TOPLINE:

Renin-angiotensin system inhibitors (RASIs) are associated with improved survival outcomes in patients with stage II/III colon cancer and hypertension following surgery. In a matched cohort of 2292 patients from multicenter databases in China, those receiving RASIs had a 3-year disease-free survival (DFS) rate of more than 83% compared with more than 78% in those not receiving RASIs, primarily due to reduced distant metastasis rates.

METHODOLOGY:

• RASIs, a common type of antihypertensive medication including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs), are considered to exert anticancer effects by inhibiting the ACE-angiotensin II-angiotensin II type 1 receptor pathway, which can lower blood pressure and potentially affect cancer progression.
• Previous cohort studies on the long-term oncologic outcomes of colorectal cancer after surgery have been contradictory, with most not clarifying significant differences of RASIs in long-term oncologic outcomes, and some reporting conflicting results regarding ACEIs vs ARBs in cancer-specific survival and overall survival.
• Researchers conducted a retrospective cohort study emulating a hypothetical randomized controlled trial using data from multicenter databases in Shanghai, China, including the Shanghai Colorectal Cancer Cohort Database and the colorectal cancer database of Zhongshan Hospital Fudan University.
• A total of 2640 eligible patients with radical resected stage II or III colon adenocarcinoma and hypertension were consecutively enrolled from January 2017 to April 2022, with 2292 patients included in the primary analysis after 1:1 propensity score matching (1146 in the RASI group and 1146 in the no-RASI group).
• Patients were classified into the RASI group if they routinely received RASIs (ACEIs or ARBs) for hypertension in the first month after surgery, or into the no-RASI group if they received other antihypertensive medications without RASIs.
• Propensity score matching was performed at a 1:1 ratio using conditional logistic regression according to factors including sex, age, BMI, preoperative carcinoembryonic antigen, hypertension grade, diabetes, cardiovascular disease, cerebrovascular disease, chronic kidney disease stage, tumor characteristics, pathologic stage, mismatch repair status, gene mutations, and chemotherapy regimen.
• The primary outcome was the 3-year DFS rate, with secondary outcomes including 3-year locoregional recurrence rate, distant metastasis rate, and overall survival rate, with a median follow-up time of 46.3 months.

TAKEAWAY:

• The RASI group demonstrated a higher 3-year DFS rate of 83.4% compared with 78.3% in the no-RASI group (P = .001; hazard ratio [HR], 0.736).
• The RASI group had a lower 3-year distant metastasis rate of 15.6% vs 20.5% in the no-RASI group (P < .001; HR, 0.717).
• The RASI group showed a higher 3-year overall survival rate of 92.4% compared with 89.6% in the no-RASI group (P = .001; HR, 0.682).
• No significant difference was observed in the 3-year locoregional recurrence rate between the RASI group at 1.8% (95% CI, 1.0-2.6) and the no-RASI group at 2.0% (95% CI, 1.2-2.8).

IN PRACTICE:

“RASIs may improve the postoperative long-term oncologic outcomes for patients with stage II/III colon cancer and hypertension,” wrote the authors of the study.

SOURCE:

The study was led by Kaiwen Chen, MD, Donghao Xu, MD, and Zhiyuan Zhang, PhD, Colorectal Surgery Department, Zhongshan Hospital, Fudan University, Shanghai, China, with Qingyang Feng, MD, as corresponding author. It was published online on May 4 in JCO Oncology Practice.

LIMITATIONS:

The study population was limited to patients with hypertension, which restricts the generalizability of findings to the broader colon cancer population without hypertension. After propensity score matching, the RASI group still had higher hypertension grade and more patients with chronic kidney disease, with borderline balance, which could suggest that the effects of RASIs in improving prognosis, especially overall survival, may stem from treatment of hypertension and comorbidities rather than direct anticancer effects. The no-RASI group exhibited higher T4 stage, higher N2 stage, and more mutant KRAS, NRAS, and BRAF, which could lead to worse prognosis and result in an overestimation of the effect of RASIs. It was uncertain when RASI therapy for preventing postoperative recurrence should be initiated, as many patients received RASI treatment for a long time before surgery, and analyses revealed no significant difference between patients who used RASIs for more than 2 years vs less than 2 years before surgery. For 654 patients, medical records were not completely obtained, and long-term use of antihypertensive medication could only be obtained through questioning, which could affect the reliability of the as-treated and per-protocol analysis.

DISCLOSURES:

This study received support from the National Natural Science Foundation of China (grant No. 82173164 to Qingyang Feng, MD) and the Shanghai Hospital Development Center, Shanghai Municipal Health Commission (grant No. SHDC2025CCS019 to Jianmin Xu, PhD). The funders of this study paid for the maintenance of the Shanghai Colorectal Cancer Cohort Database and the colorectal cancer database of Zhongshan Hospital, Fudan University. No relevant conflicts of interest were reported by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.