Induction Chemotherapy for Locally Advanced Rectal Cancer
Status:
Not yet recruiting
Trial end date:
2026-06-01
Target enrollment:
Participant gender:
Summary
Despite developments in the multidisciplinary treatment of patients with locally advanced
rectal cancer (LARC), such as the introduction of total mesorectal excision (TME) by Heald et
al. and the shift from adjuvant to neoadjuvant (chemo)radiotherapy ((C)RT), local and distant
recurrence rates remain between 5-10% and 25-40% respectively. Several studies established
tumour characteristics with particularly bad prognosis; it was demonstrated that the
occurrence of mesorectal fascia involvement (MRF+), grade 4 extramural venous invasion
(EMVI), tumour deposits (TD) and enlarged lateral lymph nodes (LLN) lead to high local and
distant recurrence rates and decreased survival when compared with LARC without these
particularly negative prognostic factors. This type of LARC is described as high risk LARC
(hr-LARC). Achieving a resection with clear resection margins (R0) is an important prognostic
factor for local (LR) and distant recurrence (DM) as well as survival. With the aim to
further reduce the risk of recurrent rectal cancer, to diminish distant metastasis and to
improve overall survival for patients with LARC, induction chemotherapy (ICT) became a
growing area of research. The addition of ICT has the ability to induce more local tumour
downstaging, possibly leading to resectability of previously unresectable tumours, more R0
resections and less extensive surgery. In the case of a complete clinical response, surgery
may even be omitted. ICT may also have the potential to eradicate micrometastases. Hence,
increased local downstaging and reducing distant metastatic spread may reduce LR and DM rates
and improve survival and quality of life. In recent years, the use of ICT was investigated
and showed promising results, but little is known about the addition of ICT in patients with
high risk LARC. Since these patients have a particularly bad prognosis, both with regard to
locoregional and distant failure, a more intensified neoadjuvant treatment with FOLFOXIRI is
anticipated to improve short- and long term results.