Outcomes of neoadjuvant chemoradiotherapy followed by radical resection for T4 colorectal cancer

Table 1 Patient and treatment characteristics (n = 88), n (%)

Characteristic	n = 88
Age, median (yr, range)	63 (34-93)
Sex
Male	42 (47.7)
Female	46 (52.3)
Location
Colon	25 (28.4)
Rectum	63 (71.6)
cT stage
T4a	44 (50)
T4b	44 (50)
cN stage
N0	7 (8)
N1	37 (42)
N2	44 (50)
cTNM stage
II	6 (6.8)
III	82 (93.2)
Tumor grade
Well differentiated	4 (4.6)
Moderately differentiated	72 (81.8)
Poorly differentiated	12 (13.6)
Pretreatment CEA (ng/mL)
≤ 5	46 (52.3)
> 5	42 (47.7)
Preoperative chemotherapy
FOLFOX	75 (85.2)
Capecitabine	13 (14.8)
Radiation technique
Tomotherapy	24 (27.9)
Volumetric arc therapy	49 (57)
Conformal radiotherapy	15 (15.1)
Radiation dose (Gy)
< 50	26 (29.5)
≥ 50	62 (70.5)
Radiation-surgery interval (wk, range)	9 (5-40)

CEA: Carcinoembryonic antigen.

Table 2 Pathological results and tumor response to neoadjuvant treatment (n = 86)¹

	n (%)
ypT
0	13 (15)
1	3 (3.8)
2	12 (13.8)
3	46 (53.4)
4	12 (14)
ypN
0	72 (83.8)
1	10 (11.6)
2	4 (4.6)
Median number of resected nodes2	9 (2-26)
Median number of involved nodes2	0 (0-8)
Lymphovascular invasion
Positive	15 (17.4)
Negative	71 (82.6)
Perineural invasion
Positive	22 (25.5)
Negative	64 (74.5)
Resection margin
Positive	7 (8.1)
Negative	79 (91.9)
Pathologic complete response
Yes	12 (14)
No	74 (86)
Tumor regression grade
0	13 (15.1)
1	30 (34.9)
2	27 (31.4)
3	16 (18.6)
Pathologic T stage
Downstaging	74 (86)
Stable	112 (14)
Progressive	0 (0)
Pathologic N stage
Downstaging	75 (87.3)
Stable	7 (8.1)
Progressive	4 (4.6)

¹Two patients (T4bN2M0 and T4aN2M0) did not undergo surgical resection.

²Median (range).

Table 3 Univariate and multivariate analyses for clinical parameters used to predict pCR

Variable	Univariate	Multivariate
	P value	OR (95%CI)	P value
Age (< 60 yr vs ≥ 60 yr)	0.471	0.556 (0.096-2.609)	0.464
Sex (female vs male)	0.416	1.722 (0.327-9.531)	0.515
Location (colon vs rectum)	0.107	2.615 (0.498-14.826)	0.251
cT stage (T4a vs T4b)	0.247	1.221 (0.218-7.667)	0.821
cN stage (N0 vs N+)	0.152	0.415 (0.104-1.337)	0.145
Tumor grade (WD/MD vs PD)	0.509	3.071 (0.341-70.370)	0.337
CEA (≤ 5 vs > 5)	0.894	0.611 (0.106-3.136)	0.556
Neoadjuvant chemotherapy (FOLFOX vs capecitabine)	0.037a	4.755 (2.118-88.203)	0.046a
Radiation dose (< 50 Gy vs ≥ 50 Gy)	0.265	0.507 (0.058-3.187)	0.478
Radiation-surgery interval (≤ 9 wk vs > 9 wk)	0.074	0.836 (0.013-3.061)	0.107

^aP < 0.05.

CEA: Carcinoembryonic antigen; MD: Moderately differentiated; pCR: Pathological complete response; PD: Poorly differentiated; WD: Well differentiated.

