Neoadjuvant Treatment of Colorectal Cancer: Comprehensive Review

Overview

Journal BJS Open

Publisher Oxford University Press

Specialty General Surgery

Date 2024 May 15

PMID 38747103

Authors

Henry G Smith

Per J Nilsson

Benjamin D Shogan

Deena Harji

Maria Antonietta Gambacorta

Angela Romano

Andreas Brandl

Camilla Qvortrup

Affiliations

Soon will be listed here.

Abstract

Background: Neoadjuvant therapy has an established role in the treatment of patients with colorectal cancer. However, its role continues to evolve due to both advances in the available treatment modalities, and refinements in the indications for neoadjuvant treatment and subsequent surgery.

Methods: A narrative review of the most recent relevant literature was conducted.

Results: Short-course radiotherapy and long-course chemoradiotherapy have an established role in improving local but not systemic disease control in patients with rectal cancer. Total neoadjuvant therapy offers advantages over short-course radiotherapy and long-course chemoradiotherapy, not only in terms of increased local response but also in reducing the risk of systemic relapses. Non-operative management is increasingly preferred to surgery in patients with rectal cancer and clinical complete responses but is still associated with some negative impacts on functional outcomes. Neoadjuvant chemotherapy may be of some benefit in patients with locally advanced colon cancer with proficient mismatch repair, although patient selection is a major challenge. Neoadjuvant immunotherapy in patients with deficient mismatch repair cancers in the colon or rectum is altering the treatment paradigm for these patients.

Conclusion: Neoadjuvant treatments for patients with colon or rectal cancers continue to evolve, increasing the complexity of decision-making for patients and clinicians alike. This review describes the current guidance and most recent developments.

Citing Articles

Patient Education on Exercise Prehabilitation Among Patients Receiving Neoadjuvant Therapy for Cancer Surgery in China: A Mixed-Methods Study.

Xu X, Zhang J, Zhang Y, Yang T, Yu X Healthcare (Basel). 2025; 13(5).

PMID: 40077038 PMC: 11899062. DOI: 10.3390/healthcare13050477.

Unveiling radiobiological traits and therapeutic responses of BRAF-mutant colorectal cancer via patient-derived organoids.

Mu P, Mo S, He X, Zhang H, Lv T, Xu R J Exp Clin Cancer Res. 2025; 44(1):92.

PMID: 40069844 PMC: 11895145. DOI: 10.1186/s13046-025-03349-z.

Multikinase and highly selective kinase inhibitors in the neoadjuvant treatment of patients with thyroid cancer.

Valerio L, Matrone A Explor Target Antitumor Ther. 2025; 6:1002291.

PMID: 40061140 PMC: 11886382. DOI: 10.37349/etat.2025.1002291.

Invited Editorial: "Role of Adjuvant Chemotherapy After Surgical Resection of Paraaortic Lymph Node Metastasis from Colorectal Cancer-A Multicenter Retrospective Study," by Nozawa et al.

Sammour T Ann Surg Oncol. 2025; .

PMID: 40009305 DOI: 10.1245/s10434-025-17044-y.

Transposition of Internal Iliac Artery to External Iliac Artery in a Case of Locally Advanced Colonic Carcinoma: A Case Report.

Tripathi M, Kumari K, Vineet K, Vadodaria D, Parekh H J Gastrointest Cancer. 2025; 56(1):64.

PMID: 39953204 DOI: 10.1007/s12029-025-01178-z.

References

Bujko K, Nowacki M, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M . Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. 2006; 93(10):1215-23. DOI: 10.1002/bjs.5506. View

Rullier E, Rouanet P, Tuech J, Valverde A, Lelong B, Rivoire M . Organ preservation for rectal cancer (GRECCAR 2): a prospective, randomised, open-label, multicentre, phase 3 trial. Lancet. 2017; 390(10093):469-479. DOI: 10.1016/S0140-6736(17)31056-5. View

Franko J, Shi Q, Meyers J, Maughan T, Adams R, Seymour M . Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) database. Lancet Oncol. 2016; 17(12):1709-1719. DOI: 10.1016/S1470-2045(16)30500-9. View

Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R . Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004; 351(17):1731-40. DOI: 10.1056/NEJMoa040694. View

Braendengen M, Tveit K, Berglund A, Birkemeyer E, Frykholm G, Pahlman L . Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol. 2008; 26(22):3687-94. DOI: 10.1200/JCO.2007.15.3858. View

Vogel J, Felder S, Bhama A, Hawkins A, Langenfeld S, Shaffer V . The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Colon Cancer. Dis Colon Rectum. 2021; 65(2):148-177. DOI: 10.1097/DCR.0000000000002323. View

Brown G, Radcliffe A, Newcombe R, Dallimore N, Bourne M, Williams G . Preoperative assessment of prognostic factors in rectal cancer using high-resolution magnetic resonance imaging. Br J Surg. 2003; 90(3):355-64. DOI: 10.1002/bjs.4034. View

Zinicola R, Pedrazzi G, Haboubi N, Nicholls R . The degree of extramural spread of T3 rectal cancer: an appeal to the American Joint Committee on Cancer. Colorectal Dis. 2016; 19(1):8-15. DOI: 10.1111/codi.13565. View

Smith H, Bodilsen A, Rose L, Altaf R, Iversen L, Walker L . Challenges presented by complete response to immune checkpoint blockade in patients with dMMR colorectal cancer: A case report. Int J Surg Case Rep. 2023; 106:108286. PMC: 10189259. DOI: 10.1016/j.ijscr.2023.108286. View

10.

Yi Y, Shen L, Shi W, Xia F, Zhang H, Wang Y . Gut Microbiome Components Predict Response to Neoadjuvant Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer: A Prospective, Longitudinal Study. Clin Cancer Res. 2020; 27(5):1329-1340. DOI: 10.1158/1078-0432.CCR-20-3445. View

11.

Helderman R, Bokan B, van Bochove G, Rodermond H, Thijssen E, Marchal W . Elevated temperatures and longer durations improve the efficacy of oxaliplatin- and mitomycin C-based hyperthermic intraperitoneal chemotherapy in a confirmed rat model for peritoneal metastasis of colorectal cancer origin. Front Oncol. 2023; 13:1122755. PMC: 10064448. DOI: 10.3389/fonc.2023.1122755. View

12.

Goere D, Glehen O, Quenet F, Guilloit J, Bereder J, Lorimier G . Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP-PRODIGE 15): a randomised, phase 3 study. Lancet Oncol. 2020; 21(9):1147-1154. DOI: 10.1016/S1470-2045(20)30322-3. View

13.

Rizvi N, Hellmann M, Snyder A, Kvistborg P, Makarov V, Havel J . Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015; 348(6230):124-8. PMC: 4993154. DOI: 10.1126/science.aaa1348. View

14.

Heald R, Moran B, Ryall R, Sexton R, Macfarlane J . Rectal cancer: the Basingstoke experience of total mesorectal excision, 1978-1997. Arch Surg. 1998; 133(8):894-9. DOI: 10.1001/archsurg.133.8.894. View

15.

. Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study. BMJ. 2006; 333(7572):779. PMC: 1602032. DOI: 10.1136/bmj.38937.646400.55. View

16.

Sugarbaker P . A narrative review of what can HIPEC do. Eur J Surg Oncol. 2023; 49(9):106976. DOI: 10.1016/j.ejso.2023.07.002. View

17.

Sargent D, Marsoni S, Monges G, Thibodeau S, Labianca R, Hamilton S . Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol. 2010; 28(20):3219-26. PMC: 2903323. DOI: 10.1200/JCO.2009.27.1825. View

18.

Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L . Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial. J Clin Oncol. 2019; 37(34):3223-3233. PMC: 6881102. DOI: 10.1200/JCO.18.02309. View

19.

Hunter C, Garant A, Vuong T, Artho G, Lisbona R, Tekkis P . Adverse features on rectal MRI identify a high-risk group that may benefit from more intensive preoperative staging and treatment. Ann Surg Oncol. 2011; 19(4):1199-205. DOI: 10.1245/s10434-011-2036-1. View

20.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View