Robotic Versus Laparoscopic Abdominoperineal Resection for Locally Advanced Rectal Cancer Following Preoperative Chemoradiotherapy

Abstract

Background/Aim

The usefulness of robotic surgery compared to laparoscopic surgery for rectal cancer has been reported; however, few reports exist on robotic abdominoperineal resection (APR). The aim of this study was to compare the outcomes of robotic and laparoscopic surgery to determine their usefulness in patients with locally advanced rectal cancer who had undergone preoperative chemoradiotherapy (CRT).

Patients and Methods

This retrospective study included 43 patients with locally advanced rectal cancer who underwent preoperative CRT and robotic (22 patients) or laparoscopic APR (21 patients) between December 2012 and September 2022. We examined the short- and long-term outcomes in the robotic and laparoscopic groups.

Results

The median follow-up durations were 36 and 48 months for the robotic and laparoscopic groups, respectively. No significant differences in operative time, intraoperative blood loss, or overall complication rates were observed. However, the incidence of organ/space surgical site infection (SSI) was significantly lower in the robotic surgery group than in the laparoscopic group (9.1% vs. 38.1%, p=0.034) and the 3-year overall survival rate was significantly higher in the robotic surgery group than in the laparoscopic group (95% vs. 67%, p=0.029).

Conclusion

Robotic APR was associated with a significantly lower rate of organ/space SSIs than the laparoscopic approach, indicating the usefulness of the robotic approach.

Minimally invasive surgery, including robotic surgery (RS) and laparoscopic surgery (LS), is the mainstay of rectal cancer treatment. RS offers various technical advantages over LS, including three-dimensional visual observation, magnification, camera stability, and high precision of surgical instruments, including articulated forceps (1,2). In this respect, RS offers flexibility and stability during rectal cancer surgery in patients with a narrow pelvis (3). Several meta-analyses have pointed out the safety and significance of RS in patients with rectal cancer (4-8). In contrast, the ROLLAR trial showed no significant difference in the risk of open conversion between RS and LS for rectal cancer (9); however, subgroup analysis of patients who faced technical difficulties showed a lower open conversion rate in men than in women (9). Furthermore, in the REAL trial, RS showed better short-term outcomes than LS for middle and low rectal cancers ≤10 cm from the anal verge (10). Compared with other rectal cancer surgeries, abdominoperineal resection (APR) requires the deepest pelvic manipulation. Consequently, increased utility of RS is expected; however, few studies have compared robotic APR with other approaches.

APR is associated with a higher incidence of postoperative surgical site infections (SSIs) than other techniques (11-13). Furthermore, although preoperative chemoradiotherapy (CRT) for rectal cancer has become the standard treatment, an increased risk of SSIs has been reported with its application (13-15). Therefore, in this study, we aimed to compare the surgical outcomes of RS and LS to determine their usefulness in patients with locally advanced rectal cancer who underwent APR and preoperative CRT.

Patients and Methods

Patients. This retrospective study included 43 patients with locally advanced rectal cancer who underwent preoperative CRT and robotic or laparoscopic APR at the University of Tokyo Hospital between December 2012 and September 2022. Clinicopathological findings were described according to the American Joint Committee on Cancer/International Union Against Cancer TNM classification (eighth edition) (16). The indications for preoperative CRT were cT3-cT4, any N, and M0. CRT involved long-course radiation with a total dose of 50.4 Gy in 28 fractions and chemotherapy. The standard CRT regimen was a combination of tegafur-uracil (UFT) and leucovorin (LV) for cases registered before October 2018 and UFT, LV, and irinotecan (TEGAFIRI) for cases registered thereafter. The regimen was modified for age and medical history (17). Surgery was performed 6-10 weeks after the completion of CRT. All patients received mechanical bowel preparation (polyethylene glycol or magnesium citrate) and oral antibiotics (metronidazole and kanamycin). All patients underwent conventional APR, and perineal wounds were closed using primary closure.

Regarding the choice of surgical approach, because RS for rectal cancer has been covered by insurance in Japan since April 2018, LS was mainly performed before this date, and RS was the primary procedure thereafter. This study protocol was approved by the Ethics Committee of the University of Tokyo [approval no. 3252-(13)]. Informed consent was obtained in the form of an opt-out option on the website (18).

APR indication criteria. APR was performed in patients with lower advanced rectal cancer in whom securing the anal-side margin was challenging, patients with invasion of the levator ani muscle, and patients at a high risk of postoperative deterioration of anal function. Computed tomography (CT) was used to identify positive lymph node metastasis. Lateral lymph nodes with a diameter ≥8 mm before CRT were considered tumor-positive nodes, and in such cases, selective lateral lymph node dissection was performed after CRT (19).

