Patients and methods
Patients and Definitions
Outcome Parameters
Statistical Analysis
Results
Patient Characteristics
Overall [n = 475] (%) | <14 weeks interval [n = 224] (%) | ≥ 14 weeks interval [n = 251] (%) | p value | |
---|---|---|---|---|
Sex
| ||||
Male | 300/475 (63.2) | 140/224 (62.5) | 160/251 (63.7) | 0.779 |
Age, years
| 0.169 | |||
<60 | 159/475 (33.5) | 84/224 (37.5) | 75/251 (29.9) | |
61–70 | 192/475 (40.4) | 91/224 (40.6) | 101/251 (40.2) | |
71–80 | 110/475 (23.2) | 43/224 (19.2) | 67/251 (26.7) | |
> 80 | 14/475 (2.9) | 6/224 (2.7) | 8/251 (3.2) | |
ASA score
|
0.026
| |||
I–II | 418/475 (88.0) | 205/224 (91.5) | 213/251 (84.9) | |
III–IV | 57/475 (12.0) | 19/224 (8.5) | 38/251 (15.1) | |
Preoperative imaging
a
| 0.061 | |||
MRI | 446/465 (96.0) | 215/220 (97.7) | 231/245 (94.3) | |
CT | 19/465 (4.0) | 5/220 (2.3) | 14/245 (5.7) | |
Distance to the anorectal junction, cm
|
0.043
| |||
< 3 | 143/475 (30.1) | 72/224 (32.1) | 71/251 (28.2) | |
3.1–7.0 | 129/475 (27.2) | 57/224 (25.4) | 72/251 (28.7) | |
> 7 | 108/475 (22.7) | 60/224 (26.8) | 48/251 (19.1) | |
Unknown | 95/475 (20.0) | 35/224 (15.6) | 60/251 (23.9) | |
MRF
| ||||
Positive | 99/475 (20.8) | 47/224 (21.0) | 52/251 (20.7) | 0.943 |
Clinical tumor stage
| ||||
cT3N0M0 | 59/475 (12.4) | 29/224 (12.9) | 30/251 (12.0) | 0.743 |
cT4N0M0 | 15/475 (3.2) | 7/224 (3.1) | 8/251 (3.2) | 0.969 |
cT1-3N1-2M0 | 269/475 (56.6) | 134/224 (59.8) | 135/251 (53.8) | 0.185 |
cT4N1-2M0 | 49/475 (10.3) | 16/224 (7.1) | 33/251 (13.1) |
0.032
|
Unknown | 20/475 (4.2) | 13/224 (5.8) | 7/251 (2.8) | 0.102 |
Procedure
| ||||
LAR with primary anastomosis | 192/475 (40.4) | 100/224 (44.6) | 92/251 (36.7) | 0.289 |
APR | 202/475 (42.5) | 89/224 (39.7) | 113/251 (45.0) | |
Hartmann | 76/475 (16.0) | 32/224 (14.3) | 44/251 (17.5) | |
Other | 5/475 (1.1) | 3/224 (1.3) | 2/251 (0.8) | |
Approach
|
0.011
| |||
Open | 249/475 (52.4) | 102/224 (45.5) | 147/251 (58.6) | |
Laparoscopic | 220/475 (46.3) | 120/224 (53.6) | 100/251 (39.8) | |
Laparoscopic conversion | 6/475 (1.3) | 2/224 (0.9) | 4/301 (1.6) | |
Multivisceral resection (additional)
b
| ||||
Yes | 60/466 (12.9) | 19/218 (8.7) | 41/248 (16.5) |
0.012
|
No | 406/466 (87.1) | 199/218 (91.3) | 207/248 (83.5) | |
Adjuvant chemotherapy
| ||||
Yes | 47/475 (9.9) | 16/224 (7.1) | 31/251 (12.4) | 0.058 |
MRI restaging after CRT
c
|
0.002
| |||
Yes | 366/461 (79.4) | 158/216 (73.1) | 208/245 (84.9) | |
No | 95/461 (20.6) | 58/216 (26.9) | 37/245 (15.1) | |
MRI restaging results
d
| 0.244 | |||
Progression | 7/361 (1.9) | 1/7 (14.3) | 6/7 (85.7) | |
Stable | 45/361 (12.5) | 19/45 (42.2) | 26/45 (57.8) | |
Partial response | 194/361 (53.7) | 130/294 (44.2) | 164/294 (55.8) | |
