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Review
. 2023 Jul 29;24(15):12159.
doi: 10.3390/ijms241512159.

Total Neoadjuvant Treatment for Locally Advanced Rectal Cancer Patients: Where Do We Stand?

Valentina Daprà  1   2 , Marco Airoldi  1   2 , Michela Bartolini  1   2 , Roberta Fazio  1   2 , Giuseppe Mondello  2 , Maria Chiara Tronconi  2 , Maria Giuseppina Prete  2 , Giuseppe D'Agostino  3 , Caterina Foppa  1   4 , Antonino Spinelli  1   4 , Alberto Puccini  2 , Armando Santoro  1   2
Affiliations
Review

Total Neoadjuvant Treatment for Locally Advanced Rectal Cancer Patients: Where Do We Stand?

Valentina Daprà et al. Int J Mol Sci. .

Abstract

The therapeutic landscape in locally advanced rectal cancer (LARC) has undergone a significant paradigm shift in recent years with the rising adoption of total neoadjuvant treatment (TNT). This comprehensive approach entails administering chemotherapy and radiation therapy before surgery, followed by optional adjuvant chemotherapy. To establish and deliver the optimal tailored treatment regimen to the patient, it is crucial to foster collaboration among a multidisciplinary team comprising healthcare professionals from various specialties, including medical oncology, radiation oncology, surgical oncology, radiology, and pathology. This review aims to provide insights into the current state of TNT for LARC and new emerging strategies to identify potential directions for future research and clinical practice, such as circulating tumor-DNA, immunotherapy in mismatch-repair-deficient tumors, and nonoperative management.

Keywords: MMR-deficient tumor; ct-DNA; locally advanced rectal cancer; nonoperative management; rectal cancer; total neoadjuvant therapy.

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Conflict of interest statement

A.S. reports honoraria and advisory board consultancy from BMS (Bristol Myers Squibb), Servier, Gilead, Pfizer, Eisai, Bayer, and MSD (Merck Sharp and Dohme); speaker honoraria from Takeda, BMS, Roche, Abb-Vie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer, Lilly, Sandoz, Eisai, Novartis, Bayer, and MSD (all outside the submitted work). The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results. The other authors declare no conflict of interest.

Figures

Figure A1
Figure A1
Study design of RAPIDO and PRODIGE-23 trials.
Figure A2
Figure A2
Study design of PROSPECT trial.
Figure 1
Figure 1
Timeline of treatments in locally advanced rectal cancer.
Figure 2
Figure 2
The proposed treatment algorithm for locally advanced rectal cancer: LARC = locally advanced rectal cancer; MMR = mismatch repair; MSI = microsatellite instability; MSS = microsatellite stability; EMVI = extramural vascular invasion; CRM = circumferential resection margin; MRF = mesorectal fascia; LN = lymph nodes; NOM = nonoperative management; TME = total mesorectal excision; LCRT = chemoradiotherapy; CT = chemotherapy; RT = radiotherapy; cCR = clinical complete response.
See this image and copyright information in PMC

References

    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Siegel R.L., Wagle N.S., Cercek A., Smith R.A., Jemal A. Colorectal cancer statistics, 2023. CA Cancer J. Clin. 2023;73:233–254. doi: 10.3322/caac.21772. - DOI - PubMed
    1. Kokelaar R.F., Evans M.D., Davies M., Harris D.A., Beynon J. Locally advanced rectal cancer: Management challenges. Onco Targets Ther. 2016;9:6265–6272. doi: 10.2147/OTT.S100806. - DOI - PMC - PubMed
    1. Kapiteijn E., Marijnen C.A., Nagtegaal I.D., Putter H., Steup W.H., Wiggers T., Rutten H.J., Pahlman L., Glimelius B., Van Krieken J.H., et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N. Engl. J. Med. 2001;345:638–646. doi: 10.1056/NEJMoa010580. - DOI - PubMed
    1. Folkesson J., Birgisson H., Pahlman L., Cedermark B., Glimelius B., Gunnarsson U. Swedish Rectal Cancer Trial: Long Lasting Benefits From Radiotherapy on Survival and Local Recurrence Rate. J. Clin. Oncol. 2005;23:5644–5650. doi: 10.1200/JCO.2005.08.144. - DOI - PubMed

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