Nine RCTs with 3,946 participants were included in the review.
Only one trial described the mode of randomisation, three described the mode of allocation concealment, seven fully described withdrawals, and none of the trials were blinded.
Neoadjuvant therapy was associated with a statistically significant increase in loco-regional disease recurrence (RR 1.22, 95% CI: 1.04, 1.43), especially when radiotherapy was used without surgery.
There were no statistically significant differences between adjuvant and neoadjuvant therapy in terms of death (RR 1.00, 95% CI: 0.90, 1.12), disease progression (RR 0.99, 95% CI: 0.91, 1.07) or distant disease recurrence (RR 0.94, 95% CI: 0.83, 1.06).
There was statistically significant heterogeneity between studies in terms of clinical response, pathological response and the use of conservative local treatment (p<0.001 for all).
Small trials did not differ from large trials in their results for death, distant disease recurrence or loco-regional recurrence. However, in smaller studies there was some indication that neoadjuvant treatment was associated with more favourable comparative overall disease progression. The summary effect size did not change over time as more data accumulated.