Locally Advanced Rectal Cancer Volume II

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Background

Locally advanced rectal cancer (LARC), defined as stage II (T3-4, node negative) or stage III (node positive) disease has experienced a paradigm shift in management over the past few decades. Advances in surgical technique, namely total mesorectal excision (TME) and the development of combined modality therapy, have led to markedly improved disease-related outcomes. Neoadjuvant chemoradiotherapy followed by interval TME is now considered a standard of care for locally advanced disease with 5-year local recurrence rates between 5%. Despite the advances in pre-operative treatment and surgical technique, health-related quality of life and survivorship still remain suboptimal among patients with LARC.

The anatomical features of LARC pose unique technical challenges and major changes in surgical technique have occurred over the past few decades. Novel approaches, including transanal TME (taTME) and robotic surgery, have been introduced to improve oncological and functional outcomes, by allowing better visualization and more accurate dissection of the mesorectum. The prognostic relevance of pre-operative high-resolution magnetic resonance imaging (MRI) has been well-defined with risk stratification of patients based on pre-operative radiological features now incorporated into routine clinical practice and surgical planning. Accurate prediction of circumferential resection margin (CRM) involvement has been shown to represent an important predictor of outcome. It is hoped that continued advances in radiological imaging will further enable the development of selective risk-modified treatment strategies and guide individually tailored pre-operative therapy and surgical approach.

The optimization of systemic therapy has been proposed as a means of improving long-term oncologic outcomes. Whilst neoadjuvant therapy reduces local disease recurrence, long-term survival has remained largely unchanged and distant disease failure rates continue to range from 20-30%. Although adjuvant chemotherapy has traditionally been recommended in the past, its role in the neoadjuvant era is less clear. Several European randomized control trials have failed to demonstrate a survival advantage. Induction chemotherapy may represent an alternative means of targeting subclinical micrometastases and improving long-term outcomes. Tumor downstaging using neoadjuvant therapy may also facilitate a more selective practice of surgery. Patients who experience significant tumor regression may become eligible for organ preservation or an expectant ‘watch and wait’ approach.

Finally, the role of genomics and molecular profiling in the management of colorectal cancer (CRC) has gained substantial momentum over the past decade. In an era of personalized medicine, refining neoadjuvant and adjuvant therapy to the molecular signature of the tumor is an exciting prospect. The introduction of reflex mismatch repair (MMR) testing has led to an increasing understanding of the heterogeneous biological profile of CRC, both in the context of sporadic and familial disease. Whether microsatellite unstable tumors respond to conventional neoadjuvant therapy in the same manner as those that are MMR proficient is unknown.

The aim of this Research Topic is to address the current challenges faced in the management of LARC. We welcome all manuscript types excluding Case Reports, covering themes of organ preservation, TaTME, lateral pelvic sidewall nodes, anterior and posterior exenteration, intersphincteric resection, robotic/laparoscopic approaches, abdominoperineal resection approaches, optimization of systemic therapy (induction and consolidation chemotherapy), the prognostic role of imaging, and genomics of LARC.

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.

Keywords: rectal cancer, surgery, chemotherapy, radiotherapy, imaging

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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