Table 1.
Univariate Analysis (Cohort1+Cohort2).
| STAGE I-II (Cohorts 1+2) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Time to Recurrence (TTR) | Unadjusted Stratified by Center | Restricted Mean Survival Time (RMST) | |||||||
| No. of Patients (%) | Rate at 5 yr % (95% CI) | p Value * | Hazard Ratio (95% CI) | p Value ** | C-Index (95% CI) | Months (95% CI) | Relative Months (95% CI) | p Value *** | |
| IS-2Level | 0.59 (0.52–0.66) | ||||||||
| 0–25% | 448 (23.8) | 78.4 (74.4–82.6) | 1.0 (reference) | 208.1 (197.1–219) | 0.0 (reference) | ||||
| 25–100% | 1437 (76.2) | 90 (88.3–91.8) | <0.0001 | 0.43 (0.32–0.57) | <0.0001 | 240.9 (236.3–245.6) | 32.9 (21–44.8) | <0.0001 | |
| IS-3Level | 0.63 (0.53–0.72) | ||||||||
| 0–25% | 448 (23.8) | 78.4 (74.4–82.6) | 1.0 (reference) | 208.1 (197.1–219) | 0.0 (reference) | ||||
| 25–70% | 890 (47.2) | 88.1 (85.7–90.4) | <0.0001 | 0.52 (0.39–0.7) | <0.0001 | 235.4 (229.1–241.7) | 27.3 (14.7–40) | <0.0001 | |
| 70–100% | 547 (29) | 93.4 (91.1–95.8) | <0.0001 | 0.27 (0.18–0.41) | <0.0001 | 250.5 (244.2–256.7) | 42.4 (29.8–55) | <0.0001 | |
| Disease free survival (DFS) | Unadjusted stratified by center | Restricted Mean Survival Time (RMST) | |||||||
| No. of patients (%) | Rate at 5 yr % (95% CI) | p Value * | Hazard ratio (95% CI) | p Value ** | C-index (95% CI) | Months (95% CI) | Relative Months (95% CI) | p Value *** | |
| IS-2Level | 0.54 (0.5–0.59) | ||||||||
| 0–25% | 448 (23.8) | 67.3 (62.9–72) | 1.0 (reference) | 124.3 (111–137.6) | 0.0 (reference) | ||||
| 25–100% | 1437 (76.2) | 78 (75.7–80.3) | <0.0001 | 0.67 (0.56–0.79) | <0.0001 | 154.9 (146.6–163.1) | 30.6 (14.9–46.3) | 0.0001 | |
| IS-3Level | 0.56 (0.5–0.61) | ||||||||
| 0–25% | 448 (23.8) | 67.3 (62.9–72) | 1.0 (reference) | 124.3 (111–137.6) | 0.0 (reference) | ||||
| 25–70% | 890 (47.2) | 76.8 (73.9–79.8) | 0.0004 | 0.72 (0.6–0.86) | 0.0005 | 151.5 (141.3–161.7) | 27.2 (10.4–44) | 0.0015 | |
| 70–100% | 547 (29) | 80 (76.4–83.7) | <0.0001 | 0.57 (0.45–0.71) | <0.0001 | 161.4 (147.2–175.6) | 37.1 (17.7–56.6) | 0.0002 | |
| STAGE I, MSS (Cohorts 1+2) | |||||||||
| Time to recurrence (TTR) | Unadjusted stratified by center | Restricted Mean Survival Time (RMST) | |||||||
| No. of patients (%) | Rate at 5 yr % (95% CI) | p Value * | Hazard ratio (95% CI) | p Value ** | C-index (95% CI) | Months (95% CI) | Relative Months (95% CI) | p Value *** | |
| IS-2Level | 0.65 (0.48–0.82) | ||||||||
| 0–25% | 30 (14.6) | 86 (74.2–99.7) | 1.0 (reference) | 156.4 (132.9–179.9) | 0.0 (reference) | ||||
| 25–100% | 176 (85.4) | 95.3 (92–98.8) | 0.0427 | 0.27 (0.08–0.87) | 0.0279 | 174.7 (168–181.4) | 18.3 (−6.1–42.7) | 0.1414 | |
| IS-3Level | 0.72 (0.45–0.98) | ||||||||
| 0–25% | 30 (14.6) | 86 (74.2–99.7) | 1.0 (reference) | 156.4 (132.9–179.9) | 0.0 (reference) | ||||
| 25–70% | 107 (51.9) | 93.5 (88.5–98.7) | 0.2068 | 0.38 (0.12–1.22) | 0.1047 | 170 (160.2–179.8) | 13.6 (−11.8–39.1) | 0.2939 | |
| 70–100% | 69 (33.5) | 98.3 (95.1–100) | 0.0056 | 0.07 (0.01–0.61) | 0.0167 | 183.1 (177.7–188.5) | 26.7 (2.6–50.8) | 0.0296 | |
