Association between the type of pre-existing adenoma and response of rectal cancer to neoadjuvant therapy.

Background: Several factors influence response to neoadjuvant therapy (NAT) for locally advanced rectal cancer. One potentially relevant factor not previously studied is the type of pre-existing adenoma. We aimed to investigate the association between the type of pre-existing adenoma and response of rectal cancer to NAT and examine the tumor characteristics by adenoma type.

Methods: This study was a retrospective review of patients with stage II-III rectal adenocarcinomas from the NCDB (2004-2017) who underwent proctectomy after NAT. Rectal cancers were classified and compared by the type of pre-existing adenomas: villous adenoma (VA), tubular adenoma (TA), and tubulovillous adenoma (TVA)-associated carcinomas. Case-control analysis of failure of response to NAT was conducted, including type of pre-existing adenoma as a potential covariate.

Results: 2760 patients (69.6 % male; mean age: 59.9 years) with stage II (44.8 %) or stage III (55.2 %) rectal cancers were included. Most adenomas were TVA (78.4 %), followed by VA (21.1 %) and TA (0.5 %). 55.5 % of patients showed complete response (10 %) and partial (downstaging; 45.5 %) response after NAT. 64.3 % of TA-associated rectal carcinomas failed to respond to NAT compared to 46.4 % and 43.9 % of VA and TVA-associated carcinomas, respectively (p = 0.388). Independent predictors of failure of response to NAT were stage II disease (OR: 1.85, p < 0.001), high tumor grade (OR: 1.94, p = 0.007), LVI (OR: 3.34, p < 0.001), PNI (OR: 1.69, p = 0.032), and elevated pretreatment CEA (OR: 1.54, p = 0.002).

Conclusions: TA-associated carcinomas exhibited the lowest response to NAT, although not statistically significant. Predictors for failure of response to NAT were stage II disease, high tumor grade, LVI and PNI, and elevated pretreatment CEA levels.