The Impact of Adjuvant Chemotherapy on Clinical Outcomes in Locally Advanced Rectal Cancer: A CHORD Consortium Analysis

TL;DR

This study finds that adjuvant chemotherapy improves survival in locally advanced rectal cancer patients after initial treatment.

Contribution

The study provides real-world evidence supporting the benefit of adjuvant chemotherapy in locally advanced rectal cancer.

Findings

Adjuvant chemotherapy improved 5-year disease-free and overall survival in locally advanced rectal cancer patients.

Multivariate analysis confirmed a significant survival benefit for patients receiving adjuvant chemotherapy.

The study highlights the need for future trials to identify optimal chemotherapy regimens and patient-specific predictors of benefit.

Abstract

Adjuvant chemotherapy remains an open question in the treatment of locally advanced rectal cancer, with conflicting data on the benefit to patient outcomes. In this study we use a large Canadian database to retrospectively examine patients with locally advanced rectal cancer who received adjuvant chemotherapy after initial neoadjuvant chemoradiotherapy and surgical management. We determine that there was a benefit to overall survival and disease-free survival in the patients who received adjuvant chemotherapy compared to patients who did not. Additionally, to identify patients who may benefit from adjuvant chemotherapy, we used multivariate analysis to determine variables associated with improved outcomes. While we did identify variables suggestive of worse prognosis, we did not identify specific variables associated with benefit. This work provides the basis for future randomized trials to determine ideal chemotherapy regimens and further identify patient-specific characteristics predictive of benefit for the use of adjuvant chemotherapy in locally advanced rectal cancer.

Background: The impact of adjuvant chemotherapy (AC) on outcomes in real-world patients with locally advanced rectal cancer (LARC) remains uncertain. Methods: Consecutive patients with LARC (stage II/III) undergoing neoadjuvant chemoradiation before curative-intent surgery from 2005 to 2013 were identified in the Canadian Health Outcomes Research Database. The impact of AC on clinical outcomes, including disease-free survival (DFS) and overall survival (OS), was evaluated using the Kaplan–Meier method and Cox proportional hazards modeling. Results: A total of 1448 patients had sufficient data available to be included for analysis with 1085 (74.9%) receiving AC. Of AC patients, 40.5% received oxaliplatin-based treatments. With a median follow-up of 66.43 months, the 5-year DFS rate was 67.7% (95% CI: 64.5–70.1%) vs. 58.7% (95% CI: 52.8–64.2%) in the AC group and non-AC group, respectively (p < 0.001). The 5-year OS rate of the whole cohort was 74.3% (95% CI: 71.5–76.85%) while the 5-year OS rate of the AC group was 77.8% (95% CI: 74.7–80.6%) compared with 63.8% (95% CI: 57.9–69.2%) for the non-AC group (p < 0.001). On multivariate analysis, patients who received AC had improved DFS (HR 0.6, 95% CI: 0.49–0.73, p < 0.001) and OS (HR 0.46, 95% CI: 0.36–0.58, p < 0.001). Conclusions: This large multi-institutional database analysis supports the use of AC in real-world LARC patients treated with nCRT followed by surgical resection.

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