Long-term results of treatment of patients with colorectal cancer in the context of familial adenomatous polyposis

INTRODUCTION: familial adenomatous polyposis (FAP) is an hereditary syndrome with an autosomal-dominant type of inheritance, in which patients of young age have dozens, hundreds, and sometimes thousands of adenomatous polyps in the colorectum. If left untreated, it leads to the development of colorectal cancer (CRC) by the third or fourth decade of life. The data presented in the world literature on the characteristics of CRC in the context of FAP, the course of the disease, and the prognosis are scarce and contradictory.

AIM: to study the long-term results of treatment of patients with CRC in the context of FAP, as well as to reveal the factors affecting survival.

PATIENTS AND METHODS: the study included 280 patients who underwent surgery for adenomatous polyposis syndrome between January 2016 and July 2024. The indication for surgery was the presence of more than 100 polyps in the colorectum and/or histologically confirmed colorectal cancer in the presence of multiple (more than 20) polyps in the colorectum. The study included only those patients who underwent radical/conditionally radical surgery with complete cytoreduction. All patients underwent molecular genetic testing (MGT) for the presence of a pathogenic variant in the APC gene, and if none was found, the study was continued with whole-exome sequencing.

RESULTS: according to the results of the MGT, 224 patients were found to have a pathogenic variant in the APC gene, and were diagnosed with familial adenomatous polyposis. Ninety-two (44 females, 48 males) of the 224 patients (41.1%) were diagnosed with colorectal cancer after the pathological examination of the removed specimens. The median age of patients with CRC at the time of surgery was 38 (19–74) years. In 30 (32.6%) of the 92 patients with CRC, the malignant disease was not diagnosed during the preoperative colonoscopy. According to the results of the pathological examination, 40 (43.5%) patients had stage I of cancer, 8 (8.7%) had stage II, 30 (32.6%) had stage III, and 14 (15.2%) had stage IV. The median follow-up period was 27.8 (5–101) months. In 14 (15.2%) patients, the disease progression was diagnosed between 5 and 36 months after surgical treatment. The median disease-free survival was 24.5 months. The actuarial 5-year survival for patients with stage I-II cancer was 100%, stage III — 82.5%, stage IV — 80%. As a result of univariant and multifactorial analyses, the following factors of a negative prognosis proved their independent importance: tumor invasion T4 (HR 14,1; 95% CI 4.62–43.2; p < 0,001), regional lymph nodes status N1a (HR 4.21; 95% CI 1.39–12.8, p = 0.011) and N2b (HR 4,85, 95% CI 1.94–18.61, p = 0.007), peritoneal dissemination M1c (HR 43.8; 95% CI 11.4–168, p < 0.001), the number of malignant tumors in the colon > 1 (HR 1.47; 95% CI 1.00–2.16, p = 0.048).

CONCLUSION: the high frequency of occult polyp malignancy in FAP patients necessitates adherence to oncological principles even during prophylactic surgery in a patient with FAP. The obtained data on the clinical features and course of CRC in patients with FAP correlate with those in patients with sporadic colorectal cancer in the same age group, which may indicate the need to apply the generally accepted approaches to the treatment of oncological patients in patients with colorectal cancer in the context of familial adenomatous polyposis.

1. Jasperson KW, Tuohy TM, Neklason DW, et al. Hereditary and familial colon cancer. Gastroenterology. 2010;138(6):2044-58.doi: 10.1053/j.gastro.2010.01.054.

2. Vasen HF, Möslein G, Alonso A, et al. Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut. 2008;57(5):704-13. doi: 10.1136/gut.2007.136127.

3. Bussey HJ. Familial polyposis coli. Pathol Annu. 1979;14 Pt 1:61-81. PMID: 514641.

4. Smith JC, Schäffer MW, Ballard BR, et al. Adenocarcinomas after prophylactic surgery for familial adenomatous polyposis. J Cancer Ther. 2013;4(1):260-270. doi: 10.4236/jct.2013.41033.

5. Syngal S, Brand RE, Church JM, et al. American College of Gastroenterology. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015;110(2):223-62; quiz 263. doi: 10.1038/ajg.2014.435.

6. Bertario L, Russo A, Sala P, et al. Survival of patients with hereditary colorectal cancer: comparison of HNPCC and colorectal cancer in FAP patients with sporadic colorectal cancer. Int J Cancer. 1999;80(2):183-7. doi: 10.1002/(sici)1097-0215(19990118)80:2<183::aid-ijc4>3.0.co;2-w.

7. Inoue Y, Ishida H, Ueno H, et al. Therapeutic approaches for patients with coexisting familial adenomatous polyposis and colorectal cancer. Jpn J Clin Oncol. 2016;46(9):819-24. doi: 10.1093/jjco/hyw086.

8. Mirinezhad SK, Moaddab SY, Bonyadi MJ, et al. Survival of familial adenomatous polyposis coexistence colorectal cancer in Iran. J Cancer Res Ther. 2019;15(1):87-91. doi: 10.4103/jcrt.JCRT_421_17.

9. Clinical Guidelines of the Ministry of Health of the Russian Federation. Clinical guidelines “Rectal cancer”, 2025 [electronic resources] - URL: https://cr.minzdrav.gov.ru/view-cr/554_4. (in Russ.).

10. Brierley JD, Van Eycken E, Rous BA, et al. TNM Classification of Malignant Tumours, 9th Edition. Hoboken, NJ: Wiley, 2025, 272 p. ISBN: 978-1-394-21687-1.

11. Aarnio M, Mustonen H, Mecklin JP, et al. Prognosis of colorectal cancer varies in different high-risk conditions. Ann Med. 1998 Feb;30(1):75-80. doi: 10.3109/07853899808999387.

12. Chernyshov S.V., Khomyakov E.A., Sinitsyn R.K., et al. Occult adenocarcinoma in adenomas. Possibilities of diagnostic methods. Koloproktologia. 2021;20(2):10–16. (in Russ.). https://doi.org/10.33878/2073-7556-2021-20-2-10-16.

13. Gibbons DC, Sinha A, Phillips RKS, et al. Colorectal cancer: no longer the issue in familial adenomatous polyposis? Fam Cancer. 2011;10:11–20.doi: 10.1007/s10689-010-9394-x.

14. Mallinson EK, Newton KF, Bowen J, et al. The impact of screening and genetic registration on mortality and colorectal cancer incidence in familial adenomatous polyposis. Gut. 2010;59(10):1378-82. doi: 10.1136/gut.2010.212449.

15. Kim TJ, Kim ER, Sung Noh Hong, et al. Long-term outcome and prognostic factors of sporadic colorectal cancer in young patients (a large institutional-based retrospective study). Medicine. 2016;95(19). doi: 10.1097/MD.0000000000003641.

16. Gunderson LL, Jessup JM, Sargent DJ, et al. Revised TN categorization for colon cancer based on national survival outcomes data. J Clin Oncol. 2010;28(2):264-71. doi: 10.1200/JCO.2009.24.0952.

17.