ABSTRACT
Background
Robot‐assisted surgery has short‐term benefits in rectal cancer surgery; however, its long‐term advantages remain unclear. This study compared short‐ and long‐term outcomes of open, laparoscopic, and robot‐assisted rectal cancer surgeries using large‐scale, database‐driven evidence.
Methods
Patients (28 711) diagnosed with clinical stages I–III rectal cancer who underwent rectal resection and were registered in the Japanese Medical Data Vision Co. Ltd. database were included. Open rectal resection (ORR), laparoscopic rectal resection (LRR), and robot‐assisted rectal resection (RARR) were identified. The primary outcomes were 5‐year overall survival (OS) and relapse‐free survival (RFS). Secondary outcomes included perioperative outcomes.
Results
After applying overlap weight, the RARR, LRR, and ORR groups had 3635 (15.3%), 17 142 (72.3%), and 2935 (12.4%) patients, respectively. Among the cohort (mean age: 69.5 years), 64.9% were male, and 24.7%, 31.5%, and 43.8% had clinical stages I, II, and III, respectively. The RARR group demonstrated the lowest postoperative complication rate, 30‐ and 90‐day mortality rates, and shortest hospital stay. The RARR group had the highest 5‐year OS (95%) and RFS (93%) compared to LRR (OS: 89%, RFS: 86%) and ORR (OS: 81%, RFS: 77%; p < 0.001). Multivariable analysis revealed that RARR was significantly associated with improved OS, whereas higher risks were observed for LRR (hazard ratio [HR]: 2.18, 95% confidence interval [CI]: 1.69–2.81) and ORR (HR: 3.96, 95% CI: 3.03–5.19).
Conclusions
The RARR group demonstrated superior short‐ and long‐term outcomes than the LRR and ORR groups, indicating robot‐assisted surgery as a potential new standard treatment for rectal cancer.
Robot‐assisted rectal resection demonstrated superior short and long‐term outcomes compared to laparoscopic and open approaches.
1. Introduction
Conventional laparoscopic surgery is widely recognized as an effective treatment for colon cancer; however, previous trials indicated that long‐term oncological outcomes for rectal cancer are comparable to those of open surgery [1, 2, 3]. Moreover, laparoscopic surgery may occasionally result in incomplete mesorectal excisions [4]. Robot‐assisted surgery represents the most recent advancement in minimally invasive techniques and provides numerous advantages over conventional laparoscopic surgery, including articulating instruments, immersive three‐dimensional view, enhanced dexterity through tremor filtration, and motion scaling.
The incidence of robot‐assisted rectal cancer surgeries has been consistently increasing globally. Although numerous studies have evaluated the short‐term outcomes of robot‐assisted in comparison to laparoscopic and open approaches, data regarding the long‐term prognosis for rectal cancer remains limited. Of the three randomized controlled trials (RCTs) [5, 6, 7] that evaluated the oncological outcomes of robot‐assisted and laparoscopic approaches, only the REAL trial [7] demonstrated superior results for robot‐assisted surgery. Similarly, the COLRAR [6] and ROLARR trials [5] reported comparable outcomes, rendering the oncological benefits a subject of ongoing debate.
The Japanese Medical Data Vision (MDV) is a comprehensive, large‐scale, real‐world claims database [8] containing anonymized demographic and diagnostic patient information. Previous studies utilizing similar databases, such as the National Clinical Database (NCD) or the Diagnosis Procedure Combination (DPC), have been published [9, 10]; however, these studies concentrated only on short‐term outcomes. Additionally, NCD‐based research has been limited to high‐volume centers and has predominantly reported on low anterior resection (LAR), highlighting the necessity for broader cohort evaluations [9].
Given the rapid global implementation of robot‐assisted rectal cancer surgery, evidence of its long‐term outcomes is essential. Furthermore, incorporating real‐world data, including those from general hospitals, which may lack expertise in robot‐assisted procedures compared to specialized centers, is imperative. Therefore, to investigate the clinical and oncological outcomes in patients with rectal cancer, we conducted this analysis to compare the short‐ and long‐term outcomes of the open, laparoscopic, and robot‐assisted approaches within a broader cohort.
2. Methods
2.1. Data Source
This study was a retrospective cohort analysis utilizing data from the MDV database [8], focusing on patients diagnosed with clinical stage I–III rectal cancer who underwent rectal resection between April 2018 and June 2024. The MDV database comprises de‐identified inpatient and outpatient administrative claims and DPC data from acute care Japanese hospitals, which treat severe illnesses for short durations. The DPC is a case‐mix classification system associated with a flat‐fee payment model. As of March 2023, the MDV database included approximately 43.2 million patients from 475 acute‐phase DPC hospitals, representing about 27% of DPC hospitals in Japan. Among these 475 hospitals, 236 were designated as cancer care hospitals. These hospitals (classified by prefecture, community, or locality) are designated by the Japan Ministry of Health, Labour, and Welfare. They deliver specialized treatments and care to patients with cancer, collaborate and cooperate with each other, and serve as information centers for patients.
