Mesorectal Fascia Involvement by Tumor Deposits or Extramural Vascular Invasion at MRI Predicts Prognosis in Rectal Cancer

Background MRI has helped to identify mesorectal fascia (MRF) positivity as a poor prognostic factor in patients with locally advanced rectal cancer. However, outcomes in patients with MRF positivity may vary. Purpose To investigate the prognosis of the four types of MRF-positive classifications and their genetic and protein-level interpretations. Materials and Methods In this multicenter retrospective study (January 2009 to May 2023), patients with locally advanced rectal cancer who underwent rectal MRI were analyzed and categorized as follows: MRF caused by tumor invasion (tumor invasion vs no tumor invasion), extramural vascular invasion (EMVI; EMVI vs no EMVI), lymph node metastasis (LNM; LNM vs no LNM), and tumor deposits (TD; TD vs no TD). Disease-free survival (DFS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors were evaluated using multivariable Cox proportional hazard models. Tumor-associated genes were sequenced, tumor mutational burden (TMB) was calculated, and immunohistochemistry was performed to quantify the expression of Ki-67, as well as the infiltration densities of CD3⁺ and CD8⁺ T cells. Results A total of 959 patients from three centers were included (median age, 56 years [IQR, 48-63 years]; 622 men). Kaplan-Meier analysis showed MRF with TD and MRF with EMVI were associated with worse DFS compared with MRF without TD (median DFS, 18 vs 99 months, respectively; <i>P</i> < .001) and MRF without EMVI (median DFS, 39 vs 99 months, respectively; <i>P</i> = .01). At multivariable Cox regression analysis, MRF with TD and MRF with EMVI were independent risk factors for poorer DFS (hazard ratio, EMVI vs TD: 1.95 [<i>P</i> = .006] vs 2.55 [<i>P</i> < .001], respectively). TMB and T cell infiltration (CD3⁺ and CD8⁺) were lower in patients with MRF and EMVI compared with MRF without EMVI (log-transformed TMB: -0.49 vs -0.44, respectively [<i>P</i> = .04]; mean counts, CD3⁺: 103.4 vs 251.4, respectively; mean counts, CD8⁺: 72.3 vs 183.0, respectively [<i>P</i> < .001 for all]). Ki-67 expression was higher in patients with MRF with TD versus MRF without TD (median, 70% vs 60%, respectively; <i>P</i> = .01). Conclusion MRF caused by TD or EMVI at pretreatment rectal MRI predicted poor prognosis in patients with locally advanced rectal cancer. © The Author(s) 2025. Published by the Radiological Society of North America under a CC BY 4.0 license. <i>Supplemental material is available for this article.</i> See also the editorial by Horvat and Kim in this issue.