Home > Cancer Types > Gastrointestinal > Anal Cancer

Anal Cancer

Anal cancer is an uncommon cancer, in which malignant cells are found in the anus (the opening at the end of the rectum through which the body passes waste). Cancer in the outer anus is more frequent in men, whilst cancer in the inner part of the rectum (the anal canal) is more frequent in women.

Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Gastrointestinal System Cancers

Information Patients and the Public (5 links)

Information for Health Professionals / Researchers (6 links)

  • PubMed search for publications about Anal Cancer - Limit search to: [Reviews]

    PubMed Central search for free-access publications about Anal Cancer
    MeSH term: Anus Neoplasms
    International US National Library of Medicine
    qualityPubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Ebrom P, Parizh D, Hajdu CH, Gadangi P
Paget's disease of the anus masking a mixed adenoneuroendocrine tumour of the rectum.
BMJ Case Rep. 2017; 2017 [PubMed] Related Publications
A man aged 83 years with vague perirectal symptoms had a delayed diagnosis of Paget's disease of the anus. A lack of thorough digital rectal examination failed to diagnose a mixed adenonueroendocrine tumour of the rectum in a timely matter.

Clemente N, Alessandrini L, Vaccher E, et al.
Multiple preinvasive and invasive HPV-related lesions of the anogenital tract in a female patient with HIV infection: A case report.
Medicine (Baltimore). 2017; 96(4):e5948 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Patients with human immunodeficiency virus (HIV) infection have been shown to be at increased risk for high-risk human papillomavirus (HR-HPV) infection of the anogenital tract. Furthermore, in the last decades, the introduction of highly active antiretroviral therapy (HAART) has increased the longevity of these patients who now live long enough to develop HPV-related cancers; hence, the impact of HPV infection on HIV-positive patients is of increasing concern.
PATIENT CONCERNS: We reported the case of an HIV-positive female patient on HAART with a good virological and immunological response and with a long history of HPV-related intraepithelial and invasive lesions of the anogenital tract.
DIAGNOSES: From 1996 to 2016, this patient was diagnosed with a high grade cervical intraepithelial neoplasia; a HR-HPV positive inguinal lymph node metastasis from clinically undetectable primary squamous cell carcinoma; a HPV-related vulvar high-grade squamous intraepithelial lesion and an invasive squamous cell carcinoma of the anus.
INTERVENTIONS: All the intraepithelial and invasive lesions detected were properly treated, and subsequent follow up visits with gynecologic examination, anoscopy, pap smear and anal cytology were performed.
OUTCOMES: After a recurrence of the anal cancer and a subsequent salvage surgery with abdominoperineal resection, at the last available follow up visit no sign of disease recurrence was found.
LESSONS: This case stresses the importance of an accurate multidisciplinary follow-up in HIV-positive patients, including not only the routine medical, immunological, and virological evaluation, but also a periodical complete examination of the anogenital tract with cervicovaginal and anal cytology, colposcopy, high resolution anoscopy, and vulvar examination.

Schaefer T, Satzger I, Gutzmer R
Clinics, prognosis and new therapeutic options in patients with mucosal melanoma: A retrospective analysis of 75 patients.
Medicine (Baltimore). 2017; 96(1):e5753 [PubMed] Free Access to Full Article Related Publications
Mucosal melanomas represent a rare entity with different risk factors and molecular features compared to cutaneous melanomas. They arise most commonly from mucosal surfaces in the head/neck region, the female genital tract (FGT) and the anorectal region. The aim of this study was to evaluate clinics, prognosis, and treatment options of patients with mucosal melanoma, in particular with regard to different primary sites.We retrospectively analyzed 75 patients with mucosal melanomas diagnosed in the years 1993 to 2015 in our department. The primary melanomas were located in the head/neck region (n = 32), the FGT (n = 24), and the anorectal region (n = 19).The median age of the patients was 66 years. At initial diagnosis the primary melanoma was not completely resectable in 11 (15%) patients, 18 (24%) patients had regional lymph node metastases, and 7 (9%) patients distant metastases. During follow-up, 22 (29%) patients suffered from a local recurrence, in particular patients with primary melanoma in the head/neck region without postoperative radiotherapy. By multivariate analysis location of the primary melanoma in the head/neck area or anorectal region and presence of metastases at time of diagnosis represented poor prognostic factors for recurrence-free survival. In 62 tested individuals 7 KIT mutations were found, 2 BRAF mutations in 57 tested patients. Four patients received targeted therapies, 14 checkpoint inhibitors, 4 (1/1 on vemurafenib, 1/7 on ipilimumab, and 2/7 on PD-1 inhibitors) patients showed responses of more than 100 days duration.Mucosal melanomas are often locally advanced or metastatic at initial diagnosis, thus they require extensive staging procedures. The high rate of local recurrences in the head/neck region can be significantly reduced by postoperative radiotherapy. For the potential use of medical treatment a mutation analysis for KIT and BRAF genes should be performed. The use of new immunologic and targeted therapies has to be further evaluated.

Tamalet C, Ravaux I, Dhiver C, et al.
Feasibility and Acceptability of Anal Self-Sampling for Human Papillomavirus Screening in HIV-Infected Patients.
Intervirology. 2016; 59(2):118-122 [PubMed] Related Publications
OBJECTIVES: Anal cancer incidence is increasing among HIV-positive patients. No consensus currently exists for the screening of anal dysplasia. This study aimed at evaluating the feasibility and acceptability of anal self-sampling and assessing the prevalence of human papillomavirus (HPV) types among HIV-positive patients from Marseille University Hospitals.
METHODS: Between October 2013 and March 2014, during their regular visits for the monitoring of their HIV infection in an HIV outpatient clinical unit of Marseille University Hospitals, patients were asked to self-sample anal swabs for HPV detection. A specimen self-collection kit was provided. HPV detection and genotyping were performed using in-house protocols. The quality of self-sampling was assessed by concurrent cellular quantification in collected samples.
RESULTS: The acceptability rate of anal self-sampling was 91%, and 91% of the self-sampled specimens were appropriate for HPV screening. In addition, 76% of the samples were positive for HPV, including 54% of HPV types with oncogenic potential.
CONCLUSIONS: This study indicates that HPV detection and typing through anal self-sampling is a valuable strategy to screen patients at high risk for anal cancer development. This could allow earlier management of anal lesions and related cancer in patients at high risk for HPV.

