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Neoadjuvant Therapy for Locally Advanced Rectal Cancer: 5 Clinical Insights from a Surgical Perspective | Interview with Prof. Li Jun, The Second Affiliated Hospital, Zhejiang University School of Med

As treatment for locally advanced rectal cancer enters a new era of precision and multidisciplinary collaboration, therapeutic concepts are undergoing profound changes. Neoadjuvant therapy, a crucial component of comprehensive treatment, demonstrates significant potential in improving local tumor control, reducing recurrence rates, and enhancing patient survival. The selection of precise and individualized neoadjuvant strategies has become a key focus in current clinical practice and research.

Professor Li Jun, Deputy Director and Chief Physician of the Colorectal Surgery Department at The Second Affiliated Hospital, Zhejiang University School of Medicine, serves as a standing committee member of the Colorectal Cancer Professional Committee of the China Anti-Cancer Association. He has participated in drafting and reviewing multiple national guidelines and consensus documents, offering valuable insights into the standardized and individualized surgical management of locally advanced rectal cancer. In this patient education video, Prof. Li Jun focuses on "neoadjuvant therapy for locally advanced rectal cancer," providing an in-depth analysis of how it impacts patient outcomes.

* Please note: Patients should undergo treatment under the guidance of a physician. Individual cases vary, and specific treatment plans and medications should be tailored to each patient's condition.

I. The Role of Preoperative Radiotherapy/Chemoradiotherapy in Rectal Cancer

The use of radiotherapy for rectal cancer has gradually shifted from postoperative to preoperative settings. Since the 1990s, increasing research has explored the efficacy of preoperative radiotherapy, demonstrating that preoperative radiotherapy helps reduce recurrence rates and improve patient survival¹. Although modern surgical techniques like total mesorectal excision (TME) can lower recurrence rates, preoperative radiotherapy can further reduce recurrence and improve the 10-year survival rate for stage III patients with negative circumferential resection margins (CRM).

Furthermore, compared to postoperative chemoradiotherapy, preoperative chemoradiotherapy moderately reduces recurrence rates and decreases toxic side effects and complications². In clinical practice, the decision to include radiotherapy should be based on MRI risk assessment and multidisciplinary team (MDT) discussions.

II. Clinical Examples Highlighting the Dual Nature of Radiotherapy

  • Radiotherapy may lead to certain complications, such as anal dysfunction, radiation proctitis, and severe anemia³⁻⁵

  • Radiotherapy may increase the risk of anastomotic leakage and complicate surgical procedures and postoperative complication management³⁻⁵

  • However, radiotherapy can help control the tumor and facilitate pathological complete response⁶

  • Radiotherapy helps reduce the risk of recurrence⁶

Real-world data from the Chinese FOWARC study indicates that approximately one-third of patients experience varying degrees of fecal incontinence after radiotherapy⁷. However, the PROSPECT study shows that the 5-year local recurrence-free survival rate for patients receiving preoperative chemoradiotherapy is 98%⁸.

Therefore, radiotherapy is viewed by surgeons as a double-edged sword. Post-radiation fibrosis and tissue thickening may be clinically mistaken for recurrence, leading to misdiagnosis. While preoperative radiotherapy increases surgical difficulty and the risk of short- and long-term complications, potentially lowering quality of life, it effectively controls tumors and reduces postoperative recurrence risk. Thus, the decision to use radiotherapy should be based on a comprehensive evaluation of the patient's condition.

Note: The related cases are solely retrospective reviews and comments by the attending physician during clinical practice, provided for scientific exchange and reference only. Individual cases vary, and specific treatment plans and medications should be tailored to each patient's condition.

III. Can Radiotherapy Be Omitted for Rectal Cancers That Surgeons Can Completely Resect?

The UK MERCURY study demonstrated that MRI has a predictive value of up to 94% for determining negative CRM, making it the current standard preoperative examination for assessing CRM status⁹. If MRI shows a negative CRM (indicating resectability), is preoperative chemoradiotherapy still necessary?

