Extramural Venous Invasion and Tumor Deposit at Diffusion-weighted MRI in Patients after Neoadjuvant Treatment for Rectal Cancer

Abstract

Background Diffusion-weighted (DW) imaging is useful in detecting tumor in the primary tumor bed in locally advanced rectal cancer (LARC) after neoadjuvant therapy, but its value in detecting extramural venous invasion (EMVI) and tumor deposit is not well validated. Purpose To evaluate diagnostic accuracy and association with patient prognosis of viable EMVI and tumor deposit on DW images in patients with LARC after neoadjuvant therapy using whole-mount pathology specimens. Materials and Methods This retrospective study included patients who underwent neoadjuvant therapy and surgery from 2018 to 2021. Innovative five-point Likert scale was used by two radiologists to independently evaluate the likelihood of viable EMVI and tumor deposit on restaging DW MRI scans in four axial quadrants (12 to 3 o'clock, 3 to 6 o'clock, 6 to 9 o'clock, and 9 to 12 o'clock). Diagnostic accuracy was assessed at both the per-quadrant and per-patient level, with whole-mount pathology as the reference standard. Weighted κ values for interreader agreement and Cox regression models for disease-free survival and overall survival analyses were used. Results A total of 117 patients (mean age, 56 years ± 12 [SD]; 70 male, 47 female) were included. Pathologically proven viable EMVI and tumor deposit was detected in 29 of 117 patients (25%) and in 44 of 468 quadrants (9.4%). Per-quadrant analyses showed an area under the receiver operating characteristics curve of 0.75 (95% CI: 0.68, 0.83), with sensitivity and specificity of 55% and 96%, respectively. Good interreader agreement was observed between the radiologists (κ = 0.62). Per-patient analysis showed sensitivity and specificity of 62% and 93%, respectively. The presence of EMVI and tumor deposit on restaging DW MRI scans was associated with worse disease-free survival (hazard ratio [HR], 5.6; 95% CI: 2.4, 13.3) and overall survival (HR, 8.9; 95% CI: 1.6, 48.5). Conclusion DW imaging using the five-point Likert scale showed high specificity and moderate sensitivity in the detection of viable extramural venous invasion and tumor deposits in LARC after neoadjuvant therapy, and its presence on restaging DW MRI scans is associated with worse prognosis. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Méndez and Ayuso in this issue.

Graphical abstract

Figure 1:

Flowchart of patient inclusion and exclusion criteria. DWI = diffusion-weighted imaging, EMVI = extramural venous invasion.

Figure 2:

Diagram of the five-point Likert scale scoring system used to assess extramural venous invasion (EMVI) and tumor deposit on diffusion-weighted images with apparent diffusion coefficient (ADC) mapping. DWI = diffusion-weighted imaging.

Figure 3:

Stacked bar plot shows the per-quadrant distribution of extramural venous invasion and tumor deposit as assessed with the diffusion-weighted imaging (DWI) five-point Likert scale and whole-mount pathology. Gray area of the stacked bar represents quadrants with nonviable cells at pathology, and the black area of the stacked bars represents quadrants with viable cells at pathology. A total of 410 quadrants were assigned a Likert score of 0 (unlikely viable), 15 quadrants were assigned a Likert score of 1 (less likely viable), 16 quadrants were assigned a Likert score of 2 (possibly viable), 22 quadrants were assigned a Likert score of 3 (suspicious viable), and five quadrants were assigned a Likert score of 4 (consistent with viable).

Figure 4:

Example application of the diffusion-weighted (DW) image five-point Likert scale for assessing extramural venous invasion (EMVI) or tumor deposit at MRI with corresponding whole-mount pathology in a 46-year-old man with locally advanced rectal adenocarcinoma. Baseline (A) axial and (B) sagittal T2-weighted MRI scans show EMVI and tumor deposit in the 12 to 3 o’clock quadrant (white arrow) and in the 3 to 6 o’clock quadrant (yellow arrow). Postneoadjuvant (C) axial and (D) sagittal T2-weighted MRI scans show regressed EMVI and tumor deposit in both the 12 to 3 o’clock quadrant (white arrow) and the 3 to 6 o’clock quadrant (yellow arrow). Postneoadjuvant therapy (E) axial DW image and (F) apparent diffusion coefficient map yielded a score of 0 (unlikely viable) in the 12 to 3 o’clock quadrant (white arrow) and a score of 3 (suspicious viable) in the 3 to 6 o’clock quadrant (yellow arrow). (G) Photomicrograph (hematoxylin-eosin stain; original magnification, ×2) shows acellular mucin corresponding to the 12 to 3 o’clock quadrant, consistent with posttreatment change without viable malignant cells (black box; magnification, ×50). On the contrary, there is viable EMVI corresponding to the 3 to 6 o’clock quadrant (red box; magnification, ×50).

Figure 5:

Example application of the diffusion-weighted (DW) image five-point Likert scale for assessing extramural venous invasion (EMVI) or tumor deposit on MRI scans with corresponding whole-mount pathology in a 36-year-old man with locally advanced rectal adenocarcinoma. (A) Baseline axial T2-weighted MRI scan shows EMVI and tumor deposit in the 6 to 9 o’clock quadrant (yellow arrow) and 9 to 12 o’clock quadrant (white arrow). (B) Postneoadjuvant therapy axial T2-weighted MRI scan shows partially regressed EMVI and tumor deposit in the 6 to 9 o’clock quadrant (yellow arrow) and 9–12 o’clock quadrant (white arrow). Postneoadjuvant therapy (C) axial DW image and (D) apparent diffusion coefficient map with a score of 4 (consistent with viable) in the 6 to 9 o’clock quadrant (yellow arrow) and in the 9 to 12 o’clock quadrant (white arrow). (E) Photomicrograph (hematoxylin-eosin stain, original magnification, ×2) shows viable tumor deposits corresponding to the 6 to 9 o’clock quadrant and 9 to 12 o’clock quadrant (red box; original magnification, ×50). Note that on A the lesion in the 9–12 o’clock quadrant presented similar to EMVI, contiguous from primary tumor bed; however, these turned out to be tumor deposits separate from primary tumor bed on E.

Figure 6:

Survival analyses using the Kaplan-Meier curve. (A) Disease-free survival based on extramural venous invasion (EMVI) and tumor deposit at postneoadjuvant MRI, and (B) disease-free survival based on EMVI and tumor deposit at pathology. Survival analyses using the Kaplan-Meier curve. (C) Overall survival based on EMVI and tumor deposit at postneoadjuvant MRI, and (D) overall survival based on EMVI and tumor deposit at pathology.