Anal Cancer - Market Insight, Epidemiology and Market Forecast - 2034

Key Highlights

• Anal cancer is relatively uncommon, accounting for about 2.7% of all reported gastrointestinal cancers in the United States.
• Anal cancer is more prevalent among women than men and is most frequently diagnosed between the ages of 45 and 75 years. Anal squamous cell cancer (ASCC) occurs most frequently, accounting for approximately 80-85% of all anal canal cancers; other rare types include adenocarcinomas, melanoma, and basal cell carcinoma.
• One well-established risk factor for ASCC is HPV infection, particularly HPV-16. Persistent anal HPV infection plays a significant role in the potential development of ASCC. Many behavioral risk factors, such as an increased number of sexual partners and anoreceptive intercourse, are mediated through HPV infection acquisition. In both males and females, those with HIV infection experienced a higher occurrence of anal HPV infection and ASCC. As the duration of HIV infection extends, the risk of ASCC also escalates. Important non-sexual risk factors include chronic immunosuppression and cigarette smoking.
• MRI is considered to be the imaging technique of choice for evaluating the stage of anal cancers, assessing treatment response following chemoradiotherapy (CRT), and identifying potential complications, because of its ability to provide high contrast and precise anatomical resolution of the anal canal. Changes in tumor size, morphology, and signal intensity on MRI can indicate the effectiveness of treatment and guide further management decisions. Other imaging modalities, such as CT and PET, are used to evaluate anal canal cancer.
• Total incident cases of anal cancer in the 7MM were approximately 20,000 in 2023, which is likely to increase by 2034 at a CAGR of 2.4% during the study period (2020-2034).
• As per the analysis, a higher number of cases were observed in localized (Stage I) anal cancer, followed by regional (Stage II-III) cases, with the fewest cases being accounted for by distant/metastatic (Stage IV) anal cancer, in the US.
• The current treatment modality for localized anal cancer is chemotherapy and radiation. The treatment of anal cancer, akin to many other malignancies, is dependent on the stage of disease at presentation. Tumors that are less than 2 cm with no lymph node involvement and are well-differentiated (T1N0, Stage I) are treated with local excision.
• The combination of MMC, 5-FU, and RT, without induction or maintenance chemotherapy or treatment breaks, remains the standard of care. In locoregional SCCA, IMRT is the preferred modality for RT, which utilizes variable radiation intensities that facilitate more precise mapping of the tumor target and spare nearby structures.
• Currently, several emerging therapies, such as retifanlimab, BMX-001, LCB84, KEYTRUDA (pembrolizumab), and others, are being evaluated in late-stage and mid-stage clinical trials. The successful launch of these potential therapies is likely to bring a positive shift in the treatment paradigm of anal cancer during the forecast period (2024-2034).
• In 2023, EU4 and the UK accounted for nearly 40% of the market size of anal cancer among the 7MM, which is expected to increase by 2034.
• The rarity of anal cancer and the lack of randomized clinical trials have resulted in a limited treatment landscape for this disease. An unmet need in the management of advanced or recurrent anal cancer is the limited availability of targeted therapies. While chemotherapy and radiation therapy serve as primary treatments, there is a demand for more effective and less toxic options.

Report Summary

• The report offers extensive knowledge regarding the epidemiology segments and predictions, presenting a deep understanding of the potential future growth in diagnosis rates, disease progression, and treatment guidelines. It provides comprehensive insights into these aspects, enabling a thorough assessment of the subject matter.
• Additionally, an all-inclusive account of the current management techniques and emerging therapies and the elaborative profiles of late-stage (Phase III and Phase II) and prominent therapies that would impact the current treatment landscape and result in an overall market shift has been provided in the report.
• The report also encompasses a comprehensive analysis of the anal cancer market, providing an in-depth examination of its historical and projected market size (2020-2034). It also includes the market share of therapies, detailed assumptions, and the underlying rationale for our methodology. The report also includes drug outreach coverage in the 7MM region.
• The report includes qualitative insights that provide an edge while developing business strategies, by understanding trends, through SWOT analysis and expert insights/KOL views, including experts from various hospitals and prominent universities, patient journey, and treatment preferences that help shape and drive the 7MM anal cancer market.

