Differences in adjuvant chemotherapy and oncological outcomes according to margin status in patients with stage III colon cancer

Figures & data

Figure 1. Consort diagram for the study cohort.

Table 1. Clinicopathological characteristics of the patient cohort.

		Margin status		p value
		R0	R1LNM
Number of patients		618	100	–
Male:female		1.15	1.04	0.634
Median age (IQR)		71 (63-77)	72 (64-77)	0.670
T stage	1	38 (6.1)	3 (3.0)	0.013
	2	45 (7.3)	5 (5.0)
	3	355 (57.4)	47 (47.0)
	4	180 (29.1)	45 (45.0)
N Stage	1	450 (72.8)	33 (33.0)	< 0.001
	2	168 (27.2)	67 (67.0)
Risk group	Low	332 (53.7)	23 (23.0)	< 0.001
	High	285 (46.1)	77 (77.0)
Extramural venous invasion		282 (45.6)	59 (59.0)	0.013
Lymphatic invasion		147 (23.8)	39 (39.0)	0.001
Perineural invasion		150 (24.3)	32 (32.0)	0.099
Lymph node yield < 12		6 (1.0)	2 (2.0)	0.363
Tumour location	Right colon	290 (46.9)	67 (67.0)	< 0.001
	Left colon	313 (50.6)	30 (30.0)
	Not specified	15 (2.4)	3 (3.0)
Mismatch repair status	Proficient	498 (80.6)	74 (74.0)	0.170
	Deficient	96 (15.5)	23 (23.0)
	Missing	24 (3.9)	3 (3.0)

Risk group defined as: low = T stage 1–3 and N stage 1; high = T stage 4 or N stage 2.

IQR: interquartile range.

Values in bold are statistically significant.

Table 2. Pattern of adjuvant/post-operative chemotherapy.

		Margin status		p value
		R0	R1LNM
Referred for chemotherapy		524 (84.8)	89 (89.0)	0.269
Received chemotherapy		399 (76.2)	73 (82.0)	0.223
Median time to chemotherapy in days (IQR)		36 (28-44)	36 (32-43)	0.816
Type of chemotherapy	Single agent	117 (29.3)	22 (30.1)	0.878
	Oxaliplatin-based combination	282 (70.7)	51 (69.9)
Duration of chemotherapy	≤3 months	143 (35.8)	20 (27.3)	0.353
	3 - < 6 months	54 (13.5)	12 (16.4)
	6 months	202 (50.6)	41 (56.2)

IQR: interquartile range.

Figure 2. 3-year oncological outcomes in patients with Stage III colon cancer stratified according to margin status (R0 = red, R1LNM = blue). (A) Local recurrence-free survival - R0 95.4% (93.2–96.9) versus R1LNM 97.8% (91.5–99.4), p = 0.336 (B) Distant metastases-free survival - R0 78.2% (74.5–81.3) versus R1LNM 58.8% (47.2-68.6), p < 0.001. (C) Disease-specific survival - R0 88.3% (85.2–90.9) versus R1LNM 78.5% (68.0–85.8), p < 0.001.

Figure 3. The impact of margin status on oncological outcomes according to perceived risk of relapse in patients with Stage III colon cancer.

Distant-metastases-free survival in (A) low-risk patients (R0 86.4% (82.1–89.8) versus R1LNM 60.1% (31.3–80.0), p = 0.014) and (B) high-risk patients (R0 68.6% (62.5–73.8) versus R1LNM 58.0% (45.1–68.9), p = 0.358). Disease-specific survival in (C) low-risk patients (R0 97.4% (94.5–98.8) versus R1LNM 86.4% (63.4–95.4), p < 0.001) and (D) high-risk patients (R0 78.1% (72.2–82.9) versus R1LNM 76.6% (64.4–85.1), p = 0.452). Low risk was defined as T1-3 and N1 disease. High risk was defined as T4 or N2 disease.

Figure 4. Oncological outcomes in patients with Stage III colon cancer who completed 6 months chemotherapy. (A) Distant-metastases-free (R0 79.4% (72.8–84.5) versus R1LNM 53.7% (36.0–68.5), p = 0.003). (B) Disease-specific survival (R0 92.1% (86.8–95.4) versus R1LNM 81.3% (64.4–90.7), p = 0.016).

Table 3. Multivariable analyses of factors associated with DMFS and DSS in patients receiving chemotherapy following potentially curative surgery for Stage III colon cancer.

		DMFS		DSS
		Hazard ratio (95% CI)	P value	Hazard ratio (95% CI)	P value
Risk group	Low	Reference	–	Reference	–
	High	1.96 (1.25–3.05)	0.003	4.34 (1.90–9.89)	< 0.001
Margin status	R0	Reference	−	Reference	–
	R1LNM	1.66 (1.07–2.60)	0.025	1.80 (0.97–3.34)	0.065
Venous invasion		2.09 (1.38–3.17)	<0.001	1.98 (1.07–3.66)	0.029
Perineural invasion		1.46 (0.99–2.16)	0.060	–	–
Lymph node yield < 12		3.57 (1.10–11.65)	0.035	–	–

DMFS: distant metastasis-free survival; DSS: disease-specific survival.

Risk group defined as: low = T stage 1–3 and N stage 1; high = T stage 4 or N stage 2.

Factors excluded after univariable analysis: age; sex; lymphatic invasion; length of chemotherapy.

Values in bold are statistically significant.

Data availability statement

In accordance with Danish law, the data on which the findings of this study are based cannot be made available for sharing.