Badiu DC, Manea CA, Mandu M, et al.
Giant Perineal Condyloma Acuminatum (Buschke-Lowenstein Tumour): A Case Report.
Chirurgia (Bucur). 2016 Sept-Oct; 111(5):435-438 [PubMed] Related Publications
The giant condyloma acuminatum, also known as Buschke- Lowenstein tumor (BLT), is a rare sexually-transmitted disease. Moreover, the condyloma acuminatum produced by Human Papilloma Virus (HPV) infection becomes one the most common sexually-transmitted infection which affects the perineal region. Under such situations, the first therapeutic option is surgical excision. The objective of this article is to present a case in which the tumor has reached giant dimensions and also to stress the importance of an in toto resection, taking into account the high rate of recurrence and the significant potential of malignant transformation of BLT.

Dale JE, Sebjørnsen S, Leh S, et al.
Multimodal therapy is feasible in elderly anal cancer patients.
Acta Oncol. 2017; 56(1):81-87 [PubMed] Related Publications
BACKGROUND: Many patients are diagnosed with an anal cancer in high ages. We here present the outcome after oncological therapy for patients above 80 years compared with younger patients.
MATERIALS AND METHODS: A series of 213 consecutive patients was diagnosed and treated at a single institution from 1984 to 2009. The patients received similar radiation doses but with different techniques, thus progressively sparing more normal tissues. The majority of patients also had simultaneous [5-fluorouracil (5FU) and mitomycin C] or induction chemotherapy (cisplatin and 5FU). The patients were stratified by age above or below 80 years. Despite that the goal was to offer standard chemoradiation treatment to all, the octo- and nonagenarians could not always be given chemotherapy.
RESULTS: In our series 35 of 213 anal cancer patients were above 80 years. After initial therapy similar complete response was observed, 80% above and 87% below 80 years. Local recurrence rate was also similar in both groups, 21% versus 26% (p = .187). Cancer-specific survival and relative survival were significantly lower in patients above 80 years, 60% and 50% versus 83% and 80%, (p = .015 and p = .027), respectively.
CONCLUSION: Patients older than 80 years develop anal cancer, but more often marginal tumors. Even in the oldest age group half of the patients can tolerate standard treatment by a combination of radiation and chemotherapy, and obtain a relative survival of 50% after five years. Fragile patients not considered candidates for chemoradiation may be offered radiation or resection to control local disease.

Konstantinova AM, Shelekhova KV, Stewart CJ, et al.
Depth and Patterns of Adnexal Involvement in Primary Extramammary (Anogenital) Paget Disease: A Study of 178 Lesions From 146 Patients.
Am J Dermatopathol. 2016; 38(11):802-808 [PubMed] Related Publications
Extramammary Paget disease (EMPD) is a rare neoplasm usually presenting in the anogenital area, most commonly in the vulva. Adnexal involvement in primary EMPD is a very common feature and serves as a pathway for carcinoma to spread into deeper tissue. The depth of carcinomatous spread along the appendages and the patterns of adnexal involvement were studied in 178 lesions from 146 patients with primary EMPD. Hair follicles and eccrine ducts were the adnexa most commonly affected by carcinoma cells. The maximal depth of involvement was 3.6 mm in this series. When planning topical therapy or developing novel local treatment modalities for EMPD, this potential for significant deep spread along adnexa should be taken into account.

Ito T, Morita S, Shimeno N, et al.
The prospect of endoscopic submucosal dissection for early anal canal squamous cell carcinoma.
Clin J Gastroenterol. 2016; 9(6):384-388 [PubMed] Related Publications
Squamous cell carcinoma (SCC) of the anal canal is seldom diagnosed at an early stage. Chemoradiation therapy is a standard in Europe and the United States, though in squamous cell carcinoma there is no evidence-based therapy. In Japan, endoscopic submucosal dissection (ESD) is the standard minimally invasive treatment for early stage cancer of the digestive tract, including the colorectum. Therefore, if the lesion is diagnosed at an early stage, ESD may be selected for anal canal lesions. We experienced two cases of early stage anal canal cancer in which the diagnosis and the extent of the lesions were confirmed using magnifying endoscopy with narrow-band imaging (NBI), as well as performing ESD. Pathological examination showed the resected specimen to be SCC in situ; the horizontal and vertical margins were free of tumor; and in one case there was no lymphovascular invasion. In the other case it showed the tumor was contained within the epithelium; horizontal and vertical margins were free of tumor; The follow-up period is not long enough to assert that ESD for anal canal squamous cell carcinoma may be an option of minimally invasive therapy. However, if there is a possibility of lymphatic invasion as in one of our cases, we need to give serious consideration to ESD for these lesions, and careful follow-up is necessary even if the lesion is in situ.

