Can we Save the rectum by watchful waiting or TransAnal microsurgery following (chemo)Radiotherapy versus Total mesorectal excision for early Rectal Cancer? - STAR-TREC study

More than 3500 patients are annualy diagnosed with rectal cancer in the
Netherlands. The introduction in 2014 of our national bowel screening program
will further increase the number of patients. This increase will lead to a high
number of patients with early stage rectal cancer (T1-3N0M0). Prognosis of
these patients is generally good with more than 80% surviving 5 years after
surgery. A partial or total mesorectal excision will be performed and a
(temporary) colostomy is frequently performed. Moreover, patients often
experience defaecation, urinary and sexual disorders. Recent studies
demonstrated that selected patients could be treated with local excision after
chemoradiation treatment leading to organ preservation. Several studies have
been performed including the CARTS study, and demonstrated organ preservation
in up to 70% of
patients after chemoradiation therapy. This treatment was not always tollerated
well and severe complications have been described. In the UK a similar organ
preservation protocol has been developed using radiotherapy only. This
treatment seemed to have less complications, but results on organ preservation
are to be awaited. Since these studies have been performed recently, it is
unknown if the excellent long term results after standard surgery are
equipoised by these organ preservation techniques. It is therefore important to
study which technique the optimal results are reached: 1) chemoradiation
followed by organpreservation, 2) radiation therapy followed by organ
preservation or 3) standard surgery. The best way studying this is by a
randomised trial. Because these treatment modalities differ significantly we
aim to study in an (international) trial if randomisation is feasible. If this
succeeds a concurrent phase III trial will be started, studying the optimal
treatment for patients with early rectal cancer.

This study has been transitioned to CTIS with ID 2024-516106-31-00 check the CTIS register for the current data.

STAR-TREC is a phase II feasibility study that will evaluate whether it is
possible to accelerate patient recruitment from 2 per month, as attained in the
previous TREC study, to 6 per month over a two-year period. This would
demonstrate deliverability of a phase III study incorporating 400 patients to
evaluate differences in pelvic relapse rates between organ saving and standard
surgery (see sample size calculation). Randomising 70-80 patients per year in
phase III would achieve this target in 4 years (including patients treated in
phase II).

Randomised fase II feasibility study

Three arm (1:1:1) randomisation using the following arms:
1. Standard TME surgery (control)
2. Organ saving using:
a. long course concurrent chemoradiation
b. short course radiotherapy
For organ-preserving strategies clinical response to radiotherapy determines
the next treatment step. Radiotherapy response is evaluated using endoscopy and
mriTRG. The first assessment at 11-13 weeks (from radiotherapy start) using MRI
and endoscopy will identify a minority of non-responders who should convert to
TME surgery. Patients demonstrating a satisfactory radiotherapy response at
11-13 weeks will be reassessed by endoscopy at 16-20 weeks. Re-evaluation
determines if the STAR-TREC criteria for complete clinical response (cCR) are
met. Patients who achieve cCR may progress directly to active surveillance.
Those who do not fulfil the criteria for cCR will progress to excision biopsy
with TME.

What are the benefits of standard treatment?
Standard treatment with radical surgery to remove the rectum has been used
successfully to treat both small and large rectal cancers for many years and we
know that it usually cures rectal cancer. We think that only 3 - 6 in out of
every 100 patients with small rectal cancers treated by radical surgery will
have their cancer come back in the pelvis. A larger number, perhaps 10-15 in
every 100 will have the cancer return in the liver or lungs. This means that
around 9585% of patients treated in this way are likely to be cured of cancer.

What are the risks of standard treatment?
Like any major operation, radical surgery may result in serious side effects.
The risk of death due to radical surgery to remove the rectum is roughly 4 in
every 100 operations. The level of risk depends upon age and overall physical
fitness. For example, in patients aged 75 - 85 years the risk of death can be
as high as 15 out of every 100 cases.
One of the most serious complications after standard radical surgery is a leak
of faeces from the bowel where it has been joined to the anus. If this problem
arises, then more surgery is usually required to control the situation. This
often involves rerouting the bowel through the tummy wall into a bag (stoma).
Although we always do our best to avoid leaks they remain quite common. Leaks
complicate 5 to 15 out of every 100 operations. Your surgeon will be able to
tell you about complication rates in your own local hospital. As mentioned
earlier your surgeon can reduce this risk by creating a temporary, diverting
stoma bag for you at they time of your rectal cancer operation.