Metastatic and Recurrent Rectal Cancer

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The role of surgery in patients affected with stage IV rectal cancer is examined. In this stage of the disease cancer has spread to distant locations: liver, lungs, bones or other sites. Should these tumours be resect ed or should patients be given only palliative care? The purpose of treatment in this case is to improve symptoms through local control of the disease, and increase a patient's chance of cure or prolonged survival. Patients with advanced rectal cancer should be divided into two groups: patients with single site cancer localisation and patients with widespread tumour (majority of cases).

Chemotherapy in metastatic disease: 5-FU with or without leucovorin was the standard treatment for a long time. This regimen with continuous infusion of 5-FU, modulated with leucovorin or methotrexate, induces remission or shrinkage of the cancer in 10-44% of patients and the average patient survives approximately one year from treatment [74-76].

More recently, several newer chemotherapeutic drugs have demonstrated an efficacy in addition or not with 5-FU: DPD (inhibitors of dihydropyrimi-dine dehydrogenase), irinotecan (CPT-11), inhibitor of thymidylate synthase (Tomudex) and oxaliplatin (in particular in non-responders to 5-FU) [77-84].

When the site of the metastasis is a single organ, such as liver or lung or ovaries, patients may benefit from local treatment directed at that single site of metastasis. Several clinical trials have reported that surgical resection of metastasis offers a chance of cure in 25% of cases, and mortality and morbidity rates in specialised centres are acceptable.

For patients with limited (3 or less) hepatic metastasis, resection may be considered with 5-year survival rates of about 40% [85, 86].

Highly selected patients with limited pulmonary metastases and patients with both hepatic and lung secondaries may be treated surgically with acceptable 5-year survival rates (30%, and 5-year disease-free 55%) [86].

Patients with non-surgical liver disease may benefit from other procedures such as hepatic artery infusion (HAI) of a chemotherapeutic drug. This procedure has the potential advantage of delivering a higher dose of a chemotherapeutic drug directly to liver metastasis while avoiding the side effects of a systemic delivered chemotherapy. A trial of hepatic arterial floxuridine plus systemic 5-FU plus leucov-orin was shown to result in improved 2-year disease-

Table 5. Radiotherapy and hyperthermia

Authors

Patients

Hyperthermia

Treatment

RPC (%)

Berdov, Manteshashvili [70]

56

Endocavitary

40 Gy

13 vs. 1.7 (RT)

Ohno et al. [71]

32

Endocavitary

RT\CHT

30.6

You et al. [72]

44

Endocavitary

30-40 Gy

22 vs. 5.3 (RT)

Rau et al. [73]

36

External

40-50 Gy/5-FU+LV

14

RT, radiotherapy; CHT, chemotherapy; 5-FU, 5-fluoruracil; LV, leucovorin

RT, radiotherapy; CHT, chemotherapy; 5-FU, 5-fluoruracil; LV, leucovorin free and overall survival (86% vs. 72%, p=0.03) but did not show a significant statistical difference in median survival when compared to systemic chemotherapy alone [87].

Radiofrequency ablation for metastatic liver disease is preferable to cryotherapy and the complication rate is approximately 10% [88].

When carried out appropriately in patients with advanced rectal disease with peritoneal involvement, surgical debulking performed by skilled surgeons plus chemotherapy improves survival compared with chemotherapy alone. Nevertheless, there is an increased mortality rate of about 8% from sepsis or gastrointestinal fistulae. Some Authors reported better median survival after intraperitoneal chemotherapy vs. systemic CHT [89] after surgical debulking.

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