Nishikawa T, Ishihara S, Ushiku T, et al.
Anal metastasis from rectal adenocarcinoma.
Clin J Gastroenterol. 2016; 9(6):379-383 [PubMed] Related Publications
The metastasis of rectal cancer to the anus is rare. Here, we report a case of advanced rectal cancer, which had a diffuse venous invasion with anal metastasis and multiple lymph node and liver metastases. The patient was a 72-year-old woman who complained of perianal pain and fresh blood in the stools for 6 months. She had neither history of fistula-in-ano nor anal surgery. Digital examination revealed a 2-cm tumor at the 7 o'clock position, and the barium enema and colonoscopy confirmed advanced rectal cancer. Abdominal computed tomography revealed thickness of the upper rectum wall, right inguinal lymph node of 10 mm and multiple liver metastases. Laparoscopically assisted anterior resection, anal tumor resection, and right inguinal lymph node resection were performed, and the histopathological examination of the resected primary and metastatic tumors confirmed similar findings of moderately differentiated adenocarcinoma, suggestive of metastasis of the rectal cancer to the anal region. In the next procedure, she had the liver lesions resected. This case suggested the importance of the careful examination of the anus during colonoscopy, or digital examination for the detection of anal metastasis.

Köhler C, Marnitz S, Biel P, Cordes T
Successful Delivery in a 39-Year-Old Patient with Anal Cancer after Fertility-Preserving Surgery Followed by Primary Chemoradiation and Low Anti-Mullerian Hormone Level.
Oncology. 2016; 91(5):295-298 [PubMed] Related Publications
Anal cancer was diagnosed in a 36-year-old nulliparous woman. Before chemoradiation was started, ovarian transposition and uterine fixation were performed in order to preserve capability for future parenthood. Despite of a low anti-Mullerian hormone level, IVF therapy was successful and resulted in a full-term delivery of a healthy baby by cesarean section. This is the first case report of successful pregnancy after full-dose pelvic radiation for anal cancer.

Vinayan A, Glynne-Jones R
Anal cancer - What is the optimum chemoradiotherapy?
Best Pract Res Clin Gastroenterol. 2016; 30(4):641-53 [PubMed] Related Publications
Radical concurrent chemoradiotherapy with 5FU and Mitomycin C is the standard-of-care for squamous-cell carcinoma of the anus (SCCA). Phase III trials combined radiation doses of 50-60 Gy with concurrent Fluoropyrimidines, Mitomycin C and Cisplatin in various doses and schedules. CRT is highly successful for early T1/T2 cancers, but results in appreciable late morbidities and still fails to control larger and node-positive tumours. Compliance to chemotherapy is important for local control. Modern radiotherapy techniques such as intensity-modulated radiotherapy (IMRT), rotational IMRT, image-guided radiotherapy (IGRT) have enabled smaller margins and highly conformal plans, resulting in decreased radiation doses to the organs at risk and ensuring a shorter overall treatment time. These advances offer the potential for integrating higher doses of radiation, escalation of the currently used drugs and the safe use of other more novel agents with acceptable toxicity. In this chapter potential novel approaches are discussed in the context of SCCA.

Gauthé M, Richard-Molard M, Fayard J, et al.
Prognostic impact of tumour burden assessed by metabolic tumour volume on FDG PET/CT in anal canal cancer.
Eur J Nucl Med Mol Imaging. 2017; 44(1):63-70 [PubMed] Related Publications
PURPOSE: The aim of this study was to confirm the prognostic value of metabolic tumour volume (MTV) at the primary site on initial work-up FDG PET/CT in patients with squamous cell carcinoma (SCC) of the anal canal.
METHODS: Patients with a recent diagnosis of SCC of the anal canal without metastases undergoing PET/CT for initial work-up and treated with (chemo)radiotherapy were retrospectively reviewed. Computer-aided MTV and SUVmax were determined. Survival rates were estimated using the Kaplan-Meier method. Cox regression analysis was used to evaluate prognostic variables of progression-free survival and overall survival (OS).
RESULTS: The study group comprised 75 patients who had an initial work-up PET/CT. Five patients (6.7 %) had stage I disease, 22 (29.3 %) stage II disease, 20 (26.7 %) stage IIIA disease, and 28 (37.3 %) stage IIIB disease. Median follow-up was 51 months (range 10 - 117 months). Global 4-year OS was 82.7 %, ranging from 100 % in patients with stage I disease to 75 % in patients with stage IIIB disease. MTV at the primary site was significantly and independently correlated with OS (p < 0.05), as patients with MTV less than 7 cm(3) had a better prognosis. SUVmax was not correlated with survival parameters. Metabolic involvement of the inguinal lymph nodes was also correlated with a poor outcome in the univariate analysis (p < 0.05).
CONCLUSION: MTV at the primary site is a prognostic biomarker in anal canal cancer. Hypermetabolic inguinal lymph nodes also appear to be correlated with survival.

Mohammadkhani Shali S, Schmitt V, Behrendt FF, et al.
Metabolic tumour volume of anal carcinoma on (18)FDG PET/CT before combined radiochemotherapy is the only independant determinant of recurrence free survival.
Eur J Radiol. 2016; 85(8):1390-4 [PubMed] Related Publications
AIM: to determine whether [(18)F]2-fluoro-2-deoxyglucose (FDG) positron emission tomography and X-ray computed tomography (PET/CT) findings and metabolic parameters before combined chemo- and radiotherapy (CRT) have a prognostic value in patients with anal carcinoma.
MATERIALS AND METHODS: 45 patients with anal cancer who underwent pre-treatment FDG-PET/CT were included. Metabolic parameters, recurrence and anal carcinoma specific survival were analyzed.
RESULTS: SUV max and metabolic volume of the primary tumour were significantly higher in patients with lymph node or distant metastases than in those with locally confined disease (p=0.020 and p=0.015, respectively). The extent of disease (local tumour only, lymph node or distant metastases) was highly predictive of both for recurrence free and disease specific survival (p=0.010 and p<0.001, respectively). Recurrence free (p=0.010) and anal carcinoma specific survival (p=0.006) differed significantly between patients with a metabolic volume ≤45ml and >45ml. Multivariate analysis revealed that a metabolic volume >45ml was the only significant independent determinant (p=0.19) for recurrence free survival whereas for anal carcinoma specific survival the extent of disease was identified as the only significant independent determinant (p=0.002).
CONCLUSIONS: the extent of disease on FDG PET/CT before combined radio-chemotherapy is strongly predictive of prognosis in anal cancer. Furthermore, patients with a large metabolic volume of the primary tumour (>45ml) are at significantly higher risk of recurrence.

