RARE DISEASE
Carcinoma of the anal canal
Carcinoma of the anal canal
Carcinoma of the anal canal
Drug discovery
6
drugs
With orphan designations
Overview
Carcinoma of the anal canal is a rare malignancy, with >90% being squamous cell carcinomas linked to HPV infection [1][14]. Early symptoms include rectal bleeding, anal pain, and masses [1][17]. Diagnosis combines digital/anoscopic exams with biopsy and imaging (CT/MRI/PET) [9]. First-line treatment employs chemoradiation (Nigro protocol: 5-FU + mitomycin-C with radiation), achieving 70-90% 5-year survival for localized disease [7][15]. Salvage surgery (abdominoperineal resection) is reserved for persistent/recurrent tumors [11][13].
Therapies
Localized disease: Chemoradiation (50.4-59 Gy radiation + 5-FU/mitomycin) preserves sphincter function in 85% [3][15]
Metastatic disease: Carboplatin/paclitaxel first-line; nivolumab/pembrolizumab second-line [3][13]
Emerging: IMRT to reduce toxicity, neoadjuvant immunotherapy trials (NCT05060471) [3][13]
Categories: rare gastroenterological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
856 drug discovery papers about Carcinoma of the anal canal, with 2 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
856 drug discovery papers about Carcinoma of the anal canal, with 2 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-05 | FDA Approval Summary: Retifanlimab for the treatment of adult patients with metastatic or inoperable locally recurrent squamous cell carcinoma of the anal canal.
On May 15, 2025, the Food and Drug Administration approved retifanlimab in combination with carboplatin and paclitaxel for treating unresectable or metastatic squamous cell carcinoma of the anal canal (SCAC), and as a single agent for second-line SCAC treatment. These approvals were based on POD1UM-303 and POD1UM-202 trials. In POD1UM-303, 308 patients with no prior systemic treatment for advanced disease were randomized 1:1 to receive retifanlimab or placebo, both combined with carboplatin and paclitaxel. The primary efficacy outcome was progression-free survival (PFS) assessed by blinded independent central review, with overall survival (OS) as a key secondary endpoint. The trial demonstrated a statistically significant PFS improvement with a hazard ratio (HR) of 0.63 (95% CI: 0.47, 0.84, p-value 0.0006). Median PFS was 9.3 months (95% CI: 7.5, 11.3) and 7.4 months (95% CI: 7.1, 7.7) in the retifanlimab and placebo arms, respectively. Interim OS results were not statistically significant (HR 0.70 [95% CI: 0.49, 1.01]), although the point estimate for OS was 29.2 months (95% CI: 24.2, NE) in the retifanlimab arm and 23 months (95% CI: 15.1, 27.9) for placebo. Second-line approval was based on POD1UM-202, a single-arm trial of 94 patients receiving single-agent retifanlimab. The independent centrally assessed overall response rate was 14% (95% CI: 8, 23). No new adverse safety signals were identified. The approval of retifanlimab as a single agent or in combination with chemotherapy provides a new therapeutic option for patients with unresectable or metastatic SCAC.
2026-08-01 | Atezolizumab, Lurbinectedin, Tarlatamab, and FOLFIRNOX in a Patient with Metastatic Small Cell Carcinoma of the Anal Canal: A Case Report and Review of the Literature
Small cell carcinoma (SCC) of the anal canal is a rare and highly aggressive neuroendocrine malignancy, and its infrequency has limited the development of evidence-based treatment approaches. As a result, management of extrapulmonary SCC (EPSCC) is often extrapolated from small cell lung cancer (SCLC), given the similar disease biology and the lack of formal approval for many SCLC-directed agents. We report the case of a 60-year-old woman who presented with metastatic SCC of the anal canal and whose disease course illustrates both the challenges and therapeutic uncertainties inherent in treating this diagnosis. Given the absence of established standards, she was treated with SCLC-based regimens and achieved a partial radiographic and clinical response to platinum-based chemotherapy in combination with the immune checkpoint inhibitor atezolizumab. Upon subsequent progression, she was treated with lurbinectedin and tarlatamab, a bispecific T-cell engager targeting delta-like ligand 3 (DLL3), reflecting evolving treatment paradigms in SCLC. Her response suggests that novel therapies developed for pulmonary small cell disease may offer benefit in select extrapulmonary cases. This case highlights the need for continued reporting of clinical experiences and prospective investigation to better define the role of emerging therapies in rare and aggressive extrapulmonary neuroendocrine malignancies.
