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Review
. 2025 Jan 20;17(2):330.
doi: 10.3390/cancers17020330.

A Comprehensive Approach to Neoadjuvant Treatment of Locally Advanced Rectal Cancer

Annalice Gandini  1 , Stefania Sciallero  1 , Valentino Martelli  1 , Chiara Pirrone  1 , Silvia Puglisi  1 , Malvina Cremante  1 , Massimiliano Grassi  1 , Valeria Andretta  1 , Giuseppe Fornarini  1 , Francesco Caprioni  1 , Danila Comandini  1 , Annamaria Pessino  1 , Serafina Mammoliti  1 , Alberto Sobrero  1 , Alessandro Pastorino  1
Affiliations
Review

A Comprehensive Approach to Neoadjuvant Treatment of Locally Advanced Rectal Cancer

Annalice Gandini et al. Cancers (Basel). .

Abstract

At the end of the past century, the introduction of Total Mesorectal Excision (TME), preceded by either short-course radiotherapy (SCRT) or chemoradiation (CRT), established the new standard of care for locally advanced rectal cancer (LARC). Recently, significant advancements were achieved for both dMMR/MSI and pMMR/MSS LARC patients. For the 2-3% of dMMR/MSI LARCs, ablative immunotherapy emerged as a curative approach, offering the possibility of avoiding chemotherapy (CT), radiotherapy, and surgery altogether. In pMMR/MSS LARCs, the intensification of preoperative treatments with Total Neoadjuvant Treatment (TNT) afforded three outcomes: (a) a reduction of distant metastases, positively impacting on survival endpoints, (b) a significant increase of complete clinical response (cCR) rate, paving the way for non-operative management (NOM), and (c) the selective omission of radiotherapy following induction CT. The choice of the most appropriate therapeutic strategy can only be made through the shared decision-making process between physician and patient based on risk stratification and patient preferences.

Keywords: locally advanced rectal cancer; therapeutic algorithm; total neoadjuvant treatment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Therapeutic options for locally advanced rectal cancer. Picture created with Biorender.com. Acronyms: LARC = Locally Advanced Rectal Cancer; MSI = microsatellite instability; NOM = Non-operative Management.
Figure 2
Figure 2
Treatment algorithm for locally advanced rectal cancer.
See this image and copyright information in PMC

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