Maejima T, Kono T, Orii F, et al.
Anal Canal Adenocarcinoma in a Patient with Longstanding Crohn's Disease Arising From Rectal Mucosa that Migrated From a Previously Treated Rectovaginal Fistula.
Am J Case Rep. 2016; 17:448-53 [PubMed] Free Access to Full Article Related Publications
BACKGROUND This study reports the pathogenesis of anal canal adenocarcinoma in a patient with longstanding Crohn's disease (CD). CASE REPORT A 50-year-old woman with a 33-year history of CD presented with perianal pain of several months' duration. She had been treated surgically for a rectovaginal fistula 26 years earlier and had been treated with infliximab (IFX) for the previous 4 years. A biopsy under anesthesia revealed an anal canal adenocarcinoma, which was removed by abdominoperineal resection. Pathological examination showed that a large part of the tumor consisted of mucinous adenocarcinoma at the same location as the rectovaginal fistula had been removed 26 years earlier. There was no evidence of recurrent rectovaginal fistula, but thick fibers surrounded the tumor, likely representing part of the previous rectovaginal fistula. Immunohistochemical analysis using antibodies against cytokeratins (CK20 and CK7) revealed that the adenocarcinoma arose from the rectal mucosa, not the anal glands. CONCLUSIONS Mucinous adenocarcinoma can arise in patients with CD, even in the absence of longstanding perianal disease, and may be associated with adenomatous transformation of the epithelial lining in a former fistula tract.

Teagle AR, Gilbert DC, Jones JR, et al.
Negative 18F-FDG-PET-CT may exclude residual or recurrent disease in anal cancer.
Nucl Med Commun. 2016; 37(10):1038-45 [PubMed] Related Publications
OBJECTIVES: The incidence of anal cancer is increasing in Western countries. Fluorine-18 fluorodeoxyglucose (F-FDG) PET-computed tomography (CT) is used in the assessment of anal cancer, but its routine use is not established. The aim of this study was to assess the value of F-FDG-PET-CT in staging and post-treatment assessment in anal cancer and to determine its impact on management.
METHODS: This was a retrospective analysis of patients with anal cancer treated at the Sussex Cancer Centre who underwent PET-CT between November 2004 and September 2014. Information was retrieved from patient notes and the local cancer register, and verified by referring consultants in all cases.
RESULTS: A total of 75 PET-CT scans in 52 patients were identified, representing 38.5% of patients diagnosed with anal cancer during this period. There were 24 staging scans and 51 post-treatment scans. Management was altered following 45.8% of staging scans and 56.0% of all scans, mostly changing treatment type or radiotherapy volume. Out of 28 positive post-treatment scans, 71.4% were true positives, 7.1% were false positives and 21.4% showed nonspecific uptake. Of the 23 negative post-treatment scans, all remained disease free at clinical/radiological follow-up (median follow-up 25 months). The sensitivity and specificity of post-treatment PET-CT were 100 and 74%, respectively. Negative predictive and positive predictive values were 100 and 71%, respectively.
CONCLUSION: Evidence is evolving for the use of PET-CT in anal cancer. Because of a high negative predictive value, our series shows that PET-CT can be used in the assessment of treatment response to exclude residual/recurrent disease.

Henkenberens C, Toklu H, Tamme C, Bruns F
Clinical Value of Squamous Cell Carcinoma Antigen (SCCAg) in Anal Cancer - A Single-Center Retrospective Analysis.
Anticancer Res. 2016; 36(6):3173-7 [PubMed] Related Publications
AIM: To assess the clinical value of squamous cell carcinoma antigen (SCCAg) in anal cancer for chemoradiotherapy (CRT) patients.
PATIENTS AND METHODS: In 24 patients with SCC of the anus, SCCAg was determined before CRT and at every follow-up visit.
RESULTS: 16/24 (66.7%) had normal SCCAg and 11/16 (68.8%) achieved complete remission (CR), while 7/8 (87.5%) with elevated SCCAg achieved CR. In two patients, elevated SCCAg was observed after radiotherapy. One was false-positive and one was true-positive leading to diagnosis of metachronous recurrent and metastatic disease after interim CR.
CONCLUSION: SCCAg was inappropriate to predict the clinical outcome but can provide additional information on the regular follow-up examinations to detect a relapse.

Tse JY, Chan MP, Zukerberg LR, Nazarian RM
Assessment of Melanocyte Density in Anorectal Mucosa for the Evaluation of Surgical Margins in Primary Anorectal Melanoma.
Am J Clin Pathol. 2016; 145(5):626-34 [PubMed] Related Publications
OBJECTIVES: Accurate histopathologic evaluation of surgical resection margins for anorectal melanoma (AM) is diagnostically challenging but essential to clinical management. We studied intraepithelial melanocyte density and growth pattern in anorectal mucosa and BRAF V600E mutation status in AM compared to controls.
METHODS: Histomorphology and melanocytic immunostains, microphthalmia transcription factor (MITF) and human melanoma black 45 (HMB45), were evaluated. Utility of VE1 immunostaining for determination of BRAF V600E mutation status was studied.
RESULTS: Immunostains aid in the distinction between "trailing" melanoma in situ (MIS) and benign melanocyte hyperplasia (BMH), by facilitating assessment of melanocyte density, and evaluation of nuclear atypia and growth pattern. While respective melanocyte densities overlapped, "trailing" MIS could be distinguished by melanocyte nuclear atypia and near confluent growth, compared to the banal cytology and scattered growth of BMH.
CONCLUSIONS: In the histopathologic assessment of AM resections, MITF and HMB45 immunostains aid in distinguishing between "trailing" MIS and BMH, by highlighting melanocyte density, nuclear atypia, and growth pattern, with the latter two being reliable features. VE1 showed nonspecific immunopositivity in anorectal glandular epithelium, a potential diagnostic pitfall when assessing BRAF mutation status.

