 Home > Active Ingredient News > Antitumor Therapy > Medical interview with Professor Li Sheng: improving the preservation rate and preoperative pathological remission rate of rectal cancer, and also recommended by international guidelines, the whole process of neoadjuvant therapy has become a "new trend" in colorectal cancer treatment

Medical interview with Professor Li Sheng: improving the preservation rate and preoperative pathological remission rate of rectal cancer, and also recommended by international guidelines, the whole process of neoadjuvant therapy has become a "new trend" in colorectal cancer treatment

 Last Update: 2023-02-02
 Source: Internet
 Author: User

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Colorectal cancer is one of the most common gastrointestinal malignancies in the world, ranking third and second in incidence and mortality among all malignant tumors^{, respectively [1].}
At present, the incidence of colorectal cancer in China is showing a significant increase trend, and about 70% of patients are locally advanced when they are found ^{[2, 3]}, and in the clinical diagnosis and treatment of rectal cancer, the multidisciplinary diagnosis and treatment model has become the standard and norm of the industry.
Neoadjuvant therapy is becoming an effective and feasible treatment strategy
.
In this issue, "Physician Daily" specially invited Professor Li Sheng, Department of Medical Oncology, Jiangsu Cancer Hospital, to talk about the progress of
neoadjuvant therapy in the treatment of rectal cancer.

The whole process of neoadjuvant therapy exploration has a long way to go

Full neoadjuvant therapy (TNT) refers to a treatment mode
in which more or all postoperative adjuvant chemotherapy is transferred to the perioperative treatment of locally advanced rectal cancer (LARC).
The current standard of care for LARC, also known as the "sandwich mode," is preoperative concurrent chemoradiotherapy (CRT) or short-course preoperative radiotherapy (SCRT).
+ total mesorectal resection (TME) + adjuvant chemotherapy
.
This model was mainly established from the German AIO-94 study, which demonstrated that the long-term local recurrence rate of preoperative concurrent chemoradiotherapy was significantly lower than that of postoperative concurrent chemoradiotherapy (Figure 1).
^[5] Based on the results of this study, the 2008 National Comprehensive Cancer Network (NCCN) guidelines were updated to recommend preoperative neoadjuvant concurrent chemoradiotherapy for patients with contraindications to radiotherapy ^[6]
。 Therefore, after that, it enters the "sandwich mode", and for colorectal cancer patients with a tumor range of less than 10cm, it is recommended to first synchronize chemoradiotherapy followed by surgery and then postoperative adjuvant chemotherapy
.
However, in China, the implementation rate of the "sandwich model" is low, and the proportion of patients receiving preoperative radiotherapy is only 10%-15%, which is far lower than the international level and much different from developed countries in Europe and the United States
.

In the EORTC 22921 study, more than 30% of LARC was treated in "sandwich mode" Patients did not receive adjuvant chemotherapy, and only 50% of patients receiving adjuvant chemotherapy completed the standard full course of treatment, and there was little change in long-term survival, with disease-free survival (DFS) and 10-year overall survival ( OS) did not differ significantly ^[7].
This may be associated with serious complications (anastomotic leak or perineal incision infection), delayed timing of chemotherapy, poor tolerance of chemotherapy drugs due to reduced postoperative immunity, protective stoma, and patient preference.

In the GCR-3 study, TNT-treated groups were compared with neoadjuvant chemoradiotherapy (nCRT) treatment groups, although there was no difference in pathologic complete response (pCR) rates between the two groups Treatment adherence was higher in the TNT group ^[8].
Retrospective studies have shown that the pCR rate in the TNT group is higher than in the nCRT group in patients with locally advanced rectal cancer ^[9].
Based on the results of the above two studies, the NCCN guidelines list TNT as one of
the recommended treatment strategies for locally advanced rectal cancer.