2.2. Study Design
This retrospective, multicenter observational study utilized data obtained from a hospital‐based administrative claims database. The International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD‐10‐CM) code C20, was used to identify cases of malignant neoplasm of the rectum [11]. Tumor staging was conducted according to the American Joint Committee on Cancer‐Union for International Cancer Control Tumor, Node, Metastasis (AJCC–UICC TNM) staging system (8th edition) [12]. In cases of simultaneous multiple tumor diagnoses, the tumor with the highest TNM stage was selected for analysis. Patients with incomplete medical records or those who underwent concurrent surgeries were excluded. The rectal resections analyzed in this study were classified as LAR and abdominoperineal resection, according to Japanese insurance criteria [11]. Robot‐assisted rectal resection (RARR), laparoscopic rectal resection (LRR), and open rectal resection (ORR) were also identified using the 10th Revision (ICD‐10) code C20 [11]. The dataset did not include information on tumor location (measured in centimeters from the anal verge), extent of lymph node dissection, or creation of diverting stomas. Only the first diagnosed tumor was incorporated into the analysis of patients diagnosed with multiple primary colorectal tumors.
2.3. Ethical Approval
The MDV database had undergone extensive ethical review and approval in relation to contracts with individual hospital data providers, which eliminated the need for ethics committee review and approval prior to study initiation was not required. Since data elements in the MDV database have been de‐identified, informed consent was not mandated. This report adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines, and the study was conducted in accordance with the principles of the Declaration of Helsinki.
2.4. Data Collected
Data were collected to establish baseline characteristics for the analysis, including sex, age, body mass index (BMI), Charlson Comorbidity Index (CCI), clinical TNM stage, neoadjuvant and adjuvant therapy status, type of surgery, hospital category, and follow‐up duration. The postoperative complications included anastomotic leakage, septic shock, peritonitis, intra‐abdominal bleeding, ileus, intestinal ischemia, surgical site infection, dysuria, urinary tract infection, myocardial infarction, pulmonary embolism, pneumonia, venous thrombosis, and cerebrovascular disease. These complications were identified using ICD‐10‐CM codes.
2.5. Study Outcomes
The primary outcomes were 5‐year overall survival (OS) and 5‐year relapse‐free survival (RFS) among the three surgical approaches. The secondary outcomes were short‐term outcomes, including 30‐day complication rates, 30‐day reoperation rates, 30‐day readmission rates, 30‐ and 90‐day mortality rates, as well as perioperative outcomes.
2.6. Statistical Analysis
The 5‐year cumulative incidences of mortality and metachronous recurrence were also estimated. Time‐to‐event was assessed from the date of surgery to the last follow‐up or death (OS) and recurrence (RFS). Baseline characteristics were compared between groups using pairwise comparisons. Continuous variables are summarized as means with standard deviations, whereas categorical variables are presented as counts and percentages. Statistical tests, including Welch's t‐test, Mann–Whitney U test, Chi‐squared test, or Fisher's exact test, were applied as appropriate based on the data distribution.
Covariates comprised patient background factors, clinical data (CCI, TNM stage, and neoadjuvant therapy), as well as surgical factors (surgery type, hospital category, and follow‐up duration). The CCI was computed using the ICD‐10 codes to allocate comorbidity scores for each patient.
To control the false discovery rate, the Benjamini–Hochberg procedure [13] was applied to adjust p‐values, maintaining a Type I error rate of 0.05 [14]. Considering that three independent hypothesis tests were performed, each with a Type I error rate of 0.05, the cumulative error rate approximated 0.143. The Benjamini–Hochberg method mitigates this by ranking p‐values and comparing them against increasing thresholds, thereby balancing the control of false positives and retaining statistical power.
Overlap weighting (OW) [15] was employed to adjust for confounding, including age, sex, BMI, CCI, TNM stage, neoadjuvant therapy, adjuvant chemotherapy, type of surgery, hospital category, and follow‐up duration. The baseline balance was evaluated using absolute standardized mean differences (ASMD), where an ASMD of < 0.1 indicates a balanced comparison between groups. Kaplan–Meier curves and log‐rank tests were used to compare survival outcomes among surgical modalities, while Cox proportional hazards models were employed to identify predictors of survival.
All statistical tests were two‐sided, with an alpha level of 0.05, and p‐values < 0.050 were considered statistically significant. Statistical analyses were conducted utilizing R software (version 4.3.1; R Foundation for Statistical Computing, Vienna, Austria).