2026-07-22 | Durable Cancer Control and Extended Long-Term Survival Following Salvage Surgery for Squamous Cell Carcinoma of the Anal Canal: A Cohort Study.
Salvage surgery is the standard-of-care for patients with squamous cell carcinoma of the anal canal (SCCa) who experience isolated locoregional failure after upfront chemoradiotherapy. While perioperative morbidity and short-term survival outcomes have been described, long-term outcomes of surgical salvage are unknown. This study examines recurrence patterns and survival in a cohort of patients with extended follow-up. A retrospective chart review was performed on a cohort of consecutive patients who underwent salvage surgery at two specialized cancer centers between 1987 and 2006. Overall, disease-specific and re-recurrence-free survival (OS, DSS, RRFS) were estimated using the Kaplan-Meier method. Prognostic variables were evaluated using univariate and multivariable Cox models. Forty patients were included (29 female, 11 male; median age 56). Median follow-up was 16.5 years (IQR 15.0-20.5) for patients alive at last follow-up. Re-recurrence developed in 52% of patients, 95% of which occurred within 3 years of salvage surgery; re-recurrence was associated with a 91% risk of subsequent SCCa-specific mortality. DSS was 45% (95% CI 30-61) at 5 years, after which point conditional 5-year DSS was 100%. Approximately half of patients who undergo salvage surgery for persistent/recurrent SCCa experience durable cancer control with extended long-term survival. Emerging treatment options such as immunotherapy should be evaluated relative to this benchmark.
2026-07-13 | Poorly Differentiated Adenocarcinoma of Anal canal Presenting as a Vulval Lump
Primary adenocarcinoma of the anal canal is a rare malignancy, accounting for fewer than 10% of anal cancers. It often presents with non-specific perianal symptoms and can be clinically mistaken for benign conditions such as a perianal abscess or Bartholin’s cyst, leading to diagnostic delay. A 69-year-old postmenopausal multipara woman presented with a three-month history of a painless, hard mass extending from the left labia majora to the left gluteal fold. She initially underwent incision and drainage for a presumed perianal abscess. Histopathological report of the excised tissue revealed poorly differentiated adenocarcinoma. Subsequent workup, including serum carcinoembryonic antigen (CEA) (2.02 ng/mL), chest x-ray, abdominal ultrasound, and CT-guided FNAC of a right lung mass, confirmed metastatic adenocarcinoma. Imaging revealed multiple pulmonary nodules in both lungs with right-sided pleural effusion, cholelithiasis, and mild endometrial collection. On immunohistochemistry (IHC), the perianal tissue sections demonstrated poorly differentiated adenocarcinoma. Our final diagnosis was carcinoma of the anal canal (Grade II, poorly differentiated adenocarcinoma) with pulmonary metastases. This case highlights that a hard, painless labio-gluteal lump in an older woman should raise suspicion for anal canal adenocarcinoma rather than benign inflammatory lesions. Early diagnosis and metastatic evaluation are essential to guide appropriate oncological management. CBMJ 2026 July: Vol. 15 No. 02 P:409-413
2026-07-07 | Knowledge gaps in tubular gut tumours: a critical appraisal of the 6th edition of the World Health Organization classification of tumours.
Gastrointestinal cancer is a global health problem. In the new 6th edition of the World Health Organization Classification of Tumours (WCT) of the Digestive System, updated evidence and guidance is provided for the aetiology, pathogenesis, diagnosis, classification, grading, staging and prognosis of these tumours. However, significant knowledge gaps remain, some of which are addressed in this review. To provide for a research framework to fill these knowledge gaps, we focused on precursor lesions and rare cancers, where the need for new evidence is most urgent. Areas with a need for further research are discussed for neoplastic precursors of the oesophagus (squamous epithelium), stomach (gastric dysplasia and adenomas), ampulla-duodenum, jejunoileum, anal canal, as well as for colorectal serrated polyposis and inflammatory bowel disease associated dysplasia (conventional and non-conventional). Knowledge gaps are also presented as they exist in rare cancers of the oesophagus (mixed type), appendix (mucinous neoplasms and mucinous adenomas), colorectum (three new subtypes) and anus, as well as for neuroendocrine tumours (grading, necrosis and two new gastric subtypes) and undifferentiated carcinomas (deficiencies of the SWI/SNF chromatin remodelling complex and mesenchymal differentiation). We identify and present research questions and persistent challenges for these entities and thus propose research frameworks that focus on specific priority areas. Progress in these core research topics for both neoplastic precursors and rare cancers will hopefully be reflected in future editions of the WCT, but many of these knowledge gaps will only be resolved with collective registries and collaborative research efforts. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
2026-08-05 | FDA Approval Summary: Retifanlimab for the treatment of adult patients with metastatic or inoperable locally recurrent squamous cell carcinoma of the anal canal.
