Current status of robotic surgery for rectal cancer: A bird's eye view.

Minimally invasive surgery for rectal cancer is now widely performed via the laparoscopic approach and has been validated in randomized controlled trials to be oncologically safe with better perioperative outcomes than open surgery including shorter length of stay, earlier return of bowel function, better cosmesis, and less analgesic requirement. Laparoscopic surgery, however, has inherent limitations due to two-dimensional vision, restricted instrument motion and a very long learning curve. Robotic surgery with its superb three-dimensional magnified optics, stable retraction platform and 7 degrees of freedom of instrument movement offers significant benefits during Total Mesorectal Excision (TME) including ease of operation, markedly lower conversion rates and better quality of the specimen in addition to shorter (steeper) learning curves. This review summarizes the current evidence for the adoption of robotic TME for rectal cancer with supporting data from the literature and from the authors' own experience. All relevant articles from PubMed using the search terms listed below and published between 2000 and 2014 including randomized trials, meta-analyses, prospective studies, and retrospective reviews with substantial numbers were included.

INTRODUCTION

Robotic total mesorectal excision (RTME) is a natural step forward in the evolution of the minimally invasive approach to rectal cancer extirpation. The evidence for the equivalence of laparoscopic total mesorectal excision (LTME) and the open approach for rectal cancer surgery essentially is based on the results of one multicenter randomized controlled trial, the MRC CLASICC trial which compared the open versus laparoscopic approach in colorectal cancers.[12] Subgroup analysis of this study revealed oncologic outcomes of LTME to be equal to that of open TME, which continues to remain the gold standard. However, the study did reveal a high conversion rate to open surgery of 34% and an increased radial margin positivity rate of 12% in the laparoscopic arm compared to 4% in the open arm though this did not translate into an increase in recurrence rate.

LTME is a difficult operation to master and has been associated with learning curves as high as 50 cases to achieve consistent results.[3] It is difficult to quantify the learning curve accurately due to the subjective nature of many studies as to what constitutes an acceptable outcome. Conversion rates decrease and stabilize by 150 cases and complication rates bottomed out at 200 cases in Kayano's study; if a low conversion rate is taken as the parameter to judge the learning curve, the laparoscopic curve could therefore be as high as 150 cases.[3] Total mesorectal excision (TME) as advocated by Heald is a technically demanding and unforgiving operation with a very low margin for error.[4] Positive margins usually herald a poor outcome and hence the need for an approach which retains the benefits of the minimally invasive approach while being easier to perform, reproduce and teach. Robotic surgery addresses many of the limitations of conventional laparoscopic surgery and provides magnified three-dimensional optics, surgeon controlled camera vision, three working arms allowing very stable retraction and unparalleled ergonomics due to 7 degrees of instrument motion. The result is an operation that satisfies all measures of oncologic adequacy while being easier to teach and associated with less fatigue for the surgeon. The evidence from ongoing randomized trials is awaited to provide concrete evidence for this approach.

Methods

All relevant articles from PubMed using the search terms, Rectal Cancer, Total Mesorectal excision, robotic surgery, laparoscopic surgery and open surgery published between 2000 and 2014 including randomized trials, meta-analyses, prospective studies and retrospective reviews with substantial numbers were retrieved and used to produce this review in addition to unpublished work from the authors’ institution.

Laparoscopic TME for Rectal Cancer: Current Status

To fully comprehend the role of robotic TME, the current evidence for laparoscopic TME must first be analysed. As alluded to earlier, the MRC CLASICC trial established the safety of this approach. There were however concerns raised due to a higher conversion rate and a trend towards a higher Circumferential Margin Positivity [CRM] rate in the laparoscopic arm [Table 1].[1] The CRM positivity however did not reach statistical significance and indeed did not worsen survival on long-term analysis. Conversion to open surgery however was not a benign event and was associated with a worse long term oncological outcome irrespective of surgeon experience indicating that conversion is a worse indicator of long term outcomes than CRM positivity in this study.[2] The COLOR II trial was specifically designed to look at outcomes of laparoscopic versus open surgery for rectal cancer and showed better short-term perioperative outcomes including less blood loss, earlier return of bowel function and shorter length of stay but with increased operative time.[5] Pathologic outcomes were similar but there was a 17% conversion rate and data on locoregional recurrence are awaited.