Roberts JM, Jin F, Thurloe JK, et al.
The value of a transformation zone component in anal cytology to detect HSIL.
Cancer Cytopathol. 2016; 124(8):596-601 [PubMed] Related Publications
BACKGROUND: In a cytology-based screening program intended to prevent anal cancer, the anal transformation zone (TZ) should be adequately sampled because it is the site most susceptible to the development of the cancer precursor, high-grade squamous intraepithelial lesion (HSIL). An adequate TZ component is defined as comprising at least 10 rectal columnar or squamous metaplastic cells. In the current study, the authors examined whether the presence of a TZ component in anal cytology correlated with the detection of histological HSIL.
METHODS: In a natural history study of anal human papillomavirus infection in homosexual men, all participants underwent liquid-based cytology and high-resolution anoscopy (HRA) with or without biopsy at each visit. True-negative cytology (negative cytology with non-HSIL biopsy or negative HRA), false-negative cytology (negative cytology with HSIL biopsy), and true-positive cytology (abnormal cytology with HSIL biopsy) were compared with regard to the presence or absence of a TZ component.
RESULTS: Of 617 participants, baseline results included 155 true-positive results, 191 true-negative results, and 31 false-negative results. The absence of an adequate TZ component was found to be significantly higher for false-negative (32.3%) than for either true-positive (11.0%; P = .0034) or true-negative (13.1%; P = .0089) results.
CONCLUSIONS: Significantly more false-negative cases lacked a TZ component compared with either true-positive or true-negative cases. TZ cells may be an important indicator of sample quality for anal cytology because, unlike cervical sampling, the anal canal is not visualized during cytology sampling. Cancer Cytopathol 2016;124:596-601. © 2016 American Cancer Society.

Dhandapani RG, Anosike C, Ganguly A
Non-small cell lung carcinoma metastasis to the anus.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
A 70-year-old man presenting with a lung mass was investigated and treated with pneumonectomy for adenocarcinoma of the lung. He re-presented 3 months later with a large perianal abscess and mass. Subsequent investigations and biopsies showed disseminated metastases from the lung primary. Immunohistochemical staining confirmed the nature of the anal metastasis from the lung adenocarcinoma. Lung cancer is notorious for metastases, hence it is important to be aware of the uncommon modes of spread, which will help obtain early diagnosis and optimise treatment.

Simpson S, Blomfield P, Cornall A, et al.
Front-to-back & dabbing wiping behaviour post-toilet associated with anal neoplasia & HR-HPV carriage in women with previous HPV-mediated gynaecological neoplasia.
Cancer Epidemiol. 2016; 42:124-32 [PubMed] Related Publications
BACKGROUND: Anal cancer is a human papillomavirus (HPV)-mediated neoplasia of the anal squamous epithelium. Anal cancer is much more common among women, particularly those with a previous high-grade gynaecological neoplasia.
METHODS: Cross-sectional study of women with a previous HPV-mediated gynaecological neoplasia in Tasmania, Australia. Women presenting for follow-up gynaecological care had anal swab samples taken for anal cytology by Hologic Liquid ThinPrep, followed by HPV genotyping. Women with abnormal anal cytology were invited for high-resolution anoscopy. Potential risk factors, including post-toilet wiping behaviours, were queried by questionnaire while clinical covariates were extracted from medical records. Covariates of anal outcomes evaluated by log-binomial and log-multinomial regression.
RESULTS: From 163 women enrolled in the study, 65 (39.9%) had abnormal cytology, with 46 (28.2%) being high-grade. Of the 50 women with abnormal anal cytology having high-resolution anoscopy, 32 (64.0%) had abnormal histology with 13 (26.0%) being high-grade. Of the 123 women tested for HR-HPV DNA, 48 (39.0%) had HR-HPV detected, the most common genotypes being 16 and 51 (14/123, 11.4% for both). In addition to some known anal cancer risk factors, we found front-to-back wiping was associated with significantly increased (Prevalence ratio (PR) range: 1.99-3.60) prevalence of cytological and histological abnormality and HR-HPV carriage/co-carriage, while dabbing post-toilet was significantly associated with decreased prevalences (PR range: 0.50-0.62).
CONCLUSIONS: Post-toilet wiping behaviours were significantly associated with the prevalence of anal cytological, histological and HR-HPV carriage outcomes. This suggests a biologically plausible mechanism for HR-HPV introduction and the higher frequencies of anal neoplasia in women.

