Top Line: After decades with no major headway, the treatment of locally-advanced rectal cancer has seen some paradigm shifts over just the past few years.
The Study: We’re referring to both total neoadjuvant therapy (TNT) as well as organ preservation, with data accumulating left and right. To add to the pile is the randomized, phase II OPRA trial where 324 patients receiving TNT for stage II-III rectal cancer were randomized to chemo then chemoradiation (CRT) or vice versa prior to standard total mesorectal excision or a watch and wait approach based on tumor response. There were two goals: to determine if TNT improved 3-year DFS compared to historical control, and to evaluate the efficacy of a watch-and-wait (WW) approach in complete or near complete responders to TNT. The chemo consisted of 4 cycles of oxaliplatin + 5FU or Xeloda, and the chemoradiation was long-course with concurrent 5FU or Xeloda. The primary outcome of disease-free survival was 76% at 3 years in both arms and it was not higher than the historical rate of 75%. Where things get interesting, though, is the secondary endpoint of TME-free survival. Overall, 74% of patients went on to WW without initial surgery, and only 27% in the CRT-first arm (v 40% in the chemo-first arm) developed tumor regrowth. TME-free survival was significantly higher at 3 years after chemoradiation first (53%) than vice versa (41%). In other words, over half of patients treated with TNT sequenced with long-course CRT followed by chemotherapy remained free of disease without surgery.
TBL: Putting radiation first in the TNT line-up for locally-advanced rectal cancer maximizes chance for organ preservation, which can be achieved in as many as half of all patients. | Garcia-Aguilar, J Clin Oncol 2022