Chapter 114: Recurrent Colorectal Cancer

BACKGROUND

Advances in the treatment of primary rectal cancer, including total mesorectal excision (TME) and neoadjuvant chemoradiation, have reduced the local recurrence (LR) rate to approximately 10% in the modern era.^1-3 While the LR rate following resection of rectal cancer significantly exceeded that of colon cancer in older publications, the two are now roughly equivalent.^4-6 Given the present incidence of colorectal cancer (CRC) in Western countries of approximately 130,000 cases annually,⁷ the burden of LR nevertheless remains significant.

Without treatment, the median survival from time of detection of LR is approximately 3 to 9 months.^8,9 With palliative chemotherapy and/or radiation median survival is approximately 17 months.^10-12 Surgical resection, in combination with other modalities, can achieve prolonged survival and even cure in appropriately selected patients. With radical extirpation, 5-year overall and recurrence-free survival rates of approximately 50% have been published in recent series.^13-19

Greater attention to technical detail, patient selection, and multidisciplinary care has improved the management of patients with recurrent CRC. Increasingly complex patients are now being treated with curative intent. However, there is limited good-quality evidence available from the literature on recurrent CRC, which consists mainly of retrospective case series that focus on locally recurrent rectal cancer (LRRC). This chapter reviews the literature and provides an approach to the assessment and management of patients with locoregional recurrence of colorectal cancer. We will focus on LRRC, with mention of recurrent colon cancer where relevant.

RISK FACTORS FOR LOCOREGIONAL RECURRENCE

Rectal Cancer

There is a greater risk of LR in men than women.²⁰ Both T and N status predict LR.^21,22 A positive circumferential margin of resection portends a higher risk of LR.^20,21 The advent of TME has been associated with a significant improvement in circumferential margin status, and many surgical series document this relationship.^20,23-25

Colon Cancer

Advanced histopathologic stage is the most significant risk factor for LR following resection of primary colon cancer.²⁶ Poorly differentiated tumors have a higher risk of LR compared to well- and moderately differentiated colon cancers. Distal colon cancers have been associated with a higher risk of LR, in some but not all studies.^27,28

MOLECULAR BIOLOGY

The overexpression of the tumor suppressor protein p53 by rectal cancers has been associated with a high rate of LR after resection and chemoradiation of the primary tumor.²⁹ In one series, rectal cancers that had both increased p53 nuclear accumulation and decreased expression of Bcl-2, which is inhibited by p53, had the highest risk of LR.³⁰

CD133 and CD44 have been identified as potential cancer stem cell markers for CRC and ...