EP456 - Upfront Surgery versus Preoperative Chemoradiation in Locally Advanced Mid Rectal Cancer: Reevaluating the Role of PCRT

Purpose/Background: Although preoperative chemoradiation therapy (PCRT) has become a standard treatment for mid-to-low locally advanced rectal cancer and has led to lower local recurrence and better sphincter-preservation, PCRT was inherent in under- or over-treatment. The aim of this study was to compare the recurrence-free survival (RFS) and local recurrence rates of patients who received preoperative chemoradiotherapy for mid locally advanced rectal cancer vs. those who did not.

Methods/Interventions: A single-institution, retrospective cohort of 451 patients with trans-rectal ultrasound (TUS) and magnetic resonance imaging (MRI)-staged cT3N0 or cT1-3N+ mid locally advanced rectal cancer was included between January, 2006 and December, 2010. All the patients underwent curative operations (R0). Mid rectal cancer defined that inferior tumor border located around anterior peritoneal reflection (≥2cm - ≤2cm). The study cohort included 251 who received PCRT and 200 who did not. The RFS and cumulative recurrence rates were compared in the two groups. We also investigated the rates of sphincter-preservation surgery in the two groups.

Results/Outcomes: There was no significant difference between the two groups in terms of median age, sex, follow-up duration, clinical stage, histologic differentiation, presence of perineural invasion, average length and status of distal resection margin, status of circumferential resection margin. Due to PCRT effect, there were significant differences in preoperative level of serum carcinoembryonic antigen (CEA), pathologic TNM stage, and presence of lymphovascular invasion (LVI); lower level of CEA, 13.1% complete remission rate, and lower presence rate of LVI in PCRT group, compared with Surgery, first group. The 5-year overall survival rate was similar in the two groups group (PCRT vs. Surgery, first; 84.8% ± 2.3% vs. 84.0% ± 2.6%, p = 0.99). The 5-year RFS rate was not significantly different between the two groups (PCRT vs. Surgery, first; 76..9% ± 2.7% vs. 78.0% ± 3.1%, p = 0.84). The cumulative recurrence rate in the study cohort was 21.3%, with similar rates in the two groups (PCRT vs. Surgery, first; 21.9% vs. 22.5%, p = 0.49) and the local recurrence rate was similar (PCRT vs. Surgery, first; 1.6% vs. 2.0%). The rate of sphincter-preservation operation in the two groups was not significantly different (PCRT vs. Surgery, first; 98.0% vs. 98.5%, P = 0.49). Although combined results of TUS and MRI were used for clinical staging, this study verified that the accuracy of clinical staging was 51.8 %, in the analysis of the Surgery, first group.

Conclusion/Discussion: PCRT did not improve the RFS, local recurrence rates, or rates of sphincter-preservation surgery, in patients with mid locally advanced rectal cancer. Considering the limitation of pretreatment clinical staging, the application scope of PCRT for patients with mid locally advanced rectal cancer should be re-evaluated in terms of oncologic outcomes, sphincter preservation, functional outcomes, and improved quality of life.

Table 1. Clinicopathologic characteristics, adjuvant treatment and recurrence patterns of the patients
The proportion of patients with elevated preoperative CEA (>6 ng/mL) was significantly higher in the surgery-first group (p = 0.02), whereas the distribution of surgery type (SSO vs. APR) was comparable between the two groups (p = 0.49). The PCRT group had a significantly greater proportion of patients with fewer than 12 harvested lymph nodes (p = 0.001). Early tumor stage (T1-2) and node-negative (N0) disease were relatively more frequent in the surgery-first group. Lymphovascular invasion was significantly more common in the surgery-first group (p = 0.001). Notably, 30% of surgery-first patients did not receive adjuvant chemotherapy, and 38.5% did not require adjuvant radiotherapy.
Figure 1. Comparison of 5-year overall survival and recurrence free survival between PCRT group and Surgery, first group
Five-year overall survival was comparable between the PCRT and surgery-first groups (84.8% vs. 84.0%, p = 0.99).

Five-year recurrence-free survival was similar between the PCRT and surgery-first groups (76.9% vs. 78.0%, p = 0.84).