Prognostic factors for local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision

Nahas, Caio Sergio Rizkallah; Nahas, Sergio Carlos; Marques, Carlos Frederico Sparapan; Ribeiro Junior, Ulysses; Bustamante-Lopez, Leonardo; Cotti, Guilherme Cutait; Imperiale, Antonio Rocco; Pinto, Rodrigo Ambar; Cecconello, Ivan

doi:10.1016/j.clinsp.2024.100464

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Original articles • Clinics 79 • 2024 • https://doi.org/10.1016/j.clinsp.2024.100464 copy

Prognostic factors for local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Prognostic factors for local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision.

Background:

The standard curative treatment for locally advanced rectal cancer of the middle and lower thirds is long-course chemoradiotherapy followed by total mesorectal excision.

Purpose:

To evaluate the prognostic factors associated with local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision.

Methods:

Retrospective study including patients with rectal cancer T3–4N0M0 or T (any)N + M0 located within 10 cm from the anal border, or patients with T2N0M0 located within 5 cm, treated by long course chemoradio-therapy followed by total mesorectal excision with curative intent. Clinical, demographic, radiologic, surgical, and anatomopathological data were collected. Local recurrence was estimated using the Kaplan-Meier function, and risk was estimated according to each characteristic using univariate and multivariate analyses.

Results:

270 patients were included, 57.8% male and mean age 61.7 (30‒88) years. At initial staging, 6.7% of patients were stage I, 21.5% stage II, and 71.8% stage III. Open surgery was performed in 65.2%, with sphincter preservation in 78.1%. Mortality within 30 postoperative days was 0.7%. After 49.4 (0.5‒86.1) months of median follow-up, overall and local recurrences were 26.3% and 5.9%. On multivariate analyses, local recurrence was associated with involvement of the mesorectal fascia on restaging MRI (HR = 9.11, p = 0.001) and with pathologic involvement of radial surgical margin (HR = 8.19, p < 0.001).

Conclusion:

Local recurrence of rectal cancer treated with long-course chemoradiation and total mesorectal excision is low and is associated with pathologic involvement of the radial surgical margin and can be predicted on restaging MRI.

Keywords:
Rectal cancer; Chemoradiotherapy; Neoadjuvant therapy; Total mesorectal excision; Prognosis; Survival

HIGHLIGHTS

Rectal cancer recurrence occurs predominantly in distant organs.

Local recurrence of rectal cancer could be predicted on restaging MRI.

Rectal cancer recurrence of patients treated with long course chemoradiation and total mesorectal excision is low and is associated with pathologic involvement of the radial surgical margin.

Variable	n (%)
Gender
Male	156 (57.8)
Female	114 (42.2)
Age
< 50 years old	39 (14.4)
≥ 50 years old	231 (85.6)
BMI (Kg/m²)
< 30	227 (84.1)
≥ 30	43 (15.9)
mriT stage
T2	52 (19.3)
T3, T4	218 (80.7)
mriN stage
N0	76 (28.1)
N+	194 (71.9)
mri Mucinous component
No	205 (75.9)
Yes	65 (24.1)
mri EMVI
No	113 (41.9)
Yes	157 (58.1)
mri FM
Negative	165 (61.1)
Positive	105 (38.9)
mri intersphincteric plane
No	244 (90.4)
Yes	26 (9.6)
mri pelvic sidewall lymph node involvement
No	224 (83)
Yes	46 (17)
ymriT stage
T0, 1, 2	101 (37.4)
T 3, 4	169 (62.6)
ymriN stage
N0	173 (64.1)
N+	97 (35.9)
TRG
TRG 1, 2, 3	143 (53)
TRG 4, 5	127 (47)
ymri Mucinous component
No	223 (82.6)
Yes	47 (17.4)
ymri EMVI
No	150 (55.6)
Yes	120 (44.4)
ymri FM
Clear	181 (67)
Involved	89 (33)
ymri intersphincteric plane
Clear	249 (92.2)
Involved	21 (7.8)
ymri pelvic sidewall lymph node involvement
No	247 (91.5)
Yes	23 (8.5)

Variable	n (%)
Surgical access
Open	176 (65.2)
Laparoscopic	94 (34.8)
Sphincter preservation
No	59 (21.9)
Yes	211 (78.1)
Multivisceral en bloc resection
No	236 (87.4)
Yes	34 (12.6)
ypT stage
T 0, 1, 2	137 (50.7)
T 3, 4	133 (49.3)
ypN stage
N0	186 (68.9)
N+	84 (31.1)
Lymphatic invasion
No	234 (86.7)
Yes	36 (13.3)
Perineural invasion
No	217 (80.4)
Yes	53 (19.6)
Pathologic complete response
No	46 (17)
Yes	224 (83)
Lymph node yield
≥ 12	233 (86.3)
< 12	37 (13.7)
Radial Margin
Clear	256 (94.8)
Involved	14 (5.2)
Mesorectum integrity
Complete/nearly complete	248 (91.8)
Incomplete	22 (8.2)