Figure 1 Two rectal cancer studies (protocol CAO/ARO/AIO-94) comparing locally advanced rectal cancer ( uioc-II.
/III.
), preoperative and postoperative chemoradiotherapy

Optimize treatment procedures to improve patient compliance and tolerability

There are two treatment modes for TNT, concurrent chemoradiotherapy followed by neoadjuvant chemotherapy, or neoadjuvant chemotherapy followed by concurrent chemoradiotherapy
.
Data from early TNT treatment studies have shown that it does not improve long-term survival, but it can reduce drug toxicity and increase patient compliance and tolerability ^[10].
However, compared with the traditional model, the TNT mode is relatively easy to complete, and the degree of patient acceptance is greatly improved
.
Recent TNT studies, such as RAPIDO [^11], PRODIGE23 ^{[ 12]}、GREECAR 4^[13]、OPRA^[14] and other studies have shown that TNT not only improves the short-term efficacy, including preservation rate and pCR, but also improves DFS and RFS, compared with the traditional "sandwich model" There was some improvement (Figure 2).

From the clinical practice of Jiangsu Cancer Hospital, the data of 30 TNT patients showed that 45% of them had reached pCR, 3 other patients achieved cCR status, thus exempting from surgery, although we still need follow-up to see the long-term effect, but this study found it TNT can achieve complete clinical or pathological remission, far beyond the efficacy
of traditional treatment.
If the original surgical first mode is adhered to, it may reduce the patient's quality of life, including prolonging the duration of the temporary ostomy, usually patients with advanced rectal cancer have a temporary ostomy but must receive postoperative adjuvant therapy, it takes about 8 months to return the ostomy to the abdominal cavity, if TNT treatment mode, temporary The ostomy may be accepted in as little as 3 months, improving the patient's
convenience.

FIG.
2 PRODIGE23 STUDY, COMPARING THE DISEASE-FREE SURVIVAL RATE (A) AND OVERALL SURVIVAL RATE (B) OF TNT TREATMENT WITH TRADITIONAL "SANDWICH MODE" TREATMENT

Recommend the whole process of neoadjuvant therapy to update doctors' new treatment ideas

At present, foreign countries have promoted the TNT model, from the short-term and long-term benefits of various studies, rectal cancer patients survival benefits and organ function retention, TNT can increase preservation rate, pCR, DFS and RFS has also improved
.
However, the domestic promotion still faces resistance, whether surgeons or rectal cancer patients, in the face of the disease traditional inherent thinking, that is, surgery radical treatment and then radiotherapy and chemotherapy in the later stage, does not consider the order of treatment, mainly due to the patient's lack of understanding and acceptance of the new model, so the practice of the new model is relatively difficult
.

TNT mode should also pay attention to bone marrow suppression, the pelvis is the most important hematopoietic site of the human body, the most common adverse reaction of radiotherapy and chemotherapy is bone marrow suppression, especially in rectal cancer patients bone marrow suppression is more serious, neutropenia is an important cause of chemotherapy delay and reduction, neutropenic fever ( FN) can be life-threatening and is one
of the emergency conditions of tumors.
At present, the effective drug for the prevention and treatment of neutropenia or deficiency caused by tumor radiotherapy and chemotherapy is long-acting white needle (such as: Xinruibai - polyethylene glycolated recombinant human granulocyte stimulating factor injection).

The timely and effective application of long-acting white needles can escort rectal cancer patients to complete the full course of radiotherapy and chemotherapy on schedule and in full dose
.

As a new model for comprehensive treatment of rectal cancer, TNT model has been used by NCCN to guide clinical treatment
.
It is hoped that the TNT model will be studied in terms of safety, tolerability, toxicity, survival and other aspects in Asian populations, so that more doctors and patients will gradually accept the new model
.

Professor Li Sheng concluded

TNT is a new mode of treatment for LARC, which improves the tolerance of patients receiving radiotherapy and chemotherapy, increases treatment compliance, and improves the rate of pCR and preservation without increasing the difficulty of surgery, and hopes to improve long-term survival
.
However, the future promotion of TNT treatment model still faces many difficulties, it is urgent to change the traditional inherent treatment concept, accept new treatment models, and bring more benefits to patients, and hope that there will be higher-level clinical trials and evidence-based medical evidence to support the implementation of
TNT in the future.