On May 15, 2025, the Food and Drug Administration approved retifanlimab in combination with carboplatin and paclitaxel for treating unresectable or metastatic squamous cell carcinoma of the anal canal (SCAC), and as a single agent for second-line SCAC treatment. These approvals were based on POD1UM-303 and POD1UM-202 trials. In POD1UM-303, 308 patients with no prior systemic treatment for advanced disease were randomized 1:1 to receive retifanlimab or placebo, both combined with carboplatin and paclitaxel. The primary efficacy outcome was progression-free survival (PFS) assessed by blinded independent central review, with overall survival (OS) as a key secondary endpoint. The trial demonstrated a statistically significant PFS improvement with a hazard ratio (HR) of 0.63 (95% CI: 0.47, 0.84, p-value 0.0006). Median PFS was 9.3 months (95% CI: 7.5, 11.3) and 7.4 months (95% CI: 7.1, 7.7) in the retifanlimab and placebo arms, respectively. Interim OS results were not statistically significant (HR 0.70 [95% CI: 0.49, 1.01]), although the point estimate for OS was 29.2 months (95% CI: 24.2, NE) in the retifanlimab arm and 23 months (95% CI: 15.1, 27.9) for placebo. Second-line approval was based on POD1UM-202, a single-arm trial of 94 patients receiving single-agent retifanlimab. The independent centrally assessed overall response rate was 14% (95% CI: 8, 23). No new adverse safety signals were identified. The approval of retifanlimab as a single agent or in combination with chemotherapy provides a new therapeutic option for patients with unresectable or metastatic SCAC.
2026-08-01 | Atezolizumab, Lurbinectedin, Tarlatamab, and FOLFIRNOX in a Patient with Metastatic Small Cell Carcinoma of the Anal Canal: A Case Report and Review of the Literature
Small cell carcinoma (SCC) of the anal canal is a rare and highly aggressive neuroendocrine malignancy, and its infrequency has limited the development of evidence-based treatment approaches. As a result, management of extrapulmonary SCC (EPSCC) is often extrapolated from small cell lung cancer (SCLC), given the similar disease biology and the lack of formal approval for many SCLC-directed agents. We report the case of a 60-year-old woman who presented with metastatic SCC of the anal canal and whose disease course illustrates both the challenges and therapeutic uncertainties inherent in treating this diagnosis. Given the absence of established standards, she was treated with SCLC-based regimens and achieved a partial radiographic and clinical response to platinum-based chemotherapy in combination with the immune checkpoint inhibitor atezolizumab. Upon subsequent progression, she was treated with lurbinectedin and tarlatamab, a bispecific T-cell engager targeting delta-like ligand 3 (DLL3), reflecting evolving treatment paradigms in SCLC. Her response suggests that novel therapies developed for pulmonary small cell disease may offer benefit in select extrapulmonary cases. This case highlights the need for continued reporting of clinical experiences and prospective investigation to better define the role of emerging therapies in rare and aggressive extrapulmonary neuroendocrine malignancies.
2026-07-22 | Durable Cancer Control and Extended Long-Term Survival Following Salvage Surgery for Squamous Cell Carcinoma of the Anal Canal: A Cohort Study.
Salvage surgery is the standard-of-care for patients with squamous cell carcinoma of the anal canal (SCCa) who experience isolated locoregional failure after upfront chemoradiotherapy. While perioperative morbidity and short-term survival outcomes have been described, long-term outcomes of surgical salvage are unknown. This study examines recurrence patterns and survival in a cohort of patients with extended follow-up. A retrospective chart review was performed on a cohort of consecutive patients who underwent salvage surgery at two specialized cancer centers between 1987 and 2006. Overall, disease-specific and re-recurrence-free survival (OS, DSS, RRFS) were estimated using the Kaplan-Meier method. Prognostic variables were evaluated using univariate and multivariable Cox models. Forty patients were included (29 female, 11 male; median age 56). Median follow-up was 16.5 years (IQR 15.0-20.5) for patients alive at last follow-up. Re-recurrence developed in 52% of patients, 95% of which occurred within 3 years of salvage surgery; re-recurrence was associated with a 91% risk of subsequent SCCa-specific mortality. DSS was 45% (95% CI 30-61) at 5 years, after which point conditional 5-year DSS was 100%. Approximately half of patients who undergo salvage surgery for persistent/recurrent SCCa experience durable cancer control with extended long-term survival. Emerging treatment options such as immunotherapy should be evaluated relative to this benchmark.
