Study on prediction model and influencing factors of progression-free survival in colorectal cancer

doi:10.3969/j.issn.1674-8115.2025.03.009

Abstract

Abstract:

Objective ·To explore the risk factors affecting progression-free survival (PFS) in colorectal cancer (CRC) patients and establish a corresponding prognostic prediction model. Methods ·A retrospective cohort study was used for analysis, including 533 patients with surgically resected and pathologically confirmed colorectal adenocarcinoma at Tongren Hospital, Shanghai Jiao Tong University School of Medicine, who were randomly divided into a training set (373 cases) and a validation set (160 cases) in a 7:3 ratio. The included clinical data were analyzed using univariate and multivariate Cox proportional hazards models to explore independent factors affecting postoperative PFS in patients with CRC and to establish a clinical prognostic prediction model based on these factors. The discrimination and calibration of the prediction model were evaluated by using concordance index (C-index), area under the receiver operating characteristic (ROC) curve (AUC), calibration curve, and survival curve. The independent effects of age, gender, and American Joint Committee on Cancer (AJCC) cancer stage on prognosis were assessed using multivariate Cox regression analysis. Results ·Multivariate Cox regression analysis revealed that age, smoking history, liver disease, carbohydrate antigen 724 (CA724), and AJCC stage were independent factors influencing PFS. In the training set, the C-index of the PFS model was 0.69, with AUCs of 0.744 and 0.713 at 3 and 5 years, respectively. In the validation set, the C-index of the PFS model was 0.64, with AUCs of 0.706 and 0.683 at 3 and 5 years, respectively. The calibration curves showed that the prediction of PFS for the training and validation sets were close to the standard curve. The survival curves suggested that the progression rate of patients in the low-risk group was significantly lower than that in the high-risk group. Stratified analysis revealed that among patients aged ≥65 years, age, liver disease, and AJCC clinical stage were independent factors affecting postoperative PFS. Among patients aged <65 years, smoking history, CA724, and AJCC clinical stage were independent factors affecting postoperative PFS. For male patients, age, smoking history, CA724, and AJCC clinical stage were independent factors affecting postoperative PFS, while for female patients, liver disease, CA724, and AJCC clinical staging were independent predictors of postoperative PFS. Among patients with AJCC stage Ⅰ‒Ⅱ, age and smoking history were independent factors affecting postoperative PFS, whereas in those with AJCC stage Ⅲ‒⁠Ⅳ, age, liver disease, and CA724 were independent factors affecting postoperative PFS. Conclusion ·The PFS prognostic model established in this study for CRC patients has good discriminative ability and provides clinicians with an effective risk assessment tool.

Key words: colorectal cancer, progression-free survival, influencing factor, predictive modeling

CLC Number:

R574.6

CHEN Jiaying, CHU Yimin, PENG Haixia. Study on prediction model and influencing factors of progression-free survival in colorectal cancer[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(3): 324-334.