Expert profiles

Professor Sheng Li

Jiangsu Cancer Hospital

Member of the Standing Committee of the 2nd Multi-primary and Unknown Primary Tumor Professional Committee of the Chinese Anti-Cancer Association

Member of MDT Branch of Digestive Tract Oncology of China Association for the Promotion of International Exchange in Healthcare

Standing Committee Member and Secretary of the Provincial Branch of China Colorectal Cancer MDT Alliance Jiangsu Branch

Youth member of MDT Committee of Precision Medicine and Oncology of China Research Hospital Association

Vice Chairman and Secretary of the Second Colorectal Cancer Expert Committee of Jiangsu Cancer Prevention and Control Alliance

Member of Tobacco Control Professional Committee of Jiangsu Health Education Association

Standing member and secretary of the Multi-primary and Unknown Primary Tumor Professional Committee of Jiangsu Anti-Cancer Association

Member of Oncology Branch of Jiangsu Geriatric Society

Member of the first gastric cancer expert committee of Jiangsu Cancer Prevention and Control Alliance

Member of Translational Medicine Professional Committee of Jiangsu Society of Immunology

Member of Hereditary Oncology Professional Committee of Jiangsu Integrative Medicine Research Association

He was selected as the "Six Talent Peaks of Jiangsu Province" talent training subsidy, presided over the Wu Jieping Fund, and participated in the project of the Jiangsu Provincial Department of Health and the National Natural Science Foundation Project; He has published more than 10 papers in Chinese and English as the first author and corresponding author; He has won the third prize of Jiangsu Province Science and Technology Progress Award (2012), the third prize of Suzhou Science and Technology Progress Award (2015), and the first prize of Jiangsu Provincial Health Commission Medical Introduction New Technology Award (2020).

References: (slide to view)

[1] Sung H, Ferlay J, Siegel RL, et al.
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J].
CA Cancer J Clin.
2021,71(3):209-249.

LI J.
, MAO L, ZHOU Xueting, et al.
MRI to evaluate complete remission in neoadjuvant therapy for rectal cancer: a meta-analysis[J].
Magnetic Resonance Imaging, 2020,11(11):1010-1018.

[3] ZHENG Ying, WANG Zezhou.
Interpretation of global colorectal cancer prevalence data[J].
Chinese Journal of Epidemiology, 2021,42(01):149-152.

[4] Hospers G A, Punt C J, Tesselaar M E, et al.
Preoperative chemoradiotherapy with capecitabine and oxaliplatin in locally advanced rectal cancer.
A phase I-II multicenter study of the Dutch Colorectal Cancer Group[J].
Ann Surg Oncol, 2007,14(10):2773-2779.

[5] Sauer R, Fietkau R, Wittekind C, et al.
Adjuvant vs.
neoadjuvant radiochemotherapy for locally advanced rectal cancer: the German trial CAO/ARO/AIO-94[J].
Colorectal Dis, 2003,5(5):406-415.

[6] Engstrom P F, Arnoletti J P, Benson A R, et al.
NCCN Clinical Practice Guidelines in Oncology: rectal cancer[J].
J Natl Compr Canc Netw, 2009,7(8):838-881.

[7] Bosset J F, Collette L, Calais G, et al.
Chemotherapy with preoperative radiotherapy in rectal cancer[J].
N Engl J Med, 2006,355(11):1114-1123.

[8] Fernandez-Martos C, Garcia-Albeniz X, Pericay C, et al.
Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trial dagger[J].
Ann Oncol, 2015,26(8):1722-1728.

[9] Cercek A, Roxburgh C, Strombom P, et al.
Adoption of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer[J].
JAMA Oncol, 2018,4(6):e180071.

[10] Nogue M, Salud A, Vicente P, et al.
Addition of bevacizumab to XELOX induction therapy plus concomitant capecitabine-based chemoradiotherapy in magnetic resonance imaging-defined poor-prognosis locally advanced rectal cancer: the AVACROSS study[J].
Oncologist, 2011,16(5):614-620.

[11] Giunta E F, Bregni G, Pretta A, et al.
Total neoadjuvant therapy for rectal cancer: Making sense of the results from the RAPIDO and PRODIGE 23 trials[J].
Cancer Treat Rev, 2021,96:102177.

[12] Conroy T, Bosset J F, Etienne P L, 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[J].
Lancet Oncol, 2021,22(5):702-715.

[13] Nougaret S, Castan F, de Forges H, et al.
Early MRI predictors of disease-free survival in locally advanced rectal cancer from the GRECCAR 4 trial[J].
Br J Surg, 2019,106(11):1530-1541.

[14] Smith J J, Chow O S, Gollub M J, et al.
Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management[J].
BMC Cancer, 2015,15:767.

Typesetting: Li Hui

Editor: Wang Lina

Review: Qin Miao

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