Objective To investigate the application value of magnetic resonance imaging(MRI) in evaluating the efficacy of anti‑PD‑1 combined with neoadjuvant therapy for microsatellite stability (MSS)/proficient mismatch repair (pMMR) locally advanced rectal cancer (LARC).

Methods The prospective single‑arm phase Ⅱ study was conducted. The clinicopathological data of 37 patients with MSS/pMMR LARC who were admitted to Beijing Friendship Hospital of Capital Medical University from April 2021 to September 2022 were collected. All patients underwent anti‑PD‑1 combined with neoadjuvant therapy and radical total mesorectal excision. Observation indicators: (1) enrolled pati-ents; (2) MRI and pathological examination; (3) concordance analysis of MRI examination reading; (4) evaluation of MRI examination. Measurement data with normal distribution were represented as Mean±SD. Count data were expressed as absolute numbers or percentages. Linear weighted κ value was used to evaluate the concordance of radiologist assessment. Sensitivity, negative predictive value, accuracy, overstaging rate and understaging rate were used to evaluate the predictive value.

Results (1) Enrolled patients. A total of 37 eligible patients were screened out, including 21 males and 16 females, aged (61±11)years. MRI examination was performed before and after combined therapy, and pathological examination was performed after radical resection. (2) MRI and pathological examination of patients. Among the 37 patients, MRI before combined therapy showed 0, 0, 5, 24 and 8 cases in stage T0, T1, T2, T3 and T4, 10, 17 and 10 cases in stage N0, N1 and N2, 28 and 9 cases of positive and negative extramural vascular invasion (EMVI), 4 and 33 cases of positive and negative mesorectal fascia (MRF), respectively. MRI examination after combined therapy showed 15, 4, 7, 10 and 1 cases in stage T0, T1, T2, T3 and T4, 34, 2 and 1 cases in stage N0, N1 and N2, 9 and 28 cases of positive and negative EMVI, 1 and 36 cases of positive and negative MRF. There were 16, 13, 8 and 0 cases of tumor regression grading (TRG) 0, 1, 2 and 3, respectively. Postoperative pathological examination showed 18, 4, 3, 11, 1 cases in stage T0, T1, T2, T3, T4, 33, 3, 1 cases in stage N0, N1, N2, positive and negative EMVI and unknown data in 1, 35, 1 cases, positive and negative circumferential margin in 0 and 37 cases, grade 0, grade 1, grade 2, grade 3 of American Joint Committee on Cancer TRG in 18, 9, 8, 2 cases, respectively. Pathological complete response rate was 48.6%(18/37) and approximate pathological complete response rate was 24.3%(9/37). (3)Concordance analysis of MRI examination reading. The κ value of T staging and N staging on MRI before combined therapy was 0.839 (P<0.05) and 0.838 (P<0.05), respectively. The κ value of T staging and N staging on MRI after combined therapy was 0.531 (P<0.05) and 0.846 (P<0.05), respectively. The κ value of EMVI and MRF was 0.708 (P<0.05) and 0.680 (P<0.05) before combined therapy, and they were 0.561 (P<0.05) and 1.000 (P<0.05) after combined therapy, respectively. The κ value of TRG 3‑round reading for TRG was 0.448 (P<0.05). (4) Evaluation of MRI examination. ① MRI evaluation of T and N staging. The accuracy of MRI examination after combined therapy for distinguishing stage T0 was 75.7%28/37, 95% confidence interval (CI) as 62.2%-89.2%, the understaging rate was 8.1%(3/37, 95%CI as 0-18.9%), the overstaging rate was 16.2%(6/37, 95%CI as 5.4%-29.7%). The accuracy of MRI examination for distinguishing stage T0-T2 was 86.5%(32/37, 95%CI as 73.0%-97.3%), its understaging rate and overstaging rate were 8.1%(3/37, 95%CI as 0-18.9%) and 5.4% (2/37, 95%CI as 0-13.5%), respectively. The accuracy of MRI examination for distinguishing N staging was 91.9%(34/37, 95%CI was 81.1%-100.0%), its understaging rate and overstaging rate were 5.4%(2/37, 95%CI as 0-13.5%) and 2.7%(1/37, 95%CI as 0-8.1%), respectively. Among 18 patients in pathological stage T0, the overstaging rate of MRI was 33.3%(6/18). All the 4 patients in pathological stage T1 and 3 pati-ents in pathological stage T2 had correct diagnosis. There were 3 cases with understaging among 12 patients in pathological stage T3-T4. Among the 37 patients in pathological stage N0-N2, 34 cases had correct diagnosis, 1 case was overstaged as stage N1 due to a round mesorectal lymph node with short diameter as 6 mm, and 2 cases were diagnosed as stage N0 due to the small lymph nodes with the maximum short diameter as 3 mm. ② MRI evaluation of EMVI and MRF. The accuracy, sensitivity and negative predictive value of MRI for evaluating EMVI were 86.5%(32/37, 95%CI as 75.0%-97.2%), 100.0% and 100.0%, respectively, and the overestimation rate of EMVI was 13.9%(5/36, 95%CI as 2.8%-25.0%), and no underestimation occurred. Of 35 pathologically negative EMVI patients, a rate of 14.3%(5/35) of patients were positive on MRI. The main reason for overestaging was that thickened fibrous tissue outside the rectal wall was mistaken for vascular invasion. The accuracy of MRI for evaluating MRF was 97.3%(36/37, 95%CI as 91.9%-100.0%), and 1 case (1/37, 2.7%, 95%CI as 0-8.1%) was overestimated as positive MRF due to misdiagnosis of pararectal MRF lymph nodes. The negative predictive value of MRI for assessing MRF was 100.0%. ③ MRI evaluation of TRG. The accuracy, understaging and overstaging rates of MRI for evaluating pathological TRG 0 were 78.4%(29/37, 95%CI as 64.9%-91.9%), 8.1%(3/37, 95%CI as 0-18.9%), 13.5%(5/37, 95%CI as 5.4%-27.0%), respectively. The accuracy, understaging and overstaging rates of MRI for evaluating pathological TRG 0-1 were 89.2%(33/37, 95%CI as 78.4%-97.3%), 8.1%(3/37, 95%CI as 0-18.9%), 2.7%(1/37, 95%CI as 0-8.1%), respectively. Of the 18 patients with pathologic complete response, 5 cases were diagnosed as pathological TRG 1 and 13 cases as pathological TRG 0. One near‑pCR patient was assessed as pathological TRG 2. Two patients with pathological TRG 3 were incorrectly diagnosed on MRI.

Conclusions Anti‑PD‑1 combined with neoadjuvant therapy can downstage the LARC pati-ents with MSS/pMMR. MRI is effective in predicting T staging, N staging, EMVI, MRF and TRG. However, overstaging should be prevented.