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Page 4 of 7 Thomas et al. Mini-invasive Surg 2018;2:17 I http://dx.doi.org/10.20517/2574-1225.2018.25

patient choice. T1, T2 and T3 tumours accounted for 35.1%, 58.0% and 6.9% of cases, respectively. Adjuvant
regimens were exclusively long course in nature and included radiotherapy either alone or combination
with chemotherapy. At a median follow-up of 51 months, the pooled local recurrence was 5.8% for pT1
[24]
tumours, 13.8% for pT2 tumours and 33.7% for pT3 tumours . This suggests that it is possible to achieve
reasonable local control in pT1 disease, even if adverse histological features are present, with post-operative
adjuvant therapy. Clearly, this treatment strategy must be offered in the context of the significant body of
evidence for radical surgery and the clinician most weigh up the balance of organ preservation, quality of
life, patient choice and oncological outcome on an individual patient basis.

AUGMENTING THE RESPONSE TO RADIOTHERAPY
Tumour regression following neo-adjuvant chemo-radiotherapy is significantly associated with 5-year
overall survival, disease-free survival and local recurrence [25,26] , thus increasing our understanding of
treatment adjuncts that might enhance tumour response to therapy. Also, adjuncts might increase the
likelihood of pCR or near-pCR in patients with rectal cancer. A systematic literature search was conducted
and all studies investigating the use of drugs to enhance response to neoadjuvant radiation in rectal cancer.
However, the small number of studies and the heterogeneity of outcomes precluded systematic review and
[27]
meta-analysis from being undertaken . We therefore outlined the evidence to date in a narrative review
and explored the potential mechanisms of action. Despite the obvious limitations, aspirin, metformin and
statins appear to be associated with down staging rectal tumours and thus could potentially play the role
of adjuncts in neoadjuvant therapy [28-31] . Moreover, provisional research strongly supports the potential
[31]
role for the use of aspirin to induce apoptosis and enhance the effect of pre-operative radiotherapy . This
has prompted us to conduct a proof of principle prospective cohort study comparing patients who are
taking aspirin to those who do not whilst receiving neo-adjuvant chemoradiotherapy prior to laparoscopic
and open resection for rectal cancer (the ASPIRE study). The end points for this proof of principle study
are both traditional surrogate markers of oncological outcome and laboratory markers of response to
chemoradiotherapy.

FOLLOW UP IN PATIENTS WITH AN APPARENT COMPLETE CLINICAL RESPONSE
Around 15%-25% of tumours have a pCR [32,33] , which is associated with a reduction in local recurrence and
improved disease-free and overall survival [34,35] . Despite the difficulties in predicting pCR based on clinical
and radiological findings, there appears to be increasing evidence that patients who exhibit an apparent
cCR could be safely managed by local procedures, such as TEMS, TEO or TAMIS, to the tumour site or
indeed intensive surveillance, the so called “watch and wait” strategy, to avoid the morbidity associated
with radical surgery and enable organ preservation [36-38] . There is a paucity of evidence on the optimum
follow up of such patients and we have therefore erred on the side of caution with intensive follow up for in
the first 2 years that consists of endoscopic evaluation ± mucosal biopsy, MRI, EUS and CT every 3 months.
The surveillance interval is then extended to 6 months, thereafter. Large prospective cohort studies will be
required to educate this debate.

CONCLUSION
We provide treatment for early rectal cancer that is both patient-centred and based on the available
evidence. This follows a detailed staging strategy that consists of clinical examination, CT, MRI, PET
and the use of colonoscopic EUS with or without fine needle aspiration of extramural pelvic disease. All
cases are discussed at a weekly multidisciplinary meeting where the patient’s comorbidities, quality of
life and preferences are discussed in conjunction with the likely oncological outcomes of the potential
treatment regimens on offer. Consent is usually a two or three-staged process where the patient’s treatment
options are discussed in detail. Rather than adopting a protocol-driven strategy, we are strong advocates