Anal Cancer: The Past, Present and Future
Abstract
:1. Introduction
2. Epidemiology
3. Risk Factors
4. Pathology
4.1. Anatomy of Anal Canal
4.2. SCC
Gene Expression Profile
4.3. Adenocarcinoma
5. Diagnostic Work Up
Imaging Modalities
6. Staging
7. Management of Localized and Locally Advanced Disease
7.1. Radiotherapy versus CRT
7.2. Chemotherapy Regimen and Sequence
7.3. Surgery
Local Excision for Stage I ASCC
7.4. Special Circumstances
7.4.1. People Living with HIV
7.4.2. Patients with Para-Aortic Node Involvement
7.4.3. SCC of the Rectum
8. Management of Recurrent and Metastatic Disease
8.1. Salvage Abdominal Perineal Resection for Locoregional Recurrent Disease
8.2. Systemic Therapy for Metastatic Anal Canal Cancer
8.2.1. Chemotherapy
8.2.2. Immunotherapy
8.2.3. Targeted Therapy
8.3. Metastasectomy
9. Surveillance and Survivorship
10. Prevention and Screening
11. Future Directions
12. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variables | Incidence Rates (95% Confidence Interval [CI]): Cases Per 100,000 Person-Years |
---|---|
HIV-positive MSM | 85 (82–89) |
non-MSM male PLHIV | 32 (30–35) |
Female PLHIV | 22 (19–24) |
HIV-negative MSM | 19 (10–36) |
Women with HPV-related gynecological precancerous lesions or cancer | |
Vulvar | 48 (38–61) |
Cervical | 9 (8–12) |
Vaginal | 10 (3–30) |
Solid organ transplant recipients | 13 (12–15) |
Patients with autoimmune diseases | |
Systemic lupus erythematosus | 10 (5–19) |
Ulcerative colitis | 6 (3–11) |
Crohn’s disease | 3 (2–4) |
Stage | Tumor | Node | Metastases |
---|---|---|---|
0 | Tis | 0 | 0 |
I | T1 | 0 | 0 |
IIA | T2 | 0 | 0 |
IIB | T3 | 0 | 0 |
IIIA | T1–2 | 1 | 0 |
IIIB | T4 | 0 | 0 |
IIIC | T3–4 | 1 | 0 |
IV | Any T | Any N | M1 |
Trial | N | Arms | Accrual Period | Follow Up Months | Response | Local Failure | Survival |
---|---|---|---|---|---|---|---|
UKCCR [49] | 585 | RT vs. CRT | 1987–1991 | 42 | Good clinical response at 6 wks: 91% vs. 92% (CR 30% to 39%) | 59% vs. 36% (P < 0.0001) | 3-year anal cancer mortality (39% vs 28%) p = 0.02 3-year OS 58% vs 65% p = 0.25 |
EORTC [50] | 110 | RT vs. CRT | 1987–1994 | 60 | CR 54% vs. 80% | 18% difference in loco-regional failure (0.002) | 5-year survival 56% for whole group |
RTOG 87-04/EORTC 1289 [51] | 310 | MMC plus 5FU or 5FU alone | 1998–1991 | 48 | Post-treatment positive biopsies 15% vs. 7.7% (p = 0.13) | Colostomy rates (9% vs. 22%; P = 0.002) | DFS favoring MMC 73% vs. 51%; P = 0.0003 |
RTOG 98–11 [52] | 682 | 5FU-MMC vs. induction 5FU-CDDP for 2 cycles followed by concurrent 5FU-CDDP | 1998–2005 | 60 | NR | 20% vs. 26.4% (p = 0.08) | 5-yr CFS, 71.9% vs. 65.0% (p = 0.05) 5-year DFS, (67.8% vs. 57.8%; P = 0.006) 5-year OS, 78.3% vs. 70.7%; P = 0.026). |
ACTII [53] | 940 | 2 × 2 MMC vs. 5FU-CDDP Maintenance 5FU-CDDP for 2 cycles vs. no-maintenance | 2001–2008 | 61 | 90.5% with MCC vs. 89.6% with cisplatin | Colostomy rates 11–16 (p = NS) |
3-year PFS 70% vs. 69% p = 0·70 with maintenance 3-year PFS 69% vs. 69% p = 0·NS with CPDD vs. MMC |
ACCORD [54] | 307 | 2 × 2 Induction chemo vs. no induction High dose boost vs. standard doses boost | 199–2005 | 50 | CR or major response with sphincter preservation 92% ICT/SD, 97% ICT/HD, 86% CRT/SD, 94% for CRT /HD | 5-year DFS70% ICT/SD; 78% ICT/HD; 67% CRT/SD; 68% CRT /HD 5-year OS 74.5% ICT 71% no ICT |
