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

Abstract

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 underwent ileostomy reversal in June 2020. He is currently under surveillance with normal CEA and no radiographic evidence of disease. He experiences urgency and clustering of bowel movements, consistent with low anterior resection syndrome. Multimodality therapy for nonmetastatic, resectable, locally advanced rectal adenocarcinoma (LARC) has been routinely administered since the late 1990s, successfully prolonging survival and decreasing local pelvic failure. More recently, the one-size-fits-all treatment paradigm has been scrutinized, with the understanding that tumor downstaging to neoadjuvant therapies correlates strongly with long-term oncologic outcome. The risk of local recurrence now remains marginal relative to the more common and fixed rate of distant failure, such that efforts to tailor therapy play an increasing role in selecting optimal treatment strategies. Tr