3. Results
3.1. Baseline Characteristics
Figure 1 illustrates the patient flowchart. Among the 64 292 patients in the MDV database who underwent rectal resection between April 2018 and June 2024, 37 191 with primary rectal cancer were screened. Following the exclusion of patients with stage IV disease (n = 3282), unknown stage (n = 4155), incomplete medical records (n = 200), and those who underwent concurrent surgery (n = 843), the final cohort comprised 28 711 patients: 5475, 19 577, and 3659 underwent RARR, LRR, and ORR, respectively.
FIGURE 1.
Patient recruitment flow chart. LRR, laparoscopic rectal resection; ORR, open rectal resection; RARR, robot‐assisted rectal resection.
Before applying OW, patients in the RARR group exhibited a younger demographics, a higher prevalence of obesity, and a higher incidence of clinical stage (cStage) I disease. Additionally, there was more frequent use of neoadjuvant therapy, an elevated rate of LAR, a higher number of treatments at university hospitals, and reduced follow‐up durations compared to patients in the LRR and ORR groups (see Table S1, which presents stages I–III baseline characteristics before OW). Post‐OW, the effective sample size comprised 23 712 patients, including 3635, 17 142, and 2935 in the RARR, LRR, and ORR groups, respectively. Table 1 indicates that after OW, all baseline characteristics were evenly distributed among the three groups (ASMD < 0.1; p > 0.05). In the weighted cohort (mean age: 69.5 years), 64.9% of patients were male; most patients (63.8%) had a normal BMI. The clinical staging distribution was as follows: cStage I, 24.7%; cStage II, 31.5%; and cStage III, 43.8%. Neoadjuvant therapy was administered to 13.5% of patients. LAR was the predominant surgical procedure, conducted in 81.3% of cases. Additionally, 92.1% of surgeries were not performed in university hospitals. The median follow‐up duration was 22 months.
TABLE 1.
Stages I–III baseline characteristics after overlap weighting.
| Characteristics | Summary statistics | p | ASMD | ||||
|---|---|---|---|---|---|---|---|
| RARR a (n = 3635) | LRR a (n = 17 142) | ORR a (n = 2935) | Overall | RARR‐LRR | RARR‐ORR | LRR‐ORR | |
| Sex | |||||||
| Female (%) | 35.36% | 34.94% | 36.23% | 0.393 | 0.009 | 0.018 | 0.027 |
| Male (%) | 64.64% | 65.06% | 63.77% | 0.009 | 0.018 | 0.027 | |
| Age (mean SD) | 69.60 (11.01) | 69.50 (11.25) | 69.74 (11.66) | 0.567 | 0.009 | 0.012 | 0.021 |
| BMI classification b | |||||||
| Normal (%) | 63.46% | 63.91% | 63.61% | 0.907 | 0.010 | 0.003 | 0.006 |
| Underweight (%) | 13.20% | 12.63% | 13.00% | 0.017 | 0.006 | 0.011 | |
| Obese (%) | 23.35% | 23.45% | 23.39% | 0.003 | 0.001 | 0.001 | |
| CCI (mean SD) | 1.30 (1.99) | 1.26 (1.84) | 1.33 (1.92) | 0.134 | 0.021 | 0.015 | 0.037 |
| Clinical stage | |||||||
| I (%) | 25.14% | 24.76% | 23.79% | 0.599 | 0.009 | 0.032 | 0.023 |
| II (%) | 30.96% | 31.69% | 31.41% | 0.016 | 0.010 | 0.006 | |
| III (%) | 43.90% | 43.56% | 44.80% | 0.007 | 0.018 | 0.025 | |
| Clinical T stage | |||||||
| T1 (%) | 11.84% | 11.74% | 11.28% | 0.684 | 0.003 | 0.017 | 0.014 |
| T2 (%) | 16.96% | 17.63% | 17.22% | 0.018 | 0.007 | 0.011 | |
| T3 (%) | 53.41% | 53.60% | 53.36% | 0.004 | 0.001 | 0.005 | |
| T4 (%) | 17.80% | 17.04% | 18.14% | 0.020 | 0.009 | 0.029 | |
| Clinical N stage | |||||||
| N0 (%) | 56.10% | 56.44% | 55.20% | 0.603 | 0.007 | 0.018 | 0.025 |
| N1 (%) | 29.18% | 28.68% | 28.95% | 0.011 | 0.005 | 0.006 | |
| N2 (%) | 14.72% | 14.87% | 15.86% | 0.004 | 0.032 | 0.027 | |
| Neoadjuvant therapy (%) | 13.42% | 13.41% | 14.11% | 0.613 | < 0.001 | 0.020 | 0.020 |
| Adjuvant therapy (%) | 38.73% | 39.86% | 40.01% | 0.421 | 0.023 | 0.026 | 0.003 |
| Type of surgery | |||||||
| LAR (%) | 81.38% | 81.41% | 80.38% | 0.427 | 0.001 | 0.025 | 0.026 |
| APR (%) | 18.62% | 18.59% | 19.62% | 0.001 | 0.025 | 0.026 | |
| Hospital category | |||||||
| University (%) | 7.60% | 7.97% | 8.10% | 0.650 | 0.014 | 0.019 | 0.005 |
| Non‐University (%) | 92.40% | 92.03% | 91.90% | 0.014 | 0.019 | 0.005 | |
| Follow‐up months (median IQR) | 22.36 (9.84–35.77) | 22.22 (8.97–37.13) | 20.74 (8.07–38.24) | 0.051 | 0.078 | 0.048 | 0.027 |
Note: Values with a p‐value < 0.05 based on the ASMD (absolute standardized mean difference) are shown in bold.