Figures/Tables 9

TrendMD

References 25

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Item	Total population (n=533)	Training set (n=373)	Validation set (n=160)	P value
Outcome/n(%)				0.573
Survival	412 (77.3)	291 (78.0)	121 (75.6)
Death	121 (22.7)	82 (22.0)	39 (24.4)
Progression/n(%)				0.491
Yes	191 (35.8)	130 (34.9)	61 (38.1)
No	342 (64.2)	243 (65.1)	99 (61.9)
Gender/n(%)				0.528
Male	324 (60.8)	230 (61.7)	94 (58.8)
Female	209 (39.2)	143 (38.3)	66 (41.3)
Age/year	68.00 (62.00, 77.00)	68.00 (62.00, 77.00)	67.00 (62.00, 76.00)	0.707
Family history of CRC/n(%)				>0.999
No	528 (99.1)	369 (98.9)	159 (99.4)
Yes	5 (0.9)	4 (1.1)	1 (0.6)
Smoking history/n(%)				0.182
No	502 (94.2)	348 (93.3)	154 (96.3)
Yes	31 (5.8)	25 (6.7)	6 (3.8)
Alcohol consumption history/n(%)				0.639
No	528 (99.1)	370 (99.2)	158 (98.8)
Yes	5 (0.9)	3 (0.8)	2 (1.3)
Hypertension/n(%)				0.275
No	294 (55.2)	200 (53.6)	94 (58.8)
Yes	239 (44.8)	173 (46.4)	66 (41.3)
Diabetes/n(%)				0.304
No	437 (82.0)	310 (83.1)	127 (79.4)
Yes	96 (18.0)	63 (16.9)	33 (20.6)
Cardiovascular disease/n(%)				0.024
No	384 (72.0)	258 (69.2)	126 (78.8)
Yes	149 (28.0)	115 (30.8)	34 (21.3)
Kidney disease/n(%)				0.018
No	509 (95.5)	351 (94.1)	158 (98.8)
Yes	24 (4.5)	22 (5.9)	2 (1.3)
Liver disease/n(%)				0.507
No	511 (95.9)	359 (96.2)	152 (95.0)
Yes	22 (4.1)	14 (3.8)	8 (5.0)
Inflammatory bowel disease/n(%)				>0.999
No	532 (99.8)	372 (99.7)	160 (100.0)
Yes	1 (0.2)	1 (0.3)	0 (0)
Hyperlipidemia/n(%)				0.639
No	478 (89.7)	333 (89.3)	145 (90.6)
Yes	55 (10.3)	40 (10.7)	15 (9.4)
Neutrophil percentage/%	67.61±9.91	66.82±10.07	69.45±9.30	0.004
Lymphocyte percentage/%	23.01±8.53	23.61±8.44	21.61±8.59	0.014
Absolute neutrophil count/n	4.15 (3.11, 5.37)	4.01 (3.01, 5.24)	4.33 (3.59, 5.60)	0.003
Absolute lymphocyte count/n	1.40 (1.10, 1.80)	1.40 (1.10, 1.80)	1.40 (1.04, 1.70)	0.263
Monocyte percentage/%	6.60 (5.20, 8.20)	1.40 (1.10, 1.80)	6.50 (5.20, 7.98)	0.298
NLR	3.00 (2.14, 4.42)	2.90 (2.07, 4.05)	3.34 (2.41, 4.95)	0.002
PLR	600.00 (438.5, 823.49)	584.76 (437.96, 834.08)	626.19 (438.76, 786.53)	0.977
LMR	3.41 (2.44, 4.58)	3.45 (2.49, 4.57)	3.33 (2.21, 4.66)	0.338
Hemoglobin/(g·L^-1)	119.00 (96.00, 134.00)	120.00 (98.00, 134.00)	118.00 (93.00, 132.00)	0.188
Platelet/(×10⁹·L^-1)	245.00 (198.00, 308.00)	245.00 (196.00, 304.00)	245.50 (200.50, 317.50)	0.609
Fasting blood glucose/(mmol·L^-1)	5.80 (5.10, 7.30)	5.70 (5.00, 7.20)	6.00 (5.40, 7.60)	0.005
Creatinine/(μmol·L^-1)	69.10 (59.70, 80.00)	69.30 (60.00, 79.60)	68.90 (58.35, 81.12)	0.571
GFR/[mL·(min·1.73 m²)^-1]	116.69 (99.34, 137.51)	118.80 (99.55, 136.77)	118.31 (99.23, 139.27)	0.646
Urea/(mmol·L^-1)	5.00 (4.07, 6.15)	5.00 (4.07, 6.10)	5.04 (4.08, 6.15)	0.910
Total protein/(g·L^-1)	70.00 (64.70, 74.90)	69.90 (64.60, 74.50)	71.00 (64.85, 75.32)	0.226
Albumin/(g·L^-1)	40.30 (36.90, 43.30)	40.40 (37.00, 43.00)	40.15 (36.22, 43.62)	0.665
Total bilirubin/(μmol·L^-1)	10.10 (7.40, 14.10)	10.10 (7.30, 14.10)	10.05 (7.40, 13.72)	0.678
GPT/(U·L^-1)	20.00 (13.00, 29.00)	20.00 (13.00, 29.00)	21.00 (13.00, 30.00)	0.539
GGT/(U·L^-1)	19.00 (14.00, 28.00)	19.00 (14.00, 29.00)	18.00 (13.00, 26.00)	0.135
GOT/(U·L^-1)	21.00 (17.00, 25.00)	21.00 (17.00, 25.00)	20.00 (16.75, 26.00)	0.987
AFP/(ng·L^-1)	2.37 (1.56, 3.53)	2.36 (1.59, 3.50)	2.40 (1.52, 3.57)	0.796
CEA/(ng·L^-1)	3.43 (1.67, 8.98)	3.43 (1.63, 9.05)	3.38 (1.76, 8.39)	0.812
CA199/(U·mL^-1)	14.08 (8.47, 28.17)	13.39 (8.19, 27.76)	16.41 (9.31, 28.47)	0.320
CA125/(U·mL^-1)	11.65 (8.37, 18.47)	11.29 (7.90, 17.24)	13.36 (9.24, 24.01)	0.004
CA153/(U·mL^-1)	7.20 (4.82, 10.61)	7.09 (4.80, 10.86)	7.70 (4.91, 10.59)	0.998
CA724/(U·mL^-1)	2.42 (1.50, 5.74)	2.21 (1.50, 5.20)	3.14 (1.50, 6.69)	0.029
D-D/(mg·L^-1)	0.47 (0.25, 0.98)	0.45 (0.25, 0.95)	0.57 (0.27, 1.14)	0.100
INR	0.99 (0.94, 1.04)	0.99 (0.94, 1.04)	0.98 (0.92, 1.05)	0.298
C-reactive protein/(mg·L^-1)	5.90 (1.80, 19.28)	5.90 (1.80, 19.28)	5.95 (1.64, 19.66)	0.879
AJCC clinical stage/n(%)				0.577
StageⅠ‒Ⅱ	263 (49.3)	187 (50.1)	76 (47.5)
Stage Ⅲ‒Ⅳ	270 (50.7)	186 (49.9)	84 (52.5)
LCR	0.24 (0.07, 0.90)	0.24 (0.07, 0.91)	0.24 (0.06, 0.90)	0.775
CAR	154.88 (42.62, 493.89)	154.93 (42.36, 502.48)	152.82 (43.00, 492.59)	0.830