NCT Number | Title | Interventions | Study Type | Phase |
---|---|---|---|---|
NCT02369939 | Effects of Deep Regional Hyperthermia in Patients With Anal Carcinoma Treated by Standard Radiochemotherapy | •Radiation: Irradiation •Drug: Mitomycin C •Drug: 5–Fluorouracil •Procedure: Hyperthermia | Interventional | Phase 3 |
NCT03233711 | Nivolumab After Combined Modality Therapy in Treating Patients With High Risk Stage II-IIIB Anal Cancer | •Biological: Nivolumab •Other: Patient Observation | Interventional | Phase 3 |
NCT04444921 | EA2176: Phase 3 Clinical Trial of Carboplatin and Paclitaxel +/−Nivolumab in Metastatic Anal Cancer Patients | •Drug: Carboplatin •Biological: Nivolumab •Drug: Paclitaxel | Interventional | Phase 3 |
NCT02526953 | Efficacy Study of Chemoradiotherapy With or Without Paclitaxel in Squamous-cell Anal Carcinoma Patients | •Drug: Paclitaxel •Drug: Capecitabine •Drug: Mitomycins •Radiation: Radiotherapy | Interventional | Phase 3 |
NCT05374252 | Chemoradiotherapy Combined With or Without PD-1 Blockade in Anal Canal Squamous Carcinoma Patients | •Drug: PD-1 inhibitor •Radiation: concurrent chemoradiotherapy | Interventional | Phase 3 |
NCT04472429 | Carboplatin-paclitaxel With Retifanlimab or Placebo in Participants With Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (POD1UM-303/InterAACT 2). | •Drug: carboplatin •Drug: paclitaxel •Drug: retifanlimab | Interventional | Phase 3 |
NCT04635423 | Efficacy, Immunogenicity, and Safety Study of the 9vHPV Vaccine in Japanese Males (V503-064) | •Biological: V503 •Other: Placebo | Interventional | Phase 3 |
NCT04269369 | Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients | •Drug: 5-Fluorouracil | Interventional | Phase 4 |
NCT04534075 | Dietary Fiber During Radiotherapy—a Placebo-controlled Randomized Trial | •Biological: Capsules containing either dietary fiber or placebo | Interventional | Phase 3 |
NCT04055142 | Clinical Trial for Evaluating the Efficacy and Safety of Electrocoagulation vs Topic Sinecatechins vs Topic Cidofovir Within the Treatment to High-grade Anal Intraepithelial Neoplasia in HIV Homosexual Males | •Procedure: electrocoagulation •Drug: cidofovir 1% topical ointment •Drug: sinecatechins 10% topical ointment | Interventional | Phase 3 |
NCT05662020 | A Study to Evaluate the Immunogenicity and Safety of HPV Vaccine in Healthy Female Participants Aged 9–26 Years in China | Biological: Recombinant Nonavalent (types 6/11/16/18/31/33/45/52/58) Human Papillomavirus (HPV) Vaccine (Escherichia coli) Biological: GARDASIL ® 9 | Interventional | Phase 3 |
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Gondal, T.A.; Chaudhary, N.; Bajwa, H.; Rauf, A.; Le, D.; Ahmed, S. Anal Cancer: The Past, Present and Future. Curr. Oncol. 2023, 30, 3232-3250. https://doi.org/10.3390/curroncol30030246
Gondal TA, Chaudhary N, Bajwa H, Rauf A, Le D, Ahmed S. Anal Cancer: The Past, Present and Future. Current Oncology. 2023; 30(3):3232-3250. https://doi.org/10.3390/curroncol30030246
Chicago/Turabian StyleGondal, Talha Ashraf, Noman Chaudhary, Husnaat Bajwa, Aribah Rauf, Duc Le, and Shahid Ahmed. 2023. "Anal Cancer: The Past, Present and Future" Current Oncology 30, no. 3: 3232-3250. https://doi.org/10.3390/curroncol30030246