Abstract
Purpose
This post-hoc analysis of the LASRE trial aims to evaluate the impact of body mass index (BMI) on surgical difficulty and oncological outcomes in patients undergoing laparoscopic or open resection for low rectal cancer.
Methods
The LASRE trial was a multicenter, randomized controlled trial comparing laparoscopic and open surgery for low rectal cancer. Patients aged 18–75 years with rectal adenocarcinoma located within 5 cm of the dentate line were enrolled and stratified into four BMI groups: underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5–23.9 kg/m2), overweight (BMI 23.9–27.9 kg/m2), and obese (BMI ≥ 28.0 kg/m2). The primary endpoints were surgical difficulty, circumferential resection margin (CRM) positivity, and postoperative complications.
Results
A total of 1,039 patients were included. Obese patients exhibited significantly longer operative times (P < 0.001) and higher intraoperative blood loss (P = 0.001). The 30-day complication rate (P = 0.030) and Clavien-Dindo classification (P = 0.040) differed significantly between groups. However, CRM positivity rates did not significantly differ between BMI groups (P = 0.42). During the median follow-up of 36 months, the 3-year OS rate was comparable across BMI groups (P = 0.709), and the 3-year DFS rate showed no significant differences among the BMI groups (P = 0.966).
Conclusions
Higher BMI increases surgical difficulty and postoperative complications in low rectal cancer but does not significantly impact CRM positivity or DFS. These findings underscore the importance of considering BMI in surgical planning and patient counseling.
Supplementary Information
The online version contains supplementary material available at 10.1007/s00384-025-04979-7.
Keywords: Low rectal cancer, Body mass index, Surgery, Laparoscopy, Trial
Introduction
Rectal cancer is a leading cause of cancer-related mortality worldwide [1]. Compared to middle or upper rectal cancer, low rectal cancer presents unique challenges in surgical management [2]. The narrow pelvic cavity, intricate anatomy, and limited operative space render surgical dissection particularly challenging, especially when attempting sphincter-saving procedures [3]. Furthermore, obesity exacerbates these challenges in rectal cancer surgery by prolonging operative times, increasing blood loss, and potentially impairing oncologic outcomes [4]. Additionally, the increased visceral fat in obese patients with rectal cancer, coupled with the narrowed pelvic spaces, impedes visualization and instrument manipulation [5]. These factors can adversely affect the quality of resection and elevate the incidence of complications, such as anastomotic leakage, particularly following rectal cancer surgery [6].
Despite the increasing utilization of laparoscopic surgery in the treatment of rectal cancer, the impact of body mass index (BMI) on surgical difficulty and oncological outcomes remains insufficiently investigated in large-scale, rigorously-controlled randomized controlled trials (RCTs) [6–8]. Previous studies [7, 8], which are predominantly retrospective or single-center in nature, have reported associations between BMI and surgical outcomes for rectal cancer. However, these studies are constrained by selection bias and confounding variables. Furthermore specific data regarding low rectal cancer resection are scarce. The LASRE (Laparoscopy-Assisted Surgery for Carcinoma of the Low Rectum) trial [9, 10], a multicenter RCT demonstrated that laparoscopic surgery yielded provided oncological outcomes that were non-inferior to those of open resection. Nonetheless, the effect of BMI on surgical difficulty and oncological outcomes within this trial was not clearly delineated. Additionally, while preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) and adjuvant chemotherapy is the standard treatment for locally advanced rectal cancer.[11, 12]; the role of BMI in this treatment paradigm remains poorly understood.
This post-hoc analysis of the LASRE trial aims to evaluate the impact of BMI on surgical difficulty and oncological outcomes in patients undergoing laparoscopic or open resection for low rectal cancer. Furthermore, it seeks to ascertain whether BMI can act as an independent predictor of oncological outcomes in this patient population.
Patients and methods
Study design and population
This study represents a post-hoc analysis of the LASRE trial [9, 10], a multicenter, randomized controlled trial designed to compare laparoscopic and open surgical approaches for the treatment of low rectal cancer. The trial enrolled patients aged 18 to 75 years who had histopathologically confirmed rectal adenocarcinoma located within 5 cm of the dentate line. Eligible tumors were clinically staged as cT1-2N0, cT3-4aN0, or cT1-4aN1-2, with a maximum diameter of 6 cm. Patients without an assessment of TME quality were excluded. Participants were randomly assigned to either laparoscopic or open surgery in a 2:1 ratio, utilizing a dynamic minimization algorithm stratified by age, sex, BMI, and American Society of Anesthesiologists (ASA) score. Additionally, patients who underwent other surgical procedures, such as abdominoperineal resection (APR), Hartmann procedure, pelvic exenteration, or transanal TME, were excluded from this post-hoc analysis. BMI categories were defined according to Chinese guidelines for obesity in adults (underweight: < 18.5 kg/m2; normal weight: 18.5–23.9 kg/m2; overweight: 23.9–27.9 kg/m2; obese: ≥ 28.0 kg/m2) [13]. These guidelines are more stringent than the WHO criteria (25.0 and 30.0 kg/m2) because Asian populations experience higher metabolic risks at lower BMI thresholds. This post-hoc analysis received approval from the ethics committee of Fujian Medical University Union Hospital. Given the retrospective nature of the study, the requirement for additional patient consent was waived. A flow chart summarizing this study is presented in Supplementary Fig. 1.
