Professor Xing Baocai, | of the new life of the intestinal tract: A multi-dimensional discussion on the translational treatment of liver metastasis of colorectal cancer

preface

The liver is the most important target organ for colorectal cancer hematogenous metastasis, and colorectal cancer liver metastasis (CRLM) is one

Hot Spots and Controversies: Translational Treatment Strategies for Patients with Multiple CRLM

Professor Xing introduced that surgical resection after non-resectable liver metastases and conversion therapy helps to prolong the survival of patients, and a small number of patients can even achieve cure

One

Number of conversion therapy with liver metastases

Prior to CRLM treatment, clinicians typically make a comprehensive assessment based on the size, number, location, biological behavior, and liver function status of liver metastases to develop an appropriate regimen

In recent years, surgical treatment has become more and more aggressive

Fig.

Professor Xing pointed out that the prognosis of CRLM patients with ≥ 10 lesions tends to be worse than that of patients with fewer lesions; Liver metastasis is removed after successful transformation in such populations, and the survival time is significantly prolonged; Oncologically unresectable CRLM, systemic therapy should be initially selected; Patients who are effective in the initial systematic treatment are the people who

Two

Translational therapy is combined with hepatic metastases and extrahepatic metastases

The liver is the most common site of colorectal cancer metastasis, and many patients will also have extrahepatic metastasis, of which lung metastasis, lymph node metastasis, and peritoneal metastasis are the top extrahepatic metastases
.

In this subset of patients with extrahepatic metastases, studies have shown that the presence of lung metastases does not affect the resection of liver metastases6
.

In patients with lymph node metastases (eg, metastasis of intraperitoneal lymph nodes, metastases of hepatic lymph nodes, etc.
), resection has a significant survival benefit
over patients who do not.

Professor Xing said that based on the existing clinical practice, patients with liver metastases should not abandon surgical treatment even if they are combined with extrahepatic metastases, and these patients still have the opportunity to obtain significant survival benefits
after active treatment.

Challenges and responses: lesions that disappear after conversion therapy

Multiple liver metastases will inevitably face the disappearance of lesions after conversion therapy, and these disappearing lesions bring new problems and thoughts to the clinic: disappearing lesions = complete pathological remission (pCR)? Do disappearing lesions still need to be treated? What should I do?

A French single-centre study published in JCO in 2006 included 38 patients with colorectal cancer from 1998 to 2004 who had not previously received local treatment, had less than 10 liver metastases, and had no extrahepatic metastases
.

Ct evaluation after preoperative chemotherapy found the disappearance of one or more liver metastases (183 lesions before chemotherapy, 66 lesions disappeared after chemotherapy, follow-up greater than 1 year).


But further studies found that more than 80% of these disappearing lesions were ^active7
.

Therefore, many researchers at that time advocated blind incision of the DLM region (the area where the lesion retreats after chemotherapy is the lesion that disappears after chemotherapy, retreating to the limit
).

In fact, different imaging tests have different
sensitivities.

Studies have found that lesions that disappear under CT do not "completely disappear" under MRI; Some lesions that cannot be seen by preoperative CT and MRI can be seen on
contrast.

Professor Xing introduced that with the progress of imaging, more and more tiny lesions have been ^discovered8, of which ultrasonography/MRI combined ultrasonography is considered to be the most sensitive detection method
at present.

If the lesion cannot be observed after the above imaging methods, it may be more appropriate to
wait and observe.

Exploration and Reflection: Transformational Therapy and Degenerative Surgery for Liver Metastases

In the treatment options for some tumors (e.
g.
, ovarian cancer, neuroendocrine tumors and liver metastases), tumor reduction surgery has been recognized
.

However, previous oncoplastic surgery for CRLM has been "impossible" to achieve radical resection of all liver metastatic lesions; Especially in patients with liver metastases and extrahepatic metastases, hepatic metastases can be radically cured, but extrahepatic metastases cannot be achieved radically
.

Therefore, in the past consensus, only systematic treatment
was chosen.

So, in the new era of colorectal cancer diagnosis and treatment, targeted drugs (such as bevacizumab) and immune checkpoint inhibitors and other systemic therapeutic drugs are booming, is CRLM tumor reduction feasible? Will there be a significant survival benefit in patients with non-radical resection?