| Disease free survival (DFS) | Unadjusted stratified by center | Restricted Mean Survival Time (RMST) | |||||||
| No. of patients (%) | Rate at 5 yr % (95% CI) | p Value * | Hazard ratio (95% CI) | p Value ** | C-index (95% CI) | Months (95% CI) | Relative Months (95% CI) | p Value *** | |
| IS-2Level | 0.55 (0.45–0.65) | ||||||||
| 0–25% | 30 (14.6) | 76 (62–93.2) | 1.0 (reference) | 141.9 (115.9–168) | 0.0 (reference) | ||||
| 25–100% | 176 (85.4) | 86.5 (81.3–92.1) | 0.2536 | 0.59 (0.27–1.3) | 0.1876 | 148.9 (138–159.8) | 7 (−21.2–35.2) | 0.6280 | |
| IS-3Level | 0.6 (0.45–0.75) | ||||||||
| 0–25% | 30 (14.6) | 76 (62–93.2) | 1.0 (reference) | 141.9 (115.9–168) | 0.0 (reference) | ||||
| 25–70% | 107 (51.9) | 83.7 (76.6–91.4) | 0.5450 | 0.69 (0.31–1.54) | 0.3627 | 143.2 (128.9–157.5) | 1.3 (−28.4–31) | 0.9313 | |
| 70–100% | 69 (33.5) | 91.1 (83.9–98.9) | 0.0737 | 0.37 (0.13–1) | 0.0511 | 158.8 (142.6–174.9) | 16.8 (−13.8–47.5) | 0.2816 | |
| STAGE II, MSS (Cohorts 1+2) | |||||||||
| Time to recurrence (TTR) | Unadjusted stratified by center | Restricted Mean Survival Time (RMST) | |||||||
| No. of patients (%) | Rate at 5 yr % (95% CI) | p Value * | Hazard ratio (95% CI) | p Value ** | C-index (95% CI) | Months (95% CI) | Relative Months (95% CI) | p Value *** | |
| IS-2Level | 0.58 (0.5–0.66) | ||||||||
| 0–25% | 183 (28.1) | 71.3 (64.7–78.6) | 1.0 (reference) | 159.9 (145.5–174.3) | 0.0 (reference) | ||||
| 25–100% | 469 (71.9) | 85.9 (82.6–89.3) | <0.0001 | 0.49 (0.36–0.66) | <0.0001 | 191.6 (184.5–198.7) | 31.7 (15.6–47.8) | 0.0001 | |
| IS-3Level | 0.61 (0.51–0.7) | ||||||||
| 0–25% | 183 (28.1) | 71.3 (64.7–78.6) | 1.0 (reference) | 159.9 (145.5–174.3) | 0.0 (reference) | ||||
| 25–70% | 336 (51.5) | 85.3 (81.4–89.4) | 0.0001 | 0.56 (0.41–0.77) | 0.0003 | 190 (181.5–198.5) | 30.1 (13.4–46.8) | 0.0004 | |
| 70–100% | 133 (20.4) | 87.4 (81.3–93.9) | 0.0007 | 0.33 (0.21–0.52) | <0.0001 | 195.8 (183.2–208.4) | 35.9 (16.7–55.1) | 0.0002 | |
| Disease free survival (DFS) | Unadjusted stratified by center | Restricted Mean Survival Time (RMST) | |||||||
| No. of patients (%) | Rate at 5 yr % (95% CI) | p Value * | Hazard ratio (95% CI) | p Value ** | C-index (95% CI) | Months (95% CI) | Relative Months (95% CI) | p Value *** | |
| IS-2Level | 0.54 (0.49–0.59) | ||||||||
| 0–25% | 183 (28.1) | 60.6 (53.8–68.3) | 1.0 (reference) | 113.2 (96.5–129.9) | 0.0 (reference) | ||||
| 25–100% | 469 (71.9) | 75.8 (71.9–79.9) | <0.0001 | 0.71 (0.58–0.85) | 0.0003 | 148 (137.8–158.3) | 34.8 (15.2–54.4) | 0.0005 | |
| IS-3Level | 0.55 (0.49–0.61) | ||||||||
| 0–25% | 183 (28.1) | 60.6 (53.8–68.3) | 1.0 (reference) | 113.2 (96.5–129.9) | 0.0 (reference) | ||||
| 25–70% | 336 (51.5) | 75.5 (70.9–80.4) | 0.0001 | 0.75 (0.61–0.91) | 0.0044 | 149.2 (137.2–161.3) | 36 (15.5–56.6) | 0.0006 | |
| 70–100% | 133 (20.4) | 76.5 (69.1–84.6) | 0.0022 | 0.63 (0.49–0.8) | 0.0002 | 147 (127.9–166.1) | 33.8 (8.4–59.1) | 0.0090 | |
* Logrank P Value. ** Wald p Value stratified by participating center. *** Restricted Mean Survival Time (RMST) p value. MSS: proficient Mismatch repair (pMMR).