Landmark trials in rectal cancer

1. LANDMARK TRIALS IN
RECTAL CANCER-
SURGERY
Department of Surgical Oncology
Centre for Oncology
GRH,Royapettah
PROF.S.SUBBIAH et al.

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INTRODUCTION
 Surgery is the cornerstone of curative therapy for rectal adenocarcinoma .
 Depending upon the clinical stage, size, and location of the primary tumor, a
rectal cancer can be treated with either local or radical excision.
 A local excision is usually performed transanally.
 A radical excision is performed transabdominally with either a sphincter-
sparing procedure such as low anterior resection or an abdominoperineal
resection

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EVOLUTION
 The recurrence rate of rectal cancer varied between 4 to 50%
 The main cause remained unproven in patients with curative resection.
 The degree of lateral spread by histopathological study vs short-term recurrence
rates in curative resections.
 Involvement of the lateral resection margin by carcinoma and the subsequent local
recurrence - 85%( 14 of 52 (27%) patients and 12 had local pelvic recurrence.

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(1) Recognition of mobility between tissues of different embryological origins
(2) Sharp dissection under direct vision in a good light
(3) Gentle opening of the plane by continuous traction with no actual tearing.
 DEFINE AN OPTIMAL DISSECTION PLANE around the cancer which must clear all forms of
extension and circumscribe predictably uninvolved tissues. ‘
 “the whole rectum and mesorectum are one distinct lymphovascular entity”

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 Local recurrence rates were 5%
 Follow up at 9 years significant improval in overall survival especially in
DUKES C was noted.

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 Circumferential resection margin (CRM) is the closest distance between the radial
resection margin and the tumor tissue by either direct tumor spread, areas of neural or
vascular invasion, or the nearest involved lymph node

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Total Mesorectal Excision

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Total Mesorectal Excision
 The intramural spread of cancer downward is very rare, but extramural
spread appears both in distal and anterior directions.
 Anatomically three space scan be distinguished around the rectum.
 The inner space is surrounded by a visceral fascia on the posterior side, and
Denonvillier’s fascia on the front of the rectum.
 Laterally they unite and are related to nerve plexus
 Intermediate space is limited by the parietal pelvis fascia on the posterior
side and the internal iliac arteries and their branches on both lateral sides,
and on the front.

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 The outer space is localized outside the internal iliac arteries and their
branches
 Total mesorectum excision means removing the internal space with the
visceral fasciation and Denon-Villiers fascia whilst preserving the pelvis nerve
plexus on both lateral sides.

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Total Mesorectal Excision

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British Journal of Surgery in 1995
Journal of American College of Surgeons 1997

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“A TME should be performed to a level of 5 cm below the distal margin of the
primary tumour in the upper rectum or to the pelvic floor (complete TME) for
in the lower or middle rectum.”
– A minimum negative proximal margin of 5 cm is required
-The minimum acceptable negative distal margin is 2 cm for cancers located above the
distal meso-rectal margin. For cancers located at or below the distal meso-rectal margin, a
1 cm negative distal margin is acceptable.

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42 and 147 patients were ligated at the origin of the IMA (high tie) and just below the
origin of the LCA combined with LND around the origin of the IMA (low tie with LND),
respectively.
No significant differences were observed in the complication rate and OS and RFS rates
between high tie and low tie groups.
The OS and RFS rates in the lymph node-positive cases in the two groups

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Transanal excision/ Transanal endoscopic surgery (TES)
 Radical surgery for stage I and II rectal cancer can expect excellent long-
term results which approach 5-year local recurrence rates of 4.5 % and 90%
5-year disease free survival (DFS) rates
 Morbidity is high (30-68%) with a mortality that approaches 7% in certain
pooled studies
Moderately to well-differentiated tumor T1N0
●Absence of lymphovascular invasion
●Absence of perineural invasion
Journal of Gastro intestinal Oncology 2015

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• When comparing the results of LE to radical surgery, local recurrence rates tend to be
higher for both T1 (8.2-23%) and T2 adenocarcinomas (13-30%) undergoing LE when
compared to radical surgery for T1-T2 disease (3-7.2%).
• However, in the studies evaluating LE there has not been a significant difference in DFS
when compared to radical surgery.
• Local Excision for T1-T2 disease the DFS at 5 years following LE was 55-93%.
• This was comparable to patients undergoing radical surgery whose DFS at 5 years was 77-
97%

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Postoperative complications of TAE are rectal bleeding which is the most
common (6%), rectal stenosis (5%), urinary retention (1.5%), fecal incontinence
(0.5%), and rectovaginal fistula (<1%)
The most common complications TEM reported are hemorrhage (27%), urinary
tract infection (21%), and suture line dehiscence (14%) and 4.3% conversion to
radical procedures
Complications following the TAMIS procedure are infrequent with an overall rate
of 7.4% with conversion rate of 4%

