Ann Surg 2023 Jan 20
Locoregional Failure During and After Short-course Radiotherapy followed by Chemotherapy and Surgery Compared to Long-course Chemoradiotherapy and Surgery - A Five-year Follow-up of the RAPIDO Trial.
Abstract
Objective
To analyze risk and patterns of locoregional failure (LRF) in patients of the RAPIDO trial at five years.
Summary background data
Multimodality treatment improves local control in rectal cancer. Total neoadjuvant treatment (TNT) aims to improve systemic control while local control is maintained. At three years, LRF rate was comparable between TNT and chemoradiotherapy in the RAPIDO trial.
Methods
920 patients were randomized between an experimental (EXP, short-course radiotherapy, chemotherapy, and surgery) and a standard-care group (STD, chemoradiotherapy, surgery, and optional post-operative chemotherapy). LRF, including early LRF (eLRF) (no resection except for organ preservation/R2 resection) and locoregional recurrence (LRR) after an R0/R1 resection, were analyzed.
Results
Totally, 460 EXP and 446 STD patients were eligible. At 5.6 years (median follow-up), LRF was detected in 54/460 (12%) and 36/446 (8%) patients in the EXP and STD groups, respectively (P=0.07), in which EXP patients were more often treated with 3D-CRT (P=0.029). In the EXP group, LRR was detected more often (44/431 (10%) vs. 26/428 (6%); P=0.027), with more often a breached mesorectum (9/44 (21%) vs. 1/26 (4); P=0.048). The EXP treatment, enlarged lateral lymph nodes, positive circumferential resection margin, tumor deposits, and node positivity at pathology were significant predictors for developing LRR. Location of the LRRs was similar between groups. Overall survival after LRF was comparable (HR 0.76 (95%CI 0.46-1.26); P=0.29).
Conclusion
The EXP treatment was associated with an increased risk of LRR whereas the reduction in disease-related treatment failure and distant metastases remained after 5 years. Further refinement of the TNT in rectal cancer is mandated.
Related Questions
How will the PROSPECT trial presented at ASCO 2023 change your current management of early rectal cancer?
I can’t overstate how much credit the Principal Investigator, Dr. @Dr. First Last, deserves for successfully completing the PROSPECT trial. The oncology community, particularly the radiation oncology community, was concerned that omitting radiation would put patients at risk. It was difficult and ch...
Do you ever utilize short-course radiation when lateral pelvic (extra-mesorectal) lymph nodes are involved?
My general preference is to use long course chemoradiation for patients with involved extramesorectal/lateral lymph nodes as it is a relatively strong risk factor for pelvic recurrence and such lymph nodes are not routinely surgically resected. While the pre-TNT era randomized trials comparing short...
For locally advanced rectal cancer, will the recent update of RAPIDO lead you to change your practice when approaching TNT?
We prefer long course chemoradiation followed by consolidation with FOLFOX and non-operative management based on the OPRA trial, which reported 60% versus 40% using this sequence versus initial chemotherapy.
How would you manage a patient with synchronous locally advanced rectal adenocarcinoma (T3N2) and a large T2N0 adenocarcinoma of mid and distal esophagus?
A tough situation no doubt. Def need an MDT agreement with medical oncology and surgery. The patient should be evaluated for surgical (especially esophageal resectability). I am going to try to be creative here : I would vote 5x5 to rectal mass then get on mFOLFOX6 based chemo per CALGB 80803 trial...
Have the results of the OPRA trial influenced your decision to recommend long course chemoradiation vs short course radiation therapy for patients receiving TNT who intend to undergo surgery?
The TME-free survival rate in the OPRA trial has solidified chemoradiation followed by consolidative chemotherapy as a standard in our practice. However, since the principal investigator is at our institution, it just meant that we continued doing what we were doing. It is important to realize that ...