Unusual Pattern of Colorectal Cancer Metastases Featuring Ocular, Skeletal, Hepatic, Pleural, and Pulmonary Lesions

Abstract

Background

A 72-year-old female patient presented with rectal cancer that was treated with neoadjuvant chemotherapy and radiation, surgery, and adjuvant chemotherapy. She subsequently developed diffuse distal metastases, including ocular metastasis.

Summary

Our 72-year-old patient presented with bright red blood per rectum. On initial staging, the patient was found to have a locally advanced (stage 3), poorly differentiated rectal adenocarcinoma without evidence of metastatic disease. The patient received neoadjuvant chemotherapy (5-fluorouracil and leucovorin) with 50.4 Gy pelvic radiation and subsequently underwent an uncomplicated laparoscopic sphincter-sparing TATA (transanal transabdominal proctosigmoidectomy) procedure with a handsewn coloanal anastomosis and a diverting loop ileostomy. The patient received adjuvant folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX) treatment. Initial postoperative carcinoembryonic antigen (CEA) was 1.7 ng/mL but rose to 109 ng/mL 14 months after the surgical resection. A positron emission tomography (PET) scan revealed multiple distant metastases. She was treated with folinic acid, 5-fluorouracil, irinotecan (FOLFIRI), and bevacizumab. During treatment, the patient developed choroidal metastases in her right eye, which were successfully treated with radiation. The patient’s vision returned to normal for the remainder of her life. She died 39 months after the diagnosis of rectal cancer. While the incidence of metastatic rectal adenocarcinoma is well-known, ocular metastases are rare and carry a poor prognosis. This patient experienced the longest survival within the reported literature with rectal cancer and ocular metastases.

Conclusion

Ocular metastases of rectal cancer are exceedingly rare. We present the case of a 72-year-old woman who developed ocular metastases after surgical resection of rectal adenocarcinoma. The ocular metastases were successfully treated. The patient died 39 months after her diagnosis of metastatic rectal cancer.

Key Words

colorectal cancer; rectal cancer; ocular metastases; carcinoembryonic antigen

Case Description

A 72-year-old female presented with bright red blood per rectum without any other gastrointestinal or constitutional symptoms, including fecal incontinence. She had no family or personal history of malignancy. She was a nonsmoker and did not consume alcohol.

On physical examination, the patient was found to have a firm, mobile mass in the suprapubic region of her abdomen. On digital rectal examination, the mass was palpable anteriorly just at the anorectal ring level and did not appear to involve the vagina or the sphincter complex. Ambulatory clinic rigid proctoscopy/anoscopy revealed a 25 to 30 percent circumferential mass located anteriorly. Neoplastic tissue was seen extending to the dentate line anteriorly. Resting anal tone was satisfactory, squeeze was excellent, and anatomically, her anal canal was quite long (approximately 4.5 cm). Her body mass index was 24.3 kg/m². Her Eastern Cooperative Oncology Group (ECOG) status was 0.

Initial bloodwork revealed mild anemia (hemoglobin of 11.4 g/dL) and an elevated carcinoembryonic antigen (CEA) level of 17.1 ng/mL. Colonoscopy confirmed a low rectal poorly differentiated adenocarcinoma on the anterior rectal wall approximately 5 cm from the anal verge. A pelvic magnetic resonance image (MRI) revealed a 3 cm x 3 cm lesion with one abnormal lymph node in the territory of the inferior mesenteric vein. A small 1 cm area of abnormal T2-weighted signaling was suggestive of the involvement of the internal anal sphincter. The MRI stage was mrT2N1. Initial computed tomography (CT) of the chest, abdomen, and pelvis revealed no evidence of metastatic disease.

The patient received six weeks of neoadjuvant capecitabine concurrently with pelvic irradiation (50.4 Gy in 28 fractions) which decreased the mass to <5 mm on follow-up pelvic MRI when she was re-staged as ymrT2N0 five weeks after her last radiation treatment. Clinical examination revealed a small residual tumor on the anterior rectal wall with surrounding scarring.

The patient underwent a laparoscopic transanal transabdominal proctosigmoidectomy (TATA) procedure with resection of the top half of the internal anal sphincter with a handsewn coloanal anastomosis and a diverting loop ileostomy eight weeks after completion of her radiation treatments to preserve her sphincter. Intraoperative pathological margin assessment revealed a distal margin from the tumor/scar of 4 mm and an anterior margin free of tumor. The final pathology review noted a poorly differentiated colorectal adenocarcinoma ypT3N1c (complete mesorectum and total mesorectal excision; uninvolved proximal and circumferential resection margins; 0.5 cm distal margin from residual invasive adenocarcinoma; zero of three lymph nodes positive; one 0.6 cm tumor deposit; further pathology review did not reveal any additional lymph nodes; 1.2 cm residual adenocarcinoma demonstrated a small focus of invasion into perirectal fat). The patient received eight cycles of adjuvant folinic acid, fluorouracil, and oxaliplatin (FOLFOX) treatment. Post-treatment CEA was 1.7 ng/mL. Proctoscopy revealed no bright red blood per rectum, no recurrence of local disease, and an intact anastomosis 2 cm from the anal verge (just at/above the dentate line). Seven months after her initial surgery, the patient underwent an ileostomy reversal. Fecal continence was satisfactory on low-dose loperamide with psyllium supplementation.