Mu Mu Shwe, Hlaing Myat Thu, Khin Saw Aye, et al.
Determination of Oncogenic Human Papillomavirus (HPV) Genotypes in Anogenital Cancers in Myanmar.
Acta Med Okayama. 2016; 70(2):103-10 [PubMed] Related Publications
Molecular and epidemiologic investigations suggest a causal role for human papillomavirus (HPV) in anogenital cancers. This study identified oncogenic HPV genotypes in anogenital cancers among men and women in a 2013 cross-sectional descriptive study in Myanmar. In total, 100 biopsy tissues of histologically confirmed anogenital cancers collected in 2008-2012 were studied, including 30 penile and 9 anal cancers from Yangon General Hospital and 61 vulvar cancers from Central Women's Hospital, Yangon. HPV-DNA testing and genotyping were performed by polymerase chain reaction-restriction fragment length polymorphism. Overall, 34% of anogenital cancers were HPV-positive. HPV was found in 44.4% of anal (4/9), 36.1% of vulvar (22/61), and 26.7% of penile (8/30) cancers. The most frequent genotypes in anal cancers were HPV 16 (75% ) and 18 (25% ). In vulvar cancers, HPV 33 was most common (40.9% ), followed by 16 (31.8% ), 31 (22.7% ), and 18 (4.6% ). In penile cancers, HPV 16 (62.5% ) was most common, followed by 33 (25% ) and 18 (12.5% ). This is the first report of evidencebased oncogenic HPV genotypes in anogenital cancers among men and women in Myanmar. This research provides valuable information for understanding the burden of HPV-associated cancers of the anus, penis, and vulva and considering the effectiveness of prophylactic HPV vaccination.

Kochhar R, Renehan AG, Mullan D, et al.
The assessment of local response using magnetic resonance imaging at 3- and 6-month post chemoradiotherapy in patients with anal cancer.
Eur Radiol. 2017; 27(2):607-617 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: To assess the use of MRI-determined tumour regression grading (TRG) in local response assessment and detection of salvageable early local relapse after chemoradiotherapy (CRT) in patients with anal squamous cell carcinoma (ASCC).
METHODS: From a prospective database of patients with ASCC managed through a centralised multidisciplinary team, 74 patients who completed routine post-CRT 3- and 6-month MRIs (2009-2012) were reviewed. Two radiologists blinded to the outcomes consensus read and retrospectively assigned TRG scores [1 (complete response) to 5 (no response)] and related these to early local relapse (within 12 months) and disease-free survival (DFS).
RESULTS: Seven patients had early local relapse. TRG 1/2 scores at 3 and 6 months had a 100 % negative predictive value; TRG 4/5 scores at 6 months had a 100 % positive predictive value. All seven patients underwent salvage R0 resections. We identified a novel 'tram-track' sign on MRI in over half of patients, with an NPV for early local relapse of 83 % at 6 months. No imaging characteristic or TRG score independently prognosticated for late relapse or 3-year DFS.
CONCLUSIONS: Post-CRT 3- and 6-month MRI-determined TRG scores predicted salvageable R0 early local relapses in patients with ASCC, challenging current clinical guidelines.
KEY POINTS: • Post-chemoradiotherapy MRI (3 and 6 months) helps local response assessment in ASCC. • The MRI-TRG system can be used reproducibly in patients with ASCC. • The TRG system facilitates patient selection for examination under anaesthesia and biopsy. • The use of MRI-TRG predicts for detection of salvageable early local relapses. • The TRG system allows for a standardised follow-up pathway.

Rengifo C, Titi S, Walls J
Anal metastasis as the sentinel and isolated presentation of invasive ductal breast carcinoma.
Ann R Coll Surg Engl. 2016; 98(5):e68-70 [PubMed] Free Access to Full Article Related Publications
Breast cancer currently affects 1 in 8 women in the UK during their lifetime. Common sites for breast cancer metastasis include the axillary lymph nodes, bones, lung, liver, brain, soft tissue and adrenal glands. There is well documented evidence detailing breast metastasis to the gastrointestinal tract but anal metastasis is exceptionally rare. We present the case of a 78-year-old woman with an anal metastasis as the sentinel and isolated presentation of an invasive ductal breast carcinoma. As advances in the treatment of breast cancer improve, and with an ageing and expanding population, there will be an increasing number of cancer survivors, and more of these unusual presentations may be encountered in the future.

Franco P, Arcadipane F, Ragona R, et al.
Locally Advanced (T3-T4 or N+) Anal Cancer Treated with Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy.
Anticancer Res. 2016; 36(4):2027-32 [PubMed] Related Publications
AIM: To report on clinical outcomes of a consecutive series of locally advanced (T3-T4N0-N3) anal cancer patients treated with intensity-modulated radiotherapy (IMRT) and a simultaneous integrated boost (SIB) approach similarly to the RTOG 05-29 trial.
PATIENTS AND METHODS: A cohort of 45 patients underwent SIB-IMRT employing a schedule consisting of 54 Gy/30 fractions to the macroscopic anal planning target volume (PTV), while clinical nodes were prescribed 50.4 Gy/30 fractions if sized ≤3 cm or 54 Gy/30 fractions if >3 cm. Elective nodal PTV was prescribed 45 Gy/30 fractions. Chemotherapy was administered concurrently following the Nigro regimen. Primary end-point was colostomy-free survival (CFS). Secondary end-points were locoregional control (LRC), disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS).
RESULTS: Median follow-up was 39.7 months. The actuarial 3-year CFS was 63.4 % (95% confidence interval (CI=44.8-77.1%). Actuarial 3-year OS and CSS were 67.7% (95%CI=48.7-80.9%) and 72.9% (95%CI=53.8-85.1%), while DFS was 55.8% (95%CI=37.5.4-70.7%). Actuarial 3-year LRC was 74.1% (95%CI=56.7-85.4%). On multivariate analysis, male sex (hazard ratio (HR)=10.9; p=0.004; 95%CI=2.2-55.5%) had a significant impact on CFS, while higher clinical stage (Stage IIIB vs. others) had borderline significance (HR=2.7; p=0.062; 95%CI=1.8-5.9%). A shorter package time (HR=0.94; p=0.007; 95%CI=0.91-0.98%) predicted for higher CFS. Maximum detected events included: skin (G3): 13%; gastrointestinal (GI) (G3): 13%; genitourinary (GU) (G2): 38%; genitalia (G2): 45%; anemia (G2): 4%; leukopenia (G3): 24%, (G4):7%; neutropenia (G3): 16%; (G4): 11%; thrombocytopenia (G3): 9%, (G4): 2%.
CONCLUSION: Our clinical results support the use of SIB-IMRT in the combined modality treatment of locally advanced anal cancer patients.

