Trial Information

RObotic Versus LAparoscopic Resection for Rectal Cancer An International, Multicentre, Prospective, Randomised, Controlled, Unblinded, Parallel-group Trial of Robotic-assisted Versus Laparoscopic Surgery for Treatment of Rectal Cancer.

The feasibility and safety of laparoscopic surgery has been established for colon cancer.
The case for rectal cancer is less clear, and of the reported multicentre trials only the
MRC CLASICC trial included an evaluation of laparoscopic compared to open rectal cancer
surgery. Although both laparoscopic and open rectal cancer resection were associated with
similar lymph node yields, concern was expressed at the higher rate of circumferential
resection margin (CRM) involvement in the laparoscopic arm (12.4%) as compared to the open
arm (6.3%) for patients undergoing anterior resection. This however did not translate into a
difference in local recurrence at either 3-year or 5-year follow-up. The difference in CRM
involvement was felt to reflect the increased technical difficulties associated with the
laparoscopic technique in the rectal cancer subgroup. This was supported by the higher
conversion rate in the laparoscopic rectal subgroup (34%) as compared to the laparoscopic
colon subgroup (25%). Analysis of CLASICC data revealed higher morbidity and mortality rates
associated with laparoscopic cases converted to open operation (30-day morbidity:
laparoscopic 29%, converted 45%; in-hospital mortality: laparoscopic 1%, converted 9%). Some
of this increased morbidity may be related to more advanced cancers requiring conversion,
but a proportion will inevitably have resulted from the increased operative time, increased
technical difficulty, and the need for a laparotomy wound in converted cases.

The introduction of robotic-assisted laparoscopic surgery using the da Vinci™ system
(Intuitive Surgical, California, USA) promises to eliminate many of the technical
difficulties inherent in laparoscopic surgery. It offers the advantages of intuitive
manipulation of laparoscopic instruments with 7-degrees of freedom of movement, a
3-dimensional field of view, a stable camera platform with zoom magnification, dexterity
enhancement, and an ergonomic operating environment. Experience has shown that the benefits
of the robot are most appreciated when surgical accuracy is required within a confined
space, such as the pelvis.

Laparoscopic rectal cancer surgery is technically demanding requiring accurate pelvic
dissection according to total mesorectal excision (TME) principles with autonomic nerve
preservation. Inadvertent injury to the nerves has been attributed to the higher rate of
male sexual dysfunction following laparoscopic surgery. The practicalities of
robotic-assisted colorectal cancer surgery have been reported in small series but only two
studies have concentrated on rectal cancer, and only one of these performed a randomised
comparison in a small number of patients.

The literature on robotic-assisted colon surgery is limited to 17 small case series. Most of
these comprise mixed benign and malignant disease. The largest by D'Annibale et al reported
53 robotic-assisted colectomies and compared outcomes with 53 laparoscopic resections. It
concluded that robotic-assisted surgery was as safe and effective as laparoscopic, was
particularly useful in pelvic dissection, but that cost-effectiveness needed further
evaluation. Other reports concur that robotic-assisted colorectal surgery is feasible and
safe, with low rates of conversion, morbidity and mortality, but with increased operative
times. There is only one study which has addressed the issue of hospital costs. This
compared 30 robotic-assisted with 27 standard laparoscopic cases and concluded that the
total hospital cost was higher for robotic surgery.

The feasibility of robotics for TME rectal cancer resection was established by Pigazzi et al
in a series of 6 low rectal cancers. A subsequent follow-up study of 39 rectal cancers
treated prospectively by robotic-assisted resection reported a zero rate of conversion with
a mortality of 0% and morbidity of 12.8%. The only randomised trial compared 18 patients
assigned to robotic-assisted resection with 18 patients assigned to standard laparoscopic
resection. No difference was observed in the operative times, the conversion rates (2
laparoscopic, 0 robotic), or the quality of mesorectal resection. The only difference was
the length of hospital stay, which was significantly shorter following robotic-assisted
laparoscopic surgery (robotic-assisted: 6.9 +/-1.3 days; standard laparoscopic: 8.7 +/-1.3
days, p<0.001) and attributed to a reduction in surgical trauma by the authors. In addition
to original reports, there has been one systematic review of robotic-assisted colorectal
surgery, which concluded that "robotic colorectal surgery is a promising field and may
provide a powerful additional tool for optimal management of more challenging pathology,
including rectal cancer".

