Solitary esophageal metastasis ten years after curative resection of stage I rectal adenocarcinoma: A case report

Abstract

BACKGROUND

We report an exceptionally rare case of a solitary esophageal metastasis occurring in the tenth year after curative resection of stage I (pT2N0M0) rectal adenocarcinoma. This represents one of the longest reported intervals to esophageal metastasis from colorectal cancer, challenging the conventional understanding of metastatic potential of early-stage tumors.

CASE SUMMARY

A 42-year-old male underwent curative resection for rectal adenocarcinoma (pT2N0M0, stage I) in 2015. Ten years later (2025), he presented with progressive dysphagia. Imaging and endoscopy revealed a mid-esophageal tumor with mediastinal lymphadenopathy. Initial biopsy suggested primary esophageal adenocarcinoma. After two cycles of neoadjuvant immunochemotherapy, dysphagia worsened. However, a multidisciplinary team re-evaluation, utilizing comparative immunohistochemistry for the esophageal lesions and rectal specimens, confirmed the diagnosis as a solitary esophageal metastasis from rectal adenocarcinoma (RAS wild-type). The patient received involved-field radiotherapy with concurrent systemic therapy (capecitabine, oxaliplatin and cetuximab). Dysphagia significantly improved one week after radiotherapy initiation. Three-month follow-up imaging after radiotherapy demonstrated a partial response. The patient was on cetuximab maintenance.

CONCLUSION

This case underscores the risk of early tumor recurrence or metastasis beyond standard follow-up windows thus long-term follow-up is necessary.

Key Words: Esophageal metastasis; Colorectal cancer; Recurrence; Tumor dormancy; Radiotherapy; Case report

Core Tip: We report a case of a solitary esophageal metastasis occurring in the tenth year after curative resection of stage I rectal adenocarcinoma, representing one of the longest intervals for rectal metastasis to the esophagus. It emphasizes that even early-stage tumors can metastasize to atypical sites after years. Furthermore, we discuss the role of immunohistochemistry in diagnosis and the potential value of radiotherapy combined with systemic treatment.

INTRODUCTION

Autopsy series show esophageal metastases most often originate from lung, breast, or gastric primaries[1]. Metastatic involvement of the esophagus from colorectal carcinoma (CRC) is exceptionally uncommon[1]. Clinically, esophageal metastases often present with dysphagia and can mimic a primary esophageal cancer[2]. Metastatic lesions typically lie in the submucosal layer with intact overlying mucosa, rendering endoscopic biopsies potentially non-diagnostic and the lesion indistinguishable from a primary tumor[1,2]. Stage I CRC generally carries an excellent prognosis, with only about 10% of patients developing any recurrence within five years[3]. In one large series of stage I colon cancer, the vast majority of relapses occurred within the first eight years after surgery[4]. We report a case of an ultra-late solitary esophageal metastasis occurring in the tenth year after curative resection of stage I rectal adenocarcinoma, which highlights the unusual latency and diagnostic challenge, expands the recognized metastatic spectrum of CRC and underscores the need for long-term vigilance even after resection of early-stage disease.

CASE PRESENTATION

Chief complaints

A 42-year-old male, who had completed two cycles of immunochemotherapy for primary esophageal adenocarcinoma, presented with aggravated dysphagia for 4 days and was subsequently referred to the multidisciplinary team (MDT) by the thoracic surgeon.

History of present illness

One month ago, the patient presented to the thoracic surgery department with progressive dysphagia for three weeks (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Oesophageal Cancer Module 18 (EORTC QLQ-OES18) dysphagia scale score: 40)[5] on February 14, 2025. Chest computed tomography (CT) scan indicated a neoplastic lesion in the esophagus. Both white-light endoscopy (Figure 1A) and the endoscopic ultrasound (Figure 1B) confirmed a tumor involving the esophagus. Biopsy pathology identified adenocarcinoma. The positron emission tomography-CT (PET-CT) examination indicated a tumorous esophageal lesion integrating with an enlarged mediastinal lymph node, with no sign of local recurrence of the rectum or systemic metastasis observed on February 17, 2025 (Nuclear Medicine Department of the Affiliated Hospital of North Sichuan Medical College (NSMC)) (Figure 2). An initial diagnosis of primary mid-thoracic esophageal adenocarcinoma [cT3N1M0, Stage III, according to the Union for International Cancer Control (UICC) 9^th edition] was made.

