The empire strikes back.

Top Line: Who needs neoadjuvant therapy for rectal cancer?

The Study: With total neoadjuvant therapy being all the rage, this seems like a straightforward question. Neoadjuvant therapy is most often recommended for those with ≥T3 tumors or node positive disease. In fact, the 2020 UK National Institute for Healthcare Excellence (NICE) guidelines for management of rectal cancer recommend neoadjuvant therapy for ≥T3 and lymph node positive disease. However, some believe these criteria are too loose and lead many patients to receive unnecessary treatment. Their argument is that not all T3 tumors are at high risk of local recurrence (with high quality resection). At two centers in the UK, MRI-defined “high risk” features that merit neoadjuvant therapy include a close circumferential resection margin (CRM, ≤1mm or low tumors encroaching the intersphincteric plane or invading the levator muscles), tumors with extramural venous invasion (EMVI), and those with mesorectal tumor deposits (MRTD). This retrospective study of two prospectively collected databases from these centers describes outcomes for patients treated with primary surgery based on either NICE or MRI-based risk stratification. Out of 462 patients, 378 (82%) had upfront resection for rectal cancer. While 66% of those patients would have been considered high risk by the NICE guidelines, only 32% had high risk MRI features. The overall recurrence rate was 21% with local recurrence in 6% and distant recurrence 18%. NICE risk stratification predicted 5-year disease free survival (DFS) for high v low risk (76% v 87%) but not overall survival (80% v 88%). MRI risk features, on the other hand, predicted both DFS (66% v 88%) and OS (71% v 89%). On multivariable analysis, only the MRI risk stratification scheme (not NICE) was associated with DFS and OS. Among various MRI and clinical features, EMVI and MRTD were the only factors associated with DFS and OS. These outcomes are great—for these two specialized centers. This editorial rightly cautions us in applying the results too broadly. The NICE guidelines and other similar national guidelines (such as NCCN) are based on large multicenter trials that demonstrate a clear benefit with low risk of detriment for neoadjuvant therapy when applied across national health systems.

TBL: While most patients with ≥T3 or node positive rectal cancer should receive neoadjuvant therapy, some patients carefully selected at specialized centers based on MRI criteria may have a low risk of recurrence with surgery alone. | Lord, Lancet Oncol 2022