Table 4.
Univariable and multivariable analysis of factors associated with overall survival (whole cohort; n = 420).
| Variable | No. (%) | Median OS (mo; 95%CI) | Univariable Analysis | p | Multivariable Analysis | p |
|---|---|---|---|---|---|---|
| HR (95%CI) | HR (95%CI) | |||||
| Patient-related factors | ||||||
| Sex | ||||||
| Female | 158 (38%) | 24.4 (16.6–32.2) | ||||
| Male | 262 (62%) | 25.3 (21.2–29.4) | 1.01 (0.81–1.26) | 0.913 | ||
| Age at first mets-dx | ||||||
| <70 | 231 (55%) | 33.4 (27.3–39.5) | ||||
| ≥70 | 189 (45%) | 18.3 (14.0–22.6) | 1.46 (1.18–1.81) | 0.001 | 0.99 (0.78–1.27) | 0.958 |
| ASA Score | ||||||
| I | 34 (8%) | 23.6 (12.9–34.3) | ||||
| II | 206 (49%) | 36.5 (31.0–42.0) | 0.97 (0.62–1.50) | 0.888 | 1.14 (0.72–1.82) | 0.579 |
| III | 155 (37%) | 17.0 (14.4–19.6) | 1.63 (1.05–2.54) | 0.031 | 1.44 (0.89–2.33) | 0.134 |
| IV/V | 25 (6%) | 4.5 (2.1–7.0) | 6.05 (3.40–10.77) | <0.001 | 3.50 (1.85–6.61) | <0.001 |
| BMI (missing = 11) | ||||||
| <25.4 (=Median) | 217 (52%) | 22.6 (17.7–27.5) | ||||
| ≥25.4 | 192 (46%) | 28.1 (23.7–32.5) | 0.90 (0.72–1.12) | 0.342 | ||
| Disease/Tumour-related factors | ||||||
| Primary tumour | ||||||
| T stage | ||||||
| T1 & T2 | 38 (9%) | 30.5 (16.9–44.1) | ||||
| T3 | 236 (56%) | 31.1 (26.8–35.4) | 1.03 (0.70–1.53) | 0.868 | 0.94 (0.61–1.44) | 0.759 |
| T4 & Tx | 146 (35%) | 15.6 (12.6–18.6) | 1.69 (1.13–2.53) | 0.011 | 1.00 (0.64–1.57) | 0.996 |
| Nodal status | ||||||
| N negative | 89 (21%) | 41.0 (27.8–54.3) | ||||
| N positive | 303 (72%) | 23.2 (19.0–27.4) | 1.55 (1.18–2.04) | 0.002 | 1.52 (1.13–2.04) | 0.006 |
| Nx (unknown) | 28 (7%) | 12.8 (3.6–22.0) | 2.91 (1.85–4.58) | <0.001 | 1.36 (0.81–2.26) | 0.245 |
| R-Status | ||||||
| R0 | 240 (58%) | 39.1 (34.5–43.7) | ||||
| R1 | 19 (5%) | 12.9 (9.4–16.42) | 1.94 (1.14–3.30) | 0.014 | 1.13 (0.63–2.03) | 0.686 |
| R2/no resection/Rx | 161 (38%) | 15.1 (12.0–18.2) | 2.84 (2.27–3.58) | <0.001 | 1.05 (0.75–1.46) | 0.782 |
| Tumour differentiation | ||||||
| G1 | 5 (1%) | 20.6 (3.9–37.4) | ||||
| G2 | 263 (63%) | 30.5 (26.6–34.4) | 0.77 (0.32–1.87) | 0.564 | ||
| G3 | 137 (33%) | 16.2 (10.5–21.9) | 1.04 (0.42–2.54) | 0.940 | ||
| G4 | 3 (1%) | 3.7 (10.8–25.2) | 1.43 (0.34–5.99) | 0.626 | ||
| Gx | 12 (3%) | 32.5 (0.0–66.1) | 0.71 (0.24–2.11) | 0.535 | ||
| Tumour location (sidedness) | ||||||
| Left Colon incl. Rectum | 291 (69%) | 29.6 (24.8–34.4) | ||||
| Right Colon | 129 (31%) | 15.3 (11.8–18.8) | 1.59 (1.26–1.99) | <0.001 | 1.33 (1.04–1.69) | 0.021 |
| Histology primary tumour | ||||||
| Adeno-Carcinoma | 411 (98%) | 25.9 (22.0–29.8) | ||||