2026-07-13 | Poorly Differentiated Adenocarcinoma of Anal canal Presenting as a Vulval Lump
Primary adenocarcinoma of the anal canal is a rare malignancy, accounting for fewer than 10% of anal cancers. It often presents with non-specific perianal symptoms and can be clinically mistaken for benign conditions such as a perianal abscess or Bartholin’s cyst, leading to diagnostic delay. A 69-year-old postmenopausal multipara woman presented with a three-month history of a painless, hard mass extending from the left labia majora to the left gluteal fold. She initially underwent incision and drainage for a presumed perianal abscess. Histopathological report of the excised tissue revealed poorly differentiated adenocarcinoma. Subsequent workup, including serum carcinoembryonic antigen (CEA) (2.02 ng/mL), chest x-ray, abdominal ultrasound, and CT-guided FNAC of a right lung mass, confirmed metastatic adenocarcinoma. Imaging revealed multiple pulmonary nodules in both lungs with right-sided pleural effusion, cholelithiasis, and mild endometrial collection. On immunohistochemistry (IHC), the perianal tissue sections demonstrated poorly differentiated adenocarcinoma. Our final diagnosis was carcinoma of the anal canal (Grade II, poorly differentiated adenocarcinoma) with pulmonary metastases. This case highlights that a hard, painless labio-gluteal lump in an older woman should raise suspicion for anal canal adenocarcinoma rather than benign inflammatory lesions. Early diagnosis and metastatic evaluation are essential to guide appropriate oncological management. CBMJ 2026 July: Vol. 15 No. 02 P:409-413
2026-07-07 | Knowledge gaps in tubular gut tumours: a critical appraisal of the 6th edition of the World Health Organization classification of tumours.
Gastrointestinal cancer is a global health problem. In the new 6th edition of the World Health Organization Classification of Tumours (WCT) of the Digestive System, updated evidence and guidance is provided for the aetiology, pathogenesis, diagnosis, classification, grading, staging and prognosis of these tumours. However, significant knowledge gaps remain, some of which are addressed in this review. To provide for a research framework to fill these knowledge gaps, we focused on precursor lesions and rare cancers, where the need for new evidence is most urgent. Areas with a need for further research are discussed for neoplastic precursors of the oesophagus (squamous epithelium), stomach (gastric dysplasia and adenomas), ampulla-duodenum, jejunoileum, anal canal, as well as for colorectal serrated polyposis and inflammatory bowel disease associated dysplasia (conventional and non-conventional). Knowledge gaps are also presented as they exist in rare cancers of the oesophagus (mixed type), appendix (mucinous neoplasms and mucinous adenomas), colorectum (three new subtypes) and anus, as well as for neuroendocrine tumours (grading, necrosis and two new gastric subtypes) and undifferentiated carcinomas (deficiencies of the SWI/SNF chromatin remodelling complex and mesenchymal differentiation). We identify and present research questions and persistent challenges for these entities and thus propose research frameworks that focus on specific priority areas. Progress in these core research topics for both neoplastic precursors and rare cancers will hopefully be reflected in future editions of the WCT, but many of these knowledge gaps will only be resolved with collective registries and collaborative research efforts. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Drug Discovery Landscape
6 orphan drug designations for Carcinoma of the anal canal, including 2 approved therapies.
6 orphan drug designations for Carcinoma of the anal canal, including 2 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
semi-synthetic chlorin-based photosensitizer | small molecules | FDA | 2025-08-18 | — | Invion Limited |
Retifanlimab [ZYNYZ] | antibodies | EMA | 2020-10-19 | 2026-03-06 | Incyte Biosciences Distribution B.V. |
retifanlimab-dlwr [Zynyz] | antibodies | FDA | 2020-03-24 | 2025-05-15 | Incyte Corporation |
nivolumab | antibodies | FDA | 2017-08-07 | — | Bristol-Myers Squibb Company |
Axalimogene filolisbac [Raligize] | vaccines | EMA | 2016-01-11 | — | Granzer Regulatory Consulting & Services GmbH |
2-Pyrazinecarbonitrile, 5-[[5-2-(3-aminopropoxy)-6-methoxyphenyl]-1H-pyrazol-3-yl]amino] monomesylate monohydrate | small molecules | FDA | 2015-04-09 | — | Acrivon Therapeutics, Inc. |
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