Oncology





Management of
colorectal liver metastases
at King Hussein Cancer Center
– The multidisciplinary approach


One third of patients with colorectal cancer presents with stage IV disease, the liver is the most common site for distant metastasis. Historically this group of patients was considered only for palliative interventions with dismal 5-year survival. Although synchronous presentation is considered a negative prognostic indicator, several studies have demonstrated that long-term survival is possible after complete surgical resection of all disease. The reported 5-year survival after resection of liver metastasis has doubled from 30% to 65% over the last 2 decades. Multiple factors have contributed to this improvement: Adoption of aggressive and safe surgical strategies is one factor, advancement in systemic chemotherapy and targeted therapy is another one, but perhaps the most important of all of these factors is the multidisciplinary (MDC) approach to this unique group of patients. This is thoroughly implemented at King Hussein Cancer Center (KHCC) in Amman, Jordan.

Physicians treating patients with stage IV colorectal cancer face multiple challenges in deciding where to start and what is the ideal sequence of interventions for optimal treatment of the primary tumour and metastatic disease. Lack of clear guidelines on the subject has resulted in the development of several new trends and strategies with variable results. With this in mind, an experienced multidisciplinary team who is familiar with all options available in the literature is necessary to ensure best outcomes for patients with stage IV colorectal cancer.



At KHCC there are multiple MDC teams for all types of tumours, the strong adherence and belief in this approach since the establishment of the centre, is the key factor for our success.

All patients with tumours in the Gastrointestinal Tract (GI) are discussed in our weekly GI MDC conference (See Figure 1) in the presence of an expert panel of Hepatobiliary and Colorectal Surgeons/Surgical Oncologists, Medical and Radiation Oncologists, Diagnostic and Interventional Radiologists, and Gastroenterologists. Treatment plans are formulated based on individual patient case and according to well-established protocols at the centre. Every team member adds significant value to the treatment plan and contributes to the excellent outcomes achieved in this group of patients.

The surgical approach to patients with CRLM has evolved significantly over the past decade, once considered a very morbid operation with high mortality rate, it is well accepted now as a standard of care with excellent perioperative outcomes. Advancement in stapling, tissue sealing and haemostatic devices in addition to liver resection under low Central Venous Pressure, have helped liver surgeons to perform liver resection safely with minimal blood loss.

Historically, the definition of resectability of CRLM was based on the number and size of metastasis being resected, based on this only 25% of patients were considered for surgical resection and possible cure. Over the years and with better understanding of liver anatomy and disease pathophysiology, the definition of resectability has shifted from what is being resected, to what is being left after resection. Our main goal is to remove all disease in the liver and leave the patient with an adequate liver remnant. This is defined as: 2 adjacent segments with adequate inflow, outflow and biliary drainage with sufficient volume (20-25% in healthy liver and 30-40% in diseased liver) (See Figure 2).

This would not have been possible without the advancement in perioperative imaging modalities (Liver Protocol CT scan, MRI with contrast, and Intraoperative Ultrasound) and the 3D software available for liver volume measurements (See Figure 3). Complete surgical resection is still possible even in patients with inadequate future liver remnant, tow-stage liver resection (Figure 4) and technology like Preoperative Portal Vein Embolization by experienced Interventional Radiologists have helped to induce hypertrophy in the future liver remnant and avoid risk of post-operative liver failure. Moreover the approach to patients with synchronous presentation has shifted from the classic approach (treating the primary tumour first) to recently described the ‘liver first’ (reverse) approach (See Figure 5).

Despite all these advances in surgery, diagnostic and interventional radiology, outcomes in this group of patients would be poor without advances in systemic treatment. As we all know, once the tumour has spread beyond its primary location, it becomes a systemic disease and should be treated with effective systemic treatment. In 1990’s, 5- Flurouracil (5-FU) was the only effective systemic chemotherapy available for patients with CRLM. In unresectable cases 5-FU resulted in a median survival of around 10 months. The discovery of Irinotecan and Oxaliplatin in early 2000’s and its addition to 5-FU (FOLFOX and FOLFIRI protocols) have resulted in significant improvement in median survival (up to 22 months) in unresectable CRLM.

Progress in systemic therapy didn’t stop at this level. Advancements in molecular biology and understanding the key steps in carcinogenesis have opened the door wide for the era of Targeted Therapy. The discovery of Bevacizumab (Monoclonal Antibody against Vascular Endothelial Growth Factor Receptor) and Cetuximab (Monoclonal Antibody against Epidermal Growth Factor Receptor) has resulted in further improvement of median survival (up to 26 months) in patients with unresectable CRLM when added to FOLFOX and FOLFIRI. The presence of such effective systemic treatment is a key factor in making surgeons more aggressive in dealing with patients with stage IV colorectal cancer. It is well accepted that response to chemotherapy is considered one of the most important prognostic indicators after surgical resection of CRLM. Even in patients with initially unresectable disease, chemotherapy can render up to one third of them resectable with hope of cure.

Similar to all other interventions made by humans, chemotherapy comes with some cost. The issue of chemotherapyinduced liver toxicity should always be kept in mind by treating physicians. Liver toxicity can result in denying the patient a possible curative surgical resection. To avoid prolonged courses of chemotherapy and its associated liver toxicity, well-established treatment protocols by developed by the GI MDC team are used with patients at KHCC with open communication between all disciplines involved all the process (Figure 6).

Stage IV rectal cancer

Management of patients with stage IV rectal cancer is even more complicated. This is mainly due to the need for radiation therapy for local control. The addition of this modality to the protocols requires extensive collaboration between different MDC members. For optimal outcomes, timing of surgical intervention and chemotherapy administration should be carefully decided in the MDC settings based on individual cases. To minimize radiation induced toxicity to adjacent organs, we utilise up-to-date protocols and techniques. This includes Intensity Modulated Radiotherapy (IMRT) by our well-trained staff (Figure 7).

Advances in Interventional Gastroenterology at KHCC has added significant value to the GI MDC team. In the past patients with symptomatic stage IV rectal cancer (bleeding or obstruction), were typically managed with resection of the primary tumour first. This resulted in significant delay in the treatment of liver metastasis with chemotherapy and liver resection. At KHCC Interventional Gastroenterology provides such patients with symptomatic relief utilising endoscopic stenting and Argon Plasma Coagulation. These temporary measures allow the patient to start the protocols of systemic treatment, without the need to first go through the morbid surgical resection of the primary tumour.

These efforts by different MDC team members will be fruitless without careful coordination. MDC team coordinators are crucial for this reason. They keep track of all patients under active treatment and ensure protocols are implemented in timely fashion. They facilitate communication between different physician members and between physicians and patients.

In conclusion, cure is possible in patients with stage IV colorectal cancer. The presence of an experienced multidisciplinary team is essential for their management. Every team member at KHCC adds significantly to the excellent outcomes achieved in this group of patients. This will not be possible without the presence of hospital administration and leadership that strongly believe in, and enforce, the multidisciplinary approach for cancer management.

The author

Osama Hamed, MD, is a Consultant Surgical Oncologist, and Hepatopancreatobiliary and Minimally Invasive Surgeon in the Department of Surgery at King Hussein Cancer Center.

Dr Hamed has won several honours and awards for his research in surgery. He has published numerous research papers on surgery for a variety of clinical journals and has contributed chapters to a number of books on the subject. 
 

 Date of upload: 22nd Jan 2013

 

                                  
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