Locally advanced rectal adenocarcinoma: Treatment sequences, intensification, and rectal organ preservation

L.B. is a 68-year-old Hispanic man who presented with hematochezia, narrowed stools, and unintentional weight loss over 4 months. A colonoscopy in May 2019 revealed a 6-cm, nonobstructing, fungating rectal mass 8 cm from the anal verge. Biopsy confirmed a moderately differentiated, invasive adenocarcinoma. Cross-sectional computed tomography (CT) and abdominal magnetic resonance imaging (MRI) did not show apparent metastatic disease, except for benign cysts in the liver. Subsequent MRI with rectal protocol showed a clinical T3N1 (cT3cN1, 8th edition American Joint Committee on Cancer [AJCC]) tumor with extramural vascular invasion and nonthreatened mesorectal fascia. The carcinoembryonic antigen (CEA) level was 38 ng/mL at the time of diagnosis. L.B. started neoadjuvant modified folinic acid, fluorouracil, and oxaliplatin (mFOLFOX6) in July 2019 and completed 8 cycles without dose reduction or delay. His rectal bleeding improved significantly, and stool caliber normalized after 2 cycles of neoadjuvant induction chemotherapy (INCT). Two weeks after completion of INCT in November 2019, restaging rectal MRI demonstrated a radiographic near complete response (CR) with resolution of pathologic lymph nodes and extramural vascular invasion. The CEA level decreased to 7.6 ng/mL yet remained elevated. Endoscopic evaluation showed an erythematous scar with slight mucosal irregularity and nodularity, consistent with partial treatment effect (Fig. 1). L.B. then proceeded with long-course chemoradiation (CRT) with capecitabine, which he completed in December 2019. Restaging CT did not demonstrate distant metastatic disease. His CEA level normalized to 4.7 ng/mL, but rectal MRI interpreted residual viable disease T1/T2N0, with persistent, intermediate T2 signal as well as a high signal on diffusion-weighted imaging (DWI). Endoscopically, he had a scar with telangiectasia and decreased mucosal erythema but persistent, subtle, pale mucosal nodules. Given the excellent treatment response to total neoadjuvant therapy (TNT), a short-interval reassessment from completion of TNT was planned to evaluate whether an additional interval of time would result in a clinical CR (cCR), so that a watch-and-wait (WW) approach might be considered. A repeated rectal MRI 10 weeks after completion of TNT again showed an intermediate T2 signal, radiographically consistent with persistent, viable tumor. However, endoscopic evaluation now showed a flat, white scar with telangiectasia and was consistent with a cCR. Given the discordance between MRI and endoscopy findings, a radical rectal resection was pursued. The patient and family expressed their understanding that there was a moderately high likelihood that no residual disease would be found in the resected specimen; however, they wished to proceed with the operation. He underwent a robotic low anterior resection with diverting loop ileostomy in April 2020, with final pathology demonstrating no residual adenocarcinoma, a pathologic CR (pCR) (negative pathologic tumor and lymph node status [ypT0ypN0]). His recovery was unremarkable and thus he