Surgery Ups Survival, So Why Are CRLM Not Referred for Resection?

Kristin Jenkins

August 04, 2020

For more than 20 years, liver surgeons have known that tailored resection of colorectal liver metastases (CRLM) provides a huge survival advantage compared with chemotherapy alone, and today more patients with CRLM may be candidates for resection than ever before.

In spite of this, only 15% of patients with CRLM are referred for resection even though it is estimated that 30% could benefit.

"As liver surgeons, we are deeply concerned that patients with CRLM are not being appropriately referred for life-extending surgery," write Alice C. Wei, MD, and William R. Jarnagin, MD, of the department of surgery at Memorial Sloan Kettering Cancer Center in New York City.

"Resection of colorectal liver metastases (CRLM) is potentially curative therapy when used as part of multimodality therapy," they write in a Viewpoint column published online July 15 in JAMA Surgery.

Long-term results from a randomized, controlled, phase 3 trial show that the 5-year overall survival after metastasectomy was more than 50% compared with an estimated 14% in patients treated with chemotherapy alone, the authors point out.

The most significant barrier to referral is the complex assessment of patient suitability for resection, Wei told Medscape Medical News.

"Understanding who will benefit from surgery for colorectal liver metastases can be complicated and ever-changing," she explained. "Engaging a liver surgeon to evaluate your patients with colorectal liver metastases early, and often, may help identify your patients who can benefit from life-extending surgery. This is simply not possible through lab tests or radiology reports."

When approached for comment, Yuman Fong, MD, chair of the Department of Surgery at City of Hope Medical Center in Duarte, California, wholeheartedly agreed.

"Median survival without surgery is less than 3 years, and almost no one is cured," Fong told Medscape Medical News. "Patients with more than five liver metastases, and sometimes more than 10 metastases, are now curable with expert surgery. Thus, patients with metastatic colorectal cancer should be sent for an opinion from an expert liver surgeon to be sure we do not miss an opportunity to extend life."

With systemic therapy, 40% of patients with CRLM can be cured with liver resection, Fong said, pointing to results from a 25-year follow-up study of 548 liver resections performed between 1970 and 1992. The findings show that surgery alone cured 20% of patients with metastatic colorectal cancer.

In California, which Fong referred to as "a state with good healthcare," results from a recent population-based study show that less than 10% of patients with liver metastases underwent liver resection. The study also identified wide variations and significant population-level disparities in the use of liver resection for CRLM across the state.

Fong also noted that surgical resection and 6 months of adjuvant chemotherapy may provide longer survival at a fraction of the cost of palliative chemotherapy.

"Systemic chemotherapy for stage 4 colorectal cancer costs upwards of $60,000-$100,000 for 6 months," he explained. "Thus, patients treated only with systemic chemotherapy, biologic agents, and immune therapy may incur charges of more than $200,000-300,000 before death. Surgical resection may be both better and cheaper."

Although results from a survey of general surgeons and medical oncologists show that patients with a single CRLM lesion were referred to a liver surgeon more than 95% of the time, referral rates plummeted for patients with multiple tumors and/or extrahepatic disease.

But even these patients with multiple tumors and/or extrahepatic disease can gain considerable benefit, Wei and Jarnigan say. Resection is usually possible: the key technical determinant is whether a functional liver remnant can be preserved after resection/ablation.

Following a formal review of the imaging by an experienced liver surgeon, a tailored procedure based on the association between tumors and vital structures is designed for each surgical candidate, they point out.

"We now understand that selected patients who have a robust, durable response to systemic therapy can benefit from resection of their liver disease," Wei and Jarnigan write. "Thus, patients whose cases were previously considered unresectable may be rendered resectable, particularly with the use of liver-preserving strategies, such as portal vein embolization to augment the future liver remnant size, hepatic artery infusion-pump chemotherapy, or planned sequential liver resections."

Although up to 40% of physicians in the US have not had access to a liver specialist with board certification in hepatopancreatobiliary (HPB) surgery or complex surgical oncology, this may be changing because of the increased use of telemedicine during the COVID-19 pandemic, Wei said.

"I think telemedicine is an excellent way for more patients to have a consultation about resection for colorectal liver metastases," she said, noting that at Memorial Sloan Kettering the use of telemedicine has increased significantly during the pandemic. "Anecdotally, patients find it very convenient, and in fact, many patients seem to prefer telemedicine."

When asked about the impact of the pandemic, Fong expressed concern that it could further decrease the availability of expert care for patients in the US with CRLM.

"For patients with advanced metastatic disease, it is often necessary to travel to major centers for expert surgery," he explained. "In other nations such as the United Kingdom and Sweden, referral to an expert center is mandated. COVID-19 now makes it hard for the patients to travel, both out of fear and also due to logistics such as quarantines."

Wei reported relationships with Celgene, Shire, Ipsen, Ethicon, Physicians Education Resource, Paradigm Medical Communications, Intuitive Surgical and Bayer. Fong, who is editor-in-chief of Molecular Therapy Oncolytics, disclosed relationships with Merck, Imugene, Intuitive, and Medtronics. Jarnagin has disclosed no relevant financial relationships.

JAMA Surg. Published online July 15, 2020. Viewpoint

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