Effect of perioperative chemotherapy on resection of isolated pulmonary metastases from colorectal cancer: A single center experience

Table 1 Clinical, radiological, and histological characteristics of the patient population, n (%)

Factors	Total
Sex
Male	73 (60.8)
Female	47 (39.2)
Age at primary cancer
Median (IQR)	59.10 (51.75-67.25)
DFI
Median (IQR)	2.47 (1.22-3.20)
Age at time of pulmonary surgery
Median (IQR)	62.00 (55.00-70.00)
Pulmonary metastasis
Synchronous	12 (10.0)
Metachronous	108 (90.0)
Access
Open	25 (20.8)
VATS	95 (79.2)
Type of resection
Sublobar resection	70 (58.3)
Lobectomy	50 (41.7)
Lymph node dissection
No	66 (55.0)
Yes	54 (45.0)
Perioperative chemotherapy
No	66 (55.0)
Yes	54 (45.0)
Primary tumor T stage
T1	3 (3.5)
T2	8 (9.3)
T3	62 (72.1)
T4	13 (15.1)
Primary tumor N stage
N0	37 (40.7)
N1 or N2	54 (59.3)
Primary tumor location
Left colon	35 (32.4)
Right colon	19 (17.6)
Rectum	54 (50.0)
Adjuvant chemotherapy for CRC
No	35 (29.2)
Yes	85 (70.8)
CEA levels
≤ 5 ng/mL	62 (61.4)
> 5 ng/mL	39 (38.6)
Number of metastatic lesions
1	96 (80.0)
2	11 (9.2)
3	12 (10.0)
5	1 (0.8)
Tumor size (cm)
≤ 2 cm	63 (53.8)
> 2 cm	54 (46.2)
CRC differentiation
Well/well-to-moderate	11 (12.2)
Moderate	76 (84.4)
Moderate-to-poor/poor	3 (3.3)
Smoking history
No	86 (71.7)
Yes	34 (28.3)
RAS
Wild type	14 (53.8)
Mutant type	12 (46.2)
Bilateral pulmonary nodules
No	113 (94.2)
Yes	7 (5.8)
LN sampling at PM
No	66 (55.0)
Yes	54 (45.0)
Positive LN at PM
No	112 (93.3)
Yes	8 (6.7)
CRC LVI
No	58 (84.1)
Yes	11 (15.9)
CRC PNI
No	50 (72.5)
Yes	19 (27.5)

CRC: Colorectal cancer; CEA: Carcinoembryonic antigen; LN: Lymph nodes; PM: Pulmonary metastases; LVI: Lymphovascular invasion; PNI: Perineural invasion.

Table 2 Comparison of baseline and tumor characteristics among groups, n (%)

