Prediction of overall survival following colorectal cancer surgery in elderly patients

Table 1 Patient, surgery, and disease characteristics

Variable	SGH cohort (n = 1267)
Age, median (range), yr	77 (70-102)
Gender
Male	658 (51.9)
Female	609 (48.1)
Race
Chinese	1148 (90.6)
Malay	50 (4.0)
Indian	30 (2.4)
Others	39 (3.1)
ECOG status
0 (asymptomatic)	751 (59.3)
1	401 (31.6)
2	85 (6.7)
3	23 (1.8)
4 (bedbound)	7 (0.2)
ASA score
1	178 (14.0)
2	857 (67.6)
3	225 (17.8)
4	7 (0.6)
Tumor site
Colon	790 (62.3)
Rectum	477 (37.6)
Surgical approach
Open	888 (70.1)
Laparoscopic	379 (29.9)
Surgery
High Anterior resection	505 (40.0)
Low Anterior resection	163 (12.9)
Ultra-Low Anterior resection	150 (11.8)
Right Hemicolectomy	286 (22.6)
Abdominoperineal resection	58 (4.6)
Others	105 (8.3)
TMN stagea
1	240 (18.9)
2	416 (32.8)
3	442 (34.9)
Tumor diameter, median (IQR), cm	4.5 (3–6)
Number of lymph nodes harvested, median (IQR)	15 (11–20)
Neoadjuvant therapy	22 (1.8)
Adjuvant therapy	219 (17.6)

^aAmerican Joint Committee on Cancer Staging, 7^th edition. All values are reported as n (%) unless otherwise stated. ECOG: Eastern Cooperative Oncology Group; ASA: American Society of Anesthesiologists; IQR: Interquartile range; SGH: Singapore General Hospital.

Table 2 30-d post-operative complications n (%)

	SGH cohort (n = 1267)
Overall 30-d complications	297 (23.4)
Clavien-Dindo classification
I	75 (5.9)
II	140 (11.0)
III	21 (1.7)
IV	31 (2.4)
V (death)	30 (2.4)
Type of complication
Cardiac/CVA	97 (7.7)
Respiratory	28 (2.2)
Urinary	24 (1.9)
Wound/stoma	55 (4.3)
Anastomotic leak	16 (1.3)
Others	77 (6.1)

SGH: Singapore General Hospital; CVA: Cerebrovascular accident.

Table 3 Unadjusted hazard ratios of individual predictors in association with 3-year survival duration obtained via univariate Royston-Parmar regression

