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IntroductionRecurrence-related risk factors and the clinical value of adjuvant radiotherapy for stage IIA (pT3N0M0) rectal cancer (RC) remain controversial. This study aimed to explore prognostic factors for disease recurrence in patients with pT3N0M0 RC and screen for subgroups most likely to benefit from postoperative radiotherapy-based regimens.Materials and MethodsWe retrospectively enrolled patients with stage IIA rectal cancer who received radical resection between 2017 and 2023. All participants were divided into three groups according to postoperative treatment: surgery alone (S), surgery plus chemotherapy (S+CT), and surgery plus radiotherapy-based therapy (S+RT based). We collected clinicopathological characteristics, details of postoperative adjuvant therapy, and follow-up data on tumor recurrence. Disease-free survival (DFS) was calculated accordingly. Univariate and multivariate analyses were used to screen independent prognostic factors for recurrence. Subgroup and interaction analyses were further performed to determine factors associated with favorable responses to radiotherapy.ResultsA total of 114 patients with pT3N0M0 RC were included. 37 patients had disease progression during follow-up. Local recurrence rates differed significantly across the three groups (P < 0.001). Compared with surgery alone, both adjuvant chemotherapy and radiotherapy substantially reduced local recurrence (both P < 0.001). The radiotherapy group showed a trend toward lower local recurrence than the chemotherapy group (5.5% vs 10.0%), without reaching statistical significance. Multivariate regression analysis identified S+RT-based therapy and tumor distance from the anal verge (TDA) as independent prognostic factors for DFS (P < 0.001; TDA= 5-10 cm: P = 0.01; TDA ≥ 10 cm: P = 0.028). Subgroup analysis with interaction testing demonstrated that the efficacy of S+RT-based therapy varied significantly according to age, percent circumferential involvement (PCI), and CD34 expression. S+RT-based therapy was associated with significantly improved DFS in patients with PCI of 1/2 to 1, age ≥ 60 years, and CD34-positive tumors (P < 0.001; P = 0.015; P = 0.03, respectively). Radiotherapy also conferred superior DFS in the overall cohort of patients with stage IIA rectal cancer (P = 0.024).ConclusionAdditional radiotherapy after radical resection improves DFS, particularly in those with PCI of 1/2 to 1, age ≥ 60 years, and positive CD34 expression. However, these findings require validation in prospective randomized controlled trials.