Abbreviations: APR, abdominoperineal resection; ASMD, absolute standardized mean difference; BMI, body mass index; CCI, Charlson comorbidity index; IQR, interquartile range; LAR, low anterior resection; LRR, laparoscopic rectal resection; ORR, open rectal resection; OW, overlap weighting; RARR, robotic‐assisted rectal resection; SD, standard deviation.
Approximate effective sample size.
The Japan Society for the Study of Obesity (JASSO) defines BMI classifications as follows: underweight < 18.5 kg/m2; normal 18.5 to < 25 kg/m2; obese ≥ 25 kg/m2.
3.2. Short‐Term Outcomes
The short‐term outcomes after applying OW are summarized in Table 2. The RARR group demonstrated the lowest rate of overall postoperative complications (RARR, 16.10%; LRR, 19.20%; ORR, 28.90%; p < 0.001), specifically anastomotic leakage (RARR, 2.64%; LRR, 3.46%; ORR, 3.68%), surgical site infection (RARR, 2.37%; LRR, 3.08%; ORR, 5.23%), dysuria (RARR, 3.45%; LRR, 5.30%; ORR, 6.09%), and pneumonia (RARR, 0.39%; LRR, 0.86%; ORR, 1.72%). Additionally, the intraoperative blood transfusion rate was lowest in the RARR group (RARR, 5.23%; LRR, 8.46%; ORR, 25.25%), whereas the incidence of ileus was lowest in the LRR group (RARR, 5.56%; LRR, 5.43%; ORR, 10.15%). No significant differences were observed among the three groups regarding septic shock, intraabdominal bleeding, intestinal ischemia, myocardial infarction, pulmonary embolism, venous thrombosis, or cerebrovascular disease.
TABLE 2.
Stages I–III short‐term outcomes after overlap weighting.
| Clinical outcome | Summary statistics | p | FDR corrected p‐value | ||||
|---|---|---|---|---|---|---|---|
| RARR a (n = 3635) | LRR a (n = 17 142) | ORR a (n = 2935) | Overall | RARR‐LRR | RARR‐ORR | LRR‐ORR | |
| Post operative Complications (%) | 16.10% | 19.20% | 28.90% | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
| Anastomotic leakage (%) | 2.64% | 3.46% | 3.68% | 0.020 | 0.023 | 0.023 | 0.515 |
| Septic shock (%) | 0.00% | 0.00% | 0.00% | 1.000 | 1.000 | 1.000 | 1.000 |
| Peritonitis (%) | 2.05% | 2.59% | 6.23% | < 0.001 | 0.061 | < 0.001 | < 0.001 |
| Intraabdominal bleeding (%) | 0.11% | 0.14% | 0.22% | 0.576 | 0.807 | 0.651 | 0.651 |
| Ileus (%) | 5.56% | 5.43% | 10.15% | < 0.001 | 0.748 | < 0.001 | < 0.001 |
| Intestinal ischemia (%) | 0.31% | 0.25% | 0.39% | 0.423 | 0.671 | 0.671 | 0.671 |
| Surgical site infection (%) | 2.37% | 3.08% | 5.23% | < 0.001 | 0.018 | < 0.001 | < 0.001 |
| Dysuria (%) | 3.45% | 5.30% | 6.09% | < 0.001 | < 0.001 | < 0.001 | 0.086 |
| Urinary tract infection (%) | 2.16% | 2.52% | 3.79% | < 0.001 | 0.217 | < 0.001 | < 0.001 |
| Myocardial infarction (%) | 0.08% | 0.06% | 0.09% | 0.510 | 0.731 | 1.000 | 0.731 |
| Pulmonary embolism (%) | 0.12% | 0.14% | 0.26% | 0.234 | 0.807 | 0.227 | 0.227 |
| Pneumonia (%) | 0.39% | 0.86% | 1.72% | < 0.001 | 0.002 | < 0.001 | < 0.001 |
| Venous thrombosis (%) | 0.55% | 0.75% | 1.04% | 0.670 | 0.196 | 0.070 | 0.139 |
| Cerebrovascular disease (%) | 0.33% | 0.32% | 0.59% | 0.102 | 0.871 | 0.207 | 0.124 |
| Intraoperative blood transfusion (%) | 5.23% | 8.46% | 25.25% | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
| Length of stay (mean SD) | 15.55 (10.38) | 18.52 (15.57) | 25.11 (33.29) | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
| Unplanned readmission (%) | 4.65% | 3.92% | 6.09% | < 0.001 | 0.058 | 0.023 | < 0.001 |
| 30‐day reoperation | 1.55% | 2.29% | 1.62% | < 0.001 | 0.017 | 0.844 | 0.036 |
| 30‐day mortality (%) | 0.10% | 0.31% | 0.67% | < 0.001 | 0.035 | < 0.001 | 0.006 |
| 90‐day mortality (%) | 0.22% | 0.64% | 1.31% | < 0.001 | 0.001 | < 0.001 | < 0.001 |
Note: Values with an FDR‐corrected p‐value and a p‐value < 0.05 are shown in bold.