Treatment
For patients diagnosed with stage II/III rectal cancer, preoperative CRT is required. The cumulative radiotherapy dose was 45–50.4 Gy, divided into 25–28 fractions, alongside concurrent fluorouracil or its analogues. After radiotherapy, patients received a 14-day course of capecitabine (1250 mg/m2, twice daily). Surgery was performed 6–8 weeks after CRT, strictly adhering to the principle of TME. Surgical procedures included low/ultralow anterior resection (LAR/ULAR), intersphincteric resection (ISR), APR, Hartmann’s procedure, and others. Central lymph node dissection was routinely conducted during the operation. Sharp pelvic dissection was excuted along the mesorectal plane while preserving the autonomic nerves. The decision regarding sphincter preservation was made collaboratively by the surgeon and the patient. For high-risk anastomoses, diverting ileostomy or colostomy was utilized. Postoperatively, adjuvant chemotherapy was recommended for patients with stage II-III who have undergone preoperative CRT, as well as for those with pT3-4Nany or pTanyN1-2 who have not received preoperative CRT. The chemotherapy regimens were CapeOx (oxaliplatin 130 mg/m2 on day 1, capecitabine 1000 mg/m2, twice daily from days 1–14) or capecitabine monotherapy (825 mg/m2, twice daily). For patients with pT3-4Nany or pTanyN1-2 who had not received preoperative CRT, postoperative adjuvant chemoradiotherapy was recommended, following a similar protocol. The total duration of peri-operative treatment was limited to a maximum of 6 months.
Follow-up
Patients underwent scheduled follow-up visits every 3 months during the first 2 years, followed by visits every 6 months for the subsequent 3 years, and annually thereafter. At each visit, a comprehensive physical examination was conducted, and serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19–9 (CA19-9) were measured. Imaging studies included abdominal and pelvic ultrasound and chest X-ray, conducted at 3- or 6-month intervals. Abdominal and pelvic magnetic resonance imaging (MRI) or computed tomography (CT) scans and colonoscopy were conducted annually.
Statistical analysis
Statistical analyses were performed using SPSS version 25.0 (IBM Corp., Armonk, NY, USA) and R software (version 4.4.1). Continuous variables were presented as means (± standard deviation) or medians (interquartile range) and compared using One-way Analysis of Variance or Kruskal–Wallis H test, as appropriate. Categorical variables were reported as frequencies (percentages) and analyzed using the Chi-square test or Fisher’s exact test. Multivariable Cox regression models were constructed to identify independent predictors of disease-free survival (DFS), adjusting for potential confounders. Variables with a P < 0.10 in univariate analyses were included in the multivariable models. P < 0.05 was considered statistically significant.
Results
Baseline characteristics
A total of 1039 patients were analyzed and categorized into four groups based on BMI: underweight (n = 53), normal weight (n = 589), overweight (n = 336), and obese (n = 61), as shown in Table 1. There were no significant differences in age, gender, comorbidities, tumor location, or preoperative levels of CEA and CA19-9 among the groups (all P > 0.05). However, obese patients exhibited higher ASA II/III scores compared to the normal weight and overweight groups (P = 0.021), indicating poorer preoperative fitness. No significant differences were observed in clinical TNM stage or preoperative therapy across the groups (both P > 0.05).
Table 1.