Figure 1 The endoscopic examination results indicated esophageal neoplastic lesions. A: White-light endoscopy showing significant mucosal stenosis at 30 cm from incisors, with a soft and friable lesion; B: Endoscopic ultrasound demonstrating loss of normal mural layer structure and serosal interruption at lesion site (max wall thickness: 1.11 cm).

Figure 2  Whole-body absorption graph.

A treatment plan of neoadjuvant immunochemotherapy (nedaplatin 120 mg, nab-paclitaxel 300 mg, tislelizumab 200 mg, q3w) followed by radical surgery was initiated. After two cycles of neoadjuvant therapy, the patient experienced significant worsening of dysphagia (EORTC QLQ-OES18 dysphagia scale score: 90). Surgical resection was deemed unfeasible, prompting referral to the MDT on March 15, 2025.

History of past illness

The patient underwent laparoscopic low anterior resection for rectal cancer in 2015. Postoperative pathology confirmed moderately differentiated rectal adenocarcinoma (lymphovascular invasion absent, perineural invasion absent, pT2N0M0, Stage I, according to the UICC 7^th edition). Standard postoperative surveillance, including annual thoracoabdominal CT and endoscopy, was performed. The most recent surveillance examination was on October 28, 2024, showing no abnormalities.

Personal and family history

The patient denied notable family history.

Physical examination

A well-healed surgical scar, approximately 3 cm in length, was observed in the right lower abdominal quadrant.

Laboratory examinations

Serum tumor markers were elevated: Carbohydrate antigen (CA) 50: 22.65 IU/mL, CA-242: 87.41 IU/mL, serum carcinoembryonic antigen (CEA): 30.60 µg/L, CA-199: 77.90 U/mL.

Imaging examinations

The chest CT result on February 14, 2025 revealed irregular wall thickening in the mid-thoracic esophagus, approximately at T6-T8 level, and subcarinal lymphadenopathy (Figure 3A). The chest CT result on March 15, 2025 indicated that the volume of the esophageal tumor had increased, causing the esophageal lumen to narrow (Figure 3B).

Figure 3 Chest computed tomography imaging. A: Showing mid-esophageal wall thickening and subcarinal lymphadenopathy when the patient presented to the thoracic surgeon; B: Showing the volume of the esophageal tumor increased, causing the esophageal lumen to narrow, after two cycles of neoadjuvant immunochemotherapy.

MULTIDISCIPLINARY EXPERT CONSULTATION

The radiation oncologist initiated an MDT discussion. The MDT pointed out that the patient's neoadjuvant treatment plan was not standard, but considering the history of rectal adenocarcinoma, a thorough re-evaluation of the esophageal pathology specimen (Figure 4A) and rectal cancer specimen (Figure 4B) was undertaken. The immunohistochemistry (IHC) results of the esophageal lesion showed: CDX2(+) (Figure 5A), CK7(-), CK20(+), SATB2(+) (Figure 5B), MSH2(+), MSH6(+), MLH1(+), PMS2(+), Ki67 index (approximately 40%), P53 (mutant pattern), HER-2(-), findings highly suggestive of colorectal origin (March 17, 2025, Pathology Center of the Affiliated Hospital of NSMC, Anti-pan-Tropomyosin Receptor Kinase Rabbit Monoclonal Antibody Reagent). The KNPB gene test did not detect any mutations in the KRAS/NRAS/PIK3CA/BRAF genes (March 19, 2025, Pathology Center of the Affiliated Hospital of NSMC, Fluorescent PCR). The original 2015 rectal cancer specimen was retrieved for comparative IHC: CDX2(+) (Figure 6A), CK7(-), CK20(+), SATB2(+) (Figure 6B), MSH2(+), MSH6(+), MLH1(+), PMS2(+), Ki67 index (approximately 10%), P53 (mutant pattern), HER-2(-) (March 19, 2025, Pathology Center of the Affiliated Hospital of NSMC, Anti-pan-Tropomyosin Receptor Kinase Rabbit Monoclonal Antibody Reagent). The KNPB gene test also detected no mutation in the KRAS/NRAS/PIK3CA/BRAF genes (March 19, 2025, Pathology Center of the Affiliated Hospital of NSMC, Fluorescent PCR). These evidences confirmed the homology, with an identical immunophenotype and the same genetic status, between the primary rectal tumor and the esophageal lesion.