Item	Total population (n=533)	Training set (n=373)	Validation set (n=160)	P value
Outcome/n(%)				0.573
Survival	412 (77.3)	291 (78.0)	121 (75.6)
Death	121 (22.7)	82 (22.0)	39 (24.4)
Progression/n(%)				0.491
Yes	191 (35.8)	130 (34.9)	61 (38.1)
No	342 (64.2)	243 (65.1)	99 (61.9)
Gender/n(%)				0.528
Male	324 (60.8)	230 (61.7)	94 (58.8)
Female	209 (39.2)	143 (38.3)	66 (41.3)
Age/year	68.00 (62.00, 77.00)	68.00 (62.00, 77.00)	67.00 (62.00, 76.00)	0.707
Family history of CRC/n(%)				>0.999
No	528 (99.1)	369 (98.9)	159 (99.4)
Yes	5 (0.9)	4 (1.1)	1 (0.6)
Smoking history/n(%)				0.182
No	502 (94.2)	348 (93.3)	154 (96.3)
Yes	31 (5.8)	25 (6.7)	6 (3.8)
Alcohol consumption history/n(%)				0.639
No	528 (99.1)	370 (99.2)	158 (98.8)
Yes	5 (0.9)	3 (0.8)	2 (1.3)
Hypertension/n(%)				0.275
No	294 (55.2)	200 (53.6)	94 (58.8)
Yes	239 (44.8)	173 (46.4)	66 (41.3)
Diabetes/n(%)				0.304
No	437 (82.0)	310 (83.1)	127 (79.4)
Yes	96 (18.0)	63 (16.9)	33 (20.6)
Cardiovascular disease/n(%)				0.024
No	384 (72.0)	258 (69.2)	126 (78.8)
Yes	149 (28.0)	115 (30.8)	34 (21.3)
Kidney disease/n(%)				0.018
No	509 (95.5)	351 (94.1)	158 (98.8)
Yes	24 (4.5)	22 (5.9)	2 (1.3)
Liver disease/n(%)				0.507
No	511 (95.9)	359 (96.2)	152 (95.0)
Yes	22 (4.1)	14 (3.8)	8 (5.0)
Inflammatory bowel disease/n(%)				>0.999
No	532 (99.8)	372 (99.7)	160 (100.0)
Yes	1 (0.2)	1 (0.3)	0 (0)
Hyperlipidemia/n(%)				0.639
No	478 (89.7)	333 (89.3)	145 (90.6)
Yes	55 (10.3)	40 (10.7)	15 (9.4)
Neutrophil percentage/%	67.61±9.91	66.82±10.07	69.45±9.30	0.004
Lymphocyte percentage/%	23.01±8.53	23.61±8.44	21.61±8.59	0.014
Absolute neutrophil count/n	4.15 (3.11, 5.37)	4.01 (3.01, 5.24)	4.33 (3.59, 5.60)	0.003
Absolute lymphocyte count/n	1.40 (1.10, 1.80)	1.40 (1.10, 1.80)	1.40 (1.04, 1.70)	0.263
Monocyte percentage/%	6.60 (5.20, 8.20)	1.40 (1.10, 1.80)	6.50 (5.20, 7.98)	0.298
NLR	3.00 (2.14, 4.42)	2.90 (2.07, 4.05)	3.34 (2.41, 4.95)	0.002
PLR	600.00 (438.5, 823.49)	584.76 (437.96, 834.08)	626.19 (438.76, 786.53)	0.977
LMR	3.41 (2.44, 4.58)	3.45 (2.49, 4.57)	3.33 (2.21, 4.66)	0.338
Hemoglobin/(g·L^-1)	119.00 (96.00, 134.00)	120.00 (98.00, 134.00)	118.00 (93.00, 132.00)	0.188
Platelet/(×10⁹·L^-1)	245.00 (198.00, 308.00)	245.00 (196.00, 304.00)	245.50 (200.50, 317.50)	0.609
Fasting blood glucose/(mmol·L^-1)	5.80 (5.10, 7.30)	5.70 (5.00, 7.20)	6.00 (5.40, 7.60)	0.005
Creatinine/(μmol·L^-1)	69.10 (59.70, 80.00)	69.30 (60.00, 79.60)	68.90 (58.35, 81.12)	0.571
GFR/[mL·(min·1.73 m²)^-1]	116.69 (99.34, 137.51)	118.80 (99.55, 136.77)	118.31 (99.23, 139.27)	0.646
Urea/(mmol·L^-1)	5.00 (4.07, 6.15)	5.00 (4.07, 6.10)	5.04 (4.08, 6.15)	0.910
Total protein/(g·L^-1)	70.00 (64.70, 74.90)	69.90 (64.60, 74.50)	71.00 (64.85, 75.32)	0.226
Albumin/(g·L^-1)	40.30 (36.90, 43.30)	40.40 (37.00, 43.00)	40.15 (36.22, 43.62)	0.665
Total bilirubin/(μmol·L^-1)	10.10 (7.40, 14.10)	10.10 (7.30, 14.10)	10.05 (7.40, 13.72)	0.678
GPT/(U·L^-1)	20.00 (13.00, 29.00)	20.00 (13.00, 29.00)	21.00 (13.00, 30.00)	0.539
GGT/(U·L^-1)	19.00 (14.00, 28.00)	19.00 (14.00, 29.00)	18.00 (13.00, 26.00)	0.135
GOT/(U·L^-1)	21.00 (17.00, 25.00)	21.00 (17.00, 25.00)	20.00 (16.75, 26.00)	0.987
AFP/(ng·L^-1)	2.37 (1.56, 3.53)	2.36 (1.59, 3.50)	2.40 (1.52, 3.57)	0.796
CEA/(ng·L^-1)	3.43 (1.67, 8.98)	3.43 (1.63, 9.05)	3.38 (1.76, 8.39)	0.812
CA199/(U·mL^-1)	14.08 (8.47, 28.17)	13.39 (8.19, 27.76)	16.41 (9.31, 28.47)	0.320
CA125/(U·mL^-1)	11.65 (8.37, 18.47)	11.29 (7.90, 17.24)	13.36 (9.24, 24.01)	0.004
CA153/(U·mL^-1)	7.20 (4.82, 10.61)	7.09 (4.80, 10.86)	7.70 (4.91, 10.59)	0.998
CA724/(U·mL^-1)	2.42 (1.50, 5.74)	2.21 (1.50, 5.20)	3.14 (1.50, 6.69)	0.029
D-D/(mg·L^-1)	0.47 (0.25, 0.98)	0.45 (0.25, 0.95)	0.57 (0.27, 1.14)	0.100
INR	0.99 (0.94, 1.04)	0.99 (0.94, 1.04)	0.98 (0.92, 1.05)	0.298
C-reactive protein/(mg·L^-1)	5.90 (1.80, 19.28)	5.90 (1.80, 19.28)	5.95 (1.64, 19.66)	0.879
AJCC clinical stage/n(%)				0.577
StageⅠ‒Ⅱ	263 (49.3)	187 (50.1)	76 (47.5)
Stage Ⅲ‒Ⅳ	270 (50.7)	186 (49.9)	84 (52.5)
LCR	0.24 (0.07, 0.90)	0.24 (0.07, 0.91)	0.24 (0.06, 0.90)	0.775
CAR	154.88 (42.62, 493.89)	154.93 (42.36, 502.48)	152.82 (43.00, 492.59)	0.830

