given before or after surgery. However, a recent
update of EORTC 22921 suggests that there is no
significant disease-free or overall survival benefit of
adjuvant chemotherapy in patients who received
preoperative radiotherapy or chemoradiotherapy.40
This finding has not yet changed clinical practice,
likely because there was a significant lack of adherence to postoperative therapy; over half of the patients in the adjuvant chemotherapy groups did not
receive the intended 4 cycles of treatment and 25%
did not receive any adjuvant therapy.
Another prospective study from Italy randomly
assigned patients who had received preoperative
chemoradiotherapy to adjuvant bolus 5-fluorouracil
and leucovorin versus observation and showed no
advantage in disease-free or overall survival.65 Similarly, the Dutch PROCTOR/SCRIPT trials randomly
assigned patients with stage II and III rectal cancers
to postoperative 5-fluorouracil and leucovorin or
capecitabine versus observation after having received neoadjuvant chemoradiotherapy. There was
no difference in overall survival between groups.66
The UK Chronicle trial randomly assigned patients
who had received neoadjuvant fluoropyrimidine
therapy to adjuvant capecitabine with oxaliplatin versus observation. Though the trial was closed early
secondary to poor accrual, there was a suggestion
of improvement in disease-free survival for the treatment arm, but this was not statistically significant.
There was no difference in overall survival.
Meta-analyses of the individual patients in these
studies have concluded that fluoropyrimidine-based
adjuvant therapy has not yet been shown to improve disease-free or overall survival.67,68 However,
this treatment remains the standard of care and
ongoing trials might definitively answer this question.66,69,70 At present, physicians should discuss
the risks and benefits of adjuvant treatment with
individual patients.
The choice of adjuvant regimen has also been
evaluated. The phase 2 ADORE study randomly
assigned rectal cancer patients with pathologic
T3/T4 or node-positive disease to FOLFOX versus
5-fluorouracil and leucovorin and showed a benefit
of FOLFOX with regards to disease-free survival.71
The overall survival data is still premature, but
there is a suggestion of overall survival benefit
with FOLFOX as well. Another study, the German
AIO trial, randomly assigned patients with T3/T4
or node-positive disease at diagnosis to oxaliplatin
as part of both neoadjuvant and adjuvant treatment, regardless of pathologic response. They
found a disease-free survival benefit compared to
5-fluorouracil alone but no improvement in overall
survival.39,58
SURVEILLANCE AND LONG-TERM EFFECTS
CASE CONTINUED
The patient receives adjuvant chemotherapy
with FOLFOX for a total of 8 cycles. Though she
has few symptoms during treatment, she develops
numbness and tingling in her feet bilaterally after
completion of chemotherapy.
•;What;are;the;current;recommendations;re-
garding;surveillance;following;treatment;for
locally;advanced;rectal;cancer?
In current standard practice, after the completion
of treatment for locally advanced rectal cancer,
patients should have a clinical encounter, including a careful history and physical exam, with their
physician every 3 to 6 months for the first 3 years
and every 6 months during years 4 and 5. A serum
CEA level should be measured at each follow-up
visit for the first 3 years. In addition, annual CT
scans of the chest, abdomen, and pelvis for at
