Anal cancer: Clinical sciences

Anal cancer is a malignancy of the anal canal or perianal area. The two main subtypes of anal cancer include squamous cell carcinoma or SCC, which is the most common, and adenocarcinoma. Although rare, the incidence of anal cancer has been increasing over the last decades likely due to the spread of human papillomavirus, or HPV, which is the number one cause of anal SCC. Treatment depends on the histopathologic subtype as well as the stage of the cancer at the time of diagnosis.

Alright, when a patient presents with a chief complaint suggestive of anal cancer, the first step is to obtain a focused history and physical. Typically, patients report rectal bleeding, anorectal pain, and the sensation of a mass within or around the anus. On further history, patients might have risk factors like previous or current HPV infection, HIV infection, immunosuppression, a high lifetime number of sexual partners, receptive anal intercourse, genital warts, or smoking.

Your examination should include a focused anorectal evaluation, including a digital rectal examination, or a DRE, and evaluation of the inguinofemoral lymph nodes. DRE can reveal a hard, fixed, ulcerated mass in the perianal region or within the anal canal. Additionally, you might also find inguinal or femoral lymphadenopathy. If you see these findings, you should suspect anal cancer. On exam, you might see anogenital warts, perianal skin irritation, or mucus or bloody discharge at the anal verge.

Okay, now let’s talk about the initial work up when you suspect anal cancer. Your next step is to perform an anoscopy with biopsy of the lesion, and a fine needle aspiration or FNA of any clinically suspicious lymph nodes. The anoscopy with biopsy can help you gain better visualization of the mass including its size and location, and provide pathologic confirmation of your diagnosis. FNA can also confirm malignant nodal spread.

Let's break this down further starting with squamous cell carcinoma. On anoscopy, you might see a tumor distal to the squamous mucocutaneous junction or in the hair-bearing skin. If the biopsy of the lesion or the FNA of a suspicious lymph node show malignant squamous cells, you can make your diagnosis of anal cancer squamous cell carcinoma or (SCC).

Once you have your diagnosis, your next step is to stage the cancer using the TNM system. This stands for Tumor size and location, lymph Node involvement, and presence of distant Metastasis. To do this, first obtain a CT of the chest, abdomen and pelvis, MRI of the pelvis, and a PET scan. Additionally, if your patient is a biological female, a gynecologic exam with cervical cancer screening should be performed because of the close association of anal cancer and HPV infection. Based on the imaging findings, you should be able to stage the cancer, which will guide your management. The first major element of staging you should focus on is the presence of distant metastases. For patients with no distant metastases, your next step is to assess the location of the tumor.

Now, if the tumor is located in the anal canal, you can treat with chemotherapy and radiation as the primary mode of therapy. Most patients respond well to chemoradiation, so if they show complete clinical response, you can follow up with surveillance. Surveillance includes evaluations with DRE, anoscopy, and an inguinal lymph node exam every 3 to 6 months; while CT of the chest, abdomen and pelvis and an MRI of the pelvis should be performed every year for 3 years.

On the other hand, if the tumor is located in the perianal region, your next step is to stage the tumor to determine appropriate treatment. For stage 1 lesions that are 2 cm or smaller in size and are well or moderately differentiated; or stage 2A lesions, which are between 2 to 5 cm in size and do not involve the sphincter, surgery should be consulted for wide local excision. In cases where inadequate margins were obtained during surgery, patients may need re-excision or local radiation and chemotherapy. If the margins are clear of malignancy or the patient responds well to chemoradiation, they can be followed up with surveillance.

Alright, now let's talk about another subset of patients. For patients with stage 1 cancer that are 2 cm or smaller but are poorly differentiated, or stage 2A lesions between 2 to 5 cm but that involve the sphincter, or stage 3 cancer, which includes any nodal involvement, the first line of treatment is chemotherapy with radiation. Surgical resection is not recommended for these patients. Once your patient completes therapy and responds well, they can go on to surveillance.