Characteristic	Univariate Cox regression		Multivariate Cox regression
Characteristic	HR (95%CI)	P value	HR (95%CI)	P value
Age	1.03 (1.01‒⁠1.05)	<0.001	1.03 (1.01‒⁠1.05)	0.007
Smoking history	1.96 (1.08‒⁠3.56)	0.028	2.10 (1.11‒⁠3.96)	0.023
Liver disease	4.03 (2.16‒⁠7.53)	<0.001	2.91 (1.50‒⁠5.62)	0.001
Hyperlipidemia	0.40 (0.19‒⁠0.86)	0.018	0.51 (0.23‒⁠1.11)	0.088
Hemoglobin	0.99 (0.98‒⁠1.00)	0.002	1.00 (0.99‒⁠1.01)	0.793
Total protein	0.96 (0.94‒⁠0.99)	0.002	0.97 (⁠0.94‒1.03)	0.161
Albumin	0.94 (0.91‒⁠0.97)	<0.001	1.01 (0.94‒⁠1.08)	0.769
GPT	0.98 (0.97‒⁠1.00)	0.046	0.99 (0.97‒⁠1.01)	0.172
CEA	1.01 (1.00‒⁠1.01)	<0.001	1.00 (1.00‒⁠1.01)	0.096
CA724	1.09 (1.06‒⁠1.13)	<0.001	1.08 (1.04‒⁠1.12)	<0.001
D-D	1.06 (1.00‒⁠1.11)	0.034	1.01 (0.94‒⁠1.10)	0.747
AJCC clinical stage	2.03 (1.42‒⁠2.91)	<0.001	1.87 (1.29‒⁠2.72)	<0.001

