Patients With Rectal Cancer: a "Wait-and-see" Approach
Patients With Rectal Cancer: a "Wait-and-see" Approach
Patients with histologically proven adenocarcinoma of the rectum will receive pelvic
 radiotherapy to a dose of 45Gy in 25 fractions with a tumor boost to a dose of 9Gy in 5
 fractions (thus total of 54Gy/30Fx to the primary tumor), combined with radio sensitizing
 chemotherapy. Patients will then be closely monitored, through endoscopy and imaging, for
 response to treatment and relapse. Salvage oncologic surgery to be offered if there is
 failure to achieve complete clinical response or in the event of a loco regional relapse.
The combination of preoperative (chemo)radiotherapy and total mesorectal excision (TME) has
 been shown to reduce the risk of local recurrence in patients with resectable adenocarcinoma
 of the rectum. The improved local control rates come at the price of an increased risk of
 surgical complications, including a postoperative death rate of 2-8 percent which may reach
 30 per cent at 6 months in those aged over 85 years, as well as long-term impact on
 anorectal, urinary and sexual function. Patients with cancers in the low rectum in close
 proximity to the sphincter muscles, may require a permanent stoma, which can be associated
 with high psychological morbidity.

 Preoperative chemoradiotherapy followed by a delay to resection can produce pathological
 complete responses. One review of phase II and III studies identified an overall pCR rate of
 13.5%, but even higher rates of pCR have been observed with doses of radiotherapy exceeding
 45 Gy . Certainly patients who proceed to radical surgery after achieving a pCR with chemo
 radiation do have favorable long-term outcomes. But do patients whose tumor has already been
 sterilized by chemo radiotherapy need to proceed with radical surgery?

 A number of studies have now emerged highlighting the rationale of a 'wait and see' policy
 for patients who achieve a complete clinical response (cCR) after chemo radiotherapy. The
 majority of the clinical data supporting this approach have come from Brazil. The Brazilian
 data suggests that observation of such patients yields survival rates similar to those of
 patients who undergo radical surgery with confirmation of pCR. More recent studies from the
 United Kingdom and the Netherlands appear to support the feasibility of this approach. To
 date there is no published prospectively collected data of a wait-and-see policy from a North
 American Centre.
Inclusion Criteria:

 -  Pelvic MRI defined disease (at least one of the following):

 -  mesorectum involved or breached - includes involvement of adjacent organ (s)
 (T3-T4)

 -  involvement of muscularis propria (T2)

 -  extra-mural vascular invasion

 -  tumour deposit within the mesorectum

 -  one or more involved mesorectal lymph node

 -  Patients are considered medically fit for oncologic resection

 -  ECOG performance status 0 or 1

 -  No evidence of established metastatic disease (CT chest and abdomen)

 -  Absolute neutrophil count >1.5x109/L; platelets >100x109/L,

 -  Serum transaminase <3 x ULN;

 -  Adequate renal function (Cockroft Gault estimation >50 mL/min)

 -  Bilirubin <1.5 x ULN

 -  Ability to comply with oral medication

 -  Willingness and ability to give informed consent and comply with treatment and follow
 up schedule

 -  Age 18 or over

 Exclusion Criteria:

 -  Previous radiotherapy to the pelvis (including brachytherapy)

 -  Enlarged extramesorectal nodes

 -  Uncontrolled cardiorespiratory comorbidity (includes patients with inadequately
 controlled angina or myocardial infarction within 6 months of randomisation)

 -  T1N0 disease without extra-mural venous invasion

 -  Unequivocal evidence of metastatic disease (includes resectable metastases)

 -  Major impairment of bowel function without defunctioning stoma/ileostomy (baseline
 grade 3 diarrhoea or clinically significant faecal incontinence)

 -  History of another malignancy within the last 5 years except successfully treated
 basal cell cancer of skin or carcinoma in situ of uterine cervix.

 -  Known dihydropyrimidine dehydrogenase deficiency

 -  Known Gilberts disease (hyperbilirubinaemia)

 -  Taking warfarin or phenytoin or sorivudine

 -  Gastrointestinal disorder which would interfere with oral therapy and its
 bioavailability

 -  Pregnant, lactating, or pre-menopausal women not using adequate contraception

 -  Unfit to receive any study treatment or subsequent surgical resection