Preoperative characteristics of patients with low rectal cancer
| Characteristics | Underweight (n = 53) |
Normal weight (n = 589) |
Overweight (n = 336) | Obesity (n = 61) | P value |
|---|---|---|---|---|---|
| Age (years), No. (%) | 0.392 | ||||
| < 50 | 17 (32.1) | 132 (22.4) | 79 (23.5) | 12 (19.7) | |
| ≥ 50 | 36 (67.9) | 457 (77.6) | 257 (76.5) | 49 (80.3) | |
| BMI (kg/m2), median (IQR) | 17.39 (16.65,18.03) | 21.55 (20.52,22.76) | 25.39 (24.57,26.4) | 29.07 (28.45,30.10) | < 0.001 |
| Sex, No. (%) | 0.246 | ||||
| Female | 28 (52.8) | 238 (40.4) | 128 (38.1) | 25 (41.0) | |
| Male | 25 (47.2) | 351 (59.6) | 208 (61.9) | 36 (59.0) | |
| ECOG performance status, No. (%) a | 0.023 | ||||
| 0 | 36 (67.9) | 460 (78.2) | 244 (72.6) | 45 (73.8) | |
| 1 | 15 (28.3) | 123 (20.9) | 92 (27.4) | 16 (26.2) | |
| 2 | 2 (3.8) | 5 (0.9) | 0 (0) | 0 (0) | |
| ASA score, No. (%) | 0.021 | ||||
| I | 38 (71.7) | 441 (75.0) | 225 (67.0) | 38 (62.3) | |
| II | 13 (24.5) | 139 (23.6) | 108 (32.1) | 108 (37.7) | |
| III | 2 (3.8) | 8 (1.4) | 3 (0.9) | 0 (0) | |
| Comorbidity, No. (%) | 17 (32.1) | 149 (25.3) | 102 (30.4) | 13 (21.3) | 0.214 |
| Tumor distance from the anal verge (mm), median (IQR) b | 50 (40, 65) | 50 (40, 60) | 50 (40, 60) | 44.5 (32.5, 60) | 0.140 |
| Tumor distance from the dentate line (mm), median (IQR) c | 40 (20, 50) | 30 (20, 40) | 35 (20, 45) | 30 (20, 40) | 0.084 |
| Preoperative CEA (U/ml) | |||||
| ≤ 5 | 45 (84.9) | 485 (82.3) | 283 (84.2) | 52 (85.2) | 0.721 |
| > 5 | 8 (15.1) | 85 (14.4) | 43 (12.8) | 6 (9.8) | |
| Unknown | 0 | 19 (3.2) | 10 (3.0) | 3 (4.9) | |
| Preoperative CA199 (U/ml) | 0.232 | ||||
| ≤ 37 | 53 (100) | 541 (91.9) | 312 (92.9) | 58 (95.1) | |
| > 37 | 0 | 28 (4.8) | 12 (3.6) | 0 | |
| Unknown | 0 | 20 (3.4) | 12 (3.6) | 3 (4.9) | |
| Clinical TNM stage, No. (%) d | 0.408 | ||||
| I | 20 (37.7) | 224 (38.0) | 111 (33.0) | 25 (41.0) | |
| II/III | 33 (62.3) | 365 (62.0) | 225 (67.0) | 36 (59.0) | |
| Preoperative therapy, No. (%) d | 0.510 | ||||
| Chemoradiotherapy | 33 (100) | 351 (96.2) | 216 (96.0) | 34 (94.4) | |
| Radiotherapy alone | 0 | 1 (0.3) | 0 | 0 | |
| Chemotherapy alone | 0 | 2 (0.5) | 0 | 1 (2.8) | |
| Preoperative therapy, No. (%) d | 33 (100) | 354 (97.0) | 216 (96.0) | 35 (97.2) | 0.819 |
Abbreviations: BMI, body mass index; IQR, interquartile range; ECOG, Eastern Cooperative Oncology Group; ASA, American Society of Anesthesiologists; CEA, Carcinoembryonic Antigen; CA199, Carbohydrate Antigen 199.
a Data were obtained from 1038 patients.
b Data were obtained from 1034 patients.
C Data were obtained from 1034 patients. Tumors that invaded the dentate line.
in 5 patients were excluded.
d Only patients with clinical stage II/III disease were included.
Impact of BMI on surgical and pathological outcomes
As shown in Table 2, the surgical approach did not differ significantly among the groups (P = 0.897). However, APR was most frequent in obese patients (51.7%) compared to underweight (15.4%), normal weight (30.6%) and overweight (29.6%) groups (P = 0.004). The rate of anal sphincter preservation was lowest in obese patients (49.2%) compared to underweight (84.9%), normal weight (69.4%) and overweight (70.5%) groups (P < 0.001). Additionally, obese patients experienced significantly longer median operative times and higher blood loss compared to normal weight and underweight groups (P < 0.001), as shown in Fig. 1. The intraoperative complication rate was also highest in overweight patients (3.6%) compared to obese patients (3.3%) and normal weight patients (0.8%, P = 0.014). Furthermore, obese patients demonstrated significantly fewer retrieved lymph nodes (P = 0.027) and highest rates of incomplete TME quality (P = 0.015), as shown in Table 2. Pathological complete response (pCR) rates were comparable across groups (P = 0.725). Negative distal resection margin (DRM) and circumferential resection margins (CRM) were similar across all groups.
