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Review
. 2022 Aug;13(4):2033-2047.
doi: 10.21037/jgo-22-13.

The evolving treatment paradigm of locally advanced rectal cancer: a narrative review

Muhammad Awawda  1 , Tarek Taha  2 , Saeed Salman  1 , Salem Billan  1 , Adham Hijab  1
Affiliations
Review

The evolving treatment paradigm of locally advanced rectal cancer: a narrative review

Muhammad Awawda et al. J Gastrointest Oncol. 2022 Aug.

Abstract

Background and objective: Surgery is still considered the mainstay of treatment of locally advanced rectal cancer (LARC). Nevertheless, "curable" disease may still pose a great risk for both local and distant relapses. Since the early eighties of the past century, we have witnessed mounting evidence supporting the multi-modality approach to tackle this disease effectively. The multi-modality approach is variable between different positive trials. In this review, we discuss the treatment evolution of LARC, highlighting the key differences between the different contemporary strategies utilized. Based on current evidence, we sought to define distinct patient subgroups and to propose a treatment algorithm that best fits patient's risk.

Methods: We conducted a literature search through PubMed and Google scholar. Eligible papers were phase 2/3 trials [in organ preservation (OP), observational and retrospective studies were also acceptable] published in English. We used keywords such as "locally advanced rectal cancer", "perioperative therapy in rectal cancer", "short course radiotherapy", "chemoradiation in rectal cancer", "interval to surgery", "Neoadjuvant therapy", "Organ preservation" and "Total neoadjuvant treatment [TNT]".

Key content and findings: Various trials consistently demonstrated the benefit of preoperative radiotherapy in LARC, the role of adjuvant chemotherapy is controversial based on published studies, TNT was associated with a risk reduction in distant metastasis, and more reassuring evidence is accumulating regarding OP.

Conclusions: The treatment landscape of LARC is rapidly changing. Clinicians should carefully tailor treatment strategy based on patient's risk.

Keywords: Locally advanced rectal cancer (LARC); organ preservation (OP); preoperative treatment; total-neoadjuvant therapy.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-13/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Hallmarks and trials shaping the treatment of locally advanced rectal cancer. APR, abdominoperineal resection; AR, anterior resection; TME, total mesorectal excision.
Figure 2
Figure 2
Proposed algorithm for treating patients with LARC. *, involved lymph nodes or T4 disease; #, T4, node positive, threatened circumferential resection margin, low-lying tumors; **, based on physician discretion according to pathological staging, risk of recurrence, patient comorbidities and performance status; ^, patient who achieve clinical complete response and decline surgery or has a high risk for postoperative morbidity, may be considered for watchful waiting (organ preservation approach). LARC, locally advanced rectal cancer; SCRT, short-course radiotherapy; LCCRT, long-course chemoradiotherapy; TME, total mesorectal excision.
See this image and copyright information in PMC

References

    1. Gollins S, Sebag-Montefiore D. Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer. Clin Oncol (R Coll Radiol) 2016;28:146-51. 10.1016/j.clon.2015.11.003 - DOI - PubMed
    1. Bahadoer RR, Dijkstra EA, van Etten B, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol 2021;22:29-42. 10.1016/S1470-2045(20)30555-6 - DOI - PubMed
    1. Conroy T, Bosset JF, Etienne PL, et al. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 2021;22:702-15. 10.1016/S1470-2045(21)00079-6 - DOI - PubMed
    1. Habr-Gama A, São Julião GP, Vailati BB, et al. Organ Preservation in cT2N0 Rectal Cancer After Neoadjuvant Chemoradiation Therapy: The Impact of Radiation Therapy Dose-escalation and Consolidation Chemotherapy. Ann Surg 2019;269:102-7. 10.1097/SLA.0000000000002447 - DOI - PubMed
    1. van der Valk MJM, Hilling DE, Bastiaannet E, et al. Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study. Lancet 2018;391:2537-45. 10.1016/S0140-6736(18)31078-X - DOI - PubMed