Table 1

MRC CLASICC trial data[12]

A more recent study, the COREAN (Comparison of Open versus laparoscopic surgery for mid and low rectal cancers After Neoadjuvant chemoradiotherapy) study from Korea compared open versus laparoscopic TME after neoadjuvant chemoradiation and showed equivalent outcomes [Table 2].[6] The conversion rates and CRM positivity were very low as compared to the CLASICC study. However it is important to note that the surgeons in the COREAN study were highly experienced with a median case load of 75 cases before the trial and that the trial was performed by only three highly trained surgeons as against a mean case load of only 20 colorectal operations in the MRC study and multiple participating centers. The implication is that the results of the MRC study are more applicable to the real world scenario and reflect what happens with surgeons with limited caseloads performing TME.

Table 2

Comparison of MRC CLASICC trial and Corean trial data

Laparoscopic TME is also a difficult operation to master and teach. The average caseload to achieve mastery varies from 50-150 cases and may be difficult to achieve outside large tertiary referral centers.[3] Robotic surgery on the other hand has markedly shorter learning curves either non-existent or of the order of about 20 cases to achieve proficiency.[78] In the context of fellowship training this essentially implies the possibility of completing the learning curve before exit from the fellowship, which is highly desirable.

Literature Review of Robotic TME

Multiple large prospective studies and retrospective reviews have firmly established the safety and feasibility of robotic surgery for rectal cancer. A variety of approaches both totally robotic and hybrid procedures performing part of the operation laparoscopically have been used. In all patients however the total mesorectal excision was performed robotically which is the critical area we appraise in this paper.[91011121314]

All the series’ are characterized by low conversion rates (0-4.9%), acceptable lymph node yield, low CRM and distal margin positivity rates. Local and systemic recurrences were also similar to the data from the MRC study. Long-term outcomes are now accruing and 3 year disease free survivals between 73.7% and 79.2% and overall survivals between 92% and 97% are reported [Tables 3 and 4].[91011121314]

Table 3

Perioperative outcomes of robotic TME for rectal cancer

Table 4

Short-term and long-term oncologic outcomes of robotic TME for rectal cancer

Comparison of Open Versus Robotic TME

Multiple large prospective series’ have proven the safety and feasibility of RTME. Our own data as that of others show perioperative outcomes comparable to open surgery, with the caveat of decreased blood loss and increased operative time in the initial phases of the robotic approach. Short term and long term oncological outcomes are equivalent especially with reference to mesorectal grade, CRM positivity, lymph node yield and disease free and overall survival [Table 5].[1516] A recent comparative study with long-term outcomes data however found a significant reduction in local recurrence rate and a higher, though not statistically significant long-term cancer specific survival in the RTME group.[17]

Table 5

Comparison of open versus robotic TME[15]

Comparison of Laparoscopic versus Robotic TME

The only published randomized data from a pilot study comparing laparoscopic and robotic TME with 18 patients in each arm, found no difference in operative time, conversion rates or pathologic quality of the specimen.[18] A statistically significant shorter hospital stay was however found favouring the robotic arm [Standard laparoscopic arm, 8.7±1.3 days; robotic assisted arm 6.9 ±1.3 days; P<0.001]. There are a plethora of publications involving systematic reviews and case matched series, which show equivalent clinical and oncologic outcomes. The meta-analysis by Trastulli which focused on short term outcomes revealed a markedly lower conversion rate compared to open surgery in the Robotic arm [2% vs 7.5%, P=0.0007] with operative time, lymph node harvest, CRM positivity rate and anastomotic leak rates being similar [Table 6].[19] Another large meta-analysis by Xiong et al., showed statistically significant lower CRM positivity and conversion rates favouring the robotic approach with operative times and local recurrence rates remaining similar [Table 6].[20]

Table 6 a

Meta-analysis of robotic versus laparoscopic TME for rectal cancer, short-term outcomes[19]

Genitourinary Function After Robotic TME

An important aspect of Robotic TME is better visualization of the autonomic plexii in the pelvis, which translates into better preservation of genitourinary function as assessed by erectile dysfunction and voiding function.

