Anal cancer diagnosis and treatment Last updated June

Anal cancer: diagnosis and treatment Last updated: June 2020

Introduction This chapter provides • A review of how anal cancer is diagnosed using a biopsy, and the role of staging in informing the treatment decision and predicting prognosis • An overview of recommended treatment approaches, and how CRT is the mainstay of treatment • A discussion of the recent developments and unmet needs in the treatment of anal cancer, such as the use of immunotherapies CRT, chemoradiotherapy.

Biopsies and imaging are used to diagnose and stage anal cancer CT, computed tomography; FDG, fluorodeoxyglucose; MRI, magnetic resonance imaging; PET, positron emission tomography; TNM, tumor-node-metastasis. 1. Glynne-Jones R, et al. Radiother Oncol 2014; 111(3): 330 9.

TNM classification of anal cancer 1 *Previously termed carcinoma in situ, Bowen disease, anal intraepithelial neoplasia II-III, high-grade anal intraepithelial neoplasia. †The terms p. M 0 and MX are not valid categories in the TNM system. Assignment of the M category for clinical classification may be c. M 0, c. M 1, or p. M 1. Any of the M categories (c. M 0, c. M 1, or p. M 1) may be used with pathological stage grouping. FNA, fine needle aspiration; SLN, sentinel lymph node; TNM, tumor-node-metastasis. 1. AJCC Cancer Staging Manual, Eighth Edition, last updated 2018. AJCC Cancer Staging Form Supplement. https: //cancerstaging. org/references-tools/deskreferences/Documents/AJCC%20 Cancer%20 Staging%20 Form%20 Supplement. pdf (Accessed June 2020).

The stage of anal cancer lesions is a prognostic indicator five-year relative survival Adapted from Cancer Stat Facts 2010 2016 (SEER data). 1 1. National Cancer Institute. Surveillance, Epidemiology, and End Results Program. https: //seer. cancer. gov/statfacts/html/anus. html (Accessed: June 2020).

The size and extent of anal cancer lesions predicts prognosis *Survival after salvage resection is possible, but this generally portends a poor prognosis. 2 1. Salati SA, et al. Int J Health Sci (Qassim) 2012; 6(2): 206 30; 2. Symer MM, et al. F 1000 Res 2018; 7: F 1000 Faculty Rev-1572.

Overview of NCCN recommendations for the treatment of metastatic anal cancer Please refer to the guidelines for full recommendations *Only chemotherapy is recommended for first-line treatment of metastatic disease following complete remission of locoregional disease or progressive disease. 5 -FU, 5 -fluorouracil; DCF, docetaxel, cisplatin, flurouracil; FOLFCIS, folinic acid, fluorouracil, cisplatin; FOLFOX, folinic acid, fluorouracil, oxaliplatin; NCCN, National Comprehensive Cancer Network; RT, radiotherapy. 1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Anal Carcinoma, version 1. 2020. November 2019. [https: //www. nccn. org/professionals/physician_gls/default. aspx] (Accessed: June 2020).

Unmet needs remain in the treatment of anal cancer CRT, chemoradiotherapy; HRQo. L, health-related quality of life; SCCA, squamous cell carcinoma of the anus; SOC, standard of care. 1. Sodergren SC, et al. Clin Oncol (R Coll Radiol) 2019; 31(2): 69 71; 2. Johnson B, et al. Clin Adv Hematol 2017; 15(12): 968 1; 3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Anal Carcinoma, version 1. 2020. November 2019. [https: //www. nccn. org/professionals/physician_gls/default. aspx] (Accessed: June 2020).

Immunotherapy may improve outcomes in anal cancer ICI, immune checkpoint inhibitor; NCCN, National Comprehensive Cancer Network; PD-1, programmed cell death protein 1; SCCA, squamous cell carcinoma of the anus; TME, tumor microenvironment. 1. Naidoo J, et al. Br J Cancer 2014; 111(12): 2214 9; 2. Bian JJ, et al. Transl Gastroenterol Hepatol 2019; 4: 57; 3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Anal Carcinoma, version 1. 2020. November 2019. [https: //www. nccn. org/professionals/physician_gls/default. aspx] (Accessed: June 2020).

Summary • Anal cancer is usually diagnosed by taking a biopsy, and staging is then performed to guide the choice of treatment and predict the prognosis 1 • Chemoradiation therapy is the mainstay of first-line treatment for locoregional disease and de novo metastatic disease, although some small lesions can be surgically excised 2 • Unmet needs with chemoradiation, including the effects of treatment toxicity, the issue of locoregional treatment failure and the lack of an SOC for chemotherapy-resistant, unresectable, metastatic SCCA, has driven interest in alternative treatments including immunotherapy 2, 3 • Two checkpoint inhibitors are recommended by NCCN for second-line treatment of metastatic SCCA after CRT or chemotherapy 2 • The use of immunotherapies, including novel combinations, in anal cancer is being actively explored in clinical trials 4 CRT; chemoradiotherapy; SCCA, squamous cell carcinoma of the anus; SOC, standard of care; NCCN, National Comprehensive Cancer Network. 1. Glynne-Jones R, et al. Radiother Oncol 2014; 111(3): 330 9; 2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Anal Carcinoma, version 1. 2020. November 2019. [https: //www. nccn. org/professionals/physician_gls/default. aspx] (Accessed: June 2020); 3. Sodergren SC, et al. Clin Oncol (R Coll Radiol) 2019; 31(2): 69 71; 4. Bian JJ, et al. Transl Gastroenterol Hepatol 2019; 4: 57.