From surface to depth: Combining white-light and ultrasound endoscopy to predict complete response in rectal cancer

Table 1 Baseline of enrolled patients, n (%)

	All	CR	Non-CR	P value
Total	145	35	110
Sex				0.633
Male	100 (69.0)	23 (65.7)	77 (70.0)
Female	45 (31.0)	12 (34.3)	33 (30.0)
Age, median (IQR), year	58 (51.5-65.5)	56 (51-65)	58 (51.3-66)	0.65
Location				0.035
Proximal	34 (23.4)	3 (8.6)	31 (28.2)
Middle	80 (55.2)	21 (60.0)	59 (53.6)
Distal	31 (21.4)	11 (31.4)	20 (18.2)
Histology				0.801
Well/moderate	125 (85.5)	31 (88.6)	93 (84.5)
Poor	17 (11.7)	3 (8.6)	14 (12.7)
Special	4 (2.8)	1 (2.9)	3 (2.7)
cT				< 0.001
cT2	11 (7.6)	8 (22.9)	3 (2.7)
cT3	83 (57.2)	23 (65.7)	60 (54.5)
cT4	51 (35.2)	4 (11.4)	47 (42.7)
cN				0.361
cN0	22 (15.2)	7 (20.0)	15 (13.6)
cN+	123 (84.8)	28 (80.0)	95 (86.4)
cM				1
cM0	141 (97.2)	34 (97.1)	107 (97.3)
cM+	4 (2.8)	1 (2.9)	3 (2.7)
Pre-nCRT level of CEA, median (IQR), ng/mL	4.84 (2.48-12.59)	2.72 (1.74-9.15)	5.5 (2.64-15.04)	0.019
Post-nCRT level of CEA, median (IQR), ng/mL	2.42 (1.57-4.14)	2.28 (1.54-3.54)	2.49 (1.57-4.42)	0.32
Interval C/RT to endoscopy, median (IQR), weeks	9 (7-10)	9 (7-11)	8 (7-10)	0.207
Interval endoscopy to surgery, median (IQR), weeks1	3 (2-5)	5 (2-6)	3 (2-5)	0.094

¹Data in patients undergoing surgery.

CR: Complete response; nCRT: Neoadjuvant chemoradiotherapy; CEA: Carcinoembryonic antigen; IQR: Interquartile range.

Table 2 Correlation between endoscopic biopsy and assessment of histologic response

Biopsy histology, n	CR	Non-CR	Total	Diagnostic performance	Value (%)
Negative	2	1	3	Accuracy	77.8
Positive	1	5	6	Sensitivity	66.7
Adenoma	0	1		Specificity	83.3
LGD	1	0		PPV	66.7
HGD	0	2		NPV	83.3
Adenocarcinoma	0	2		Youden’s index	0.5
Total	3	6	9	(P = 0.226)

LGD: Low-grade dysplasia; CR: Complete response; HGD: High-grade dysplasia; PPV: Positive predictive value; NPV: Negative predictive value.

Table 3 Positive predictive value for a complete response of endoscopic feature and endoscopic ultrasound feature

	R1, % (n/N)	95%CI	R2, % (n/N)	95%CI
Endoscopic features
eCR	78.6 (11/14)	52.4-94.3	76.9 (10/13)	49.8-92.5
Near-eCR	45.2 (14/31)	27.8-63.4	41.4 (12/29)	24.3-59.9
Non-eCR	10.0 (10/100)	5.3-17.5	12.6 (13/103)	7.1-20.5
Endoscopic ultrasound features
Completely restored	66.7 (10/15)	42.8-90.5	85.7 (12/14)	57.2-98.2
Partially restored	35.0 (14/40)	20.2-49.8	34.0 (16/47)	20.8-49.3
Mass echo	12.2 (11/90)	5.5-19.0	8.3 (7/84)	3.4-16.4

eCR: Endoscopic complete response; near-eCR: Near-endoscopic complete response; non-eCR: Non-endoscopic complete response; CI: Confidence interval.

Table 4 Diagnostic accuracy of endoscopy using a confidence level score for the prediction of a complete response

	Stringent strategy1 (only eCR)		Lenient strategy2 (eCR + near-eCR)
	R1	R2	R1	R2
Sensitivity, % (n/N)	31.4 (11/35)	28.6 (10/35)	71.4 (25/35)	62.9 (22/35)
95%CI	16.1-46.8	13.6-43.5	56.5-86.4	46.9-78.9
Specificity, % (n/N)	97.3 (107/110)	97.3 (107/110)	81.8 (90/110)	81.8 (90/110)
95%CI	94.2-100.0	94.2-100.0	74.6-89.0	74.6-89.0
Accuracy, % (n/N)	81.4 (118/145)	80.7 (117/145)	79.3 (115/145)	77.2 (112/145)
95%CI	75.1-87.7	74.3-87.1	72.7-85.9	70.4-84.1
PPV, % (n/N)	78.6 (11/14)	76.9 (10/13)	55.6 (25/45)	52.4 (22/42)
95%CI	57.1-100.0	54.0-99.8	41.0-70.1	37.3-67.5
NPV, % (n/N)	81.7 (107/131)	81.1 (107/132)	90.0 (90/100)	87.4 (90/103)
95%CI	75.1-88.3	74.4-87.7	84.1-95.9	81.0-93.8

¹The stringent strategy: Only “endoscopic complete response” was considered as a positive test result.

²The lenient strategy: Both “endoscopic complete response” and “near-endoscopic complete response” were considered as positive test results.

eCR: Endoscopic complete response; near-eCR: Near-endoscopic complete response; PPV: Positive predictive value; NPV: Negative predictive value; CI: Confidence interval.

Table 5 Correlation between maximum thickness by endoscopic ultrasonography and tumor response (n = 73)

	CR
	Correlation factor	P value
EUS1	-0.014	0.907
EUS2	-0.232	0.048
EUS2/EUS1	-0.226	0.055

CR: Complete response; EUS: Endoscopic ultrasound.

Table 6 Univariate and multivariate logistic regression analyses of endoscopic features to predict complete response

Characteristics	Univariate analysis			Multivariate analysis
	OR	95%CI	P value	OR	95%CI	P value
Location
Middle vs proximal	3.678	1.017-13.301	0.047	2.505	0.589-10.655	0.214
Distal vs proximal	5.683	1.409-22.929	0.015	2.792	0.547-14.244	0.217
WLE feature
Near-eCR vs eCR	0.218	0.049-0.963	0.045	0.425	0.079-2.283	0.319
Non-eCR vs eCR	0.036	0.009-0.146	< 0.001	0.140	0.025-0.792	0.026
EUS feature
Partially vs completely restored	0.101	0.020-0.517	0.006	0.219	0.035-1.373	0.105
Mass echo vs completely restored	0.02	0.004-0.106	< 0.001	0.093	0.013-0.658	0.017
Max thickness (EUS2)	0.823	0.711-0.954	0.01	0.969	0.831-1.13	0.691

Reference groups: Proximal (location); endoscopic complete response (white light endoscopy); completely restored (endoscopic ultrasound). OR: Odds ratio; CI: Confidence interval; eCR: Endoscopic complete response; near-eCR: Near-endoscopic complete response; WLE: White light endoscopy; EUS: Endoscopic ultrasound.