The MRC CLASICC trial showed a trend towards increased sexual dysfunction in the laparoscopic arm in comparison to the open group.[1] Comparison of robotic and laparoscopic groups in the study by Kim et al.[21] showed decreased sexual desire and voiding function in both groups 1 month after surgery with more rapid and complete recovery of both parameters in the robotic group; possibly due to a more delicate operation with the robotic apparatus. Luca et al., found better preservation of voiding and sexual function with robotic TME in comparison with open and laparoscopic TME with complete recovery of both functions 1 year after surgery.[22]

For surgeons starting the learning process of minimally invasive proctectomy for rectal cancer, it appears reasonable to invest more time in learning the robotic approach as against the laparoscopic approach to attain the goal of curative radical rectal resection. However as we describe in detail below proficiency in laparoscopic techniques is still mandatory regardless of whether a purely robotic approach or a hybrid laparoscopic-robotic approach is used, to maximize the efficiency of the operation.

Technical Aspects of RTME

The three essential components of the operation namely:

Inferior mesenteric pedicle ligation and left colon mobilization.

Splenic flexure mobilization.

Total Mesorectal excision and anastomosis.

Can be performed using a purely robotic approach with multiple docking, moving the robot around the patient from the left shoulder to the left hip and then to the position between the legs or as a hybrid laparoscopic robotic approach which we propagate as it is more efficient and utilizes the robot for the more difficult part of the operation which is the pelvic component.

The completely robotic approach has also been described with a single position of the robot at the left hip, with use of two sets of port positions with two dockings, one set for steps 1 and 2 and one for step 3.[23] A purely robotic approach is more time consuming and does not provide any benefit over the hybrid approach.

Robotic TME in the Obese Patient

Obesity BMI≥ 30 Kg/m2 is a rapidly increasing epidemic in the western world with an estimated 35.7% of the American population being obese.[24] The age-adjusted prevalence of obesity was 35.5% (95% CI, 31.9-39.2%) among adult men and 35.8% (95% CI, 34.0-37.7%) among adult women in the 2009-2010 National Health and Nutrition Examination Survey (NHANES).[24]

Obesity is associated with several anatomic issues specific to colorectal surgery including:

Problems with exposure.

Fragile peritoneum.

Bulky and heavy omentum.

Heavy mesorectum with fragile mesorectal fascia.

Abundant presacral tissue.

A more vertical course of the levator muscles.

All of these make TME in the obese pelvis especially in the male patient with a low rectal cancer after preoperative radiation a difficult proposition. Obesity is a known risk factor for worse perioperative outcomes and morbidity including anastomotic leaks in open and laparoscopic rectal cancer surgery.[25] Recurrence rates and sphincter preservation rates are also inversely correlated with BMI in some studies.[26] Increasing BMI has also been identified as a risk factor for conversion from laparoscopy to open approach in rectal cancer surgery[27282930] [Table 7] and the conversion from laparoscopy to the open approach leads to longer operating times, increasing cost, higher perioperative complications and a longer hospital stay, besides the possibility of worse long term survival.[2] It is in this subgroup that robotic surgery shows its greatest promise and our experience shows that the robot levels the playing field and enables equivalent outcomes irrespective of BMI and regardless of whether the patient is male or female [Table 8].