Predictors	n	HR (95%CI)	P value
Gender	1267	1.03 (0.81-1.31)	0.807
Age	1267	1.00 (0.98-1.03)	0.826
Race
Chinese	1148	1.00 (ref)
Malay	50	1.14 (0.60-2.14)	0.682
Indian	30	1.43 (0.78-2.68)	0.272
Others	39	0.67 (0.25-1.82)	0.433
Smoking status
Non-smoker	1055	1.00 (ref)
Smoker	212	1.07 (0.78-1.47)	0.692
Primary lesion site
Colon	790	1.00 (ref)
Rectum	477	1.40 (1.09-1.80)	0.008
Tumor stage
Tis/T1	97	1.00 (ref)
T2	188	1.52 (0.31-7.41)	0.605
T3	752	10.8 (2.7-43.1)	0.001
T4a	97	42.9 (10.5-173.5)	< 0.001
T4b	133	37.9 (9.38-153.2)	< 0.001
Tumor grade
Well differentiated	117	1.00 (ref)
Moderately differentiated	1009	3.85 (1.82-8.15)	< 0.001
Poorly differentiated or mucinous	141	8.59 (3.90-18.94)	< 0.001
Past medical history
Diabetes Mellitus	331	1.07 (0.81-1.41)	0.655
Hypertension	416	1.17 (0.91-1.51)	0.217
End stage renal failure	26	1.73 (0.54-5.53)	0.354
Previous myocardial infarction	47	0.95 (0.50-1.81)	0.881
Previous PCI, cardiac surgery or angina	140	1.36 (0.88-2.09)	0.161
Congestive heart failure	41	1.18 (0.52-2.69)	0.698
Peripheral vascular disease	30	1.14 (0.52-2.53)	0.744
Impaired sensorium, e.g., dementia	14	2.77 (0.40-19.2)	0.304
Chronic obstructive pulmonary disease	61	0.44 (0.29-0.68)	< 0.001
Previous stroke or TIA	90	1.08 (0.66-1.76)	0.758
Previous stroke with neurological deficits	38	1.19 (0.53-2.69)	0.675
Dependent functional status	60	0.81 (0.43-1.54)	0.529
ECOG
0	751	1.00 (ref)
1	404	0.98 (0.76-1.28)	0.903
2 or more	116	1.13 (0.72-1.79)	0.595
ASA
1	178	1.00 (ref)
2	857	0.75 (0.53-1.06)	0.099
3 or more	232	0.78 (0.51-1.19)	0.250
Laboratory parameters
Serum albumin (g/L)	1119	0.94 (0.92-0.96)	< 0.001
Carcinoembryonic antigen (µg/L)	1196	1.01 (1.00-1.01)	< 0.001
White blood cell count (× 109/L)	1267	1.11 (1.06-1.15)	< 0.001
Platelet count (× 103/L)	1267	1.00 (1.00-1.00)	< 0.001
Serum sodium (mmol/L)	1247	0.95 (0.91-0.98)	0.002
Serum creatinine (µmol/L)	1265	1.00 (0.99-1.00)	0.244
Serum potassium (mmol/L)	1263	0.75 (0.56-0.99)	0.049
Serum urea (mmol/L)	1264	0.98 (0.93-1.04)	0.517
Hemoglobin (g/dL)	1243	0.85 (0.79-0.91)	0.002
Lesion size (cm)	1267	2.03 (1.53-2.70)	< 0.001
Dichotomized predictorsa
Age ≥ 80 yr	1267	0.92 (0.70-1.21)	0.540
Serum albumin < 35 g/L	1266	2.16 (1.69-2.76)	< 0.001
Carcinoembryonic antigen ≥ 20 µg/L	1247	4.33 (3.39-5.54)	< 0.001
White blood cell count ≥ 8.5 × 109/L	1265	1.78 (1.40-2.28)	0.001
Platelet count ≥ 450 × 103/L	1263	2.36 (1.67-3.35)	< 0.001
Serum sodium < 135 mmol/L	1264	1.62 (1.20-2.20)	0.002
Serum creatinine ≥ 135 µmol/L	1243	0.56 (0.31-1.02)	0.057
Serum potassium < 3.5 mmol/L	1267	1.37 (1.01-1.85)	0.043
Serum urea ≥ 7 mmol/L	1267	1.00 (0.71-1.40)	0.999
Hemoglobin < 11 g/dL	1243	1.48 (1.16-1.89)	0.002
Lesion size ≥ 4 cm	1267	2.03 (1.53-2.70)	< 0.001

^aCorrected P values for dichotomized variables due to multiple testing. ECOG: Eastern Cooperative Oncology Group; Ref: Reference; PCI: Percutaneous coronary intervention; TIA: Transient ischemic attack.

Table 4 Multivariable model predicting all-cause mortality, truncated at 3 years from time of surgery

Variable	Hazard ratio	2.5thpercentile	97.5thpercentile	P value
Serum albumin < 35 g/dL	1.41	1.08	1.83	0.011
CEA ≥ 20 µg/L	2.51	1.92	3.28	< 0.001
T stage
T1/Tis	1.00 (ref)	-	-	-
T2	1.11	0.23	5.41	0.894
T3	6.18	1.55	24.6	0.010
T4	17.9	4.45	72.1	< 0.001
Tumor grade
Well differentiated	1.00 (ref)	-	-	-
Moderately differentiated	2.24	1.04	4.82	0.040
Poorly differentiated or mucinous	3.54	1.54	8.15	0.003
Rectal lesion	1.47	1.11	1.96	0.007
Chronic obstructive lung disease	1.87	1.11	3.17	0.019

These factors were identified following progressive elimination of non-significant candidate predictors until all predictors retained in the final model had P values below 0.05. CEA: Carcinoembryonic antigen; ref: Reference.