Market

Various key players are leading the treatment landscape of anal cancer, such as Incyte Corporation, BioMimetix, and others. The details of the country-wise and therapy-wise market size have been provided below.

• The total market size of anal cancer was around USD 7 million in 2023 in the US, which is further expected to increase by 2034 with the approval of several new therapies in the market.
• Among EU4 and the UK, Germany accounted for the highest market size, which was approximately USD 1 million in 2023.
• In 2023, Japan accounted for approximately 2% market share of anal cancer, which is expected to increase during the study period (2020-2034).
• The launch of the retifanlimab is expected to transform the treatment landscape, potentially becoming a market leader in the 7MM by 2034.

Anal Cancer Drug Chapters

The section dedicated to drugs in the anal cancer report provides an in-depth evaluation of late-stage pipeline drugs (Phase III and Phase II) related to anal cancer.

The drug chapters section provides valuable information on various aspects related to clinical trials of anal cancer, such as the pharmacological mechanisms of the drugs involved, designations, approval status, patent information, and a comprehensive analysis of the pros and cons associated with each drug. Furthermore, it presents the most recent news updates and press releases on drugs targeting anal cancer.

Emerging Therapies

Retifanlimab: Incyte Corporation

Retifanlimab (formerly INCMGA0012), an investigational intravenous anti-PD1 antibody, is currently under evaluation in registration-directed trials as a monotherapy for patients with microsatellite instability-high endometrial cancer and squamous cell carcinoma of the anal canal. Currently, the drug is being evaluated in the POD1UM-303/InterAACT 2 (NCT04472429) Phase III clinical trial.

BMX-001: BioMimetix

BioMimetix is pioneering the advancement of BMX-001, a novel class of small molecules known as redox-active metalloporphyrins (MnPs), which have demonstrated robust anti-inflammatory effects. The mechanism of action of BMX-001 involves a dual impact on tumor cells and normal tissues. In tumor cells, BMX-001 inhibits the NF-?B and HIF-1?? pathways, leading to heightened tumor cell destruction, angiogenesis inhibition, and decreased long-term tumor proliferation. Currently, the company is recruiting patients in its Phase I/II clinical trial of patients with newly diagnosed anal cancer.

Anal Cancer Market Outlook

The first-line treatment option for locoregional anal cancer is combination chemoradiotherapy (CRT). The exception is early-stage perianal disease excluding the anal sphincter and superficially invasive SCC of the anus, for which wide local excision is a treatment option.

In anal cancer, the treatment paradigm has shifted from surgery to combined chemoradiation therapy. With this shift, the function of the anus could be preserved. After several randomized trials of induction chemotherapy, maintenance chemotherapy, and planned treatment breaks, the combination of MMC, 5-FU, and RT, without induction or maintenance chemotherapy or treatment breaks, remains the standard of care. Over the past decade, intensity-modulated radiotherapy (IMRT) has replaced older treatment techniques as the standard of care.

Moreover, strategies to decrease radiation-associated toxicities are an additional focus of current research on SCCA. A potential strategy to decrease hematologic toxicity is bone marrow-sparing IMRT. Immunotherapy is presently recommended as a second-line treatment option in the metastatic setting but is currently being explored in the locoregional setting. Immune checkpoint inhibitors (ICI) have been an active focus of recently published studies on patients with locoregional SCCA.

Nevertheless, the treatment landscape is undergoing substantial changes with ongoing research and studies encompassing chemotherapy, immunotherapy, radiation therapy, and innovative combinations throughout the different stages of ASCC. These advancements in therapeutic exploration are indicative of a dynamic and evolving field with the potential to enhance treatment options and outcomes for individuals with anal cancer.

Anal Cancer Disease Understanding and Treatment

Anal Cancer Overview

Anal cancer is relatively rare, comprising only approximately 2.5% of gastrointestinal tumors; however, the incidence of anal cancer has been steadily increasing in recent years, with a notable rise observed over the past three to four decades.

