Adjuvant chemotherapy for isolated resectable colorectal lung metastasis: A retrospective study using inverse probability treatment weighting propensity analysis

Table 1 Clinical, radiological, and histological characteristics of the population

Factors	Total, n (%)
Gender
Male	58 (60.4)
Female	38 (39.6)
Age at CRC diagnosis
Median (IQR)	59.7 (49.8-69.6)
Age at time of pulmonary surgery
Median (IQR)	62.6 (53-72.2)
Access
Open	20 (20.8)
VATS	76 (79.2)
Type of resection
Sublobar resection	54 (56.2)
Lobectomy	42 (43.8)
Adjuvant chemotherapy for PM
No	62 (64.6)
Yes	34 (35.4)
Primary tumor T stage
T1 or T2	8 (11.8)
T3 or T4	60 (88.2)
Primary tumor N stage
N0	28 (39.4)
N1 or N2	43 (60.6)
Primary tumor location
Left colon	29 (33.0)
Right colon	17 (19.3)
Rectum	42(47.7)
Adjuvant chemotherapy for CRC
No	30 (31.2)
Yes	66 (68.8)
CEA levels
≤ 5 ng/mL	47 (60.3)
> 5 ng/mL	31 (39.7)
Number of metastatic lesions
1	76 (79.2)
> 1	20 (20.8)
Tumor size (cm)
≤ 2 cm	51 (54.8)
> 2 cm	42 (45.2)
Prior extra-thoracic metastasis
No	86 (89.6)
Yes	10 (10.4)
CRC differentiation
Well/well to moderate	8 (11.8)
Moderate	57 (83.8)
Moderate to poor/poor	3 (4.4)
Smoking history
No	68 (70.8)
Yes	28 (29.2)
RAS
Wild type	10 (62.5)
mutant type	6 (37.5)
Bilateral pulmonary nodules
No	91 (94.8)
Yes	5 (5.2)
LN sampling at PM
No	51 (53.1)
Yes	45 (46.9)
Positive LN at PM
No	90 (93.8)
Yes	6 (6.2)

CRC: Colorectal cancer; CEA: Carcinoembryonic antigen; LN: Lymph nodes; PM: Pulmonary metastases; RAS: Rat sarcoma; VATS: Video-assisted thoracoscopic surgery; DFI: Disease-free interval; IQR: Interquartile range.

Table 2 Baseline characteristics and clinical outcomes of patients among groups before propensity analysis, n (%)

Factors	Levels	Surgery alone (n = 62)	Adjuvant chemotherapy (n = 34)	P value
Gender	Male	39 (62.9)	19 (55.9)	0.649
	Female	23 (37.1)	15 (44.1)
Age at CRC diagnosis	mean ± SD	61.3 ± 9.9	56.9 ± 9.4	0.038
Age at time of pulmonary surgery	mean ± SD	64.4 ± 9.6	59.4 ± 9.0	0.014
Smoking history	No	39 (62.9)	29 (85.3)	0.038
	Yes	23 (37.1)	5 (14.7)
Prior extra-thoracic metastasis	No	55 (88.7)	31 (91.2)	0.977
	Yes	7 (11.3)	3 (8.8)
Access	Open	16 (25.8)	4 (11.8)	0.175
	VATS	46 (74.2)	30 (88.2)
Type of resection	Lobe	30 (48.4)	12 (35.3)	0.307
	Segmental wedge	32 (51.6)	22 (64.7)
Number of metastatic lesions	1	50 (80.6)	26 (76.5)	0.827
	> 1	12 (19.4)	8 (23.5)
Tumor size (cm)	≤ 2cm	33 (53.2)	20 (58.8)	0.754
	> 2 cm	29 (46.8)	14 (41.2)
Bilateral pulmonary nodules	No	59 (95.2)	32 (94.1)	1.000
	Yes	3 (4.8)	2 (5.9)
LN sampling at PM	No	31 (50)	20 (58.8)	0.539
	Yes	31 (50)	14 (41.2)
Positive LN at PM	No	59 (95.2)	31 (91.2)	0.741
	Yes	3 (4.8)	3 (8.8)
CEA	≤ 5 ng/mL	40 (64.5)	21 (61.8)	0.963
	> 5 ng/mL	22 (35.5)	13 (38.2)
DFI	mean ± SD	1070.1 ± 754.2	946.0 ± 620.6	0.415
Primary tumor location	Left colon	18 (29)	11 (32.4)	0.340
	Rectal	29 (46.8)	19 (55.9)
	Right colon	15 (24.2)	4 (11.8)

CRC: Colorectal cancer; CEA: Carcinoembryonic antigen; LN: Lymph nodes; PM: Pulmonary metastases; VATS: Video-assisted thoracoscopic surgery; DFI: Disease-free interval.