Figure 4 Hematoxylin and eosin stain of tumor biopsy (100 ×). A: Esophageal tumor; B: Primary rectal adenocarcinoma.

Figure 5 Immunohistochemistry results of esophageal tumor. A: CDX-2; B: SATB2.

Figure 6 Immunohistochemistry results of primary rectal adenocarcinoma. A: CDX-2; B: SATB2.

FINAL DIAGNOSIS

Given the inaccuracy of the previous treatment plan, the patient immediately underwent CT scans of the neck, chest and abdomen, magnetic resonance imaging of the head and pelvis, radionuclide bone imaging, and colonoscopy, in order to determine whether new lesions had appeared among the past two months (March 22, 2025, Imaging Center and Endoscopy Center of the Affiliated Hospital of NSMC). All results supported a solitary esophageal metastasis without local recurrence of the rectum or distant metastasis. The final diagnosis was revised to a solitary esophageal metastasis from rectal adenocarcinoma (RAS wild-type).

TREATMENT

The MDT immediately adjusted the treatment plan for metastatic CRC. Adding cetuximab to chemotherapy including capecitabine and oxaliplatin (CAPOX) in RAS wild-type metastatic CRC has been shown to significantly increase response rates and prolong survival. In order to quickly alleviate the patient's dysphagia, simultaneous radiotherapy was performed on the solitary metastatic lesion, which enabled the local tumor to shrink to the greatest extent and relieved the symptom. Concurrent oral administration of capecitabine has also been proven to be an effective radiosensitizing component. On March 24, 2025, the patient received involved-field radiotherapy using volumetric modulated arc therapy. The planning target volume, encompassing the esophageal metastasis and involved mediastinal lymph nodes, was prescribed a total dose of 50.4 Gy in 28 fractions (1.8 Gy per fraction), delivered five days per week (Figure 7). The doses to surrounding organs at risk were rigorously constrained within accepted tolerance limits to minimize toxicity, as detailed below: Lungs: The mean dose (Dmean) was kept below 8.05 Gy, with the volume of lungs receiving 20 Gy below 9.01% and 5 Gy below 48.14%; Spinal cord: The maximum dose was strictly limited to below 41.46 Gy; Heart: The Dmean was kept below 21.96 Gy, with the volume of heart receiving 30 Gy below 18.63% and 40 Gy below 7.11%. CAPOX plus cetuximab was administered for six 3-week cycles: Capecitabine 1000 mg/m² bid on days 1-14, oxaliplatin 130 mg/m² on day 1, and cetuximab 400 mg/m² loading dose followed by 250 mg/m² weekly.

Figure 7  Radiotherapy target graph showing planning target volume.

OUTCOME AND FOLLOW-UP

Dysphagia improved significantly within one week after radiotherapy initiation (EORTC QLQ-OES18 dysphagia scale score: 30). Three weeks after radiotherapy initiation, the patient experienced grade one bone marrow suppression with WBC 3.23 × 10⁹ /L (according to Common Terminology Criteria for Adverse Events Version 5.0). The patient was treated symptomatically and recovered. Additionally, no more adverse reactions were observed during the treatment period. One month after radiotherapy completion, dysphagia had nearly completely resolved (EORTC QLQ-OES18 dysphagia scale score: 10). On August 1, 2025, three-month follow-up CT imaging after radiotherapy completion demonstrated a partial response (Figure 8). Serum tumor markers showed substantial decreases: CA-50: 19.15 IU/mL, CA-242: 10.40 IU/mL, CEA: 13.50 µg/L, CA-199: 32.90 U/mL. The patient was on maintenance cetuximab therapy (500 mg/m² every two weeks) at last follow-up.

