What is the diagnosis and treatment of anorectal (rectal) cancer?

From the Guidelines

Definitive chemoradiation therapy (CRT) is the standard of care for stage I-III anal squamous cell carcinoma, as it offers similar cure rates to surgery and improves survival outcomes, with a 5.6% higher survival rate and 25.3% lower locoregional recurrence rate compared to radiotherapy alone 1. The treatment of anorectal cancer typically involves a multimodal approach, taking into account the cancer stage, location, and patient factors.

Key Considerations

• For early-stage anorectal cancers, surgery may be sufficient, ranging from local excision to more extensive procedures like abdominoperineal resection.
• Advanced cases often require a combination of chemoradiation therapy before or after surgery.
• The standard chemotherapy regimen includes 5-fluorouracil with mitomycin C or cisplatin, typically administered concurrently with radiation over 5-6 weeks.
• Radiation doses generally range from 45-54 Gy. Some key points to consider in the management of anorectal cancer include:
• The importance of recognizing symptoms such as rectal bleeding, pain, or changes in bowel habits, which should prompt immediate medical evaluation.
• The increasing incidence of anorectal cancer, particularly among younger adults, highlights the need for early detection and treatment.
• Regular surveillance is essential, including physical examinations, endoscopy, and imaging studies every 3-6 months for the first two years, then less frequently thereafter.

Treatment Outcomes

• Early detection significantly improves outcomes, with 5-year survival rates exceeding 80% for localized disease.
• The goal of treatment is not only to achieve cure but also to preserve quality of life, including maintaining or restoring normal bowel function and anal continence, as well as preserving genitourinary functions 1. In summary, the treatment of anorectal cancer should prioritize definitive chemoradiation therapy for stage I-III anal squamous cell carcinoma, with a focus on improving survival outcomes and preserving quality of life 1.

From the FDA Drug Label

1. 1 Metastatic Colorectal Cancer First-Line Therapy in Combination with 5-FU/LV: Studies 1 and 2 Two phase 3, randomized, controlled, multinational clinical trials support the use of irinotecan hydrochloride injection as first-line treatment of patients with metastatic carcinoma of the colon or rectum.

The FDA drug label mentions metastatic carcinoma of the colon or rectum, which includes anorectal cancer as the rectum is part of the anorectal region.

• Irinotecan is used in combination with 5-FU/LV for the treatment of metastatic colorectal cancer, which encompasses anorectal cancer.
• The label provides information on the efficacy of irinotecan in combination with 5-FU/LV for the treatment of metastatic colorectal cancer, including anorectal cancer, in terms of objective tumor response rates, time to tumor progression, and survival 2.

From the Research

Anorectal Cancer Treatment

• The standard treatment for anal cancer is concurrent chemoradiotherapy with 5-fluorouracil (5-FU) and mitomycin-C (MMC) 3.
• Studies have compared the use of one versus two cycles of MMC, with no significant difference in outcomes, but increased acute toxicity with two cycles 3.
• Radiation doses of 50-60 Gy are commonly used, but technological advances in radiation therapy, such as intensity-modulated radiotherapy (IMRT), are improving patient outcomes and quality of life 4.

Radiation Therapy

• The American Society for Radiation Oncology recommends definitive treatment with combined modality therapy using concurrent 5-FU or capecitabine plus mitomycin, with cisplatin as a conditional alternative to mitomycin with RT 5.
• RT target volumes should include the primary tumor/anal canal and rectum, and mesorectal, presacral, internal and external iliac, obturator, and inguinal lymph nodes 5.
• Intensity modulated RT-based treatment approaches are recommended, with doses of 4500 to 5940 cGy in 25 to 33 fractions for the primary tumor 5.

Comparative Effectiveness

• Chemoradiation therapy (CRT) with 5-FU and mitomycin C probably shows a benefit in locoregional failure, disease-specific survival, and colostomy-free survival compared to radiation therapy alone 6.
• CRT with 5-FU plus mitomycin C may show a benefit in locoregional failure, disease-specific survival, and colostomy-free survival rates compared to 5-FU alone 6.
• Evidence is insufficient for comparing posttreatment surveillance strategies and patient-reported outcomes, highlighting research opportunities 6.

Prevention and Management

• The development of anal squamous cell carcinoma (SCCA) is commonly linked to a prior history of HPV, and HPV vaccination is underutilized in the United States 7.
• Primary chemoradiotherapy (CRT) is the standard of care, but more advanced cancers still fare poorly with this treatment, and alternative radiation doses and/or novel combinations of agents with CRT are needed to improve quality of life and oncologic outcomes 7.
• Immune checkpoint inhibition appears to have a promising role in the setting of patients with refractory disease, and several clinical trials with immunotherapeutic and vaccine approaches for locally advanced and metastatic anal cancer are ongoing 7.