Table 5 Comparison between Singapore General Hospital; and Kyungpook National University Chilgok Hospital cohorts

Variable	SGH(n = 1267)		KNUCH(n = 910)
	n		n
Age, median (range), yr	1267	77 (70-102)	910	75 (70-96)
Gender
Male	658	(51.9)	496	(54.5)
Female	609	(48.1)	414	(45.5)
Lesion sites
Colon	790	(62.3)	540	(59.3)
Rectum	477	(37.6)	370	(40.7)
Tumor grade
Well differentiated	117	(9.0)	29	(3.2)
Moderately differentiated	1009	(79.6)	809	(88.9)
Poorly differentiated	70	(5.5)	29	(3.2)
Mucinous/signet ring cell	71	(5.6)	43	(4.7)
Laboratory parameters, mean (SD)
Creatinine, µmol/L	1267	88.9 (54.9)	910	83.8 (38.6)
Urea, mmol/L	1267	5.5 (2.7)	910	2.7 (1.1)
Hemoglobin, g/dL	1267	11.8 (1.8)	910	12.0 (2.1)
WBC count, × 109/L	1267	7.9 (2.6)	908	8.0 (18.2)
Platelet count, × 109/L	1267	300.6 (104.6)	910	287.1 (95.3)
Serum albumin, g/L	1119	33.7 (5.5)	910	39.9 (4.6)
CEA, median (IQR), µg/L	1196	4.3 (2.6–14.2)	887	2.4 (1.5–4.8)
Comorbidities
Diabetes	331	(26.1)	167	(18.4)
Hypertension	416	(32.8)	415	(45.6)
Ischemic heart disease	47	(3.7)	14	(1.5)
Congestive heart failure	41	(3.2)	20	(2.2)
PVD	30	(2.4)	0	(0.0)
COPD	61	(4.8)	66	(7.3)
Previous stroke	90	(7.1)	50	(5.5)
End stage renal disease	26	(2.1)	6	(0.7)
ASA
1	178	(14.0)	152	(16.7)
2	857	(67.6)	724	(79.6)
3	225	(17.8)	34	(3.7)
4	7	(0.6)	0	(0.0)
T stagea
Tis	2	(0.2)	8	(0.9)
T1	95	(7.5)	72	(7.9)
T2	188	(14.8)	134	(14.7)
T3	752	(59.4)	587	(64.5)
T4a	97	(7.7)	76	(8.4)
T4b	133	(10.5)	29	(3.2)
ypCR	0	(0.0)	4	(0.4)
N stagea
N0	688	(54.3)	577	(63.4)
N1a	148	(11.7)	124	(13.6)
N1b	185	(14.6)	109	(12.0)
N1c	4	(0.3)	1	(0.1)
N2a	99	(7.8)	58	(6.4)
N2b	143	(11.3)	41	(4.5)
Short term outcomes
Anastomotic leak	16	(1.3)	44	(4.8)
30-d morbidity	297	(23.4)	212	(23.3)
30-d mortality	30	(2.4)	1	(0.001)

^aAmerican Joint Committee on Cancer Staging, 7^th edition. All values are reported as n (%) unless otherwise stated. KNUCH: Kyungpook National University Chilgok Hospital; SGH: Singapore General Hospital; WBC: White blood cell; CEA: Carcinoembryonic antigen; PVD: Peripheral vascular disease; COPD: Chronic obstructive pulmonary disease; ASA: American Society of Anesthesiologists; ypCR: Pathological complete response following neoadjuvant therapy.