Figure 8  Chest computed tomography imaging showing a partial response at the three-month follow-up after radiotherapy completion.

DISCUSSION

PubMed, EMBASE, and Web of Science databases were systematically queried on November 14, 2025, using the following search terms: (“colorectal” OR “colon” OR “rectal”) AND (“esophagus” OR “esophageal” OR “oesophageal”) AND (“metastasis” OR “metastases” OR “secondary” OR “metastatic”). No language or date restrictions were applied. Titles and abstracts were screened. Reports describing metastasis to the esophagus originating from a colorectal or rectal primary were included. Data extracted from each report included: Interval between the primary tumor and esophageal metastasis, primary tumor site and stage, location and characteristics of the esophageal lesion, diagnostic method, treatment, and outcome (Table 1). Based on these data[2,6-12], our case, occurring in the tenth year after curative resection of stage I rectal adenocarcinoma, represents an ultra-late and exceptionally rare presentation, and can be considered one of the longest reported intervals of esophageal metastasis from CRC.

Table 1 A mini review summarizing reported esophageal metastases from colorectal carcinoma.

No.	Ref.	Interval	Primary site/stage	Esophageal site/pattern	Diagnostic method	Treatment	Outcome
1	Kagaya et al[6]	14 months	Cecal adenocarcinoma/stage IV	Lower esophagus/submucosal tumor	Histology	Palliative stent + bypass surgery	Well 6 months after surgery
2	Watanabe et al[7]	3 years	Rectal adenocarcinoma/stage IIIB	Mid-thoracic esophagus/submucosal tumor	Biopsy + IHC	FOLFOX + bevacizumab	Died 16 months after recurrence
3	Sönmez et al[8]	Synchronous	Rectal adenocarcinoma/stage IV	Polypoid esophageal lesion	Biopsy + IHC	Plan to surgery after radiation radiotherapy to the rectum	NR
4	Tanaka et al[2]	1 year	Cecal signet-ring cell carcinoma/stage I	Multiple longitudinal submucosal tumors	Biopsy + IHC	FOLFOX + bevacizumab	Died 1 year and 5 months after surgery
5	Thomasset et al[9]	1 year	Sigmoid carcinoma/Dukes C	Lower esophagus/polypoidal lesion	Histology	5fluorouracil + folinic acid	Died six months after metastases
6	Bhurgri et al[10]	3 years	Sigmoid colon carcer/stage IIB	Esophageal lesion	Biopsy + IHC	Gastrostomy tube + FOLFOX	NR
7	Vashi et al[11]	4 years	Colon carcinoma/stage III	Gastroesophageal junction and mid esophagus/ multiple nodules	Histological and immunostains	Irinotecan + cetuximab	NR
8	Lohsiriwat et al[12]	1 year	Rectal carcinoma/stage IV	Proximal esophagus/ a 4-mm sessile polyp	Biopsy	Supportive therapy	Died 2 months later
9	This study	10 years	Rectal adenocarcinoma/stage I	Mid-thoracic esophagus/submucosal involvement	Biopsy + IHC + KNPB gene test	VMAT + CAPOX + cetuximab	Partial response at 3 months

VMAT: Volumetric modulated arc therapy; IHC: Immunohistochemistry; CAPOX: Capecitabine and oxaliplatin; NR: Not reported.