Table 3 Univariable Cox proportional hazards model for overall survival after inverse probability of treatment-weighting

Factors		HR (univariable)
Gender	M
	F	0.8556 (0.3201-2.287, P = 0.756)
Age at primary cancer	≤ 60 years
	> 60 years	1.1914 (0.4402-3.224, P = 0.730)
Smoking history	No
	Yes	1.07988 (0.3514-3.319, P = 0.893)
Age lung surgery	≤ 60 years
	> 60 years	0.6498 (0.2495-1.692, P = 0.377)
Surgical approach for PM	Open
	VATS	0.5052 (0.1863-1.37, P = 0.18)
Type of resection	Lobectomy
	Sublobar resection	0.6032 (0.2248-1.619, P = 0.065)
Lymph node dissection	No
	Yes	1.2383 (0.4682-2.728, P = 0.667)
Positive LN at PM	No
	Yes	0.9268 (0.1181-7.271, P = 0.942)
Adjuvant chemotherapy	No
	Yes	0.4204 (0.1632-1.083, P = 0.0726)
Primary tumor location	Left colon
	Right colon	0.4590 (0.1093-1.928, P = 0.288)
	Rectum	0.6267 (0.2328-1.687, P = 0.355)
CEA levels	≤ 5 ng/mL
	> 5 ng/mL	2.7261 (1.075-6.913, P = 0.0347)
Number of metastatic lesions	1
	> 1	2.1928 (0.8496-5.66, P = 0.105)
Bilateral pulmonary nodules	No
	Yes	2.478 (0.9703-6.329, P = 0.0578)
Tumor size (cm)	≤ 2 cm
	> 2 cm	0.7971 (0.2961-2.146, P = 0.653)
Prior extra-thoracic metastasis	No
	Yes	4.627 (1.01-21.2, P = 0.0485)

CRC: Colorectal cancer; CEA: Carcinoembryonic antigen; PM: Pulmonary metastases; VATS: Video-assisted thoracoscopic surgery; HR: Hazard ratio; M: Male; F: Female.

Table 4 Multivariate analysis of overall survival after inverse probability of treatment-weighting

Survival		HR	95%CI	P value
Adjuvant chemotherapy	No
	Yes	0.43	0.16-1.18	0.10
Number of metastatic lesions	1
	≥ 2	1.95	0.64-5.93	0.24
Prior extra-thoracic metastasis	No
	Yes	4.97	1.03-24.08	0.046
Bilateral pulmonary nodules	No
	Yes	1.84	0.36-9.43	0.47
CEA	≤ 5 ng/mL
	> 5 ng/mL	2.00	0.76-5.28	0.16
Type of resection	Lobectomy
	Sublobar resection	0.53	0.21-1.35	0.19

HR: Hazard ratio; CEA: Carcinoembryonic antigen; CI: Confidence interval.

Table 5 Univariable Cox proportional hazards model for overall survival in the original cohort

Factors		HR (univariable)
Gender	M
	F	0.78 (0.35-1.77, P = 0.555)
Age at primary cancer	≤ 60 years
	> 60 years	1.41 (0.65-3.05, P = 0.381)
Smoking history	No
	Yes	1.11 (0.48-2.55, P = 0.814)
Age lung surgery	≤ 60 years
	> 60 years	0.98 (0.45-2.12, P = 0.956)
Surgical approach for PM	Open
	VATS	0.77 (0.32-1.84, P = 0.556)
Type of resection	Lobectomy
	Sublobar resection	0.47 (0.21-1.04, P = 0.062)
Lymph node dissection	No
	Yes	1.18 (0.55-2.55, P = 0.674)
Positive LN at PM	No
	Yes	0.62 (0.08-4.60, P = 0.642)
Adjuvant chemotherapy	No
	Yes	0.47 (0.20-1.12, P = 0.087)
Primary tumor location	Left colon
	Right colon	0.91 (0.32-2.63, P = 0.863)
	Rectum	0.60 (0.24-1.53, P = 0.288)
CEA levels	≤ 5 ng/mL
	> 5 ng/mL	1.48 (0.66-3.31, P = 0.335)
Number of metastatic lesions	1
	> 1	1.75 (0.73-4.23, P = 0.211)
Bilateral pulmonary nodules	No
	Yes	1.88 (0.44-8.08, P = 0.398)
Tumor size (cm)	≤ 2 cm
	> 2 cm	0.67 (0.29-1.53, P = 0.337)
Prior extra-thoracic metastasis	No
	Yes	1.94 (0.58-6.50, P = 0.283)
DFI	≤ 600
	> 600	0.48 (0.22-1.04, P = 0.063)

CEA: Carcinoembryonic antigen; HR: Hazard ratio; M: Male; F: Female; LN: Lymph nodes; PM: Pulmonary metastases; VATS: Video-assisted thoracoscopic surgery; DFI: Disease-free interval.

