Paradigm shift in rectal cancer therapy? Some may not need surgery, now some may not need radiotherapy.
Prospective Correlation of Magnetic Resonance Tumor Regression Grade With Pathologic Outcomes in Total Neoadjuvant Therapy for Rectal Adenocarcinoma
Dr. Maen Hussein's Thoughts
Tumor regression grade defined as the ratio between fibrosis and residual tumor, is routinely used to assess response to therapy and demonstrated to be an important predictor of patient’s outcome. In the era of TNT (total Neoadjuvant Therapy) this will help assess response to avoid surgery. It will be nice to add MRD testing in the blood as another tool.
Total neoadjuvant therapy (TNT) is a newly established standard treatment for rectal adenocarcinoma. Current methods to communicate magnitudes of regression during TNT are subjective and imprecise. Magnetic resonance tumor regression grade (MR-TRG) is an existing, but rarely used, regression grading system. Prospective validation of MR-TRG correlation with pathologic response in patients undergoing TNT is lacking. Utility of adding diffusion-weighted imaging to MR-TRG is also unknown.
We conducted a multi-institutional prospective imaging substudy within NRG-GI002 (ClinicalTrials.gov identifier: NCT02921256) examining the ability of MR-based imaging to predict pathologic complete response (pCR) and correlate MR-TRG with the pathologic neoadjuvant response score (NAR). Serial MRIs were needed from 110 patients. Three radiologists independently, then collectively, reviewed each MRI for complete response (mriCR), which was tested for positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity with pCR. MR-TRG was examined for association with the pathologic NAR score. All team members were blinded to pathologic data.
A total of 121 patients from 71 institutions met criteria: 28% were female (n = 34), 84% White (n = 101), and median age was 55 (24-78 years). Kappa scores for T- and N-stage after TNT were 0.38 and 0.88, reflecting fair agreement and near-perfect agreement, respectively. Calling an mriCR resulted in a kappa score of 0.82 after chemotherapy and 0.56 after TNT reflected near-perfect agreement and moderate agreement, respectively. MR-TRG scores were associated with pCR (P < .01) and NAR (P < .0001), PPV for pCR was 40% (95% CI, 26 to 53), and NPV was 84% (95% CI, 75 to 94).
MRI alone is a poor tool to distinguish pCR in rectal adenocarcinoma undergoing TNT. However, the MR-TRG score presents a now validated method, correlated with pathologic NAR, which can objectively measure regression magnitude during TNT.
Author Affiliations1Froedtert and the Medical College of Wisconsin, Milwaukee, WI; 2The University of Pittsburgh, Pittsburgh, PA; 3University of Texas MD Anderson Cancer Center, Houston, TX; 4Memorial Sloan Kettering Cancer Center, New York, NY; 5University of Florida, Gainesville, FL; 6University of Florida Health Cancer Center, Gainesville, FL; 7Imaging and Radiation Oncology Core (IROC) Group, and the University of Pennsylvania, Philadelphia, PA; 8Baylor Scott and White Health Baylor University Medical Center at Dallas, Dallas, TX; 9University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, OH; 10Dana-Farber/Harvard Cancer Institute, Boston, MA; 11Department of Surgery, David Geffen School of Medicine at UCLA, and VA Greater Los Angeles Healthcare System, Los Angeles, CA; 12Dayton Clinical Oncology Program, Dayton, OH; 13NSABP Foundation, Pittsburgh, PA; 14Missouri Baptist Medical Center/Heartland NCORP, St Louis, MO; 15Stephenson Cancer Center University of Oklahoma Health Sciences Center, Oklahoma City, OK; 16Trinity Health Ann Arbor Hospital, Michigan Cancer Research Consortium (NCORP), Ann Arbor, MI; 17Mayo Clinic, Rochester, MN; 18University of California Davis Comprehensive Cancer Center/UC Davis School of Med/UC Davis Health, Sacramento, CA; 19Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Neoadjuvant Chemotherapy, Excision, and Observation for Early Rectal Cancer: The Phase II NEO Trial (CCTG CO.28) Primary End Point Results
Nice study showing a non-radiation approach to node-negative, earlier stage, low-lying rectal cancer, using FOLFOX/CAPEOX x 3 months followed by local excision for those with downstaging to T0/T1 disease. 79% of patients achieved organ preservation, and 2-year locoregional RFS was 90%. A good option for those who are not good candidates for radiation yet still want to avoid an APR-type surgery.
Very impressive results that may change treatment-paradigm. However, number of patients treated, and duration of follow-up are significant issues here for early adoption.