WHAT PREDICTS COMPLETE RESPONSE TO TNT IN LOCALLY ADVANCED RECTAL CANCER?
Sumeyye Yilmaz*, Naz Tursun, Madison Conces, Doua Elamin, Ilker Ozgur, Marianna Maspero, David R. Rosen, Smitha Krishnamurthi, Alok Khorana, Ehsan H. Balagamwala, Sudha Amarnath, David Liska, Michael Valente, Scott Steele, Emre Gorgun
Cleveland Clinic, Cleveland, OH
Background:
Total neoadjuvant therapy (TNT) in the treatment of locally advanced rectal cancerinvolves administration of chemoradiotherapy (CRT) and consolidation chemotherapy prior to surgery.Complete response (CR) following TNT is defined as combination of patients who underwent surgery and hadpathological complete response (pCR) with watch-and-wait (WW) patients who had a sustained clinicalcomplete response (cCR) for at least 12 months in previous studies. The aim of the current study is todetermine the predictors of CR after TNT.
Methods:
Following Institutional Review Board approval, stage 2-3 rectal cancer patients whoreceived TNT at a tertiary care center from January 2015 to December 2021 were identified retrospectively.Our TNT protocol included concurrent CRT (50-50.4 Gy in 25-28 fractions with 5-FU or Capecitabine) and 4months of consolidation chemotherapy (FOLFOX or CAPOX). Following completion of CRT and TNT, patientswere evaluated with digital rectal exam, flexible sigmoidoscopy and MRI. Patients with a cCR were offered aWW approach. Data were presented as mean (standard deviation), median [25-75 percentiles] or frequency(percent). Univariable and multivariable logistic regression models were used to identify the predictors of CR.
Results:
Total of 119 patients with rectal cancer (19 patients with stage 2, 100 with stage 3) wereincluded. Mean age was 56 (11.3) years with 47 (39.5%) patients being female. Median tumor size was 5.10[4.00-6.45] cm. Median distance from the anal verge and to the top of internal anal sphincter were 5.00 [3.2-9.0] and 1.40 [0.00-5.50] cm, respectively. Median baseline CEA was 3.1 [1.7-8.3] ng/mL. Of the 88 (73.9%)patients that underwent surgery, 20 (22.7%) had pCR. Of the 31 (26.1%) patients that underwent WW, 24(77.4%) had sustained cCR after a year. CR rate was 36.9% (44 patients). Closer distance to anal verge andthe top of internal anal sphincter, absence of extramural vascular invasion (EMVI), low baseline CEA,complete/near complete response on endoscopy, and magnetic resonance tumor regression grade (mrTRG) 1-2 were predictors of CR in the univariate analysis. In the multivariate analysis, absence of EMVI andcomplete/near complete response in endoscopy were associated with CR. Compared to MRI, endoscopy wasmore sensitive in predicting CR (76.9% vs. 65.9%). Endoscopy, when combined with MRI, was more specific inpredicting CR compared to endoscopy alone (82.6% vs. 72.5%). During a median follow-up of 18.9 months,recurrence was observed in 24 (20%) patients. Disease-free and overall survival rates were 75% and 77.2%following 2 years of completion of TNT, respectively.
Conclusions:
In this cohort of locally advanced rectal cancer patients, TNT achieved 36.9% CR.Absence of EMVI was the only independent predictor of CR at the time of diagnosis. Following TNT,endoscopy is a better predictor of CR than MRI.
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