Factors	Levels	Surgery alone (n = 66)	Perioperative chemotherapy (n = 54)	P value
Sex	Male	43 (65.2)	30 (55.6)	0.377
	Female	23 (34.8)	24 (44.4)
Age at CRC diagnosis	mean ± SD	61.2 ± 9.7	56.6 ± 10.1	0.012
Age at time of pulmonary surgery	mean ± SD	64.1 ± 9.4	58.6 ± 9.9	0.002
Smoking history	No	40 (60.6)	46 (85.2)	0.006
	Yes	26 (39.4)	8 (14.8)
Adjuvant chemotherapy for CRC	No	24 (36.4)	11 (20.4)	0.086
	Yes	42 (63.6)	43 (79.6)
CRC differentiation	Moderate	36 (81.8)	40 (87.0)	0.744
	Moderate to poor/poor	2 (4.5)	1 (2.2)
	Well/well to moderate	6 (13.6)	5 (10.9)
Primary tumor T stage	0	1 (2.5)	2 (4.3)	0.969
	II	4 (10.0)	4 (8.7)
	III	29 (72.5)	33 (71.7)
	IV	6 (15.0)	7 (15.2)
Primary tumor N stage	0	17 (39.5)	20 (41.7)	0.560
	1	18 (41.9)	17 (35.4)
	2	8 (18.6)	11 (23.0)
MSS	pMMR	26 (100.0)	31(100.0)
RAS	Wild type	5 (71.4)	9 (47.4)	0.517
	Mutant type	2 (28.6)	10 (52.6)
Access	Open	18 (27.3)	7 (13.0)	0.090
	VATS	48 (72.7)	47 (87.0)
Type of resection	Lobe	33 (50.0)	17 (31.5)	0.063
	Segmental wedge	33 (50.0)	37 (68.5)
Number of metastatic lesions	1	53 (80.3)	43 (79.6)	1.000
	> 1	13 (19.7)	11 (20.4)
Tumor size (cm)	≤ 2 cm	32 (50.0)	31 (58.5)	0.465
	> 2 cm	32 (50.0)	22 (41.5)
Bilateral pulmonary nodules	No	62 (93.9)	51 (94.4)	1.000
	Yes	4 (6.1)	3 (5.6)
LN sampling at PM	No	32 (48.5)	34 (63.0)	0.161
	Yes	34 (51.5)	20 (37.0)
Positive LN at PM	No	63 (95.5)	49 (90.7)	0.508
	Yes	3 (4.5)	5 (9.3)
CEA	≤ 5 ng/mL	33 (61.1)	29 (61.7)	1.000
	> 5 ng/mL	21 (38.9)	18 (38.3)
Pulmonary metastasis	Synchronous	3 (4.5)	9 (16.7)	0.058
	Metachronous	63 (95.5)	45 (83.3)
DFI	mean ± SD	1005.3 ± 774.6	771.9 ± 701.5	0.089
Primary tumor location	Left colon	18 (31.0)	17 (34.0)	0.363
	Rectum	27 (46.6)	27 (54.0)
	Right colon	13 (22.4)	6 (12.0)

CRC: Colorectal cancer; CEA: Carcinoembryonic antigen; LN: Lymph nodes; PM: Pulmonary metastases; MSS: Microsatellite instability; RAS: Rat sarcoma; pMMR: Proficient mismatch repair; VATS: Video-assisted thoracoscopic surgery; DFI: Disease-free interval.

Table 3 Univariable Cox proportional hazards model for cancer-specific survival

Factors		HR (univariable)
Sex	Male
	Female	1.01 (0.47-2.17, P = 0.980)
Age at CRC diagnosis	≤ 60 years
	> 60 years	1.32 (0.63-2.78, P = 0.460)
Age at time of pulmonary surgery	≤ 60 years
	> 60 years	0.86 (0.48-2.03, P = 0.970)
Smoking history	No
	Yes	1.37 (0.63-2.97, P = 0.420)
Pulmonary metastasis	Synchronous
	Metachronous	2.52 (0.34-18.7, P = 0.360)
Surgical approach for PM	Open
	VATS	0.56 (0.25-1.24, P = 0.150)
Type of resection	Lobectomy
	Sublobar resection	0.51 (0.24-1.08, P = 0.077)
Lymph node dissection	No
	Yes	1.24 (0.59-2.61, P = 0.560)
Perioperative chemotherapy	No
	Yes	0.52 (0.24-1.14, P = 0.100)
Primary tumor T stage	T1-T3
	T4	1.70 (0.57-5.08, P = 0.370)
Primary tumor N stage	N0
	N1 or N2	1.39 (0.57-3.33, P = 0.460)
Primary tumor location	Left colon
	Right colon	0.61 (0.26-1.42, P = 0.260)
	Rectum	0.56 (0.17-1.78, P = 0.320)
CEA levels	≤ 5 ng/mL
	> 5 ng/mL	1.38 (0.64-3.00, P = 0.420)
Number of metastatic lesions	1
	> 1	2.47 (1.11-5.51, P = 0.027)
Tumor size (cm)	≤ 2 cm
	> 2 cm	0.81 (0.37-1.77, P = 0.600)
DFI	≤ 600
	> 600	0.44 (0.20-0.94, P = 0.030)

Bold values indicate P values below the statistical significance threshold. CRC: Colorectal cancer; CEA: Carcinoembryonic antigen; PM: Pulmonary metastases; DFI: Disease-free interval; VATS: Video-assisted thoracoscopic surgery; HR: hazard ratio.