Outcome variables. The patients were divided into robotic (RG) and laparoscopic (LG) groups. Then, the following clinicopathological factors were evaluated: age, sex, body mass index (BMI), American Society of Anesthesiology Physical Status (ASA-PS), diabetes mellitus, chronic steroid use, Charlson comorbidity index (CCI), tumor distance from the anal verge, clinical T stage, clinical N stage, period operation, operative time, blood loss, lateral lymph node dissection, conversion to open surgery, tumor size, tumor differentiation, pathological T stage, pathological N stage, and resection margin. Additionally, the following short- and long-term outcomes were assessed: postoperative complication rate, hospital stay, drainage volume and duration, and 3-year overall survival (OS), relapse-free survival (RFS), and local recurrence rates (LRRs). In all patients, a pelvic drain was placed in the anterior sacral plane. The drainage volume from returning to the hospital room to midnight on the second postoperative day was counted as the drainage volume on the first postoperative day; it was measured every 24 hours thereafter. OS was defined as the interval between the date of surgery and the date of death or last follow-up. RFS was measured from the date of surgery to the date of any type of recurrence, death, or last follow-up.

Pathologists evaluated the pathological factors and determined whether the resection margins were positive. Postoperative complications were assessed using the Clavien-Dindo classification, and a Clavien-Dindo classification of ≥II was defined as a postoperative complication. Urinary dysfunction was defined as a residual urine volume ≥50 ml after urinary catheter removal (20). Organ/space SSI was defined as a clinical finding of postoperative fever and increased inflammatory response, with intra-abdominal abscess formation on CT or bacteria in the drainage fluid from a perineal wound or from a drain placed in the pelvic cavity.

Statistical analyses. Categorical variables were analyzed using Pearson’s chi-square test or Fisher’s exact test, as appropriate, and continuous variables were analyzed using the Mann-Whitney U-test. The Kaplan-Meier method was used to plot overall and disease-free survival curves, and log-rank tests were performed. Statistical significance was set at p<0.05. All analyses were performed using JMP Pro 16.0 (SAS Institute Inc., Cary, NC, USA).

Results

Overall, 43 patients were included: 22 and 21 in the RG and LG, respectively. The median follow-up period was 36 months (range=14-59 months) for the RG and 48 months (range=8-133 months) for the LG. Table I shows the patient characteristics and operative findings by group. There were no significant between-group differences in age, sex ratio, BMI, ASA-PS, diabetes mellitus, chronic steroid use, CCI, distance from the anal verge, cT stage, or cN stage. However, there were significant differences in the CRT regimen (p<0.01). The surgical approaches differed significantly according to the operation period, with more LS procedures performed until March 2018 and more RS procedures performed thereafter. No difference in operative time was observed between the groups when the cases of lateral dissection were excluded. No significant differences were found in the volume of intraoperative blood loss or the number of lateral dissection cases, and none of the patients were converted to open surgery.

Table I. Patient characteristics and operative findings.

RG: Robotic group; LG: laparoscopic group; BMI: body mass index; ASA-PS: American Society of Anesthesiologists Physical Status; CCI: Charlson comorbidity index; CRT: chemoradiotherapy; RT: radiotherapy; SD: standard deviation. *Excluding lateral lymph node dissection cases.

The pathological outcomes are listed in Table II. No significant difference was found in tumor size and tumor differentiation. However, there were significant differences in the ypT and ypN stages. Three patients in the LG and no patient in the RG had a positive resection margin.

Table II. Pathological outcomes in the robotic and laparoscopic surgery groups.

RG: Robotic group; LG: laparoscopic group; CR: complete response; SD: standard deviation.

Table III lists the postoperative outcomes. Perioperative mortality was not observed in either group. There were no significant differences in the rates of overall complication, ileus, or urinary dysfunction. The incidence of incisional SSIs did not significantly differ between the groups, but that of organ/space SSIs was significantly lower in the RG than in the LG (9.1% vs. 38.1%, p=0.034). No significant difference was found in the postoperative hospital stay duration between the groups.

Table III. Postoperative outcomes in the robotic and laparoscopic surgery groups.

RG: Robotic group; LG: laparoscopic group; CD: Clavien-Dindo; DVT: deep vein thrombosis; SD: standard deviation.

Table IV shows the drainage volumes from the second to the fourth postoperative day and the duration of postoperative drain retention in all patients, excluding those with complications of ureteral injury. The RG had significantly fewer cases with drainage volumes >500 ml on the fourth postoperative day than the LG (0% vs. 20.0%, p=0.043). No significant differences in the duration of postoperative drainage were observed.

Table IV. Postoperative drainage volume and duration in the robotic and laparoscopic surgery groups.

RG: Robotic group; LG: laparoscopic group; POD: postoperative day; SD: standard deviation. *Excluding ureteral injury case.

The 3-year OS was better in the RG than in the LG (95% vs. 67%, p=0.029); however, the 3-year RFS did not significantly differ (73% vs. 62%, p=0.342) (Figure 1A and B). The 3-year LRRs was also not significantly different between the groups (0% vs. 10%, p=0.121).