Characteristic	Univariate Cox regression		Multivariate Cox regression
Characteristic	HR (95%CI)	P value	HR (95%CI)	P value
Age	1.03 (1.01‒⁠1.05)	<0.001	1.03 (1.01‒⁠1.05)	0.007
Smoking history	1.96 (1.08‒⁠3.56)	0.028	2.10 (1.11‒⁠3.96)	0.023
Liver disease	4.03 (2.16‒⁠7.53)	<0.001	2.91 (1.50‒⁠5.62)	0.001
Hyperlipidemia	0.40 (0.19‒⁠0.86)	0.018	0.51 (0.23‒⁠1.11)	0.088
Hemoglobin	0.99 (0.98‒⁠1.00)	0.002	1.00 (0.99‒⁠1.01)	0.793
Total protein	0.96 (0.94‒⁠0.99)	0.002	0.97 (⁠0.94‒1.03)	0.161
Albumin	0.94 (0.91‒⁠0.97)	<0.001	1.01 (0.94‒⁠1.08)	0.769
GPT	0.98 (0.97‒⁠1.00)	0.046	0.99 (0.97‒⁠1.01)	0.172
CEA	1.01 (1.00‒⁠1.01)	<0.001	1.00 (1.00‒⁠1.01)	0.096
CA724	1.09 (1.06‒⁠1.13)	<0.001	1.08 (1.04‒⁠1.12)	<0.001
D-D	1.06 (1.00‒⁠1.11)	0.034	1.01 (0.94‒⁠1.10)	0.747
AJCC clinical stage	2.03 (1.42‒⁠2.91)	<0.001	1.87 (1.29‒⁠2.72)	<0.001

Item	Age≥65 years		Age<65 years
Item	HR (95%CI)	P value	HR (95%CI)	P value
Age	1.03 (1.01‒⁠1.05)	0.009	1.01 (0.97‒⁠1.05)	0.649
Smoking history	1.78 (0.86‒⁠3.72)	0.123	2.40 (1.02‒⁠5.68)	0.046
Liver disease	2.82 (1.50‒⁠5.28)	0.001	1.80 (0.55‒⁠5.83)	0.330
CA724	1.03 (0.99‒⁠1.08)	0.118	1.12 (1.07‒⁠1.16)	<0.001
AJCC clinical stage	2.15 (1.50‒⁠3.07)	<0.001	3.50 (1.89‒⁠6.50)	<0.001