Abbreviations: 95% CI, 95% confidence interval; FDR, false discovery rate; LRR, laparoscopic rectal resection; ORR, open rectal resection; OW, overlap weighting; RARR, robotic‐assisted rectal resection; SD, standard deviation.
Approximate effective sample size.
The RARR group also had the shortest length of hospital stay (RARR, 15.55 [SD: 10.38] days; LRR, 18.52 [SD: 15.57] days; ORR, 25.11 [SD: 33.29] days; p < 0.001). Furthermore, both the 30‐day (RARR, 0.10%; LRR, 0.31%; ORR, 0.67%; p < 0.001) and 90‐day (RARR, 0.22%; LRR, 0.64%; ORR, 1.31%; p < 0.001) mortality rates were significantly lower in the RARR group.
3.3. Long‐Term Outcomes
Table 3 summarizes the long‐term outcomes after OW. The 5‐year OS rate was highest in the RARR group (RARR, 95% [95% CI: 93%–97%]; LRR, 89% [95% CI: 88%–90%]; ORR, 81% [95% CI: 79%–84%]). The Kaplan–Meier curves demonstrated that the RARR group consistently had the highest survival rates during the follow‐up period, followed by the LRR group (Figure 2). Comparable trends were observed across all clinical stages (see Figures S1–S3 and Table 3). The Kaplan–Meier curves before OW showed a consistent trend (see Figure S4, which depicts the Kaplan–Meier curve of OS for stages I–III before OW).
TABLE 3.
Stages I–III long‐term outcomes after overlap weighting.
| Clinical outcome | Summary statistics | p | FDR corrected p‐value | ||||
|---|---|---|---|---|---|---|---|
| RARR a (n = 3635) | LRR a (n = 17 142) | ORR a (n = 2935) | Overall | RARR‐LRR | RARR‐ORR | LRR‐ORR | |
| 5‐year OS b (95% CI) | 95% (93%–97%) | 89% (88%–90%) | 81% (79%–84%) | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
| Stage I b (95% CI) | 97% (95%–100%) | 94% (93%–96%) | 86% (80%–92%) | < 0.001 | 0.002 | < 0.001 | 0.001 |
| Stage II b (95% CI) | 97% (95%–98%) | 90% (88%–91%) | 82% (78%–86%) | < 0.001 | 0.002 | < 0.001 | < 0.001 |
| Stage III b (95% CI) | 92% (88%–97%) | 84% (83%–86%) | 77% (74%–81%) | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
| 5‐year RFS b (95% CI) | 93% (92%–95%) | 86% (85%–87%) | 77% (74%–79%) | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
| Stage I b (95% CI) | 96% (94%–98%) | 92% (91%–93%) | 81% (75%–87%) | < 0.001 | 0.001 | < 0.001 | < 0.001 |
| Stage II b (95% CI) | 94% (92%–96%) | 86% (84%–88%) | 78% (74%–82%) | < 0.001 | 0.021 | < 0.001 | < 0.001 |
| Stage III b (95% CI) | 91% (88%–94%) | 81% (79%–82%) | 73% (69%–77%) | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
| 5‐year local recurrence (%) | 2.19% | 3.19% | 4.36% | < 0.001 | 0.002 | < 0.001 | 0.002 |
Note: Values with an FDR‐corrected p‐value and a p‐value < 0.05 are shown in bold.
Abbreviations: 95% CI, 95% confidence interval; FDR, false discovery rate; LRR, laparoscopic rectal resection; ORR, open rectal resection; OS, overall survival; OW, overlap weighting; RARR, robotic‐assisted rectal resection; RFS, relapse‐free survival.
Approximate effective sample size.
Log‐rank test.
FIGURE 2.
Kaplan–Meier curve of overall survival for stage I–III after OW. LRR, laparoscopic rectal resection; ORR, open rectal resection; OW, Overlap weighting; RARR, robot‐assisted rectal resection.
