Surveillance for asymptomatic recurrence in resected stage III colon cancer: does it result in a more favorable outcome?

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In patients with resected stage III colon cancer who had asymptomatic recurrences detected by surveillance were more likely to receive potentially curative metastasectomy and chemotherapy, according to a study published in the Journal of Gastrointestinal Oncology; however, the impact of detecting asymptomatic recurrences in these patients on overall survival is unclear.

Previous research has shown a modest survival benefit for intensive surveillance in patients with resected colon cancer. Therefore, researchers sought to evaluate surveillance in a modern population-based cohort of patients with stage III colon cancer.

Researchers analyzed the records of 635 patients who received oxaliplatin-based adjuvant chemotherapy between 2006 and 2011 at the British Columbia Cancer Agency in Canada. Of those, 27.5% experienced disease recurrence and 18.6% died during a median follow-up of 67.7 months.

Results showed that 149 of 175 recurrences were detected by surveillance, either via CEA elevation of abnormal imaging. The rest of recurrence cases were detected by symptoms.

Researchers found that median relapse-free survival was nearly 7 months shorter in those with surveillance-detected recurrences. Patients with surveillance-detected recurrences also had a longer median overall survival when measured from date of recurrence, but not when measured from date of initial surgery.

The study also demonstrated that patients whose disease recurrence was detected with surveillance were 32% and 20% more likely to receive potentially curative metastasectomy and chemotherapy, respectively.

This study evaluates survival outcomes of intensive surveillance post CRC resection in a modern, population-based cohort study.
This study evaluates survival outcomes of intensive surveillance post CRC resection in a modern, population-based cohort study.

Background: Evidence from dated and moderate quality trials supports a modest survival benefit for intensive surveillance in resected colon cancer (CC). This study evaluates surveillance in a modern population-based cohort of stage III CC patients (pts).

Methods: Records of pts who initiated oxaliplatin-based adjuvant chemotherapy (AC) for stage III CC between 2006-2011 at the British Columbia Cancer Agency (BCCA) were reviewed. Kaplan-Meier and log rank test were generated to investigate whether diagnosis of recurrence based on symptoms was associated with worse overall survival (OS). OS1 and OS2 were measured from date of recurrence or date of initial surgery, respectively.

Results: Of 635 pts who received AC for stage III CC, 175 pts (27.5%) recurred and 118 (18.6%) died at a median follow-up of 67.7 months. Recurrences were detected by surveillance in 149 pts (41% by CEA elevation and 44% by abnormal imaging), and symptoms in 26 pts (15%).

Patients with surveillance-detected recurrences had a shorter median relapse-free survival (RFS) (18.5 vs. 25.3 months, HR 1.82, P<0.001), and longer median OS1 (28.5 vs. 6.5 months, HR 0.37, P<0.001).

However, median OS2 was not significantly different (50.9vs. 39.1 months, HR 0.66, P=0.091). Pts with surveillance-detected recurrence received more potentially curative metastasectomy (39% vs.7%, P=0.002) and chemotherapy (70% vs. 50%, P=0.03).

Conclusions: In this modern population-based cohort study, the OS impact of detecting asymptomatic recurrences in stage III CC is unclear. However, pts with asymptomatic recurrences were more likely to receive potentially curative metastasectomy and chemotherapy.

Keywords: Colon cancer (CC); survival rate; carcinoembryonic antigen/blood; tomography X-ray computed; humans; neoplasm recurrence local/diagnosis


Submitted Jan 12, 2015. Accepted for publication Jan 20, 2015.

doi: 10.3978/j.issn.2078-6891.2015.019


INTRODUCTION

Colorectal cancer (CRC) is the third most common malignancy and cause of cancer related mortality in North America. The death rate from CRC has been annually declining by 3% since 2000, largely attributed to early detection and/or treatment1.

Around 80% of patients do not have metastatic disease at the time of diagnosis and are potentially eligible for curative intent surgery2. Subsequently, adjuvant chemotherapy (AC) improves survival in patients with early stage high-risk colon cancer (CC)3-5.

Unfortunately, approximately one-third of curatively treated patients suffer a recurrence, mostly within the first three years following surgery6.

Complete resection of CRC liver metastases can result in close to 40% 5-year survival7, and similar results have been observed with complete resection of lung metastases8.Consequently, many organizations have published surveillance recommendations, primarily in an attempt to identify recurrences at a resectable stage9-11.

Several randomized clinical trials (RCT) have been published on intensive surveillance post CRC resection, spanning many decades, and examining various permutations of follow-up schedules and tests12-20.

Meta-analyses have suggested an overall survival (OS) benefit to intensive follow-up, perhaps mediated through earlier (approximately 6 months) recognition of metastatic disease amenable to potentially curative metastasectomy21-23.

However, many of these RCTs were performed with moderate methodological quality21. Furthermore, disease-specific survival, when reported, was not improved15,17, thereby questioning whether the observed OS is attributable to CC directed therapy or perhaps other factors23.

Indeed, it has been estimated that only about 20% of the observed OS benefit could be attributed to resection of metastatic disease, and the balance of benefit may come from increased psychological support and well being, changes in dietary and lifestyle factors, or improved treatment of coincidental co-morbidities24.

Lastly, many of these RCTs were performed before or during landmark changes in AC25, introduction of new agents in advanced disease, and uptake of hepatic resection26. The results of these RCTs may therefore not be generalizable to the contemporary oncology clinic.

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