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Locally advanced rectal adenocarcinoma: Treatment sequences, intensification, and rectal organ preservation
CA: A Cancer Journal for Clinicians  (IF508.702),  Pub Date : 2021-02-16, DOI: 10.3322/caac.21661
Alec Bigness, Iman Imanirad, Ibrahim Halil Sahin, Hao Xie, Jessica Frakes, Sarah Hoffe, Danielle Laskowitz, Seth Felder

Case Presentation

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).

Figure 1
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Endoscopic and Magnetic Resonance Imaging (MRI) Tumor Assessments Throughout Total Neoadjuvant Treatment (Induction Chemotherapy Followed by Chemoradiation) and Resection Specimen. A semi‐circumferential primary tumor is observed endoscopically and by a primary rectal MRI staging study (sagittal), which also demonstrates a marked enlargement of the prostate indenting the bladder. The patient underwent interval tumor reassessment approximately 3 weeks after receipt of 8 cycles of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) induction chemotherapy (INCT). This interval reassessment is useful to ensure and document tumor response for later comparison after the completion of all neoadjuvant therapies. Notably, primary tumor progression during neoadjuvant systemic chemotherapy is very low (<5%). Endoscopic findings at this time demonstrated subtle mucosal irregularities and nodularity, with erythema of the mucosa, and the MRI showed an intermediate, T2‐weighted (T2W) signal, consistent with persistent, viable tumor. The patient then completed chemoradiation (CRT) and was again reassessed for tumor response. This occurred approximately 4 weeks after CRT completion (or approximately 13 weeks after completion of INCT). Endoscopically, a scar was present with subtle, pale, peripheral mucosal irregularity, and MRI continued to demonstrate an intermediate T2W signal, now also showing a high signal on DWI, consistent with persistent, viable tumor. Given the favorable endoscopic response, a short interval reassessment 6 weeks later (now 10 weeks after completion of CRT and 19 weeks after completion of INCT) was pursued to assess for a clinical complete response. Endoscopically, a flat scar was apparent with no mucosal abnormalities, consistent with a clinical complete response. The rectal MRI, however, interpreted a persistent T2W signal, although the DWI signal was no longer apparent. The resected specimen shows a 22‐mm, flat scar (blue mucosal staining represents endoscopic tattoo). mFOLFOX indicates modified folinic acid, fluorouracil, and oxaliplatin; ypT0ypN0 (pathologic complete response).

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.