Surveillance, Epidemiology, and End Results-based analysis of the impact of preoperative or postoperative radiotherapy on survival outcomes for T3N0 rectal cancer

Abstract

Purpose: Preoperative chemoradiation has been established as standard of care for T3/T4 node-positive rectal cancer. Recent work, however, has called into question the overall benefit of radiation for tumors with lower risk characteristics, particularly T3N0 rectal cancers. We retrospectively analyzed T3N0 rectal cancer patients and examined how outcomes differed according to the sequence of treatment received. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to analyze T3N0 rectal cancer cases diagnosed between 1998 and 2008. Treatment consisted of surgery alone (No RT), preoperative radiation followed by surgery (Neo-Adjuvant RT), or surgery followed by postoperative radiation (Adjuvant RT). Demographic and tumor characteristics of the three groups were compared using t-tests for the comparison of means. Survival information from the SEER database was utilized to estimate cause-specific survival (CSS) and to generate Kaplan–Meier survival curves. Multivariate analysis (MVA) of features associated with outcomes was conducted using Cox proportional hazards regression models with Adjuvant RT, Neo-Adjuvant RT, No RT, histological grade, tumor size, year of diagnosis, and demographic characteristics as covariates. Results: 10-Year CSS estimates were 66.1% (95% CI 62.3–69.6%; P = 0.02), 73.5% (95% CI 68.9–77.5%; P = 0.02), and 76.1% (95% CI 72.4–79.4%; P = 0.02), for No RT, Neo-Adjuvant RT, and Adjuvant RT, respectively. On MVA, Adjuvant RT (HR = 0.688; 95% CI, 0.578–0.819; P < 0.001) was associated with significantly decreased risk for cancer death. By contrast, Neo-Adjuvant RT was not significantly associated with improved cancer survival (HR = 0.863; 95% CI, 0.715–1.043; P = 0.127). Conclusion: Adjuvant RT was associated with significantly higher CSS when compared with surgery alone, while the benefit of Neo-Adjuvant RT was not significant. This indicates that surgery followed by Adjuvant RT may still be an important treatment plan for T3N0 rectal cancer with potentially significant survival advantages over other treatment sequences.

Introduction

The role of radiotherapy (RT) in the treatment of locally advanced rectal cancer has evolved over time. Although adjuvant chemoradiation had been the standard of care for stage II or III rectal cancer well into the 1990s, the advent and success of total mesorectal excision (TME) called into question the role of RT for preventing local recurrences [1]. In just the past decade, however, the Dutch Colorectal Study Group showed that preoperative (Neo-Adjuvant) RT did improve rates of local control, though they found no significant increase in overall survival [2], [3], [4]. Most recently, the 2004 German Rectal Cancer Study and 2009 National Surgical Adjuvant Breast and Bowel Project (NSABP) definitively established Neo-Adjuvant RT over postoperative (Adjuvant) RT as standard of care for cT3/T4 or node-positive rectal cancer [5], [6].

Some controversy persists, however, for lower risk patients with stage II/III disease – specifically those with T3N0 staging. The question of whether the benefits of RT outweigh the risks for these patients remains largely unanswered, but without definitive evidence to the contrary, the standard treatment continues to be Neo-Adjuvant RT followed by TME [7]. In order to shed more light on this particular subset of rectal cancer patients, we queried the Surveillance, Epidemiology, and End Results (SEER) database to examine cases of T3N0 rectal cancer diagnosed between 1998 and 2008 where treatment consisted of surgery alone, Neo-Adjuvant RT followed by surgery, or surgery followed by Adjuvant RT.