GASTROINTESTINAL CANCERS (J MEYER, SECTION EDITOR)
Systemic Therapies for Advanced Squamous Cell Anal Cancer
Published online: 4 May 2018
Springer Science+Business Media, LLC, part of Springer Nature 2018
Purpose of Review We aim to summarise the available evidence on systemic therapies for advanced anal cancer.
Recent Findings There is no universal consensus on the management of this condition and the prognosis remains poor.
Nevertheless, significant progress has been recently made including completion of the first, ever-conducted, randomised trial
in the first-line setting, investigation of immunotherapy in the refractory setting and use of comprehensive genomic profiling for a
better molecular characterisation of this disease and the identification of novel potential targets.
Summary The combination of a platinum agent and a fluoropyrimidine is generally considered the standard first-line treatment.
Other cytotoxic agents, especially docetaxel and paclitaxel, have shown activity in both the chemotherapy-naive and chemo-
refractory setting and are currently being investigated in clinical trials. Finally, further to the promising results of early clinical
trials, immunotherapy with checkpoint inhibitors (i.e. nivolumab and pembrolizumab) is likely to become a standard second-line
Keywords Advanced anal cancer
Anal cancer is a rare disease that accounts for < 1% of all new
cancer diagnoses and < 3% of all gastrointestinal tumours .
Its incidence, however, has recently increased. In the USA, the
number of new, age-adjusted, cases per 100,000 people per
year has more than doubled over the last 40 years, increasing
from 0.8 in 1975 to 1.8 in 2014 . A similar trend has been
reported in other countries, and approximately 40,000 incident
cases of anal cancer are estimated to have occurred worldwide
in 2012 [1–3]. The median age at diagnosis is 61 and inci-
dence by gender follows a geographic distribution with males
being at higher risk in less developed countries while females
in more developed countries . The vast majority of tumours
(≈ 90%) are attributable to human papillomavirus (HPV), es-
pecially genotypes 16 and 18, and main risk factors include
high number of lifetime sexual partners, unsafe sexual prac-
tices, a prior history of anogenital warts or lower genital tract
malignancies, human immunodeficiency virus (HIV) infec-
tion and other immunosuppressive conditions [3–7].
Squamous cell carcinoma is by far the most common his-
tological variant of tumours arising from the anal canal, in
some cases developing from pre-malignant lesions (i.e. anal
intra-epithelial lesions [AIN] or squamous intra-epithelial le-
sions [SIL]) . Until recently, a variety of subtypes were
routinely reported by pathologists (i.e. basaloid, cloacogenic,
transitional, keratinizing, non-keratinizing, etc.) but the most
recent WHO classification recommends using only the term
squamous cell carcinoma given the poor reproducibility and
limited clinical usefulness of this sub-classification .
Approximately 80 % of patients present with tumours that
are localised or have spread to the loco-regional lymph nodes
while in only 13% of cases, metastatic lesions are detected at
diagnosis . In the former group, chemoradiotherapy is a
standard treatment (concurrent chemotherapy consisting of
mitomycin plus either 5-fluorouracil [5-FU] or capecitabine)
and is given with curative intent and to preserve the sphincter
function [10–15]. Nevertheless, after 5 years, approximately
This article is part of the Topical Collection on Gastrointestinal Cancers
* Sheela Rao
Department of Medicine, The Royal Marsden NHS Foundation
Trust, Sutton, Surrey SM2 5PT, UK
Current Oncology Reports (2018) 20: 53