Neoadjuvant Radiotherapy Versus Surgery Alone for Stage II/III Mid-low Rectal Cancer With or Without High-risk Factors

Abstract

Objective: The aim of this study was to compare stage II/III rectal cancers with or without high-risk factors, and evaluate the effect of neoadjuvant radiotherapy (NRT) in these 2 cohorts. Background: NRT is often used in stage II/III rectal cancers to improve local control, while not affecting overall survival. However, good-quality surgery without NRT may also achieve good local control in selected patients. Methods: According to risk-stratification criteria and clinical staging, consecutive eligible participants of stage II/III rectal cancer were preoperatively classified into patients with (high-risk) or without (low-risk) high-risk factors. Both groups were respectively randomized to receive either short-course radiotherapy (SCRT) + total mesorectal excision (TME) or TME alone, forming the following 4 groups: high-risk patients with (HiR) or without (HiS) radiation, and low-risk patients with (LoR) or without (LoS) radiation. The primary endpoint was local recurrence. The secondary endpoints included overall survival, disease-free survival, distant recurrence, quality of surgery, and safety (NCT01437514). Results: In total, 401 patients were analyzed. With a median 54 months’ follow-up, low-risk patients obtained better 3-year cumulative incidence of local recurrence (2.2% vs 11.0%, P = 0.006), overall survival rate (86.9%vs 76.5%, P = 0.002), disease-free survival rate (87.0% vs 67.9%, P < 0.001), and cumulative incidence of distant recurrence (12.5% vs 29.4%, P < 0.001) than high-risk patients. With regard to 3-year cumulative incidence of local recurrence, no differences were observed between the LoR and LoS groups (1.2% vs 3.0%, P = 0.983) or the HiR and HiS groups (12.9% vs 8.9%, P = 0.483). Conclusions and Relevance: Stratification of stage II/III rectal cancers according to risk factors to more precise subclassifications may result in noteworthy differences in survivals and local pelvic control. An extremely low cumulative incidence of local recurrence and survivals in low-risk patients can be achieved with upfront good quality of surgery alone. This trial, owing to the insufficient power, could not prove the noninferiority of surgery alone, but suggest a discriminative use of NRT according to clinical risk stratification in stage II/III rectal cancer.

A Postsurgical Prognostic Nomogram for Locally Advanced Rectosigmoid Cancer to Assist in Patient Selection for Adjuvant Chemotherapy

“…The long-term advantage of preoperative radiotherapy is to reduce the local recurrence rate (23)(24)(25). Deng et al (26) found no statistical differences in OS between direct surgery and neoadjuvant radiotherapy in low-risk patients (HR=1.486, 95% CI: 0.716-3.087; P=0.287), in the local recurrence rate (HR=1.018, 95% CI: 0.205-5.046; P=0.983), or in the distant recurrence rate (HR=1.675, 95% CI: 0.812-3.455; P=0.163). In high risk patients, direct surgery had no effect on local or distant recurrence rates compared with neoadjuvant radiotherapy (P>0.05).…”

Effect of Tumor Location on Outcome After Laparoscopic Low Rectal Cancer Surgery: A Propensity Score Matching Analysis

“…From July 2011 to December 2015, a randomized controlled trial (RCT) exploring the effect of neoadjuvant short-course radiotherapy on stage II/III mid or low rectal cancer with or without high-risk factors was ongoing at our institution. 13 Therefore, during this period, patients with clinical stage II to III were randomly assigned to receive neoadjuvant short-course radiotherapy or surgery alone. Only patients with fixed T3 and T4b were recommended to receive long-course neoadjuvant chemoradiotherapy (CAPOX and pelvic radiotherapy), a practice similar to that suggested by the Japanese Society for Cancer of the Colon and Rectum guidelines.…”

Tailored total neoadjuvant therapy for locally advanced rectal cancer: One size may not fit for all!

“…Yet, neoadjuvant CRT fails to improve the risk of distant recurrence, disease free survival (DFS) and overall survival (OS) [8]. The absolute improvement in distant disease control and overall survival may be achieved with better control of systemic disease [5,7,8].…”

“…Due to different selection criteria for patients with LARC in the current trials, there are no generally accepted criteria for patients to be selected for a TNT protocol. Patients with T4 rectal tumours, anal sphincter invasion, radiologically threatened circumferential radial margin, tumours with extramural venous invasion and extra-mesorectal lymph nodes with clinically malignant features are generally accepted as 'high risk' [4,5].…”