Almost
80%
of
patients
with
early-stage
rectal
cancer
remained
surgery-free
for
a
year
or
longer
after
treatment
with
chemoradiation
therapy
(CRT),
a
large
randomized
study
showed.

Among
341
patients
who
chose
not
to
have
upfront
surgery
(total
mesorectal
excision,
TME),
78.5%
of
those
randomized
to
CRT
remained
TME-free
at
12
months,
as
did
60%
of
the
patients
randomized
to
a
short
course
of
radiotherapy
(RT)
alone.
Both
organ-preserving
strategies
were
associated
with
low
rates
of
adverse
events
in
the
STAR-TREC
study.

Though
still
early,
the
results
support
a
response-adapted
organ-preservation
strategy,
suggesting
better
12-month
outcomes
with
CRT,
reported
researchers
led
by
Simon
Bach,
MD,
of
University
College
London,
in


Lancet
Oncology.

Organ-preservation
strategies
for
rectal
cancer
are
not
new,
but
most
studies
to
date
focused
on
“opportunistic”
organ
preservation,
involving
patients
who
received
CRT
as
part
of
routine
care
for
locally
advanced
disease
to
reduce
the
risk
of
pelvic
recurrence
after
radical
surgery,
Bach
told

MedPage
Today.
In
general,
the
studies
showed
that
as
many
as
20%
of
patients
had
complete
resolution
of
tumors
with
CRT
and
might
have
avoided
surgery.

“What
is
new
in
STAR-TREC
is
that
we
tested
organ
preservation
as
a
deliberate
strategy
in
patients
with
early-
and
intermediate-stage
rectal
cancer
who
would
normally
proceed
straight
to
radical
surgery,”
said
Bach.
“In
this
group,
chemoradiotherapy
is
not
required
to
achieve
high
levels
of
local
control,
so
it
isn’t
part
of
standard
treatment.
We
found
that
four
out
of
five
patients
who
received
chemoradiotherapy
still
retained
their
rectum
at
1
year.”

“We
also
showed
that
the
organ-preservation
approach
was
associated
with
less
serious
toxicity
than
radical
surgery,
and
with
improvements
in
quality
of
life
over
the
first
12
months,”
he
added.
“This
may
seem
intuitive,
but
very
few
studies
have
actually
documented
quality
of
life,
which
makes
the
finding
important.”

“The
key
unresolved
issue
is
the
need
for
longer
follow-up
to
be
confident
the
cancers
do
not
return,”
said
Bach.
“We
would
expect
the
majority
of
recurrences
to
occur
within
the
first
2
years,
and
our
next
readout
from
the
trial
will
be
at
36
months.”

Results
of

STAR-TREC
and
other
studies,
including
the

multicenter
randomized
TESAR
trial
published
earlier
this
year,
inform
decision-making
in
clinical
practice
and
expand
the
use
of
organ-preservation
strategies.

In
TESAR,
limited
surgery
followed
by
CRT
failed
to
show
noninferiority
to
upfront
TME
for
locoregional
recurrence
at
3
years
(5%
vs
1.1%
in
200
randomized
patients).

However,
four
of
the
five
total
recurrences
in
both
groups
were
successfully
salvaged,
resulting
in
a
3-year
unsalvageable
rate
of
1.1%
with
adjuvant
CRT
and
0%
with
TME.
Moreover,
local
excision
plus
CRT
substantially
reduced
treatment-related
morbidity
and
stoma
rates.

“These
findings
challenge
[completion]
TME
as
the
standard
of
care
for
patients
with
locally
excised
high-risk
pT1
and
low-risk
pT2
rectal
cancer,”
the
TESAR
authors
concluded.

Together,
the
two
studies
provide
much-needed
high-level
clinical
evidence
supporting
organ
preservation
in
early-stage
rectal
cancer,
according
to
authors
of
an

invited
commentary.

“The
new
findings
of
the
STAR-TREC
and
TESAR
trials
further
consolidate
the
shift
in
clinical
thinking,
in
which
selective
organ
preservation
also
in
patients
with
early
and
intermediate
tumors
can
safely
be
integrated
into
routine
decision-making
alongside
radical
surgery,”
concluded
Ralf-Dieter
Hofheinz,
MD,
of
the
University
of
Heidelberg
Mannheim
in
Germany,
and
Emmanouil
Fokas,
MD,
of
University
Hospital
Cologne
in
Germany.

The
influence
of
organ-preservation
studies
is
reflected
in
a

clinical
guideline
recently
adopted
by
the
European
Society
for
Medical
Oncology,
which
“explicitly
suggests
distinct
treatment
algorithms
for
rectal
cancer,
based
on
the
intention
of
treatment,”
Hofheinz
and
Fokas
added.
“One
algorithm
centered
on
planned
radical
surgery
and
one
dedicated
to
organ
preservation.”

Follow-up
continues
in
STAR-TREC,
a
multicenter,
open-label
phase
II/III
trial
conducted
in
five
countries.
Eligible
patients
had
early-stage
rectal
adenocarcinoma
(MRI-defined
T1-3bN0).
Phase
II
objectives
related
to
feasibility,
as
patients
were
randomly
assigned
to
CRT,
short-course
RT,
or
TME.
During
phase
III,
patients
could
choose
TME
or
organ
preservation,
and
those
who
opted
for
organ
preservation
were
randomized
to
CRT
or
RT.

The
overall
objective
was
to
determine
whether
CRT
or
RT
could
increase
organ
preservation
and
reduce
surgery,
toxicity,
and
quality-of-life
harm
without
compromising
oncologic
outcomes.

The
primary
endpoint
of
phase
III
was
organ
preservation
at
30
months,
defined
as
no
TME,
stoma,
or
local
recurrence.
After
an
interim
analysis
of
the
phase
II
data
showed
a
TME-free
survival
benefit
with
CRT
(12
vs
7.6
months
for
RT),
the
endpoint
was
changed
to
a
modified
intention
to
treat
(ITT)
analysis
of
12-month
outcome
data.

Investigators
at
37
sites
enrolled
a
total
of
503
patients
with
phase
II
and
III
combined.
The
modified
ITT
analysis
included
426
patients,
120
from
phase
II
and
306
from
phase
III.
Data
analysis
included
409
evaluable
patients:
163
randomized
to
CRT,
168
to
RT,
and
78
to
primary
TME.

Analysis
of
TME-free
survival
at
12
months
continued
to
show
an
advantage
for
CRT
over
RT
(78.5%
vs
60.6%)
among
those
who
opted
for
organ
preservation.
The
difference
translated
into
a
hazard
ratio
of
1.90
(95%
CI
1.29-2.81).

The
most
common
serious
adverse
events
were
gastrointestinal
disorders
(2%
with
CRT,
4%
with
RT,
8%
with
TME)
and
procedural
complications
(2%,
3%,
and
6%).
One
patient
who
underwent
primary
TME
died
after
an
anastomotic
leak.

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