Table 7

Relation between BMI and conversion rates

Table 8

Comparison of outcomes of RTME obese versus nonobese patients

Robotic Cylindrical APR

The abdominoperineal resection is the only oncologically sound operation for patients with low rectal cancers with sphincter complex involvement or encroachment into the anal canal. The absence of mesorectum in the terminal portions of the rectum however make it difficult to achieve a wide cuff of soft tissue at this location and it is known that CRM positivity and iatrogenic perforation rates tend to be higher with a corresponding worse clinical outcome in this subgroup of patients when a standard resection is performed.[31] The technique of extralevator APR [eLAPR] is now the preferred approach to these tumors, but is difficult to perform using the open or laparoscopic technique because the wide transection of the levators is performed via the perineum and is essentially blind with respect to the planes already developed abdominally. Our technique of robotic cylindrical levator transection allows a controlled wide levator transection from above and completes the essential oncologic steps under vision.[32] Only the skin and ischioanal fat need to be transected perineally. This allows for a better quality of specimen and avoids CRM positivity and perforation and produces a cylindrical specimen.

Cost Issues with RTME

Robotic surgery is more expensive than laparoscopic or open surgery due to:

The fixed costs of purchase and maintenance which has to be amortized.

Consumables (drapes and instruments with limited lifespan).

Increased operative time.

Cost needs to be weighed against parameters like shorter length of stay and oncologic outcomes. Without robust randomized data however cost continues to remain an issue especially in systems where robotic surgery is paid on par with laparoscopic surgery. The additional cost is borne either by the hospital or the patient and does not make for a good economic model.

The da Vinci surgical system [Intuitive surgical Inc, Sunnyvale CA, USA] is the only surgical robot currently available for use. The lack of competition may be a factor keeping costs static and high today.

One modifiable factor, which can decrease this cost, is an increase in the annual caseload of robotic procedures, which reduces the amortized costs of the robot and the annual maintenance per procedure.[33] This can be achieved in 2 ways: By increasing the number of surgeons who are trained in the use of the robotic system and secondly by having a well trained perioperative nursing team. Having a consistent team of surgeons, perioperative nurses and scrub personnel also reduces setup times markedly as shown by Hanly et al., who demonstrated reduced setup times by 29.2% and 56.1% on the second and third robotic setups respectively.[34]

Operative Time and RTME

Operative time is a critical issue when studying outcomes of robotic rectal surgery because it decreases the number of procedures that can be performed and drives up the operating room costs. Operative times are related to some extent to the learning curves and with increasing surgeon and institution volumes the gulf between robotic and laparoscopic colorectal procedure times is steadily decreasing. D’Annibale et al., published their experience showing no difference in total operating times between laparoscopic and robotic groups, though patient preparation and operating room times were prolonged in the robotic group.[35] They found that the time added in robotic docking was balanced by faster, more accurate dissection due to use of the robot.

Standardization of the procedure, consistency of surgical-nursing teams, and incremental increase in surgeon experience and volumes all have the potential to decrease operative time.

Ongoing Trials of RTME

The ROLARR Trial [Robotic assisted versus laparoscopic assisted resection for rectal cancer] is an ongoing pan world multicenter prospective, controlled, unblended, parallel group superiority trial of robotic-assisted versus standard laparoscopic surgery for the curative treatment of rectal cancer, which aims to randomize 200 patients in each arm.[36] The primary outcome measure is rate of conversion to open surgery. The secondary outcome measures are pathological CRM positivity and 3-year local recurrence rates. This trial should provide conclusive evidence regarding the role of robotic assisted resection for rectal cancer.

CONCLUSION

In conclusion, Robotic total mesorectal excision has several benefits in the treatment of rectal cancer and should be part of the armamentarium of the experienced surgeon dealing with this disease. The intraoperative ergonomics are superb, facilitated by excellent vision and manoeuvrability in the narrow confined pelvic space and this translates into a more reproducible operation for the master surgeon and the trainee. While cost remains an issue, as with laparoscopy costs are expected to decrease with time especially in a multispecialty setup where multiple departments are using the robot. Operative time while still higher than the laparoscopic approach, rapidly decreases with experience and is likely to be less of an issue once advanced platforms that permit multiquadrant surgery without the need for redocking are more widely available. Short term and long-term oncological outcomes satisfy all measures of oncologic adequacy and the results of the ROLARR trial are awaited to clearly give a direction to this technique.

Table 6b

Meta-analysis of robotic versus laparoscopic TME, short term and long-term outcomes [20]