The 5‐year RFS was also highest in the RARR group (RARR, 93% [95% CI: 92%–95%]; LRR, 86% [95% CI: 85%–87%]; ORR, 77% [95% CI: 74%–79%]), again demonstrating that RARR consistently yielded the best outcomes, followed by LRR and ORR (Figure 3). Similar patterns were observed at each clinical stage (see Figures S5–S7 and Table 3). Additionally, the 5‐year local recurrence rates were significantly lower in the RARR than in the LRR and ORR groups (RARR, 2.19%; LRR, 3.19%; ORR, 4.36%; p < 0.001; Table 3).
FIGURE 3.
Kaplan–Meier curve of relapse‐free survival for stage I–III after OW. LRR, laparoscopic rectal resection; ORR, open rectal resection; OW, Overlap weighting; RARR, robot‐assisted rectal resection.
3.4. Risk Predictors for Overall Survival
Table 4 presents the results of univariable and multivariable Cox regression analyses of factors associated with poorer OS. Multivariable analysis revealed that LRR (HR: 2.18; p < 0.001), ORR (HR: 3.96; p < 0.001), male sex (HR: 1.52; p < 0.001), age ≥ 75 years (HR: 2.95; p < 0.001), underweight (HR: 2.10; p < 0.001), CCI ≥ 2 (HR: 1.23; p < 0.001), cStage II (HR: 1.43; p < 0.001), cStage III (HR: 2.40; p < 0.001), abdominoperineal resection (HR: 1.65; p < 0.001), postoperative adjuvant therapy (HR: 1.35; p < 0.001), and treatment at non‐university hospitals (HR: 2.53; p < 0.001) were significant predictors of poor survival. Conversely, RARR demonstrated significant protective effects on OS.
TABLE 4.
Stages I–III Cox regression analysis of the overall survival.
| Factor | Univariable | Multivariable | ||||
|---|---|---|---|---|---|---|
| HR | 95% CI | p | HR | 95% CI | p | |
| Surgical approach | ||||||
| RARR | Reference | — | — | Reference | — | — |
| LRR | 2.18 | 1.69–2.80 | < 0.001 | 2.18 | 1.69–2.81 | < 0.001 |
| ORR | 3.97 | 3.04–5.19 | < 0.001 | 3.96 | 3.03–5.19 | < 0.001 |
| Sex | ||||||
| Female | Reference | — | — | Reference | — | — |
| Male | 1.34 | 1.17–1.54 | < 0.001 | 1.52 | 1.32–1.74 | < 0.001 |
| Age | ||||||
| < 75 | Reference | — | — | Reference | — | — |
| ≥ 75 | 2.68 | 2.38–3.03 | < 0.001 | 2.95 | 2.61–3.33 | < 0.001 |
| BMI classification a | ||||||
| Normal | Reference | — | — | Reference | — | — |
| Underweight | 1.96 | 1.66–2.31 | < 0.001 | 2.10 | 1.78–2.47 | < 0.001 |
| Obese | 0.87 | 0.75–1.02 | 0.079 | 0.97 | 0.83–1.13 | 0.679 |
| CCI | ||||||
| 0–1 | Reference | — | — | Reference | — | — |
| ≥ 2 | 1.30 | 1.15–1.47 | < 0.001 | 1.23 | 1.09–1.39 | < 0.001 |
| Clinical stage | ||||||
| I | Reference | — | — | Reference | — | — |
| II | 1.72 | 1.44–2.08 | < 0.001 | 1.43 | 1.17–1.73 | < 0.001 |
| III | 2.83 | 2.39–3.36 | < 0.001 | 2.40 | 1.99–2.90 | < 0.001 |
| Neoadjuvant therapy | ||||||
| No | Reference | — | — | Reference | — | — |
| Yes | 1.33 | 1.12–1.58 | 0.001 | 1.18 | 0.99–1.41 | 0.071 |
| Postoperative adjuvant therapy | ||||||
| No | Reference | — | — | Reference | — | — |
| Yes | 1.43 | 1.27–1.62 | < 0.001 | 1.35 | 1.18–1.54 | < 0.001 |
| Type of surgery | ||||||
| LAR | Reference | — | — | Reference | — | — |
| APR | 1.90 | 1.65–2.18 | < 0.001 | 1.65 | 1.43–1.90 | < 0.001 |
| Hospital category | ||||||
| University | Reference | — | — | Reference | — | — |
| Non‐University | 2.15 | 1.58–2.93 | < 0.001 | 2.53 | 1.85–3.46 | < 0.001 |
Note: Values with a p‐value < 0.05 are shown in bold.
Abbreviations: APR, abdominoperineal resection; BMI, body mass index; CCI, Charlson comorbidity index; CI, confidential interval; LAR, low anterior resection; LRR, laparoscopic rectal resection; ORR, open rectal resection; RARR, robotic‐assisted rectal resection.
The Japan Society for the Study of Obesity (JASSO) defines BMI classifications as follows: underweight < 18.5 kg/m2; normal 18.5 to < 25 kg/m2; obese ≥ 25 kg/m2.
