Long-course preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: long-term results of the randomized Polish II study

Abstract

Background: This trial evaluated whether preoperative short-course radiotherapy and consolidation chemotherapy (CCT) were superior to chemoradiation in rectal cancers with clinical (c)T4 or fixed cT3. Previously, we reported early results showing no differences in the radical surgery rate (primary end point). In the short-course/CCT group, we observed lower acute toxicity of preoperative treatment and better overall survival (OS). We updated results to determine whether the benefit in OS was sustained and to evaluate late complications.Patients and methods: Patients with cT4 or fixed cT3 rectal cancer were randomized either to preoperative 5 Â 5 Gy and three cycles of FOLFOX4 or to chemoradiation (50.4 Gy with bolus 5-Fu, leucovorin and oxaliplatin).Results: Patients (N ¼ 515) were eligible for analysis, 261 in the short-course/CCT group and 254 in the chemoradiation group. The median follow-up was 7.0 years. The difference in OS was insignificant [hazard ratio (HR) 0.90; 95% confidence interval (CI) 0.70-1.15; P ¼ 0.38). However, the difference in early OS favouring short-course/CCT previously reported was observed again, being 9% at 3 years (95% CI 0.5% to 17%). This difference disappeared later; at 8 years OS was 49% in both groups. There was no difference in disease-free survival (HR 0.95; 95% CI 0.75-1.19; P ¼ 0.65) at 8 years 43% versus 41% in the short-course/CCT group versus the chemoradiation group, respectively. The corresponding values for cumulative incidences of local failure and distant metastases did not differ and were HR ¼ 1.08, 95% CI 0.70-1.23, P ¼ 0.60, 35% versus 32% and HR ¼ 1.10, 95% CI 0.68-1.23, P ¼ 0.54, 36% versus 34%, respectively. The rate of late complications was similar (P ¼ 0.66), grade 3þ being 11% versus 9% in the short-course/CCT group versus the chemoradiation group, respectively. Conclusion:The superiority of preoperative short-course/CCT over chemoradiation was not demonstrated.

Neoadjuvant chemoradiotherapy in rectal cancer

“…Preoperative treatment toxicity was lower in the SCRT with CCT group and R0 resection rates showed a trend towards favoring SCRT with CCT over LCRT (p = 0.07) [23]. Interestingly, early benefits for SCRT with CCT in terms of OS did not persist after a longer follow-up and superiority of SCRT with CCT over chemoradiotherapy could not be demonstrated [24]. Similarly, the randomized phase III RAPIDO trial [NCT01558921] compares conventional neoadjuvant LCRT with SCRT followed by six cycles of CPAEOX (capecitabine and oxaliplatin) and subsequent surgery [25].…”

MRI Lymph Node Evaluation for Prediction of Metastases in Rectal Cancer

“…Long-course RT, 2×25 or 1.8×28 Gy, is also followed by a waiting period before surgery, to allow for RTinduced down-staging of primary tumour and regional lymph nodes. Short-course RT with delay gives biological effect and oncological results equal to those of long-course RT with delay (23,24), and can be regarded as comparable therapies. When RT is followed by a delay, it is common practice to perform an MRI after 6 weeks, ahead of surgery, in order to rule out progression.…”

Recurrence Risk after Radical Colorectal Cancer Surgery—Less Than before, But How High Is It?

“…Time to recurrence rate/freedom from recurrence and recurrence-free or disease-free survival in adjuvant trials in rectal cancer with a surgery alone group and where systemic chemotherapy was provided in the experimental group. The old trials were identified in one meta-analysis/systematic overview [77] and the more recent ones in three overviews/meta-analysis [7,8,103] and four further studies where the recurrence risk could be described after preoperative RT [97] or CRT [98][99][100][101] were identified. The key publications for all trials were scrutinized to find information of recurrence rates and not only DFS or OS as mostly presented in the overviews.…”

“…One of the most recent trials [177] included only patients at high risk for relapse. Also [100] included only high-risk patients. In these trials preoperative chemoradiotherapy was given to all and adjuvant chemotherapy to some.…”