Franco P, Arcadipane F, Ragona R, et al.
Early-stage Node-negative (T1-T2N0) Anal Cancer Treated with Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy.
Anticancer Res. 2016; 36(4):1943-8 [PubMed] Related Publications
AIM: To report clinical outcomes of a consecutive series of patients with early-stage (T1-T1N0) anal cancer treated with intensity-modulated radiotherapy (IMRT) and a simultaneous integrated boost (SIB) approach similarly to the RTOG 05-29 trial.
PATIENTS AND METHODS: A cohort of 43 patients underwent SIB-IMRT employing a schedule consisting of 50.4 Gy/28 fractions to the gross tumor volume and 42 Gy/28 fractions to the elective nodal volumes for cT1N0 cases, and 54 Gy/30 fractions and 45 Gy/30 fractions to the same volumes for cT2N0 cases. Chemotherapy was administered concurrently following Nigro's regimen. The primary endpoint was colostomy-free survival (CFS). Secondary endpoints were locoregional control (LRC), disease-free (DFS), cancer-specific (CSS) and overall (OS) survival.
RESULTS: Median follow-up was 39.7 months. The actuarial 3-year CFS was 79.4% [95% confidence interval (CI)=61.4-89.7%]. Actuarial 3-year OS and CSS were 90.8% (95% CI=74.1-96.9%) and 93.8% (95% CI=77.3-98.4%), while DFS was 75.5% (95% CI=56.4-87.1%). Actuarial 3-year LRC was 86.1% (95% CI=69.6-94%). On multivariate analysis, tumor size >3 cm showed a trend towards significance in predicting CFS [hazard ratio (HR)=8.6, 95% CI=84.7-88.1%; p=0.069]. Maximum detected adverse events included: skin (G3): 18%; gastrointestinal tract (G2): 67%; genitourinary tract (G3): 3%; genitalia (G2): 30%; anemia (G2): 7%; leukopenia (G3): 26%, leukopenia (G4):7%; neutropenia (G3): 15%; neutropenia (G4): 12%; thrombocytopenia (G3): 9%.
CONCLUSION: Our clinical results support the use of SIB-IMRT in the combined modality treatment of patients with anal cancer.

Sauter M, Keilholz G, Kranzbühler H, et al.
Presenting symptoms predict local staging of anal cancer: a retrospective analysis of 86 patients.
BMC Gastroenterol. 2016; 16:46 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Incidence of anal carcinoma (AC) is increasing and timely diagnosis is critical for efficient therapy. However, there is a paucity of recent studies addressing clinical symptoms and physical findings of anal carcinoma.
METHODS: We performed a retrospective study reviewing history, symptoms and physical findings from 86 patients with newly diagnosed AC. We analyzed frequency of symptoms and physical findings according to T and TNM stage and their predictive value regarding tumor stage.
RESULTS: Most patients presented with T2 (37 %) or T3 (29 %) cancer. 85 of 86 patients were symptomatic with anal bleeding (78 %), anal/perianal pain (63 %), weight loss (31 %) and foreign body sensation (22 %). 95 % of patients had ≥1 finding on physical examination including a visible tumor, palpable resistance and pain/blood during digital rectal examination. Patients with locally advanced disease (T3/T4) presented with more symptoms (p < 0.01) and more physical findings (p = 0.04) than patients with T1/T2 disease. On multivariate regression analysis perianal pain, painful defecation and weight loss were significantly associated with T3/T4 disease.
CONCLUSION: Clinical symptoms and physical findings are present in nearly all AC patients. Pain referred to the perianal region, painful defecation and weight loss have predictive value for locally advanced disease.

Koeck J, Lohr F, Buergy D, et al.
Genital invasion or perigenital spread may pose a risk of marginal misses for Intensity Modulated Radiotherapy (IMRT) in anal cancer.
Radiat Oncol. 2016; 11:53 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: While intensity modulated radiotherapy (IMRT) in anal cancer is feasible and improves high-dose conformality, the current RTOG/AGITG contouring atlas and planning guidelines lack specific instructions on how to proceed with external genitalia. Meanwhile, the RTOG-Protocol 0529 explicitly recommends genital sparing on the basis of specific genital dose constraints. Recent pattern-of-relapse studies based on conventional techniques suggest that marginal miss might be a potential consequence of genital sparing. Our goal is to outline the potential scope and increase the awareness for this clinical issue.
METHODS: We present and discuss four patients with perigenital spread in anal cancer in both early and advanced stages (three at time of first diagnosis and one in form of relapse). Genital/perigenital spread was observed once as direct genital infiltration and thrice in form of perigenital lymphatic spread.
RESULTS: We review the available data regarding the potential consequences of genital sparing in anal cancer. Pattern-of-relapse studies in anal cancer after conventional radiotherapy and the current use of IMRT in anal cancer are equivocal but suggest that genital sparing may occasionally result in marginal miss. An obvious hypothesis suggested by our report is that perigenital lymphovascular invasion might be associated with manifest inguinal N+ disease.
CONCLUSIONS: Local failure has low salvage rates in recent anal cancer treatment series. Perigenital spread may pose a risk of marginal misses in IMRT in anal cancer. To prevent marginal misses, meticulous pattern-of-relapse analyses of controlled IMRT-series are warranted. Until their publication, genital sparing should be applied with caution, PET/CT should be used when possible and meeting genital dose constraints should not be prioritized over CTV coverage, especially (but not only) in stage T3/4 and N+ disease.