The rectum and the anal canal are structurally connected. The rectum begins at the point where the taenia converges and extends to the upper border of the puborectalis muscle; the anal canal starts at the upper border of the puborectalis muscle and extends to the anal verge. Rectal and anal cancers are different types of tumors. Adenocarcinomas are the most common form of rectal cancer, whereas anal cancers are generally squamous-cell carcinomas (SCCs) that arise from the squamous mucosa of the anal canal.

SCCs are the most common type of anal cancer; other rare types include adenocarcinomas, melanoma, and basal cell carcinoma. Many behavioral risk factors, such as increased number of sexual partners and anoreceptive intercourse, are mediated through HPV infection acquisition. Important non-sexual risk factors include chronic immunosuppression and cigarette smoking.

Most anal cancers seem to be linked to infection with HPV. While HPV infection seems to be important in the development of anal cancer, the vast majority of people with HPV infections do not get anal cancer. A great deal of research is being done to learn how HPV might cause anal cancer. There is good evidence that HPV causes many anal squamous cell carcinomas. But the role of this virus in causing anal adenocarcinomas is less certain.

Anal Cancer Diagnosis

The initial diagnostic evaluation of anal cancer includes digital rectal examination (DRE) and proctoscopy with biopsy.

According to joint guidelines from the European Society for Medical Oncology, the European Society of Surgical Oncology, and the European Society of Radiotherapy and Oncology (ESMO-ESSO-ESTRO), as well as guidelines from the American Society of Colon and Rectal Surgeons, MRI of the pelvis and endoanal ultrasound (EAUS) should be used for the standard management of anal cancer. If MRI is not available, EAUS is recommended as an alternative. However, EAUS should be reserved for small T1 lesions because of its limited field of view, which may restrict the identification of regional lymph nodes.

CT of the chest, abdomen, and pelvis with intravenous contrast is commonly used to evaluate distant metastatic disease and lymphadenopathy. CT offers several advantages in the assessment of ASCC. The 18F-FDG PET/CT technique exhibits sensitivity in detecting the primary tumor; however, its ability to fully characterize the tumor is limited. The 18F-FDG PET/CT technique is currently recommended for radiation treatment planning because of its ability to detect nodal disease. PET/CT is more sensitive than CT alone in identifying nodes; however, it has modest specificity, leading to false-positive findings in cases of inflammatory conditions.

Anal Cancer Treatment

The landscape of treatment for this cancer is rapidly evolving with novel combination strategies, including immunotherapy, radiation therapy, and biomarker-guided therapy. The recent focus on locoregional SCCA management is to tailor treatment according to tumor burden and minimize treatment-related toxicities.

Mitomycin plus either infusional 5-fluorouracil (5-FU) or capecitabine is used for first-line CRT, and intensity-modulated radiotherapy (IMRT) is the preferred modality for radiation for locoregional anal cancer. Locally recurrent disease is managed with surgical resection. Systemic treatment is first-line for metastatic SCCA and immunotherapy, with nivolumab and pembrolizumab being included as second-line agents. Current and future clinical trials are evaluating treatments for SCCA, including immunotherapy alone or in combination regimens, radiotherapies, targeted treatments, and novel agents.

Another critical aspect of SCCA is the personalization of CRT and immunotherapies based on molecular characterization and biomarkers such as the programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR), and circulating tumor DNA.

Anal Cancer Epidemiology

The anal cancer epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by incident cases of anal cancer, gender-specific cases, age-specific cases, histology-specific cases, HPV status-specific cases, stage-specific cases, and linewise treated cases of anal cancer in the United States, EU4 countries (Germany, France, Italy, Spain) and the United Kingdom, and Japan from 2020 to 2034.

• The United States accounted for the highest cases of incident cases of anal cancer among the 7MM countries, which is expected to increase at a CAGR of 3.6% for the study period i.e. 2020-2034.
• In 2023, in the United States, approximately 82% of patients who tested positive for HPV were diagnosed with anal cancer, with HPV being the primary causative factor.
• EU4 and the UK collectively accounted for nearly 9,000 incident cases of anal cancer in 2023, which is likely to increase by 2034. Among the EU4 countries, Germany accounted for the highest number of incident cases of anal cancer.
• In Japan, there is a different trend compared to other 6MM markets regarding histology-specific cases of anal cancer. While Squamous Cell Carcinoma (SCC) accounts for the highest number of cases in other markets, in Japan, the highest histology-specific cases are accounted for by Adenocarcinoma and other types, followed by SCC type.

