Primary Tumor Resection in Patients With Colon Cancer

Introduction:

Colorectal cancer is the third most common cancer and the second most common cause of cancer-related death. Primary tumor resection is the treatment for patients with stage-four colorectal cancer with distant metastasis. This is done to reduce tumor-associated complications and to avoid life-threatening conditions like intractable bleeding, intestinal obstruction, and perforation. However, it is still unclear whether upfront primary tumor resection is required in asymptomatic, unresectable metastases of colorectal patients.

Primary tumor resection in asymptomatic patients with stage-IV colorectal cancer can avert obstruction and emergent circumstances induced by primary cancer. These difficulties are associated with improved mortality and morbidity. Upfront primary tumor resection is chosen to prevent tumor-related complications, which can develop during chemotherapy. In addition, a reduction in tumor burden after primary tumor resection is predicted to increase the survival chances.

Several retrospective studies and meta-analyses have observed survival benefits of primary tumor resection resembled upfront chemotherapy. Some studies showed primary tumor resection helps in extended cancer-specific survival compared to upfront chemotherapy. A nationwide study in the Netherlands discovered that primary tumor resection followed by systemic chemotherapy provided better survival benefits than chemotherapy alone. Upfront chemotherapy is used as an initial therapy. The advancement of modern systemic chemotherapy utilizing combined chemotherapy with molecular target agents enhanced the survival rate of patients with metastatic colorectal cancer.

What Are the Complications of Primary Tumor Resection?

The primary tumor-related complication is intestinal obstruction. Postoperative complications of primary tumor resection are fever, wound seroma, and postoperative ileus.

What Are the Treatments Available for Metastatic Colorectal Cancer?

Metastasis of colorectal cancer is restricted to the liver, and curative treatment can be achieved by resection of metastasis surgically. Complete surgical resection of metastatic lesions enhances survival rates to 35 % to 60 % in selected patients. The extrahepatic disease is no longer a contraindication for surgery in selected patients.

Hyperthermic intraperitoneal chemotherapy is a favorable treatment in selected patients with limited peritoneal carcinomatosis, and long-term survival can be attained. In some cases, colorectal cancer patients with unresectable metastasis are treated with systemic combination chemotherapy regimens. Common mixtures are oxaliplatin or irinotecan in addition to fluoropyrimidine, capecitabine, or 5-fluorouracil.

The targeted biotherapies have been administered, such as antiangiogenic therapy, bevacizumab, and anti-epidermal growth factor receptor antibodies, including panitumumab and cetuximab, in the setting of tumors. These systemic chemotherapeutic combinations have presented 40% to 75% response rates, resulting in a median overall survival rate. Recent chemotherapy regimens have led to around 20 % of the tumors originally judged unresectable being transformed into resectable. It has provided opportunities for secondary curative surgery and an equivalent prognosis as in patients who underwent surgery for initially resectable liver metastasis.

What Are the Impacts of Primary Tumor Resection on the Survival of Patients With Colorectal Cancer and Unresectable Synchronous Liver Metastasis?

In asymptomatic primary tumors with unresectable synchronous liver metastasis, it is still unclear whether to do primary tumor resection before systemic treatment. Studies were done to analyze the survival of patients with unresectable stage-IV colorectal cancer undergoing primary tumor resection and compared with those without.

The major drawback of these studies is that patients with a better World Health Organization performance status (WHO-PS) and better prediction at baseline, that is, have fewer metastatic sites affected and were more likely to undergo surgery. Conversely, patients with the extensive disease were offered chemotherapy rather than surgery.

Similarly, only patients with good World Health Organization performance status could accept a whole course of potentially toxic chemotherapeutic agents such as irinotecan and oxaliplatin. Another limitation is that documented data on the usage of systemic therapy are short, which toughens the examination of the influence of primary tumor resection on effect.

Which Group of Patients With Colorectal Cancer and Unresectable Synchronous Liver Metastasis Are Likely to Benefit From Primary Tumor Resection?

Along with primary tumor resection, various other factors have independent prognostic effects.

They are:

• Age.

• American society of anesthesiology (ASA) score.

• World Health Organization performance status, preoperative CEA levels.

• Location of the primary tumor.

• Size and differentiation.

• The extent of the metastatic liver spread.

• Peritoneal dissemination and extrahepatic metastasis.

• Other independent factors include serum albumin, alkaline phosphatase levels, lymph node involvement, ascites, number of metastatic sites, and the administration of targeted therapy. Bilobar liver metastasis is associated with a reduced survival rate compared to the unilobar location. Peritoneal and omental metastasis is associated with poor survival.

Studies proposed that a liver burden of more than fifty percent and extrahepatic metastatic diseases that include peritoneal carcinomatosis and lung metastasis were poor prognostic factors in patients with colorectal cancer and unresectable at an advanced age and with poor World Health Organization performance status. Despite surgery and systemic therapy advancements, this seems to have stayed unaffected with time. Thus, selecting patients is a critical issue, and the judgment for primary tumor resection should consider these prognostic factors.

What Are the Underlying Hypotheses for Increased Survival in Patients Undergoing Primary Tumor Resection?

The advancement in survival after primary tumor resection is attributed to a more acceptable reaction to chemotherapy after the deduction of the tumor. The confirmed advantage of resecting primary renal and ovarian tumors in the existence of metastatic disease verifies this. The relations between primary tumor and target organs of metastasis dictate the advancement from micro- to macrometastasis. Primary tumors induce, in these distant organs, a successful atmosphere to improve the growth of metastatic deposits. Vascular endothelial growth factor receptor 2 (VEGFR-2) expressing circulating tumor cells settled in the pre-metastatic niches, previously colonized by hematopoietic cells expressing VEGFR-1. A recent study by van der Wal et al. suggested that primary tumor resection could prevent the liver parenchyma from soiling from micrometastasis.

What Are the Risks and Complications After Palliative Primary Tumor Resection in the Metastatic Setting?

Several studies suggest that primary tumor resection is associated with increased mortality and morbidity postoperatively in the presence of metastasis. In addition, there is a complication of wound infection, and most of it is managed conservatively.

Conclusion

Primary tumor resection followed by chemotherapy improved the two-year cancer-specific survival of patients with asymptomatic stage-IV colorectal cancer resembling chemotherapy alone. In addition, primary tumor resection-related main complications were rare as approximated to primary tumor-related complications originating during chemotherapy.

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