Table 4 Comparison of clinical staging with pathologic T and N staging (n = 86)¹

Clinical staging	Pathologic T staging						ypN negative	ypN positive	Total
	ypT0	ypT1	ypT2	ypT3	ypT4a	ypT4b
cT4a	7 (8.1)	3 (3.5)	5 (5.8)	24 (27.9)	3 (3.5)	2 (2.3)			44 (51.2)
cT4b	6 (7)	0 (0)	7 (8.1)	22 (25.6)	4 (4.6)	3 (3.5)			42 (48.8)
cN negative							6 (7)	1 (1.1)	7 (8.1)
cN positive							66 (76.8)	13 (15.1)	79 (91.9)
Total	13 (15.1)	3 (3.5)	12 (13.9)	46 (53.5)	7 (8.1)	5 (5.8)	72 (83.8)	14 (16.2)	86 (100)

c: Clinical (in this case evaluated by imaging); ypT: Pathologic T-stage posttreatment; ypN: Pathologic N-stage posttreatment.

¹Two patients (T4bN2M0 and T4aN2M0) did not undergo surgical resection.

Table 5 Univariate and multivariate analyses for clinical parameters used to predict disease-free survival and overall survival

Variable	Disease-free survival			Overall survival
	Univariate P value	Multivariate		Univariate P value	Multivariate
		HR (95%CI)	P value		HR (95%CI)	P value
Age (< 60 vs ≥ 60 yrs)	0.492	0.770 (0.255-1.618)	0.492	0.729	0.621 (0.314-1.245)	0.177
Sex (female vs male)	0.493	0.773 (0.375-1.626)	0.493	0.678	0.906 (0.442-1.812)	0.783
Location (colon vs rectum)	0.353	0.216 (0.102-1.231)	0.153	0.346	0.291 (0.054-1.154)	0.082
cT stage (T4a vs T4b)	0.127	2.423 (0.604-9.836)	0.258	0.206	2.611 (0.752-9.054)	0.128
cN stage (N0 vs N+)	0.127	0.690 (0.139-3.014)	0.157	0.102	0.336 (0.094-1.087)	0.078
Tumor grade (WD/MD vs PD)	0.335	0.503 (0.098-1.936)	0.413	0.423	0.840 (0.247-2.500)	0.765
CEA (≤ 5 ng/mL vs > 5 ng/mL)	0.418	1.422 (0.614-3.391)	0.383	0.528	1.219 (0.581-2.622)	0.602
Neoadjuvant chemotherapy (FOLFOX vs Capecitabine)	0.142	3.549 (0.944-7.467)	0.082	0.117	2.846 (0.860-8.715)	0.158
Radiation dose (< 50 Gy vs ≥ 50 Gy)	0.351	0.291 (0.054-1.154)	0.182	0.327	2.525 (0.347-5.843)	0.221
Radiation-surgery interval (≤ 9 wk vs > 9 wk)	0.086	1.236 (0.792-5.276)	0.097	0.106	2.064 (0.589-7.062)	0.167
ypT stage (ypT3-4 vs ypT0-2)	0.237	2.484 (0.744-5.691)	0.636	0.097	2.150 (0.820-6.123)	0.121
ypN stage (ypN+ vs ypN0)	0.005	3.120 (1.245-8.357)	0.017a	0.073	1.771 (0.435-6.255)	0.405
Lymphovascular invasion (positive vs negative)	0.363	2.503 (0.724-7.788)	0.141	0.175	3.046 (0.961-9.081)	0.069
Perineural invasion (positive vs negative)	0.072	2.649 (0.869-8.976)	0.087	0.091	1.222 (0.323-4.078)	0.757
Resection margin (positive vs negative)	0.001	3.549 (1.004-12.747)	0.014a	0.013	4.136 (1.675-10.829)	0.001a
Pathological response (non-pCR vs pCR)	0.045	2.560 (1.186-6.013)	0.042a	0.031	2.977 (1.420-6.369)	0.003a

^aP < 0.05.

CEA: Carcinoembryonic antigen; MD: Moderately differentiated; pCR: Pathological complete response; PD: Poorly differentiated; WD: Well differentiated.

Table 6 Failure patterns according to tumor location and clinical tumor stage

Recurrence	Colon		Rectum
	cT4a (%)	cT4b (%)	cT4a (%)	cT4b (%)
Local/regional only	2 (16.7)	1 (7.7)	1 (3.3)	3 (9.7)
Distant only	1 (8.3)	2 (15.4)	5 (16.7)	5 (16.1)
Local/regional/distant	0 (0)	2 (15.4)	2 (6.6)	2 (6.5)
No recurrence	9 (75)	8 (61.5)	22 (73.4)	21 (67.7)
Total	12 (100)	13 (100)	30 (100)	31 (100)