Table 2.
Surgical and pathological outcomes of patients with low rectal cancer
| Characteristics | Underweight (n = 53) | Normal weight (n = 589) | Overweight (n = 336) | Obesity (n = 61) | P value |
|---|---|---|---|---|---|
| Surgical characteristics | |||||
| Surgical approach, No. (%) | 0.897 | ||||
| Open | 14 (26.4) | 185 (28.8) | 103 (30.7) | 19 (31.1) | |
| Laparoscopic | 39 (73.6) | 457 (71.2) | 233 (69.3) | 42 (68.9) | |
| Conversion to open surgery, No. (%) a | 2 (3.8) | 12 (1.9) | 3 (0.9) | 2 (3.3) | 0.162 |
| Type of surgery, No. (%) | 0.004 | ||||
| Low anterior resection | 40 (76.9) | 359 (61.4) | 206 (61.5) | 26 (43.3) | |
| Intersphincteric resection | 4 (7.7) | 47 (8.0) | 30 (9.0) | 3 (5.0) | |
| Abdominoperineal resection | 8 (15.4) | 179 (30.6) | 99 (29.6) | 31 (51.7) | |
| Anal sphincter preservation b | 45 (84.9) | 409 (69.4) | 237 (70.5) | 30 (49.2) | < 0.001 |
| Diverting ostomy, No. (%) c | 38 (84.4) | 314 (76.8) | 181 (76.4) | 22 (73.3) | 0.637 |
| Type of diverting ostomy, No. (%) | 0.808 | ||||
| Ileostomy | 38 (100) | 303 (96.5) | 170 (93.9) | 21 (95.5) | 0.298 |
| Colostomy | 0 | 11 (3.5) | 11 (6.1) | 1 (4.5) | |
| Combined multivisceral resection, No. (%) | 3 (5.7) | 15 (2.5) | 5 (1.5) | 1 (1.6) | 0.222 |
| Operative time (min), median(IQR) | 150 (120, 196) | 180 (145, 225) | 191 (165, 244.5) | 217.5 (183.5, 252.5) | < 0.001 |
| Estimated blood loss (ml), median (IQR) | 50 (20, 100) | 50 (50, 100) | 50 (40, 100) | 100(50, 100) | 0.001 |
| Intraoperative complications, No. (%) | 0 | 5 (0.8) | 12 (3.6) | 2 (3.3) | 0.014 |
| Pathological outcomes | |||||
| pT stage, No. (%) | 0.10 | ||||
| 0/Tis | 7 (13.2) | 77 (13.1) | 49 (14.6) | 7 (11.5) | |
| 1 | 6 (11.3) | 51 (8.7) | 40 (11.9) | 3 (4.9) | |
| 2 | 20 (37.7) | 205 (34.8) | 125 (37.2) | 24 (39.3) | |
| 3 | 11 (20.8) | 229 (38.9) | 103 (30.7) | 24 (39.3) | |
| 4 | 9 (17.0) | 27 (4.6) | 19 (5.7) | 3 (4.9) | |
| pN stage, No. (%) | 0.672 | ||||
| 0 | 36 (67.9) | 436 (74.0) | 261 (77.7) | 44 (72.1) | |
| 1 | 12 (22.6) | 117 (19.9) | 58 (17.3) | 14 (23.0) | |
| 2 | 5 (9.4) | 36 (6.1) | 17 (5.1) | 3 (4.9) | |
| pTNM stage, No. (%) | 0.725 | ||||
| 0/pCR | 7 (13.2) | 73 (12.4) | 47 (14.0) | 7 (11.5) | |
| I | 20 (37.7) | 208 (35.3) | 133 (39.6) | 23 (37.7) | |
| II | 9 (17.0) | 154 (26.1) | 82 (24.4) | 14 (23.0) | |
| III | 17 (32.1) | 154 (26.1) | 74 (22.0) | 17 (27.9) | |
| No. of retrieved lymph nodes, median (IQR) | 14 (11, 20) | 13 (9, 17) | 12 (9, 16) | 12 (7, 14) | 0.027 |
| Histopathology, No. (%) | 0.314 | ||||
| Adenocarcinoma | 52 (98.1) | 557 (94.6) | 310 (92.3) | 57 (93.4) | |
| Mucinous adenocarcinoma/Signet-ring cell carcinoma | 1 (1.9) | 32 (5.4) | 26 (7.7) | 4 (6.6) | |
| Tumor differentiation, No. (%) | 0.551 | ||||
| Well differentiated | 2 (3.8) | 46 (7.8) | 28 (8.3) | 7 (11.5) | |
| Moderately differentiated | 36 (67.9) | 327 (55.5) | 191 (56.8) | 38 (62.3) | |
| Poorly differentiated | 4 (7.5) | 41 (7.0) | 18 (5.4) | 3 (4.9) | |
| Undifferentiated | 0 | 3 (0.5) | 1 (0.3) | 1 (1.6) | |
| Unknown | 11 (20.8) | 172 (29.2) | 98 (29.2) | 12 (19.7) | |
| TME quality, No. (%) d | 0.015 | ||||
| Complete | 44 (88.0) | 443 (85.7) | 259 (85.8) | 41 (78.8) | |