Table 6 Multivariate analysis of overall survival in the original cohort

Survival		HR	95%CI	P value
Adjuvant chemotherapy	No
	Yes	0.50	0.21-1.18	0.114
Type of resection	Lobectomy
	Sublobar resection	0.45	0.20-1.00	0.049
DFI	≤ 600
	> 600	0.45	0.20-0.98	0.044

HR: Hazard ratio; CI: Confidence interval; DFI: Disease-free interval.

Table 7 Clinical, radiological, and histological characteristics of the population: Pre-imputation and post-imputation, n (%)

Factors	Levels	Post-imputation (n = 96)	Pre-imputation (n = 96)	P value
Gender	Male	58 (60.4)	58 (60.4)	1.000
	Female	38 (39.6)	38 (39.6)
Age at CRC diagnosis	mean ± SD	59.7 ± 9.9	59.7 ± 9.9	1.000
Age at time of pulmonary surgery	mean ± SD	62.6 ± 9.6	62.6 ± 9.6	1.000
Smoking history	No	68 (70.8)	68 (70.8)	1.000
	Yes	28 (29.2)	28 (29.2)
Adjuvant chemotherapy for CRC	No	30 (31.2)	30 (31.2)	1.000
	Yes	66 (68.8)	66 (68.8)
CRC differentiation	Moderate	84 (87.5)	57 (83.8)	0.760
	Moderate to poor	4 (4.2)	3 (4.4)
	Well to moderate	8 (8.3)	8 (11.8)
Primary tumor T stage	T1 or T2	10 (10.4)	8 (11.8)	0.985
	T3 or T4	86 (89.6)	60 (88.2)
Primary tumor N stage	N0	39 (40.6)	28 (39.4)	1.000
	N1 or N2	57 (59.4)	43 (60.6)
Prior extra-thoracic metastasis	No	86 (89.6)	86 (89.6)	1.000
	Yes	10 (10.4)	10 (10.4)
Access	Open	20 (20.8)	20 (20.8)	1.000
	VATS	76 (79.2)	76 (79.2)
Type of resection	Lobe	42 (43.8)	42 (43.8)	1.000
	Segmental wedge	54 (56.2)	54 (56.2)
Number of metastatic lesions	1	76 (79.2)	76 (79.2)	1.000
	> 1	20 (20.8)	20 (20.8)
Tumor size (cm)	≤ 2	53 (55.2)	51 (54.8)	1.000
	> 2	43 (44.8)	42 (45.2)
Bilateral pulmonary nodules	No	91 (94.8)	91 (94.8)	1.000
	Yes	5 (5.2)	5 (5.2)
LN sampling at PM	No	51 (53.1)	51 (53.1)	1.000
	Yes	45 (46.9)	45 (46.9)
Positive LN at PM	No	90 (93.8)	90 (93.8)	1.000
	Yes	6 (6.2)	6 (6.2)
CEA levels	≤ 5 ng/mL	61 (63.5)	47 (60.3)	0.774
	> 5 ng/mL	35 (36.5)	31 (39.7)
CRC LVI	No	81 (84.4)	45 (81.8)	0.858
	Yes	15 (15.6)	10 (18.2)
CRC PNI	No	77 (80.2)	41 (74.5)	0.545
	Yes	19 (19.8)	14 (25.5)
Adjuvant chemotherapy	No	62 (64.6)	62 (64.6)	1.000
	Yes	34 (35.4)	34 (35.4)
DFI	mean ± SD	1026.2 ± 708.9	1026.2 ± 708.9	1.000
Primary tumor location	Left colon	29 (30.2)	29 (33)	0.921
	Rectal	48 (50)	42 (47.7)
	Right colon	19 (19.8)	17 (19.3)

CRC: Colorectal cancer; CEA: Carcinoembryonic antigen; LN: Lymph nodes; PM: Pulmonary metastases; VATS: Video-assisted thoracoscopic surgery; DFI: Disease-free interval; LVI: Lymphovascular invasion; PNI: Perineural invasion.