Updated analysis of adjuvant chemotherapy after radical resection of metachronous colorectal cancer metastases.

Abstract

e15618 Background: The role of adjuvant systemic therapy following complete (R0) resection of metachronous colorectal cancer (CRC) metastases or local recurrence remains a subject of debate. This non-randomized study was designed to assess outcomes associated with adjuvant chemotherapy compared with surgery alone after radical resection of metachronous CRC metastases. Methods: Patients aged ≥18 years with histologically confirmed CRC and resectable metachronous metastases (disease-free interval ≥6 months) at any site were assigned to either surgery alone (active surveillance) or adjuvant mFOLFOX6 for 6 months. The primary endpoints were 2-year disease-free survival (DFS) and second disease-free survival (DFS2). Non-inferiority was defined as an absolute difference in 24-month DFS between the surgery-alone and adjuvant chemotherapy groups not exceeding 10%, with the upper bound of the one-sided 95% confidence interval below this margin. Results: Between June 2008 and December 2022, 145 patients were enrolled and assigned to the surgery alone or ACT groups; baseline demographic and clinicopathologic characteristics were well balanced between groups. Median follow-up was 39.8 months (95% CI, 34.3–52.5) in the surgery alone and 45.3 months (95% CI, 39.1–52.5) in the ACT group. Median DFS was 24.4 months (95% CI, 14.6–41.2) and 17.9 months (95% CI, 14.4–26.7), respectively. Two-year DFS rates were 51.2% (95% CI, 39.1–67.0) and 43.2% (95% CI, 33.7–55.3) (p = 0.30). Non-inferiority of surgery alone compared with ACT for 2-year DFS was demonstrated according to the prespecified margin (non-inferiority p = 0.022). In post-progression analysis, DFS2 was significantly longer in the surgery alone group (median 70.4 months [95% CI, 32.7–NR] vs 35.5 months [29.3–50.8]; HR 0.52, 95% CI 0.31–0.89, p = 0.014). After progression, repeat surgery without chemotherapy was more common in the non-adjuvant group (33% vs 19%), whereas surgery followed by chemotherapy was more frequent in the ACT group (22% vs 38%). The majority of patients in both groups subsequently received palliative systemic therapy (44% vs 43%). Conclusions: In patients with completely resected metachronous CRC metastases, omission of adjuvant chemotherapy did not compromise DFS and was associated with longer DFS2. These findings support a more individualized approach to adjuvant treatment selection. Prospective randomized studies are warranted to confirm these observations.