Table 4 Univariable Cox proportional hazards model for recurrence

Factors		HR (univariable)
Sex	Male
	Female	0.82 (0.44-1.52, P = 0.530)
Age at CRC diagnosis	≤ 60 years
	> 60 years	0.86 (0.46-1.58, P = 0.630)
Age at time of pulmonary surgery	≤ 60 years
	> 60 years	0.58 (0.32-1.06, P = 0.077)
Smoking history	No
	Yes	1.33 (0.70-2.50, P = 0.380)
Pulmonary metastasis	Synchronous
	Metachronous	1.62 (0.50-5.27, P = 0.420)
Surgical approach for PM	Open
	VATS	0.98 (0.48-1.99, P = 0.950)
Type of resection	Lobectomy
	Sublobar resection	0.82 (0.45-1.48, P = 0.510)
Lymph node dissection	No
	Yes	0.98 (0.54-1.78, P = 0.950)
Perioperative chemotherapy	No
	Yes	0.86 (0.48-1.57, P = 0.640)
Primary tumor T stage	T1-T3
	T4	2.63 (1.18-5.87, P = 0.017)
Primary tumor N stage	N0
	N1 or N2	1.94 (0.95-3.96, P = 0.069)
Primary tumor location	Left colon
	Right colon	0.71 (0.26-1.91, P = 0.500)
	Rectum	0.96 (0.47-1.96, P = 0.920)
CEA levels	≤ 5 ng/mL
	> 5 ng/mL	1.11 (0.58-2.14, P = 0.750)
Number of metastatic lesions	1
	> 1	2.34 (1.21-4.53, P = 0.012)
Tumor size (cm)	≤ 2 cm
	> 2 cm	0.82 (0.44-1.53, P = 0.540)
DFI	≤ 600
	> 600	0.60 (0.33-1.09, P = 0.090)

Bold values indicate P values below the statistical significance threshold. CRC: Colorectal cancer; CEA: Carcinoembryonic antigen; PM: Pulmonary metastases; DFI: Disease-free interval; VATS: Video-assisted thoracoscopic surgery; HR: Hazard ratio.

Table 5 Multivariate analysis of recurrence and survival

		HR	95%CI	P value
Recurrence
Age at time of pulmonary surgery	≤ 60 years
	> 60 years	0.59	0.32-1.10	0.099
Number of metastatic lesions	1
	≥ 2	2.22	1.12-4.38	0.022
Primary tumor N stage	N0
	N1 or N2	1.51	0.79-2.87	0.215
DFI	≤ 600
	> 600	0.78	0.42-1.45	0.432
Survival
Age at time of pulmonary surgery	≤ 60 years
	> 60 years	1.57	0.69-3.58	0.286
Primary tumor T stage	T1 or T2
	T3 or T4	1.16	0.38-3.57	0.079
Primary tumor N stage	N0
	N1 or N2	1.35	0.58-3.13	0.485
Pulmonary metastasis	Synchronous
	Metachronous	2.35	0.29-18.85	0.423
Perioperative chemotherapy	No
	Yes	0.48	0.21-1.09	0.079
Number of metastatic lesions	1
	≥ 2	2.51	1.02-6.15	0.045
Type of resection	Lobectomy
	Sublobar resection	0.42	0.19-0.94	0.035
DFI	≤ 600
	> 600	0.35	0.15-0.82	0.016

Bold values indicate P values below the statistical significance threshold. DFI: Disease-free interval; HR: hazard ratio; 95%CI: 95% confidence interval.