China's multicenter PSSR study enrolled patients with locally advanced mid-rectal cancer and MRI-indicated negative CRM. The study results showed¹⁰:

  • The 3-year disease-free survival rate in the direct surgery group was 5% lower than in the chemoradiotherapy group;

  • The risk of recurrence and metastasis in the direct surgery group was twice as high as in the chemoradiotherapy group;

These findings highlight the importance of preoperative chemoradiotherapy.

IV. Modern Models of Neoadjuvant Therapy for Rectal Cancer

The core goal of rectal cancer treatment is to help patients live better, which means meeting two key requirements: preventing recurrence + preserving good anal function.

Modern neoadjuvant therapy for rectal cancer is primarily based on the "Three M (MRI + MSI + MDT)" strategy: Under continuous MDT discussion, treatment is stratified based on MRI results and MSI status.

The modern approach combining radiotherapy and immunotherapy not only helps achieve tumor remission but also raises some concerns:

1) Some patients still require surgery after combined radiotherapy and immunotherapy, but surgical difficulty and complication risks may be significantly higher at that stage;

2) A small number of patients may experience severe immune-related adverse events during treatment.

Note: Please be aware that patients should undergo treatment under a physician's guidance. Individual cases vary, and specific treatment plans and medications should be tailored to each patient's condition.

V. Application of MRD in Neoadjuvant Therapy

Tumor disappearance after radiotherapy ≠ Cure! MRD provides early warning!

Clinical observations show that even when imaging indicates complete remission, some patients still develop liver or retroperitoneal metastases within a year. Research has found that detecting minimal residual disease (MRD) signals in the blood can predict recurrence risk in advance¹¹. MRD-positive patients face a higher risk of recurrence, while MRD-negative status predicts a lower recurrence probability and better long-term prognosis. During follow-up, combining MRD testing can accurately identify patients who are truly safe for a "watch-and-wait" approach, avoiding overtreatment while providing a predictive basis for intensified therapy.


This material is supported by Hutchmed.

NP-AYT-25N542-Valid Until-2027-August

This material aims to facilitate communication and exchange of medical information, not for advertising. The content cannot replace professional medical guidance in any way and should not be considered as medical advice. For more information on diseases, please consult healthcare professionals.

1. Swedish Rectal Cancer Trial; Cedermark B, Dahlberg M, Glimelius B, Påhlman L, Rutqvist LE, Wilking N. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med. 1997 Apr 3;336(14):980-7.

2. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40.

3. Peeters KC, van de Velde CJ, Leer JW, et al. Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients-a Dutch colorectal cancer group study. J Clin Oncol, 2005, 23(25):6199-6206.

4. Marijnen CA, van de Velde CJ, Putter H, et al. Impact of short-term preoperative radiotherapy on health-related quality of life and sexual functioning in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol, 2005, 23(9):1847-1858.

5. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, et al. 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.

6. Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med, 2004, 351(17):1731-1740.

7. DENG Y, CHI P, LAN P, et al. Modified FOLFOX6 With or Without Radiation Versus Fluorouracil and Leucovorin With Radiation in Neoadjuvant Treatment of Locally Advanced Rectal Cancer: Initial Results of the Chinese FOWARC Multicenter Open-Label, Randomized Three-Arm Phase III Trial. J Clin Oncol, 2016, 34(27):3300-7.

8. Deborah Schrag, et al. PROSPECT: A randomized phase III trial of neoadjuvant chemoradiation versus neoadjuvant FOLFOX chemotherapy with selective use of chemoradiation, followed by total mesorectal excision (TME) for treatment of locally advanced rectal cancer (LARC) (Alliance N1048). J Clin Oncol 41, 2023 (suppl 17; abstr LBA2).

9. MERCURY Study Group. Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study. BMJ. 2006 Oct 14;333(7572):779.

10. https://doi.org/10.1200/JCO.2022.40.16_suppl.3515

11. 563P Preliminary analysis in Protector-C study: A prospective, multicenter cohort of utilizing circulating tumor DNA (ctDNA) methylation as postoperative surveillance for colorectal cancer (CRC). Liu, Z. et al. Annals of Oncology, Volume 35, S462


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