Metastatic involvement of the esophagus is uncommon (0.3%-6.1% in autopsy series), most commonly originating from breast or lung cancers[1]. Esophageal metastasis from CRC is exceedingly rare[13]. Proposed mechanisms include hematogenous spread, lymphatic dissemination (including retrograde flow), or direct invasion[14]. Clinical presentation, typically dysphagia, and radiological/endoscopic findings such as circumferential wall thickening or luminal narrowing are often indistinguishable from primary esophageal cancer[1,14]. Biopsies may be inconclusive due to submucosal tumor deposits, which represent a common growth pattern in metastases[14]. In this case, the patient's PET-CT and endoscopic examinations indicated a solitary esophageal lesion, so the thoracic surgeon misdiagnosed it as primary esophageal adenocarcinoma. Thanks to the MDT discussion, the comparative IHC results supported that the esophageal lesion originated from the rectum. Therefore, in patients presenting with esophageal tumors with a prior history of malignancy, clinical vigilance is warranted. Appropriate IHC or genetic testing is crucial for accurate diagnosis[15,16]. However, it must be noted that while IHC profiles are highly indicative, they do not constitute definitive proof of clonal origin. The most conclusive evidence would be the demonstration of identical somatic mutation patterns via next-generation sequencing in both lesions[16], which could not be performed in this case. Nonetheless, in clinical practice, conclusive IHC profiles remains a robust and widely accepted diagnostic tool[15].

This patient remained disease-free for ten years under regular surveillance, yet developed the esophageal metastasis merely three months after an unremarkable follow-up. This decade-long interval strongly suggests tumor dormancy: A state where disseminated tumor cells (DTCs) or circulating tumor cells/DNA (CTCs/ctDNA) persist in a quiescent state before reactivation[17]. At the time of primary tumor resection, DTCs may have already disseminated via vascular/Lymphatic routes to distant sites (e.g., bone marrow, lung, liver) but remained dormant[17-19]. Mechanistically, tumor dormancy can be sustained by angiogenic suppression, where DTCs remain avascular and unable to expand until neovascularization is triggered, and by immune editing, in which cytotoxic immune surveillance maintains equilibrium by eliminating proliferative clones[17,20]. Studies have shown that non-metastatic CRC can still occur late recurrence and secondary primary cancers within five to ten years after curative treatment[21]. The ten-year latency here far exceeds the typical five-year high-risk window for CRC recurrence, indicating that even after curative resection of early-stage disease, the risk of ultra-late metastasis persists[21]. ctDNA-based minimal residual disease (MRD) assays permit sensitive detection of molecular relapse prior to radiographic or clinical progression[22]. Studies find that ctDNA positivity strongly predicts recurrence and survival in resectable CRC, and serial monitoring increases detection yield[22]. This underscores the potential value of ongoing research into biomarkers like ctDNA for monitoring MRD and predicting ultra-late recurrence[17,22].

Due to the rarity of esophageal metastases, treatment consensus is lacking[13]. Approaches often involve local resection or stenting for palliation[11]. Employing an MDT strategy, we opted for a combined modality approach focusing on local control with radiotherapy and biologically targeted systemic therapy[23,24]. Significant dysphagia relief occurred after one week of therapy initiation, considerably faster than the timeframe for chemotherapy response[25]. This early outcome highlights radiotherapy as a highly effective modality for rapid symptom palliation in such scenarios. However, it is critical to emphasize that our data represent only an interim analysis of three months. The long-term efficacy and durability of this combined-modality approach remain to be established through ongoing follow-up.

CONCLUSION

This case of an extremely late solitary esophageal metastasis exemplifies the unpredictable spatiotemporal dynamics of tumor dormancy and recurrence. Even beyond standard follow-up windows, early-stage tumors still have the possibility of metastasizing to atypical sites, which should draw the attention of clinicians. The development of relevant biomarkers for long-term monitoring of the potential for tumor recurrence and metastasis is valuable. Furthermore, the case demonstrates the critical role of MDT review, IHC, and molecular profiling in diagnosing atypical metastases, and the efficacy of a tailored combined-modality approach integrating radiotherapy and targeted therapy.

ACKNOWLEDGEMENTS

The authors thank the patient for his kind consent for the publication of this case report and accompanying images.