How best to combine DWI and T2WI to predict pathologic complete response: a multi-center study on interpreting MRI following chemoradiotherapy of rectal cancer

Objectives: To explore the different criteria of integrating diffusion-weighted imaging (DWI) for predicting pathologic complete response (pCR) of rectal cancer on post-chemoradiotherapy (CRT) MRI. Materials and methods: In this multi-center retrospective study, five radiologists reviewed pre- and post-CRT MRIs of patients with rectal cancer diagnosed in 2017–2021. In addition to mrTRG, three criteria were assessed: “AND” criterion (mrTRG 1–2 and absence of DWI restriction considered as CR), “OR” criterion (mrTRG 1–2 or absence of restriction), and a modified MR tumor regression grade (modMR-TRG). A crossed random effects model was used to pool sensitivity and specificity across five radiologists. F1 score and positive predictive value (PPV) were analyzed across varying pCR rates. Results: In 146 patients (median age [IQR], 63 [57–70] years; 87 men), the AND criterion yielded higher specificity (77.4% [63.3–80.0%] vs 75.3% [60.5–79.0%], p = 0.001) without significant difference in sensitivity (63.9% [42.8–75.3%] vs 67.5% [45.3–76.0%], p = 0.063) compared with mrTRG. OR criterion yielded higher sensitivity (86.1% [65.3–89.3%]; p < 0.001) but lower specificity (49.5% [36.2–62.6%]; p < 0.001). The modMR-TRG demonstrated similar effects to the OR criterion. Assuming a 20% pCR rate, PPV and F1 score of the AND criterion (point estimate of 41.4% and 50.3%, respectively) were higher than those of the OR criterion (PPV, 29.9%; F1 score, 44.4%), although the difference diminished with increasing pCR rate. Conclusion: The AND criterion—which utilizes DWI complementarily to further exclude patients with residual tumors after initial screening on T2WI—should be preferred over other criteria giving greater emphasis on DWI. Key Points: Question How should diffusion-weighted images be combined with T2-weighted images in predicting complete tumor response of rectal cancer on MRI following CRT? Findings Compared to mrTRG, the AND criterion yielded higher specificity without a significant difference in sensitivity, while the OR and modMR-TRG criteria yielded higher sensitivity but lower specificity. Clinical relevance Our study explores practical strategies for integrating DWI with T2WI that can be applied in daily practice. The AND criterion by using DWI conservatively is preferred over OR criteria, which results in a disproportionately higher number of additional false-positives than additional true-positives.