KOL Views

To stay abreast of the latest trends in the market, we conduct primary research by seeking the opinions of Key Opinion Leaders (KOLs) and Subject Matter Experts (SMEs) who work in the relevant field. This helps us fill any gaps in data and validate our secondary research.

We have reached out to industry experts to gather insights on various aspects of anal cancer, including the evolving treatment landscape, patients’ reliance on conventional therapies, their acceptance of therapy switching, drug uptake, and challenges related to accessibility. The experts we contacted included medical/scientific writers, professors, and researchers from prestigious universities in the US, Europe, the UK, and Japan.

Our team of analysts connected with more than 15 KOLs across the 7MM. We contacted institutions such as Duke University, the American Academy of Family Physicians, the University of Munich, the University of Glasgow, Anal Cancer Foundation, etc., among others. By obtaining the opinions of these experts, we gained a better understanding of the current and emerging treatment patterns in the anal cancer market, which will assist our clients in analyzing the overall epidemiology and market scenario.

Qualitative Analysis

We perform Qualitative and Market Intelligence analysis using various approaches, such as SWOT analysis and Conjoint Analysis. In the SWOT analysis, strengths, weaknesses, opportunities, and threats in terms of disease diagnosis, patient awareness, patient burden, competitive landscape, cost-effectiveness, and geographical accessibility of therapies are provided. These pointers are based on the Analyst’s discretion and assessment of the patient burden, cost analysis, and existing and evolving treatment landscape.

Conjoint Analysis analyzes multiple approved and emerging therapies based on relevant attributes such as safety, efficacy, frequency of administration, designation, route of administration, and order of entry. Scoring is given based on these parameters to analyze the effectiveness of therapy.

In efficacy, the trial’s primary and secondary outcome measures are evaluated; for instance, in trials for anal cancer, important primary endpoints are objective response rate (ORR), progression-free survival (PFS), overall survival (OS), etc. Based on these parameters, the overall efficacy is evaluated.

Further, the therapies’ safety is evaluated wherein the acceptability, tolerability, and adverse events are majorly observed, and it sets a clear understanding of the side effects posed by the drug in the trials. In addition, the scoring is also based on the route of administration, order of entry and designation, probability of success, and the addressable patient pool for each therapy. According to these parameters, a final weightage score is decided based on which the emerging therapies are ranked.

Market Access and Reimbursement

Because newly authorized drugs are often expensive, some patients escape receiving proper treatment or use off-label, less expensive prescriptions. Reimbursement plays a critical role in how innovative treatments can enter the market. The cost of the medicine, compared to the benefit it provides to patients who are being treated, sometimes determines whether or not it will be reimbursed. Regulatory status, target population size, the setting of treatment, unmet needs, the number of incremental benefit claims, and prices can all affect market access and reimbursement possibilities.

The report further provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenario of approved therapies, programs making accessibility easier and out-of-pocket costs more affordable, insights on patients insured under federal or state government prescription drug programs, etc.

Anal Cancer Report Insights

• Patient Population
• Therapeutic Approaches
• Anal Cancer Market Size and Trends
• Existing Market Opportunity

Anal Cancer Report Key Strengths

• Eleven-year Forecast
• The 7MM Coverage
• Anal Cancer Epidemiology Segmentation
• Key Cross Competition

Anal Cancer Report Assessment

• Current Treatment Practices
• Reimbursements
• Market Attractiveness
• Qualitative Analysis (SWOT, Conjoint Analysis, Unmet needs)

Key Questions

• Would there be any changes observed in the current treatment approach?
• Will there be any improvements in anal cancer management recommendations?
• Would research and development advances pave the way for future tests and therapies for anal cancer?
• Would the diagnostic testing space experience a significant impact and lead to a positive shift in the treatment landscape of anal cancer?
• What kind of uptake will the new therapies witness in the coming years in anal cancer patients?