrospective study design for their study (Table 1).…”

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“…Nine studies reported on the use of chemotherapy for treatment, with five (18, 19, 25, 28, 30) describing adjuvant chemotherapy, two (17,26) describing surgery combined with chemotherapy, one describing chemotherapy and rofecoxib (5), and one describing only chemotherapy (16). One study (20) documented radiotherapy in conjunction with chemoradiotherapy (27), while another study (24) recommended neo-adjuvant radiotherapy in conjunction with radiotherapy as a treatment option.…”