Results of a prospective randomised control 6 vs 12 trial: Is greater tumour downstaging observed on post treatment MRI if surgery is delayed to 12-weeks versus 6-weeks after completion of neoadjuvant chemoradiotherapy?

Randomized clinical trial of short or long interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer

“…Oncological outcomes (comparing 7 and 11 weeks) have not been published, but pCR rates were similar in the two groups (15⋅0 versus 17⋅4 per cent), whereas morbidity rates (particularly medical complications) were significantly higher and TME quality was lower in the LI group 26 . In support of the present findings, another study, which compared 6-and 12-week waiting periods in randomized patients, found a significantly higher pCR rate in the LI group, but these results are currently available only in abstract form 35 . It should be noted that the main difference between these three studies is the pCR rates of the SI groups; the rate was 15⋅0 per cent in the GRECCAR-6 study, considerably higher than those reported in the other two studies (9⋅0 per cent 35 and 10⋅0 per cent in the present study).…”

“…In support of the present findings, another study, which compared 6-and 12-week waiting periods in randomized patients, found a significantly higher pCR rate in the LI group, but these results are currently available only in abstract form 35 . It should be noted that the main difference between these three studies is the pCR rates of the SI groups; the rate was 15⋅0 per cent in the GRECCAR-6 study, considerably higher than those reported in the other two studies (9⋅0 per cent 35 and 10⋅0 per cent in the present study). It is difficult to explain this difference.…”

What is most relevant in preoperative rectal cancer chemoradiotherapy – the chemotherapy, the radiation dose or the timing to surgery?

“…However, to delay surgery to achieve more pCRs or to see more mrTRGs (tumor regression detected with MRT) and thus improve treatment outcomes with the motivation that both pCR and mrTRG are associated with (disease-free) survival is a leap of logic. This was, however, the conclusion in the British study [32] and has been a conclusion in most studies the past decade having explored the value of delaying surgery. The prognostic importance of pCR or mrTRG has been seen after CRT with a fluoropyrimidine to about 50 Gy.…”

“…Morbidity was increased and the quality of the mesorectal excision poorer in the longer interval group. In the British study, also including patients considered to be locally advanced (likely intermediate risk), tumor downstaging recorded with MRI (mrT) was higher in the group of patients having waited for 12 weeks rather than six weeks (58% vs. 43%, p ¼ .02), as were the rate of pCRs (20% vs. 9%, p < .05) [32].…”

“…For the patients more relevant outcomes as risk of recurrence, survival and toxicity have not differed according to the length of the interval. The time interval after CRT has now also been subject to randomized studies [32,33]. The two trials reached different results in pCR rates, being the primary endpoint in one of the studies, and secondary in the other.…”