The current proposal aims to test the hypothesis that robotic-assistance facilitates
laparoscopic rectal cancer surgery. On short-term follow-up this should result in a
reduction in the conversion rate and no worsening of the CRM positivity rate. On longer-term
follow-up, the increased accuracy should improve post-operative bladder and sexual function,
enhance quality of life (QoL), and ensure there is no increase in local disease recurrence.

There is a growing enthusiasm for robotics in many surgical specialities. This enthusiasm is
often not supported by data on clinical or cost-effectiveness derived from rigorous
evaluation by randomised controlled trials. This is the case for robotic-assisted rectal
cancer surgery. Given the expense associated with the robotic systems and the limited
evidence to support clinical and economic benefits, it is essential that a proper
assessment of this new technology is performed in timely manner before its widespread
recommendation or implementation. A randomized trial of robotic-assisted versus standard
laparoscopic rectal cancer surgery is now urgently needed.

Rationale for current study

The safety and efficacy of robotic-assisted laparoscopic surgery have been established for
certain operations, most notably radical prostatectomy. Pelvic surgery, including rectal
cancer surgery, lends itself to robotic-assistance. However, the experience with robotic-
assisted rectal cancer surgery is limited to a few small personal series and one randomised
clinical trial. Although this data suggests it is feasible, it has not established a benefit
over standard laparoscopic surgery in terms of technical, functional or oncological
outcomes. The primary aim of any curative cancer surgery is complete oncological resection
of the tumor with minimal morbidity. It is therefore of utmost importance that prior to the
widespread use of robotics in rectal cancer surgery, it is subjected to rigorous evaluation.
The use of this new technology incurs additional financial burdens on already overstretched
health care resources and it is therefore essential to assess the health economics and cost-
effectiveness in comparison to alternative treatments. As this trial is unlikely to be
repeated, 3-year outcomes and cost effectiveness will be included within this trial.
Specifically, it is aimed to provide information on the ability of the robotic system to
facilitate laparoscopic rectal cancer resection, its impact on oncological outcomes
(short-term and long-term), its effect on functional outcomes and QoL, and its
cost-effectiveness in terms of future healthcare decision-making. Currently, and for the
foreseeable future, there is only one surgical robotic system, the da Vinci™ robot. To avoid
any criticism of commercial bias, it is imperative that an evaluation of this robotic
technology is performed independently of the manufacturer.

Justification for a randomized controlled trial

Since this is a new technology, it is essential that a proper evaluation is performed and
disseminated prior to its widespread implementation. A timely assessment is imperative and
for this reason there is no plan to perform a prior pilot study, which would inevitably
delay evaluation by proper scientific methods. The feasibility of robotic-assisted rectal
cancer surgery has already been established and preliminary data upon which to base sample
size calculations are available. The time is right for a formal randomised controlled trial
to provide a definitive answer to the proposed research question.

Aims and Objectives

The purpose of the trial is to perform a rigorous evaluation of robotic-assisted rectal
cancer surgery by means of a randomised, controlled trial. The chosen comparator is standard
laparoscopic rectal cancer resection, which is essentially the same procedure but without
the use of the robotic device. The two operative interventions will be evaluated for short-
and longer-term outcomes. The key short-term outcomes will include assessment of technical
ease of the operation, as determined by the clinical indicator of low conversion rate to
open operation, and clear pathological resection margins as an indicator of surgical
accuracy and improved oncological outcome. In addition, QoL assessment and analysis of cost-
effectiveness will be performed to aid evidence-based knowledge to inform NHS and other
service providers and decision-makers. These short-term outcomes will be analyzed after the
last randomised patient has had 6 months of follow-up to provide a timely assessment of the
new technology, and made available to the public, clinicians and healthcare providers to
inform health-care decision making. Longer-term outcomes will concentrate on oncological
aspects of the disease and its surgical treatment with analysis of disease-free and overall
survival and local recurrence rates at 3-year follow-up.