4. Discussion
To our knowledge, this study represents the first large‐scale, real‐world analysis demonstrating the significant long‐term survival advantages of robot‐assisted surgery compared to both laparoscopic and open approaches for rectal cancer treatment. Based on a large, robust database, our findings revealed a distinct advantage in outcomes, with robot‐assisted surgery achieving the highest survival rates, succeeded by laparoscopic and open approaches. Furthermore, the robot‐assisted approach demonstrated favorable short‐term outcomes, including reduced postoperative complications, shorter hospital stays, and reduced mortality rates, highlighting its efficacy in improving both long‐ and short‐term outcomes.
Specifically, the robot‐assisted approach's long‐term prognostic superiority was demonstrated by the 5‐year OS rates of 95% for RARR, 89% for LRR, and 81% for ORR (p < 0.001), whereas the 5‐year RFS rates were 93% for RARR, 86% for LRR, and 77% for ORR (p < 0.001). The 5‐year OS rates observed in the ORR group were lower than those documented in the JCOG0212 trial [16], which included patients with stage II and III rectal cancer (5‐year OS: mesorectal exenteration alone, 90.2%; mesorectal exenteration with lateral lymph node dissection, 92.6%). The nature of real‐world data is likely the cause of this discrepancy. Notably, the advantages became more pronounced as the disease progressed, particularly in cStage II and III disease (Figures S1–S3, S5–S7).
To date, no RCTs have reported long‐term outcomes comparing robot‐assisted surgery with other approaches. Additionally, retrospective studies, including meta‐analyses [17], have reported no significant difference regarding this issue. However, recent findings from the REAL trial [7] have highlighted the advantages of robot‐assisted surgery in attaining a more comprehensive TME and decreasing the incidence of CRM positivity compared with the laparoscopic approach. The significant increase in the risk of both local and distant recurrence associated with CRM positivity, which can be as high as fourfold [18, 19], suggests that the enhancement of CRM completeness likely plays a role in improving long‐term prognosis. Accordingly, our study further supports the potential merits of robot‐assisted approaches in enhancing long‐term outcomes. In addition, a recent report from ASCO 2024 presented the results of the REAL trial [20], an RCT comparing robotic and laparoscopic surgery. The study demonstrated a significantly higher 3‐year recurrence‐free survival rate for robotic surgery compared to laparoscopic surgery (87.3% vs. 83.6%, log‐rank p = 0.035). This finding supports the long‐term superiority of robotic surgery over laparoscopic surgery observed in our study.
Data from Japan's NCD covering 2023 indicate that approximately 60% of rectal cancer surgeries employed minimally invasive techniques, including laparoscopic and robot‐assisted approaches, whereas open surgery constituted about 40% of cases. This significant proportion of open surgeries emphasizes the continued relevance of traditional techniques and highlights the importance of incorporating an open approach as a comparative element in this study.
No RCTs have directly compared the long‐term outcomes between robot‐assisted and open approaches in rectal cancer surgery, nor have any studies [21, 22] demonstrated a clear advantage of robot‐assisted surgery. To the best of our knowledge, this study represents the largest cohort that illustrates the advantages of robot‐assisted surgery. The potential advantages of the robot‐assisted approach over the open approach regarding long‐term prognosis can be attributed to precise maneuvers [7] that could help enhance oncological safety; however, a large‐scale cohort study or RCT is warranted to validate this result.
The long‐term outcomes of laparoscopic versus open approaches were evaluated in the large, representative, randomized controlled COLOR II [1] and COREAN [2] trials, which demonstrated comparable results. No other RCTs have indicated an advantage of laparoscopic surgery over open approaches. Similarly, a retrospective cohort study, including meta‐analyses, reported equivalence between the approaches, with no evidence supporting any superiority of the laparoscopic approach [23, 24]. To our knowledge, this study also represents the largest cohort to demonstrate the potential long‐term prognostic benefit of laparoscopic surgery compared to the open approach for rectal cancer treatment.
Additionally, this study corroborated previous reports [7] by demonstrating the short‐term advantages of the robot‐assisted approach regarding postoperative complications, expedited recovery, and improved recovery of urinary and sexual function [25, 26, 27, 28, 29]. The reduced incidence of anastomotic leakage in RARR may be attributed to enhanced visualization and superior dexterity inherent in the robot‐assisted technique [7]. Regarding urinary dysfunction, while earlier RCTs [5, 6, 7], including the REAL trial [7], indicated comparable outcomes between robot‐assisted and laparoscopic approaches, recent retrospective cohort studies [28, 29, 30] have revealed significantly lower rates of urinary dysfunction associated with robot‐assisted surgery, consistent with our findings. The observed outcomes may be attributed to enhanced visualization and precise maneuvers that aid in preserving autonomic nerves. Additionally, the 30‐ and 90‐day mortality rates were significantly lower in the robot‐assisted group. Although the underlying reasons for this remain ambiguous, a reduction in major complications, such as anastomotic leakage, peritonitis, and pneumonia, likely contributed to these findings, consistent with the study from the NCD showing lower 30‐day mortality in the robot‐assisted group [9]. Furthermore, postoperative complications have been associated with unfavorable oncological outcomes and act as independent prognostic factors for disease‐free survival [31]. This suggests that the favorable short‐term outcomes in the RARR group in this study may have led to both reduced short‐term mortality and improved long‐term survival.