Variable	Estimated medium time (months)	95% CI		HR	95% CI		Local recurrence	N total	%	p
Variable	Estimated medium time (months)	Inferior	Superior	HR	Inferior	Superior	Local recurrence	N total	%	p
Gender										0.328
Male	82.7	80.2	85.2	1.00			7	156	4.5
Female	80.2	76.7	83.6	1.63	0.61	4.38	9	114	7.9
Age										0.297
< 50 years old	78.7	71.8	85.7	1.00			4	39	10.3
≥ 50 years old	81.9	79.8	84.0	0.55	0.18	1.71	12	231	5.2
BMI (Kg/m²)										0.800
< 30	81.9	79.6	84.1	1.00			13	227	5.7
≥ 30	73.6	68.8	78.3	1.18	0.34	4.13	3	43	7.0
mriT Stage										0.033
T2	80.9	80.9	80.9	1.00			0	52	0.0
T3, T4	80.6	78.0	83.2	29.67	0.19	4693.83	16	218	7.3
mriN Stage										0.462
N0	77.6	74.6	80.5	1.00			3	76	3.9
N+	81.3	78.7	83.8	1.60	0.45	5.60	13	194	6.7
mri Mucinous component										0.422
No	81.7	79.4	84.0	1.00			11	205	5.4
Yes	80.4	75.6	85.1	1.54	0.53	4.42	5	65	7.7
mri EMVI										0.011
No	84.5	83.0	86.1	1.00			2	113	1.8
Yes	79.4	76.0	82.7	5.54	1.26	24.37	14	157	8.9
mri MF										<0.001
Clear	85.0	83.6	86.3	1.00			3	165	1.8
Involved	75.6	70.8	80.4	7.85	2.24	27.57	13	105	12.4
mri Intersphincteric plane
Clear	82.2	80.1	84.3	1.00			13	244	5.3
Involved	77.8	69.4	86.1	2.20	0.63	7.72	3	26	11.5
mri pelvic sidewall lymph node involvement
No	82.1	80.1	84.2	1.00			11	224	4.9
Yes	78.2	71.5	84.8	2.27	0.79	6.54	5	46	10.9
ymriT Stage										0.005
T0, 1, 2	82.5	81.4	83.7	1.00			1	101	1.0
T3, 4	79.3	76.0	82.6	10.42	1.38	78.89	15	169	8.9
ymriN Stage										0.318
N0	75.6	73.0	78.1	1.00			12	173	6.9
N+	83.1	80.1	86.0	0.57	0.18	1.76	4	97	4.1
TRG										0.714
1, 2, 3 (good response)	76.6	74.2	79.1	1.00			8	143	5.6
4, 5 (poor response)	81.4	78.2	84.6	1.20	0.45	3.21	8	127	6.3
ymri Mucinous component										0.319
No	82.1	79.9	84.3	1.00			12	223	5.4
Yes	78.7	72.4	85.1	1.77	0.57	5.48	4	47	8.5
ymri EMVI										0.006
No	81.5	79.9	83.0	1.00			4	150	2.7
Yes	78.3	74.1	82.5	4.25	1.37	13.18	12	120	10.0
ymri MF										<0.001
Clear	85.0	83.7	86.3	1.00			3	181	1.7
Involved	74.6	69.1	80.1	9.88	2.82	34.68	13	89	14.6
ymri Intersphincteric plane
Clear	81.7	79.6	83.9	1.00			15	249	6.0
Involved	71.8	65.5	78.1	0.84	0.11	6.35	1	21	4.8
ymri pelvic sidewall lymph node involvement
No	82.0	79.8	84.1	1.00			14	247	5.7
Yes	72.0	65.1	78.8	1.67	0.38	7.36	2	23	8.7

Variable	Estimated medium time (months)	95% CI		HR	95% CI		Local recurrence	N total	%	p
Variable	Estimated medium time (months)	Inferior	Superior	HR	Inferior	Superior	Local recurrence	N total	%	p
Surgical access										0.174
Open	80.7	77.8	83.5	1.00			13	176	7.4
Laparoscopic	79.0	76.8	81.2	0.43	0.12	1.51	3	94	3.2
Sphincter preservation										0.006
No	76.1	70.0	82.2	1.00			8	59	13.6
Yes	83.3	81.3	85.2	0.27	0.10	0.73	8	211	3.8
Multivisceral en bloc resection										0.228
No	82.2	80.2	84.3	1.00			13	236	5.5
Yes	77.5	68.8	86.2	2.13	0.61	7.49	3	34	8.8
ypT stage										0.079
yp T 0, 1, 2	80.8	78.8	82.8	1.00			5	137	3.6
yp T 3, 4	79.8	76.2	83.4	2.50	0.87	7.19	11	133	8.3
ypN stage										0.219
ypN0	82.2	80.0	84.4	1.00			9	186	4.8
ypN+	79.7	75.2	84.3	1.84	0.69	4.95	7	84	8.3
Limphatic invasion										0.069
No	82.0	80.0	84.0	1.00			12	234	5.1
Yes	77.1	68.8	85.3	2.75	0.88	8.55	4	36	11.1
Perineural invasion										0.038
No	82.8	80.7	84.8	1.00			10	217	4.6
Yes	76.9	70.4	83.4	2.79	1.01	7.68	6	53	11.3
complete pathologic response										0.564
No	81.5	79.2	83.8	1.00			14	224	6.3
Yes	78.2	74.4	82.0	0.65	0.15	2.85	2	46	4.3
Lymph node yield										0.944
< 12	74.5	69.1	79.9	1.00			2	37	5.4
≥ 12	81.8	79.6	84.0	0.95	0.22	4.18	14	233	6.0
Surgical Radial margin										<0.001
Free	82.9	81.1	84.8	1.00			11	256	4.3
Compromised	53.8	40.6	67.0	9.54	3.31	27.54	5	14	35.7
Mesorectum integrity
Complete/nearly complete	83.1	81.2	84.4	1.00			14	248	5.6	0.183
Incomplete	79.4	69.7	83.2	2.21	0.83	5.48	2	22	9.1

Variable	HR	95% CI		p
Variable	HR	Inferior	Superior	p
ymri Mesorectal Fascia+ (involved)	9.11	2.59	32.10	0.001
Surgical Radial margin (involved)	8.19	2.78	24.10	< 0.001

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E-mail: clinics@hc.fm.usp.br

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[1] *Corresponding author. E-mail address:leonardoabustamante@gmail.com (L. Bustamante-Lopez).