Figure 1. Comparison of patient survival among groups. A) Overall survival rates in the robotic (solid line) and laparoscopic (dashed line) surgery groups. B) Relapse-free survival rates in the robotic (solid line) and laparoscopic (dashed line) surgery groups.

Discussion

We found that the incidence of organ/space SSIs was lower, and the 3-year OS was higher in the RG than in the LG, although there were no significant differences in diabetes, chronic steroid use, CCI, and bowel preparation method. Organ/space SSIs lead to poor short-term outcomes, including extended hospital stays and high medical costs (13). The incidence of organ/space SSIs after APR for rectal cancer with preoperative CRT reportedly ranges from 10% to 40% (13,14,21). In our study, the incidence was 9.1% in the RG and 38.1% in the LG. According to some reports, APR is an independent risk factor for organ/space SSIs (12,13), with several potential contributing factors. Accelerated bacterial growth due to fluid accumulation in the pelvic dead space (22), cytokine action due to peritoneal injury (23), and delayed wound healing in irradiated fields due to radiation therapy may affect pelvic floor tissue recovery (24).

There are few reports on the usefulness of RS compared with that of other APR approaches (10,25-28). In contrast to the present study, in a previous study, which mainly included patients who were not treated preoperatively and excluded those who underwent lateral lymph node dissection, the incidence rates of postoperative urinary dysfunction and postoperative perineal wound infection were lower in the robotic APR group than in the laparoscopic APR group (27). RS may facilitate the dissection of the levator ani muscle and access to the ischiorectal fossa during abdominopelvic manipulation, thereby reducing dead space in the pelvis and perineal wounds (27).

In addition, it has been reported that the postoperative drainage volume is lower, and the drainage duration is shorter with robotic than with laparoscopic rectal cancer surgery (29). An increase in the drainage volume above a certain threshold may be associated with an increase in the fluid remaining in the dead space in the pelvis, which may be related to the development of organ/space SSIs. Therefore, in this study, we compared the RG and LG based on whether the daily drainage volume exceeded a set criterion. In RS, precise surgical instruments and magnification may facilitate dissection with an optimal dissection surface, resulting in reduced effusion, and this may decrease the incidence of organ/space SSIs.

Furthermore, prolonged operative time is a known risk factor for SSIs (30). In previous studies, RS was associated with a longer operative duration than LS for rectal cancer (3,5,8,31). However, in the present study, we found no significant difference in the operative time between RS and LS. Generally, RS requires additional time outside of the surgical operation (e.g., docking time) (32-34). Moreover, although this study did not examine the time for each manipulation, the operative time for abdominopelvic manipulation might have been longer with RS than with LS because RS allows for a deeper approach to the pelvis with articulated forceps. However, considering that no significant difference in the operative time between RS and LS exists, the perineal manipulation time might be shorter for RS than for LS. Therefore, the reduced operative time for perineal procedures may have contributed to a decreased incidence of organ/space SSIs.

In patients with rectal cancer, organ/space SSIs, including anastomotic leakage, have been reported to be associated with decreased long-term survival (35-37). Although the RG had a better 3-year OS in the present study, this finding is not definitive because of the shorter postoperative observation period in the RG than in the LG. Furthermore, differences in CRT regimens between the RG and LG may have affected the difference between ypT and ypN stages, which may have led to the significant difference in 3-year OS. However, we cannot rule out the possibility of RS resulting in a good long-term prognosis because of the fewer complications associated with organ/space SSIs.

SSI development is an independent risk factor for sepsis (38), and in patients with advanced digestive system cancer, approximately 15% of those with organ/space SSIs developed sepsis (39). Additionally, postoperative sepsis increases the risk of mortality, length of hospital stay, and hospital costs (40). Therefore, the reduced risk of organ/space SSI after APR, as described in this study, is a worthwhile benefit of RS.

Study limitations. First, this was a single-center retrospective study with a small number of patients, thus a multivariate analysis could not be performed. Second, RS for rectal cancer has been covered by insurance in Japan since April 2018. Therefore, a chronological change in the type of procedure performed was observed, with a higher number of LS cases at the beginning of the study period and a subsequent increase in the number of RS cases. Finally, patients in the study also underwent various CRT regimens, which may have influenced the outcomes.

Conclusion

Robotic APR resulted in significantly fewer organ/space SSIs than laparoscopic APR. Therefore, RS may be a useful approach for patients with lower rectal cancer who undergo APR after CRT.

Funding

The Authors did not receive support from any organization for the submitted work.

Conflicts of Interest

The Authors have no competing interests to declare that are relevant to the content of this article.

Authors’ Contributions

All Authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Tatsuki Watanabe, Kazuhito Sasaki, and Soichiro Ishihara. The first draft of the manuscript was written by Tatsuki Watanabe, and all Authors commented on previous versions of the manuscript. All Authors read and approved the final manuscript.

Acknowledgements

The Authors would like to thank Editage (www.editage.jp) for English language editing.