| Nearly complete | 5 (10.0) | 63 (12.2) | 35 (11.6) | 5 (9.6) | |
| Incomplete | 1 (2.0) | 11 (2.1) | 8 (2.6) | 6 (11.5) | |
| Length of PRM (mm), median (IQR) |
116 (80,150) |
125 (95, 150) |
125 (95, 150) |
125 (95, 150) |
0.126 |
| Length of DRM (mm), median (IQR) | 22 (15, 35) | 20 (13, 30) | 20 (13, 30) | 20 (13, 30) | 0.579 |
| Negative DRM, No. (%) | 53 (100) | 588 (99.8) | 333 (99.1) | 61 (100) | 0.332 |
| Negative CRM, No. (%) | 52 (98.1) | 632 (98.4) | 333 (99.1) | 61 (100) | 0.305 |
Tis, Carcinoma in situ; pCR, pathological complete response; IQR, interquartile range; PRM, proximal resection margin; DRM, distal resection margin; CRM, circumferential resection margin; TME, total mesorectal excision; NA, not applicable.
a Data were obtained from 1032 patients. In the Underweight group, 1 patient underwent underwent transanal total mesorectal excision. In the Normal weight group, 2 patients underwent the Hartmann procedure, 1 underwent total proctocolectomy, and 1 underwent posterior pelvic resection. In the Overweight group, 1 patient underwent transanal total mesorectal excision. In the Obesity group, 1 patient underwent the Hartmann procedure.
b In the Underweight group, 40 patients underwent low anterior resection, 4 underwent intersphincteric resection, and 1 underwent transanal total mesorectal excision. In the Normal weight group, 359 patients underwent low anterior resection, 37 underwent intersphincteric resection, 2 underwent the Hartmann procedure, and 1 underwent posterior pelvic resection. In the Overweight group, 206 patients underwent low anterior resection, 30 underwent intersphincteric resection, and 1 underwent transanal total mesorectal excision. In the Obesity group, 26 patients underwent low anterior resection, 3 underwent intersphincteric resection, and 1 underwent the Hartmann procedure.
c Only patients who underwent sphincter-preserving surgery were included.
d Data were obtained from 921 patients.
Fig. 1.
Violin plot of operative time (A), estimated blood loss (B), No. of retrieved lymph nodes (C), and duration of hospitalization (D) across BMI groups
Impact of BMI on postoperative complications and recovery
As shown in Table 3 and Supplementary Fig. 2, the 30-day complication rate (P = 0.030) and Clavien-Dindo classification (P = 0.040) differed significantly between groups, with the overweight group experiencing more complications. The re-operation rate approached significance (P = 0.057). Although overall 30-day postoperative complication rates were similar (P = 0.030), overweight patients had higher rates of incision complications (P = 0.057), while underweight patients had higher rates of intraabdominal bleeding (P = 0.014). Postoperative recovery was delayed in obese patients, who had longer times to liquid diet (P = 0.014) and prolonged hospital stays (P = 0.002). Recovery times to first flatus, defecation, and normal diet did not differ significantly among underweight, normal weight, overweight, and obese groups. However, the time to liquid diet varied significantly (P = 0.014), with the underweight group having the shortest duration.
Table 3.