Complete response | 15/361 (4.2) | 4/15 (26.7) | 11/15 (73.3) | |
Interval CRT–MRI (weeks)
e
|
< 0.001
| |||
<6 | 7/341 (2.0) | 5/146 (3.4) | 2/195 (1.0) | |
6–8 | 21/341 (6.2) | 14/146 (9.6) | 7/195 (3.6) | |
8–10 | 114/341 (33.4) | 73/146 (50.0) | 41/195 (21.0) | |
10–12 | 117/341 (34.3) | 47/146 (32.2) | 70/195 (35.9) | |
12–14 | 50/341 (14.7) | 7/146 (4.8) | 43/195 (22.1) | |
14–16 | 21/341 (6.2) | – | 21/195 (10.8) | |
> 16 | 13/341 (3.8) | – | 11/195 (5.6) | |
Interval MRI–surgery (weeks)
f
|
< 0.001
| |||
< 1 | 9/340 (2.6) | 6/146 (4.1) | 3/194 (1.5) | |
1–2 | 28/340 (8.2) | 21/146 (14.4) | 7/194 (3.6) | |
2–3 | 63/340 (18.5) | 43/146 (29.5) | 20/194 (10.3) | |
3–4 | 69/340 (20.3) | 36/146 (24.7) | 33/194 (17.0) | |
4–5 | 62/340 (18.2) | 24/146 (16.4) | 38/194 (19.6) | |
5–6 | 41/340 (12.0) | 13/146 (8.9) | 28/194 (14.4) | |
6–7 | 25/340 (7.4) | 3/146 (2.1) | 22/194 (11.3) | |
7–8 | 17/340 (5.0) | – | 17/194 (8.8) | |
8–9 | 8/340 (2.4) | – | 8/194 (4.1) | |
> 9 | 18/340 (0.3) | – | 18/194 (9.3) | |
Pathological, surgical and long-term oncologic outcomes
| ||||
Histological type tumorg | ||||
Adenocarcinoma | 431/461 (93.5) | 206/219 (94.1) | 225/242 (93.0) | 0.087 |
Mucinous | 10/461 (2.2) | 7/219 (3.2) | 3/242 (1.2) | |
Signet ring cell | 15/461 (0.2) | 1/19 (0.5) | 14/242 (5.8) | |
Other | 5/461 (4.1) | 5/219 (2.2) | 0/242 (0.0) | |
CRMh | 0.145 | |||
Positive | 47/365(12.9) | 17/176 (9.7) | 30/189 (15.9) | |
Negative | 318/365 (87.1) | 159/176 (90.3) | 159/189 (84.1) | |
Unknown | 29/365 (8.0) | 14/176 (8.0) | 15/189 (7.9) | |
ypTN classification | ||||
ypT0N0 (pCR) | 81/475 (17.0) | 34/224 (15.2) | 47/251 (18.7) | 0.305 |
ypT1N0 (near pCR) | 30/475 (6.3) | 17/224 (7.6) | 13/251 (5.2) | 0.281 |
ypT0N1-2 | 9/475 (1.9) | 1/224 (0.4) | 8/251 (3.2) |
0.029
|
Postoperative transfusioni | ||||
Yes | 59/475 (12.4) | 19/222 (8.6) | 40/245 (16.3) |
0.021
|
Any perineal wound problems | ||||
<1 year (APR) | 64/202 (31.7) | 33/89 (37.1) | 31/113 (27.4) | 0.144 |
Overall leak rate (LAR)j | 42/192 (21.9) | 19/100 (19.0) | 23/92 (25.0) | 0.329 |
Chronic sinus rate (LAR)k | 25/192 (13.0) | 11/100 (11.0) | 14/92 (15.2) | 0.366 |
30-day overall complication ratel | 166/471 (35.2) | 74/222 (33.3) | 92/249 (36.9) | 0.445 |
30-day surgical complication rate | 103/475 (21.7) | 45/224 (20.1) | 58/251 (23.1) | 0.943 |
Length of stay (median [IQR])m | 8 [6–14] | 7 [6–12] | 9 [7–15] | 0.131 |
Re-intervention < 30 days | 64/475 (13.5) | 28/224 (12.5) | 36/251 (14.3) | 0.557 |
Re-admission < 30 days | 2/475 (0.4) | 1/224 (0.5) | 1/251 (0.4) | 0.211 |
Follow-up months (median [IQR])n | 43 [35–47] | 43 [36–47] | 42 [32–47] | 0.349 |