In this regard, Professor Xing introduced that studies have shown that for the treatment of non-resectable liver metastases, the efficacy of chemotherapy + ablation is significantly better than that of chemotherapy ^alone9
.

In many cases, R0 resection cannot be achieved, and R1 resection can also benefit patients, but attention should be paid to the biology of the tumor
.

Advances in medical science and technology have changed clinicians' understanding of
the "radical" nature of previous liver resection.

Current "radical treatment" often refers to maximum tumor reduction
.

Finally, Professor Xing also introduced the conditions to be met for tumor reduction surgery, and concluded that CRLM has relatively special biological characteristics; Systemic therapy is highly effective, and tumor growth is relatively slow; Systemic therapy combined with topical therapy can provide a clear survival benefit to patients; The adapted population of translational therapy should not have too many contraindications at the subjective level, and should first choose intensive systematic therapy; For systemic treatment of effective liver metastases, topical therapy should be more aggressive
.

Expert Profiles

Professor Xing Baocai

• Chief Physician, Doctoral Supervisor

• Director of Peking University Cancer Hospital Hepatobiliary and Pancreatic Surgery

• He is a national member of the Liver Surgery Group of the Surgery Branch of the Chinese Medical Association

• Chairman of the Liver Metastasis Committee of colorectal tumor branch of the Chinese Medical Doctor Association

• Deputy Leader of the Liver Metastasis Group of the Colorectal Cancer Committee of the Chinese Anti-Cancer Association

• Vice Chairman of the MDT Committee of the Surgical Branch of the Chinese Medical Doctor Association

• Vice Chairman of liver surgery branch of Chinese Medical Promotion Association

• Vice Chairman of the Oncology Surgery Committee of the Chinese Association of Research Hospitals

• Chairman of the Hepatobiliary and Pancreatic Professional Committee of Beijing Anti-Cancer Association

References:

1.
China Healthcare International Exchange Promotion Association.
Consensus on the diagnosis and treatment of colorectal cancer liver metastasis MDT of colorectal cancer liver metastasis branch of the Chinese Medical Promotion Association.
E-Journal of Liver Cancer.
2017,4(2):1-12.

2.
Surgeon Branch of Chinese Medical Doctor Association.
Chinese Guidelines for the Diagnosis and Comprehensive Treatment of Liver Metastases for Colorectal Cancer (2020).
Chinese Clinical Medicine.
2021.
28(1):26-41.

3.
Van Cutsem E, Cervantes A, Adam R,et al.
ESMO consensus guidelines for the management of patients with metastatic colorectal cancer.
Ann Oncol.
2016 Aug; 27(8):1386-422.

4.
Conrad C, You N, Vauthey JN.
In patients with colorectal liver metastases, can we still rely on number to define treatment and outcome? Oncology (Williston Park).
2013 Nov; 27(11):1078, 1083-4, 1086.

5.
Tang JB.
Long-term outcomes of patients with 10 or more colorectal liver metastases.
Br J Cancer.
2017 Aug 22; 117(5):604-611.

6.
Sahara K, Watanabe J, Ishibe A, et al.
Long-term outcome and prognostic factors for patients with para-aortic lymph node dissection in left-sided colorectal cancer.
Int J Colorectal Dis.
2019 Jun; 34(6):1121-1129.

7.
Fujisaki S, Takashina M, Suzuki S, et al.
Complete response of colorectal liver metastases after chemotherapy: does it mean cure? J Clin Oncol.
2006 Aug 20; 24(24):3939-45.

8.
Chen JY, Dai HY, Li CY,et al.
Contrast-Enhanced Intraoperative Ultrasound Improved Sensitivity and Positive Predictive Value in Colorectal Liver Metastasis: a Systematic Review and Meta-Analysis.
Ann Surg Oncol.
2021 Jul; 28(7):3763-3773.

9.
Xu D, Wang HW, Yan XL, et al.
Sub-millimeter surgical margin is acceptable in patients with good tumor biology after liver resection for colorectal liver metastases.
Eur J Surg Oncol.
2019 Sep; 45(9):1551-1558.

EDIT: Large circle

Typography: Uni

Execution: Small garden