Postoperative complications and recovery of patients with low rectal cancer
| Characteristics | Underweight (n = 53) |
Normal weight (n = 589) |
Overweight (n = 336) |
Obesity (n = 61) |
P value |
|---|---|---|---|---|---|
| Postoperative complications | |||||
| 30-d Postoperative complications, No. (%) | 8 (15.1) | 71 (12.1) | 64 (19.0) | 7 (11.5) | 0.030 |
| Type of postoperative complications, No. (%) a | |||||
| Presacral hemorrhage | 0 | 2 (0.3) | 0 | 0 | 0.633 |
| Active intraabdominal bleeding | 2 (3.8) | 1 (0.2) | 2 (0.6) | 1 (1.6) | 0.014 |
| Anastomotic bleeding | 1 (1.9) | 2 (0.3) | 2 (0.6) | 0 | 0.286 |
| Anastomotic leakage | 3 (5.7) | 14 (2.4) | 9 (2.7) | 0 | 0.264 |
| Chylous leakage | 0 | 3 (0.5) | 1 (0.3) | 0 | 1.000 |
| Ileus | 1 (1.9) | 13 (2.2) | 8 (2.4) | 3 (4.9) | 0.536 |
| Incision complications | 0 | 16 (2.7) | 19 (5.7) | 1 (1.6) | 0.057 |
| Stoma-related complications | 1 (1.9) | 0 | 1 (0.3) | 0 | 0.045 |
| Urinary disorder | 0 | 9 (1.5) | 5 (1.5) | 1 (1.6) | 1.000 |
| Urinary tract infection | 1 (1.9) | 3 (0.5) | 5 (1.5) | 0 | 0.253 |
| Cardiovascular event | 0 | 1 (0.2) | 5 (1.5) | 0 | 0.117 |
| Pneumonia | 0 | 7 (1.2) | 4 (1.2) | 1 (1.6) | 0.890 |
| Others | 1 (1.9) | 10 (1.7) | 11 (3.3) | 2 (3.3) | 0.340 |
| Clavien-Dindo classification, No. (%) | 0.040 | ||||
| I-II | 7 (13.2) | 68 (11.5) | 56 (16.7) | 7 (11.5) | |
| IIIa-IVa | 1 (1.9) | 3 (0.5) | 8 (2.4) | 0 | |
| Re-operation, No. (%) | 1 (1.9) | 4 (0.6) | 8 (2.4) | 0 | 0.057 |
| 30-d Mortality, No. (%) | 0 | 0 | 0 | 0 | NA |
| Postoperative recovery | |||||
| Time to first flatus (h), median (IQR) |
41.8 (17.5, 51.38) |
40.5 (18.7, 64.2) |
41.9 (20.4, 65.6) |
42.9 (34.8, 65.2) |
0.407 |
| Time to first defecation (h), median (IQR) |
68.5 (22.7, 92.0) |
62.5 (30.0, 98.9) |
64.3 (28.7, 105.0) | 64.1 (45.1, 115.5) | 0.550 |
| Time to liquid diet (h), median (IQR) |
42.6 (22.2, 69.7) |
44.9 (20.6, 71.6) |
63.7 (32.0, 90.3) |
65.1 (39.8, 96.5) |
0.014 |
| Time to normal diet (h), median (IQR) |
121.2 (68.9, 160) |
115.88 (69.5, 166.7) |
126.8 (70.1, 165.0) |
131.5 (89.7, 64.1) |
0.828 |
| Postoperative hospital stay < 14 (d), No. (%) | 44 (83.0) | 509 (86.4) | 272 (81.0) | 53 (86.9) | 0.155 |
| Duration of hospitalization (d), median (IQR) | 8 (7, 12) | 8 (6, 11) | 8 (7, 12) | 9 (7, 11) | 0.002 |
a The number of individual complications exceeded the total number of complications because patients may have had 2 or more complications
Impact of BMI on survival
During the median follow-up period of 36 months, the 3-year overall survival (OS) rate was comparable across BMI groups in patients with low rectal cancer (P = 0.709), as depicted in Fig. 2. Similarly, the 3-year DFS rate showed no significant differences among the BMI groups (P = 0.966). As shown in Fig. 3, multivariate Cox regression analysis revealed that sex (male vs. female, HR = 1.387, P = 0.043), comorbidity (HR = 1.410, P = 0.034), tumor distance from the dentate line (HR = 0.986, P = 0.020), preoperative CEA (HR = 1.475, P = 0.036), preoperative CA199 (HR = 2.467, P = 0.002), preoperative therapy (HR = 1.861, P < 0.001), and pT classification (T3: HR = 2.772, P < 0.001; T4: HR = 2.061, P = 0.056) were independent prognostic factors for DFS in patients with low rectal cancer. Additionally, pN classification (N1: HR = 2.131,P < 0.001; N2: HR = 2.965, P < 0.001) also emerged as significant predictors of DFS. Notably, BMI was not found to be a significant prognostic factor for DFS in low rectal cancer, as shown in Supplementary Table 1.
Fig. 2.
Kaplan-Meier curves of low rectal cancer across BMI groups A. Overall survival curves across BMI groups B. Disease-free survival curves across BMI groups C. Overall survival curves across BMI groups in patients undergoing open surgery D. Disease-free survival curves across BMI groups in patients undergoing open surgery E. Overall survival curves across BMI groups in patients undergoing laparoscopic surgery F. Disease-free survival curves across BMI groups in patients undergoing laparoscopic surgery Abbreviation: BMI, body mass index
Fig. 3.