3-year local recurrence (Kaplan–Meier) | 26/475 (5.5) | 9/224 (4.0) | 17/251 (6.8) | 0.169 |
3-year distant recurrence (Kaplan–Meier) | 90/475 (18.9) | 45/224 (20.1) | 45/251 (17.9 | 0.769 |
3-year disease-free survival (Kaplan–Meier) | 343/475 (72.2) | 167/223 (74.6) | 176/251 (70.1) | 0.267 |
3-year overall survival (Kaplan–Meier)o | 404/474 (85.2) | 196/223 (87.9) | 208/251 (82.9) | 0.178 |
Magnetic Resonance Imaging Restaging Results
MRI restaging results | |||||
---|---|---|---|---|---|
Progression (%) | Stable (%) | Partial response (%) | Complete response (%) | p value | |
CRT–MRI restaging intervala | |||||
< 6 weeks | 0 | 0 | 2/2 (100) | 0 | 0.447 |
6–8 weeks | 0 | 5/32 (15.6) | 27/32 (84.4) | 0 | |
8–10 weeks | 1/121 (0.8) | 18/121 (14.9) | 99/121 (81.8) | 3/121 (2.5) | |
> 10 weeks | 6/183 (3.3) | 18/183 (9.8) | 148/183 (80.9) | 11/183 (6.0) | |
Overall | 7/338 (2.1) | 41/338 (12.1) | 276/338 (81.7) | 14/338 (4.1) | |
MRI restaging—surgery intervalb | |||||
Time interval, weeks (median [IQR]) | 3 [2–4] | 4.5 [3–6] | 3 [2–5] | 3.5 [2–4] | 0.598 |
< 2 weeks | 1/7 (14.3) | 4/40 (10) | 29/276 (10.5) | 2/14 (14.2) | |
2–4 weeks | 3/7 (42.9) | 10/40 (25) | 113/276 (40.9) | 5/14 (35.7) | |
> 4 weeks | 3/7 (42.9) | 26/40 (65) | 134/276 (48.6) | 7/14 (50.0) | |
pCR | 1/7 (14.3) | 6/40 (15) | 49/276 (17.8) | 7/14 (50.0) | 0.022 |
Pathological and Surgical Outcomes
Long-Term Oncologic Outcomes
Predictors of Circumferential Resection Margin Involvement, Recurrence, and Survival
Variable | Univariable analysis | Multivariable analysis | ||
---|---|---|---|---|
OR (95% CI) | p value | OR (95% CI) | p value | |
Sex
| ||||
Male | 1.15 (0.61–2.16) | 0.675 | ||
Female | Ref | |||
BMI, kg/m
2
| ||||
< 25 | 0.72 (0.37–1.38) | 0.319 | ||
25–30 | Ref | |||
> 30 | 0.85 (0.35–2.08) | 0.724 | ||
Distance to the anorectal junction, cm
| ||||
< 3 | 0.82 (0.33–2.00) | 0.658 | ||
3.1–7 | 1.10 (0.46–2.61) | 0.832 | ||
> 7 | Ref | |||
Approach
| ||||
Open | Ref | Ref | ||
Laparoscopic |
0.54 (0.28–1.05)
|
0.068
| 0.56 (0.27–1.15) | 0.113 |
Laparoscopic conversion |
39.46 (4.45–350)
|
0.001
|
39.1 (3.87–395)
|
0.002
|
Intraoperative complication
| ||||
Yes |
3.65 (1.11–11.97)
|
0.033
|
5.22 (1.43–19.11)
|
0.013
|
Multiple visceral resection
| ||||
Yes |
2.31 (1.10–4.83)
|
0.026
| 1.98 (0.75–5.26) | 0.170 |
Tumor stage
| ||||
ypT0 | Ref | Ref | ||
ypT1-3 |
3.40 (1.02–11.28)
|
0.046
| 2.62 (0.74–9.27) | 0.135 |
ypT4 |
8.46 (2.03–35.20)
|
0.003
| 2.14 (0.39–11.79) | 0.381 |
Nodal stage
| ||||
ypN0 | Ref | Ref | ||
ypN1-2 |
3.47 (1.87–6.41)
|
< 0.001
|
3.13 (1.60–6.16)
|
0.001
|
Interval group
| ||||
Short | Ref | |||
Long | 1.65 (0.89–3.09) | 0.115 |