A notable strength of this study is the application of the OW methodology, which has demonstrated the ability to yield robust and balanced outcomes similar to those of RCTs [32, 33], thereby mitigating bias and enhancing the reliability of comparative analyses of surgical outcomes. This study emphasizes the significance of real‐world data, encompassing results across a broader spectrum of patients and facilities than those usually represented in RCTs, thereby offering insights relevant to clinical practice. Additionally, this study included a broad cohort from various hospitals, categorized and adjusted, yielding results that mirror real‐world conditions. Overall, this broad cohort study and the utilization of sophisticated statistical methods represent a novel contribution to the field.
However, this study has some limitations; first, the retrospective design introduced a selection bias. Second, our analysis was constrained by the absence of comprehensive pathological data and specific surgical details including conversion rate from laparoscopic or robotic surgery to open surgery that could enhance outcome comparisons. Third, the relatively short median follow‐up duration of 22 months represents a limitation of this study. Moreover, data from hospitals that did not use the MDV database were excluded, potentially constraining the generalizability of our findings to real‐world conditions. Further studies incorporating these clinical variables as confounding factors are essential for a more reliable assessment of the benefits of robot‐assisted rectal cancer surgery.
5. Conclusion
In conclusion, our findings provide the first large‐scale, database‐driven evidence of significant short‐ and long‐term survival benefits of robot‐assisted surgery for rectal cancer in Japan. These results underscore the potential of robot‐assisted surgery as a new standard for rectal cancer treatment. Although further RCTs are essential to validate these outcomes, our study provides critical insights that may shape future surgical approaches.
Author Contributions
Marie Hanaoka: methodology, visualization, writing – original draft. Hiroyasu Kagawa: writing – review and editing. Ataru Igarashi: formal analysis. Hiroshi Yoshihara: formal analysis. Shinichi Yamauchi: writing – review and editing. Masanori Tokunaga: writing – review and editing. Lin Peng‐Lin: data curation. Minkyung Shin: data curation. Yusuke Kinugasa: conceptualization, supervision, writing – review and editing.
Ethics Statement
Since data elements in the MDV database have been de‐identified, informed consent was not mandated. This report adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines, and the study was conducted in accordance with the principles of the Declaration of Helsinki.
Approval of the research protocol by an Institutional Reviewer Board: N/A.
Informed consent: N/A.
Registry and the registration no. of the study/trial: N/A.
Animal studies: N/A.
Conflicts of Interest
Yusuke Kinugasa received speaker honoraria from Intuitive Surgical Inc., Johnson & Johnson KK, and Medtronic, Japan, and Associate Editor of Annals of Gastroenterological Surgery. Masanori Tokunaga received speaker honoraria from Johnson & Johnson KK, Medtronic Japan, Olympus, and Intuitive Surgical Inc. Access to the MDV database was funded by Intuitive Surgical Inc. Ataru Igarashi and Hiroshi Yoshihara received grants from Intuitive Surgical Inc. Lin Peng‐Lin and Minkyung Shin are employees of Intuitive Surgical Inc. The other authors declare no conflicts of interest, funding, or other sources of support related to this submitted article.
Supporting information
Table S1. Stages I–III baseline characteristics before overlap weighting.
Figure S1. Kaplan–Meier curve of overall survival for stage I.
Figure S2. Kaplan–Meier curve of overall survival for stage II.
Figure S3. Kaplan–Meier curve of overall survival for stage III.
Figure S4. Kaplan–Meier curve of overall survival for stages I–III before overlap weighting.
Figure S5. Kaplan–Meier curve of relapse‐free survival for stage I.
Figure S6. Kaplan–Meier curve of relapse‐free survival for stage II.
Figure S7. Kaplan–Meier curve of relapse‐free survival for stage III.
Acknowledgments
The authors have nothing to report.
Funding: The authors received no specific funding for this work.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1. Stages I–III baseline characteristics before overlap weighting.
Figure S1. Kaplan–Meier curve of overall survival for stage I.
Figure S2. Kaplan–Meier curve of overall survival for stage II.
Figure S3. Kaplan–Meier curve of overall survival for stage III.
Figure S4. Kaplan–Meier curve of overall survival for stages I–III before overlap weighting.
Figure S5. Kaplan–Meier curve of relapse‐free survival for stage I.
Figure S6. Kaplan–Meier curve of relapse‐free survival for stage II.
Figure S7. Kaplan–Meier curve of relapse‐free survival for stage III.