We investigated tumor regression grading (TRG) as a prognostic marker for disease-free survival (DFS) in patients with advanced rectal cancer treated within phase III randomized study. The study was prospective trial of preoperative hyperfractionated radiotherapy (HART) compared with concomitant hyperfractionated radiotherapy with co-administration of chemotherapy based on 5FU (HART-CT) in patients with T2/N+ or T3/any N resectable mid-low primary rectal cancer.
The 136 patients were randomly assigned to HART (n = 69) and HART-CT (n = 67). The pelvis was irradiated twice a day (28 fractions of 1.5 Gy), with a minimal interfraction interval of 8 hrs to total dose 42 Gy over 18 days (HART) or mentioned scheme with concurrent chemotherapy: 5FU-325mg/m2 (bolus) on days 1-3 and days 16-18 (HART-CT). Surgery was performed 5-6 weeks after HART/HART-CT. The TRG was recorded using 4-point scale: TRG0 (pCR) denoted no cancer cells; TRG1 - cancer cells less than 10% of a tumor mass; TRG2 cancer cells in 10-50% or TRG3 - cancer cells in more than 50% of tumor mass. Multivariable analysis was performed using Cox regression models adjusted for treatment arm, resection status and pathologic stage. Cox proportional hazard model was used in survival analysis.
The crude rate of patients with any serious adverse events during the follow-up was 12% vs. 17% for HART and HART-CT. Anterior resection was performed in 52% vs. 62% for HART and HART-CT respectively (p = 0.06). Of the 136 patients evaluable for pathologic response there were 3(4%) vs. 9(13%), 16(23%) vs. 24(36%), 40(58%) vs. 30(45%), and 10 (15%) vs. 4(6%) patients with TRG 0, 1, 2 and 3, respectively in HART vs. HART-CT, the difference was statistically significant p = 0.002. The actuarial 2-year cumulative loco-regional relapse free survival control rates (LRC) for HART vs. HART-CT were 86% vs. 91% and actuarial DFS control rates were 70% vs. 76%, respectively.
Significant differences in the tumor regression grading (TRG) were found. Both LRC and DFS of rectal cancer patients treated with HART vs. HART-CT had favorable outcomes in those allocated to HART-CT. Also the sphincter preservation rate tended to favor HART-CT.
Clinical trial identification
Legal entity responsible for the study
Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, 44-100 Gliwice, Poland.
Has not received any funding.
All authors have declared no conflicts of interest.