Eleven months after her surgery, her CEA level rose to 109 ng/mL. A fluorodeoxyglucose positron emission tomography (FDG PET) scan revealed multiple, focal, hypermetabolic lesions in the pulmonary parenchyma, pleura, liver, and skeleton (multiple vertebral lesions, right femoral lesion, a lesion in the right iliac bone) compatible with metastatic disease. There was no clinical or radiographic evidence of local, pelvic recurrence. The second round of FOLFOX treatment was initiated but was not tolerated and was changed to folinic acid, fluorouracil and irinotecan (FOLFIRI) and bevacizumab.

Sixteen months after her surgery, the patient endorsed decreased visual acuity in her right eye (OD). Two retinal specialists diagnosed retinal detachment from choroidal metastases OD. The patient received palliative radiation OD (17 Gy in 2 fractions). Two months after this palliative treatment, she reported an improvement in her right eye vision, which remained stable for the remainder of her life. The patient’s ECOG status slowly deteriorated from 0 to 2, and her CEA level rose to 5500 ng/mL over the ensuing six months. She was started on panitumumab after confirmatory wild-type k-RAS testing. The patient died 36 months after her surgery for rectal cancer.

Discussion

Colorectal cancer is a common malignancy, representing the second most common malignancy in women and men.¹ Approximately 20 percent of patients presenting with colorectal cancer have metastatic disease at the time of diagnosis.² Of all patients with metastatic colon cancer, the most common sites of distant metastasis are liver (70 percent) thorax (32 percent), and peritoneum (21 percent). In rectal cancer, the most common sites are liver (70 percent), thorax (47 percent), and bone (12 percent).

The most common intraocular neoplasm is a metastasis from non-ophthalmic primary cancer.³ Metastatic tumors to the uvea, retina, optic disk, and vitreous are regarded as equivalent to metastases to the brain, with corresponding unfavorable prognoses for survival.3 Median survival after detecting uveal metastasis is six months.³ The patient reported here survived 20 months after the diagnosis of ocular metastases.

Although distant metastases are common in colorectal cancer, ocular metastasis is very rare. There are limited reports in the literature, and the summary of those reports is in Table 1. In a 1975 study of 26 patients with carcinoma metastatic to the eye and orbit, Ferry et al.⁴ reported only one patient where the primary tumor was rectal in origin. In a study by Shields et al.⁵ in 1995, only 2 of 40 patients with metastasis to the iris had primary cancers of colorectal origin. The patient reported here experienced an extended survival compared to the eight previously reported cases (39 months from diagnosis), summarized in Table 1. Only in one case, the symptoms of ocular metastasis were presented before the colorectal cancer was diagnosed.⁶ Treatment methods of the ocular metastasis have consisted of ocular radiation, systemic chemotherapy, intravitreous chemotherapy, and enucleation of the affected eye. Including this present case report, four patients experienced ocular symptom improvement posttreatment. Only two patients were alive at three months after ocular metastasis was diagnosed.

Table 1. Previously reported patients with colorectal cancer and ocular metastasis

Conclusion

Ocular metastases from colorectal cancer are rare. They are usually associated with other sites of metastatic disease and carry a poor prognosis. Palliative treatment may improve the function of the affected eye. The current case experienced the longest survival from the literature of patients with colorectal cancer with ocular metastases, suggesting improvements in this disease’s systemic treatments.

Lessons Learned

Ocular metastasis from colorectal cancer is very rare and is associated with a poor prognosis. Appropriate follow-up with repeat serum CEA testing is critical for detecting recurrent disease. Despite the poor prognosis of ocular metastases, modest overall survival with improved eye function is possible with appropriate multi-modal radiation and systemic treatments.

Authors

Authors

Kegel F; Hodgson E; Zalai C

Author Affiliation

McGill University
Faculty of Medicine and Health Sciences
Montreal (QC) H3G 2M1

Corresponding Author

Christian Zalai, MD, FACS
McGill University
West Island Integrated University Health and Social Services Centre, Lakeshore Hospital
175 Stillview Avenue, Ste. 200
Pointe-Claire, Québec, H9R 4S3
Phone: (514) 694-4848
E-mail: christian.zalai@mcgill.ca

Disclosure Statement

The authors have no conflicts of interest to disclose.

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