Franco P, Ragona R, Arcadipane F, et al.
Dosimetric predictors of acute hematologic toxicity during concurrent intensity-modulated radiotherapy and chemotherapy for anal cancer.
Clin Transl Oncol. 2017; 19(1):67-75 [PubMed] Related Publications
PURPOSE: This study aimed at investigating whether the irradiated volume of pelvic bone marrow (PBM) and specific subsites may predict the occurrence of acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent chemo-radiation.
METHODS: 50 patients, submitted to IMRT and concurrent chemotherapy, were analyzed. Several bony structures were defined on planning-CT: PBM and lumbar-sacral (LSBM), lower pelvis (LPBM) and iliac (IBM) bone marrow. On dose-volume histograms, dosimetric parameters were taken. Endpoints included white blood-cell-count (WBC), absolute-neutrophil-count (ANC), hemoglobin (Hb) and platelet nadirs and acute hematologic toxicity (HT) according to RTOG scoring scale. Generalized linear modeling was used to find correlations between dosimetric variables and blood cell nadirs, while logistic regression analysis was used to test correlation with ≥G3 HT. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the optimal cut-off points for predictive dosimetric variables with the Youden method.
RESULTS: Maximum detected acute HT comprised 38 % of ≥G3 leukopenia and 32 % of ≥G3 neutropenia. Grade 2 anemia was observed in 4 % of patients and ≥G3 thrombocytopenia in 10 %. On multivariate analysis a higher PBM-V 20 was associated with lower WBC nadir. Increased LSBM-V 40 was correlated with a higher likelihood to develop ≥G3 HT. A cut-off point at 41 % for LSBM-V 40 was found. Patients with LSBM-V 40 ≥41 % were more likely to develop ≥G3 HT (55.3 vs. 32.4 %; p < 0.01).
CONCLUSIONS: Increased low-dose to pelvic bony structures significantly predicted for WBC decrease. Medium-high dose to specific osseous subsites was associated with a higher probability of HT. LSBM-V 40 was a strong predictor of ≥G3 HT. A threshold at 41 % for LSBM-V 40 could be used to limit HT.

De Bari B, Jumeau R, Bouchaab H, et al.
Efficacy and safety of helical tomotherapy with daily image guidance in anal canal cancer patients.
Acta Oncol. 2016; 55(6):767-73 [PubMed] Related Publications
Background and purpose Intensity-modulated radiotherapy (IMRT), also using volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) techniques, has been only recently introduced for treating anal cancer patients. We report efficacy and safety HT, and daily image-guided RT (IGRT) for anal cancer. Materials and methods We retrospectively analyzed efficacy and toxicity of HT with or without chemotherapy for anal cancer patients. Local control (LC) and grade 3 or more toxicity rate (CTC-AE v.4.0) were the primary endpoints. Overall (OS), disease-free (DFS), and colostomy-free survival (CFS) are also reported. Results Between October 2007 and May 2014, 78 patients were treated. Fifty patients presented a stage II or stage IIIA (UICC 2002), and 33 presented a N1-3 disease. Radiotherapy consisted of 36 Gy (1.8 Gy/fraction) delivered on the pelvis and on the anal canal, with a sequential boost up to 59.4 Gy (1.8 Gy/fraction) delivered to the anal and to nodal gross tumor volumes. Concomitant chemotherapy was delivered in 73 patients, mainly using mitomycin C and 5-fluorouracil (n = 30) or mitomycin C and capecitabine combination (n = 37). After a median follow-up period of 47 months (range 3-75), the five-year LC rate was 83.8% (95% CI 76.2-91.4%). Seven patients underwent a colostomy because of local recurrence (n = 5) or pretreatment dysfunction (n = 2). Overall incidence of grade 3 acute toxicity was 24%, mainly as erythema (n = 15/19) or diarrhea (n = 7/19). Two patients presented a late grade 3 gastrointestinal toxicity (anal incontinence). No grade 4 acute or late toxicity was recorded. Conclusions HT with daily IGRT is efficacious and safe in the treatment of anal canal cancer patients, and is considered in our department standard of care in this clinical setting.

Alfa-Wali M, Dalla Pria A, Nelson M, et al.
Surgical excision alone for stage T1 anal verge cancers in people living with HIV.
Eur J Surg Oncol. 2016; 42(6):813-6 [PubMed] Related Publications
INTRODUCTION: Anal cancer accounts for a small percentage of colorectal malignancies. Early stage (T1N0M0) cancers of the anal verge have been treated with local surgical excision alone in individuals without human immunodeficiency virus (HIV) infection. The risk of anal cancer is higher in people living with HIV (PLWH). We present results of the outcomes of T1 anal verge cancers treated by local excision only in a series of PLWH.
METHODS: Demographic and clinicopathological data was prospectively collected from all HIV positive individuals with anal cancer, treated between 1986 and 2015. The date from anal cancer diagnosis until the date of the last follow up were collected.
RESULTS: Fifteen patients had T1N0M0 cancer of the anal verge from a total of 92 patients with HIV-associated anal cancer. The mean age was 49 years (range 36-57). The average age of HIV diagnosis was 35 years (range 19-48) and four patients had a diagnosis of AIDS prior to the diagnosis of anal cancer. All patients were surgically managed with complete local excision of the tumour. There were no complications or need for any adjuvant therapy. No patients have relapsed and at a median follow up of 4 years (range 3-15), the overall survival was 100%.
CONCLUSION: Surgical resection for early stage anal verge cancers is an effective strategy in PLWH. Increasing awareness of anal cancer and anoscopy surveillance in PLWH will hopefully continue to identify anal cancers at an early stage that are amenable to minimally invasive surgical management.

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

[Home]    Page last updated: 07 March, 2017     © CancerIndex, Established 1996