| Mucinous or Signet-Cell | 9 (2%) | 12.4 (0.0–27.6) | 2.80 (1.44–5.46) | 0.002 | 3.18 (1.55–6.55) | 0.002 |
| Metastases | ||||||
| Occurrence of metastases | ||||||
| Metachronous (>6 months) | 140 (33%) | 32.5 (24.7–40.3) | ||||
| Synchronous (≤6 months) | 280 (67%) | 21.7 (17.7–25.7) | 1.52 (1.20–1.93) | <0.001 | 1.25 (0.90–1.72) | 0.180 |
| CEA at mets-dx | ||||||
| ≤200 ng/mL | 312 (74%) | 28.3 (23.4–33.2) | ||||
| >200 ng/mL | 69 (16%) | 13.6 (9.0–18.3) | 2.22 (1.68–2.93) | <0.001 | 1.74 (1.27–2.39) | <0.001 |
| Missing | 39 (9%) | 31.7 (16.2–47.2) | 0.83 (0.56–1.24) | 0.833 | 0.94 (0.61–1.45) | 0.779 |
| Metastatic extent | ||||||
| Liver limited | 188 (45%) | 29.8 (24.1–35.6) | ||||
| Lung limited | 57 (13%) | 46.8 (34.7–59.0) | 0.57 (0.40–0.83) | 0.003 | 0.70 (0.47–1.04) | 0.080 |
| Liver-lung limited | 42 (10%) | 25.5 (9.9–41.1) | 1.46 (1.01–2.11) | 0.042 | 0.95 (0.63–1.43) | 0.803 |
| Other organs involvement | 133 (32%) | 15.6 (11.9–19.3) | 1.80 (1.41–2.30) | <0.001 | 1.24 (0.91–1.69) | 0.167 |
| Treatment-related factors | ||||||
| Initial treatment strategy | ||||||
| Curative | 170 (41%) | 52.1 (39.9–54.3) | ||||
| Palliative | 250 (60%) | 14.0 (11.6–16.4) | 4.36 (3.42–5.57) | <0.001 | 3.68 (2.64–5.12) | <0.001 |
| CTX since mets-dx (miss = 3) | ||||||
| Any chemotherapy | 341 (82%) | 29.8 (25.7–40.0) | ||||
| BSC/no chemo | 76 (18%) | 4.0 (2.7–5.3) | 2.42 (1.84–3.18) | <0.001 | ** | |
| Type of CTX | ||||||
| Including IRI and/or OX | 316 (75%) | 30.8 (27.1–34.5) | ||||
| 5-FU-based only/BSC/no CTX | 93 (22%) | 6.7 (3.3–10.1) | 2.00 (1.55–2.59) | <0.001 | 2.57 (1.92–3.45) | <0.001 |
| Unknown | 11 (3%) | 21.6 (17.2–26.0) | 1.17 (0.62–2.20) | 0.627 | 2.05 (1.06–3.99) | 0.034 |
| Received biological | ||||||
| At any time since mets-dx | 249 (59%) | 29.8 (26.4–33.2) | ||||
| Never | 161 (38%) | 14.4 (8.3–20.5) | 1.13 (0.90–1.42) | 0.289 | ||
| Missing | 10 (3%) | 20.6 (16.3–24.9) | 1.04 (0.53–2.03) | 0.905 | ||
| Time period of mets-dx | ||||||
| 2003–2006 | 146 (35%) | 21.9 (17.3–26.5) | ||||
| 2007–2010 | 142 (34%) | 24.2 (17.5–30.9) | 0.91 (0.71–1.16) | 0.428 | ||
| 2011–2014 | 132 (31%) | 36.5 (26.6–46.4) | 0.67 (0.51–0.89) | 0.005 | ** |
The first category serves as reference (HR 1.0); ** After sensitivity analysis, these factors were not included in the multivariable model due to (multi-)collinearity with other factors (e.g., age). ASA = American Society of Anaesthesiologists; BMI = Body mass index; BSC = best supportive care; CEA = carcinoembryogenic antigen; CTX = chemotherapy; IRI = irinotecan; mets-dx = diagnosis of metastases; miss = patients with missing values; OX = oxaliplatin.