Forest plot of the multivariate Cox analysis of risk factors for disease-free survival
Subgroup analysis stratified by laparoscopic or open resection
In laparoscopic surgery for low rectal cancer, higher BMI was associated with prolonged operative time (P < 0.001), increased intraoperative blood loss (P = 0.027), and more intraoperative complications (P = 0.040), as shown in Supplementary Table 2. While overall 30-day complication rates did not differ significantly (P = 0.347), obese patients exhibited trends toward fewer retrieved lymph nodes (P = 0.050) and lower complete TME rates (P = 0.106). Subgroup analysis revealed higher rates of incision complications (P = 0.046) in obese patients and reoperations (P = 0.009) in overweight patients.
In open surgery for low rectal cancer, increasing BMI correlated with significantly prolonged operative time (P < 0.001), higher intraoperative blood loss (P = 0.035), and increased postoperative complications (P = 0.043), as shown in Supplementary Table 3. Obese patients demonstrated higher rates of incision complications (P = 0.021) and prolonged hospital stays (P = 0.004), while trends toward poorer TME quality (P = 0.099) were observed. No significant differences in oncological outcomes (e.g., CRM positivity, lymph node retrieval) were noted across BMI groups.
As shown in Fig. 2, the 3-year OS rate was comparable across BMI groups undergoing laparoscopic surgery for low rectal cancer (P = 0.659), and the 3-year DFS rate was also comparable (P = 0.862). Similarly, among those undergoing open surgery, the 3-year OS and DFS rates were comparable across BMI groups (P = 0.397 and P = 0.823, respectively).
Discussion
This post-hoc analysis of the LASRE trial, which originally compared laparoscopic and open surgery for low rectal cancer, investigates the role of BMI in surgical difficulty and oncologic outcomes. Higher BMI increases surgical difficulty but does not adversely affect key oncologic outcomes such as CRM positivity or 3-year DFS. These findings provide high-level evidence to inform preoperative counseling and personalized treatment strategies.
BMI is a critical determinant of technical difficulties in rectal cancer surgery [8, 14]. Elevated BMI contributes to technical challenges, primarily due to anatomical alterations and increased visceral adipose tissue within the narrow pelvic cavity, complicating dissection and instrument maneuverability [15]. Specifically, obesity-related distortions, such as thickened adipose layers and obscured surgical planes, heighten the complexity of TME. In this study, high BMI was associated with longer operative times and greater intraoperative blood loss, consistent with previous findings [16]. Additionally, obese patients experienced higher APR rates and lower rates of sphincter preservation, likely due to impaired visualization and restricted instrument mobility. Furthermore, the use of diverting ostomies in high-risk anastomosis cases was similar across BMI groups, reflecting adherence to standardized protocols by experienced surgeons.
Obese patients undergoing laparoscopic surgery for rectal cancer face increased surgical difficulty but exhibited no significant differences in key oncologic outcomes compared to non-obese patients. In our study, obese patients had fewer retrieved lymph nodes and lower rates of complete TME, likely attributed to increased intra-abdominal fat and altered pelvic anatomy. Notably, the negativity of DRM and CRM were similar across all BMI groups, suggesting that obesity does not significantly influence surgical radicality [17]. This observation can be attributed to—the quality control measures mandated by the LASRE trial [9, 10], which included the stringent criteria for surgeon qualifications and surgical skills, likely mitigating the impact of adiposity on visual field compromise.
The relationship of BMI and surgical complications, as well as postoperative recovery in rectal cancer surgery, is well-documented [16, 18]. Elevated BMI has been associated with increased rates of anastomotic leakage, wound infections, and pulmonary complications, primarily due to limited pelvic visibility and the presence of excess intra-abdominal fat, which complicate dissection and extend operative duration [19, 20]. In our study, underweight patients exhibited higher ECOG 2 and ASA III statuses, more comorbidities, and the shortest operative times with the least blood loss; however, they also experienced the highest rates of postoperative complication rates. In contrast, obese patients had the longest operative times, and the fewest retrieved lymph nodes. Mechanistically, increased visceral adipose tissue hinders wound healing by reducing vascularity and prolonging inflammation, whereas sarcopenia in underweight patients contributes to delayed functional recovery [21]. These findings highlight the necessity for preoperative nutritional optimization in underweight patients and the implementation of tailored surgical strategies, such as robotic-assisted or trans-anal TME [22–24], for obese patients to improve recovery outcomes. Overweight patients may experience greater tissue trauma during dissection due to increased adipose tissue, elevating complication risk. Underweight patients often have reduced tissue integrity and nutritional deficiencies, increasing bleeding risk. Clinically, these findings highlight the need for tailored perioperative management: stricter hemostasis measures in underweight patients and careful soft-tissue handling in overweight patients.