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MSKCC 2015 , 79 patients were included. Toxicity 39%
Annal of Surgical Oncology 2007
Diseases of colon and Rectum 2008

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NON OPERATIVE MANAGEMENT IN DISTAL RECTAL CANCER
• Two-hundred sixty-five patients with distal rectal adenocarcinoma considered
resectable were treated by neoadjuvant chemoradiation (CRT) with 5-FU,
Leucovorin and 50.4 Gy. ( Sao Paulo , Brazil 2004)
• In 71 patients (26.8%) complete clinical response was observed following CRT
(Observation group).
• There were 3 systemic recurrences in each group and 2 endorectal recurrences in
Observation Group.( Follow up 57 months)

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. Five-year overall and disease-free survival rates were 88% and 83%, respectively,
in Resection Group and 100% and 92% in Observation Group
NCCN 2021:
“ In select patients achieving complete clinical response as demonstrated by
clinical examination, imaging and endoscopy following neoadjuvant chemo
radiotherapy may be advised observation with strict serial monitoring after
multidisciplinary team discussion in select high volume centres”

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Laparoscopic Vs Open rectal surgeries
 Two previous large RCT and several meta-analyses showed similar pathological
and oncological outcomes between laparoscopic and open approaches for
rectal cancer
 The laparoscopic approach was regarded as a standardized alternative to the
open approach

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“ Laparoscopic assisted resection of rectal cancer was not
found to be significantly different to OPEN resection of
rectal cancer based on the outcomes of DFS and
recurrence”.

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• Robotic assistance has the potential to overcome limitations of laparoscopic surgery
• Meta analysis - failed to show superiority of robotic assisted over conventional
laparoscopic surgery
• Safety, efficacy , short and long term outcomes were analysed ( 2017)
• 40 surgeons from 29 sites across 10 countries (United Kingdom, Italy, Denmark, United
States, Finland, South Korea, Germany, France, Australia, and Singapore)

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 471 patients with rectal adenocarcinoma suitable for curative resection conducted
at 29 institutions across 10 countries between January 7, 2011, to September 30,
2014, follow-up was conducted at 30 days and 6 months.
 Robotic-assisted (n = 237) or conventional (n = 234) laparoscopic rectal cancer
resection.
 The primary outcome - conversion to open laparotomy.
 Secondary end points included intraoperative and postoperative complications,
circumferential resection margin positivity (CRM+) and other pathological outcomes,
quality of life, bladder and sexual dysfunction and oncological outcomes

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 Conversion to open surgery occurred in 47 of 466 patients (10.1%) overall
 28 of 230 patients (12.2%) in the conventional laparoscopic and 19 of 236
patients (8.1%) in the robotic assisted laparoscopic group
 Was not statistically significant difference noted

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 These findings suggest that robotic-assisted laparoscopic surgery, when
performed by surgeons with varying experience with robotic surgery, does not
confer an advantage in rectal cancer resection.

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 701 patients were randomized to the ME with LLND (n = 351) and ME alone (n =
350) groups. ( 2017 Fujita et al )
 The 5-year relapse-free survival in the ME with LLND and ME alone groups were
73.4% and 73.3%, respectively
 The 5-year overall survival, and 5-year local-recurrence-free survival in the ME with
LLND and ME alone groups were 92.6% and 90.2%, and 87.7% and 82.4%,
respectively.
 The numbers of patients with local recurrence were 26 (7.4%) and 44 (12.6%) in
the ME with LLND and ME alone groups, respectively

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 Ishihara et al reported that the incidence of LLN metastasis was estimated to
be 8.1% (18/222) even after preoperative CRT.
 Kusters et al reported that the lateral local recurrence rate was significantly
higher in patients with LLN larger than 10 mm in pre treatment imaging.
 The safety and feasibility of laparoscopic versus open LLND showed similar
oncological outcomes between the groups.
 Establishment of criteria to accurately predict LLN status as well as
standardization of the technique of LLND is necessary in the future

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228 patients with low rectal cancer <5cm from anal verge between 1996 to 2004 were
enrolled
86% successful
24% morbidity and 0.4% mortality
Five year overall survival 91.9% and 83.4% DFS
Curability with intersphincteric resection was verified histologically, and acceptable
oncologic and functional outcomes were obtained by using these procedures in
patients with very low rectal cancer.

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TAKE HOME POINTS
 T1N0 – select patients with low risk features – Local Excision
 Other T1,T2 – Radical Abdominal surgery with TME
 T3, T4 N+ - Neoadjuvant chemo RT  Surgery
 Operable Early rectal cancer – NACRT- not useful due to significant toxicity
 LAP > OPEN Radical Rectal Surgery
 Evolving – Robotic Surgery , Lateral Node dissections