Management of Two Cases of Recurrent Anal Carcinoma
A 58-year-old female presented for consultation at our center with a prior medical history of recurrent anal/rectal carcinoma first diagnosed 3 years earlier when a poorly differentiated infiltrating squamous cell carcinoma at the distal anorectal junction was found during colonoscopic evaluation performed to investigate symptoms of pain, bleeding and poor bowel function unresponsive to laxative treatment of 5 months’ duration. The patient tested negative for human papilloma virus (HPV). The first recurrence 9 months later presented as an infiltrating poorly differentiated squamous cell carcinoma in the anorectal resection specimen. Lymph nodes and resection margins were negative. A biopsy of a 2-cm mass 11 months later revealed a second local recurrence of a keratinizing and nonkeratinizing anal carcinoma with basilar features. A positron emission tomography-computed tomography (PET-CT) scan of the pelvic/abdominal region revealed a new opaque mass at the anorectal junction with increased focal activity consistent with local recurrence of a primary anal carcinoma. Pathology reports at the time of the second recurrence revealed malignant metastatic squamous cell carcinoma of the anus and left retroperitoneal lymph node. The patient was staged as T2, N1 based on endoscopic ultrasound examination.\nTreatment included chemoradiation therapy and concomitant cisplatin/capecitabine at the time of initial diagnosis followed by anal resection at the first recurrence. Cisplatin/capecitabine was repeated following gamma knife surgery of the anus at the time of the second recurrence.\nWhen presenting to our center 1 year following the second recurrence, a third recurrence was suspected. A CT-guided periureteral core biopsy obtained 6 months after the initial consult confirmed the presence of a third recurrence presenting as poorly differentiated squamous cell carcinoma. The patient had additionally developed ambulatory difficulty and was dragging her left foot. Her performance status was rated as ECOG 3. An MRI revealed a small disk herniation at C6–C7 and bulging disks at L3–L4 and L4–L5 but no evidence of metastasis, and the differential diagnosis at the time was sacral plexopathy following an electromyogram study. Leg pain was eventually diagnosed as secondary to foraminal disk herniation at L3–L4 exerting compression on the exiting L3 nerve.\nThe patient was treated with radiation therapy for the second time (concurrent with weekly carboplatin). There was a short interval of response observed by PET scan, but after 3 months further evidence of disease progression was demonstrated.\nMolecular profiling was performed on the initial pathology specimen at diagnosis. The patient expressed a wild-type genotype for K-RAS and BRAF, no epidermal growth factor receptor (EGFR) amplification by fluorescent in situ hybridization analysis, high RRMI expression by immunohistochemistry, low PTEN expression by immunohistochemistry, and ERCC-1 underexpression by immunohistochemistry.\nApproximately 3 months after the chemoradiation with carboplatin and after discussion with the patient who wished to pursue an ‘aggressive approach’ to her cancer management, treatment with irinotecan plus cetuximab was initiated. The regimen was reasonably well tolerated with occasional mild diarrhea and a stable rash. Imaging studies revealed stable disease and the treatment was continued for a total of 4 cycles followed by observation. However, when there was radiographic evidence of disease progression 2 months later, the treatment program was reinitiated for several additional cycles. Of note, the time to subsequent disease progression after the documentation of a third recurrence of the anal carcinoma was 17 months. Unfortunately, with progression the patient experienced a decline in her performance status, was referred to a hospice and eventually succumbed to the disease.