Obesity may influence tumor progression and treatment response through mechanisms such as chronic inflammation and metabolic disturbances [17, 25]. The relationship between BMI and prognosis in rectal cancer surgery is influenced by multiple factors [26]. The phenomenon known as “obesity paradox” in cancer patients may be attributed to the anti-inflammatory effects of adipose tissue [27, 28], which releases cytokines that regulate endovascular homeostasis and neutralize tumor necrosis factor-α. Additionally, excess adipose tissue provides a physiological reserve that protects against malnutrition and high energy expenditures during surgery, potentially benefiting cancer patients. While some studies suggest that both underweight and obese patients exhibit poorer long-term survival outcomes, others report no significant difference in survival between BMI groups [26, 29–32]. Pathologically, our study demonstrated that obese patients had fewer retrieved lymph nodes and highest rates of incomplete TME quality, which may compromise oncological outcomes. Paradoxically, we found no significant differences in CRM positivity or 3-year DFS across BMI groups, suggesting that laparoscopy remains a viable option for obese rectal cancer patients when performed by experienced surgeons. Our results align with studies showing that obesity does not worsen long-term survival in rectal cancer, likely due to effective TME and adjuvant therapy offsetting potential biological risks.
While 3-year outcomes (DFS and CRM positivity) are unaffected, these findings raise long-term concerns. The 12 lymph nodes meet minimum staging standards but may miss micrometastases, risking tumor understaging and suboptimal adjuvant therapy. Standardized adjuvant therapy in the LASRE trial likely mitigates these risks, but longer follow-up is needed to confirm.
This study has several limitations. First, the small sample size of obese patients and the exclusively Asian population in the LASRE trial may limit the generalizability of the findings to other ethnic groups. Second, BMI alone may not fully capture metabolic dysfunction or sarcopenia, which are known modifiers of surgical outcomes. Other measures [33], including waist circumference, body fat percentage, and muscle mass, may provide more detailed information about the patient’s metabolic and nutritional status and may be more closely associated with surgical outcomes. Third, unmeasured variables such as surgeon experience and hospital volume may have influenced the results despite adjustment for potential confounders. Fourth, BMI was assessed at a single point in time, and changes in weight over time were not evaluated. Fifth, the number of obese patients relatively small in our study (n = 61), which may limit the generalizability of the findings in the obese group and reduce statistical power. Nevertheless, this study represents the first RCT-based analysis systematically evaluating the impact of BMI on surgical complexity and oncological outcomes in low rectal cancer, thereby providing valuable evidence for preoperative counseling and personalized treatment strategies. Future research should focus on larger, international cohorts and investigate the impact of BMI in different patient subgroups to address these limitations.
This post-hoc analysis of the LASRE trial, which included 1039 BMI-stratified patients, demonstrates that higher BMI increases surgical difficulty in low rectal cancer surgery but does not significantly affect CRM positivity or 3-year DFS. Laparoscopic surgery is feasible for obese patients with low rectal cancer but presents greater technical challenges, including longer operative times, increased blood loss, and higher intraoperative complication rates compared to non-obese patients. It should be performed by surgeons experienced in managing complex pelvic and adipose tissue, with thorough preoperative planning to reduce risks.
Supplementary Information
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Acknowledgements
The authors thank all the staff in Department of colorectal surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, People’s Republic of China.
Author’s contribution
Conceptualization: Yanwu Sun, Zhenyu Xu, Yongqin Tang, Yu Deng; Methodology: Yanwu Sun, Yongqin Tang, Zihan Tang and Yu Deng; Formal analysis and investigation: Yanwu Sun, Zhenyu Xu, Zihan Tang; Writing—original draft preparation: Yanwu Sun, Zhenyu Xu and Yu Deng; Writing—review and editing: Yanwu Sun, Zhenyu Xu, Ying Huang and Pan Chi; Funding acquisition: Pan Chi; Resources: Weizhong Jiang and Pan Chi; Supervision: Weizhong Jiang, Ying Huang and Pan Chi. All authors commented on previous versions of the manuscript. All authors read and approved the fnal manuscript.
Funding
This study was supported by the Construction Project of Fujian Province Minimally Invasive Medical Center ([2017]171).
Data availability
No datasets were generated or analysed during the current study.
Declarations
Ethical approval
Not applicable.
Consent to participate
Not applicable.
Consent for publication
Not applicable.
Conflict of interests
The authors declare no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Yanwu Sun, Zhenyu Xu, Yongqin Tang, and Yu Deng contributed equally to this study.
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Supplementary Materials
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Data Availability Statement
No datasets were generated or analysed during the current study.