Prognostic Significance of Mucinous Histology in Metastatic Colorectal Cancer Patients Treated with Regorafenib
Received Date : 09 Nov 2022
Accepted Date : 27 Mar 2023
Available Online : 10 Apr 2023
Doi: 10.37047/jos.2022-94250 - Article's Language: EN
J Oncol Sci. 2023;9(2):53-61
This is an open access article under the CC BY-NC-ND license
Objective: Prognostic factors for regorafenib therapy have not been fully defined. Mucinous adenocarcinoma (MAC) is a distinct subtype of colorectal cancer (CRC). We investigated the significance of mucinous histology in patients treated with regorafenib for metastatic CRC (mCRC). Material and Methods: In this retrospective study, patients were stratified according to the presence of mucinous histology; >1% extracellular mucin was defined as mucinous component adenocarcinoma (MCAC), and containing no mucin was defined as non-MAC. The prognostic significance of mucinous histology for progression-free survival (PFS) and overall survival (OS) was evaluated by univariate and multivariate analyses. Results: A total of 103 patients were included, including 20 (19.4%) patients with MCAC and 83 (80.6%) patients with non-MAC. The median follow-up time was 8.6 months (range 1.8-31.6 months). The median PFS was lower in cases with MCAC than those with non-MAC (3.2 months vs. 3.6 months, respectively, p=0.01). Median OS was lower in MCAC patients than in non-MAC patients (4.3 months vs. 9.6 months, respectively, p=0.008). In multivariate analyses, mucinous histology was an independent risk factor [hazard ratio (HR): 2.2, p=0.003] for PFS and Eastern Cooperative Oncology Group-Performance Status (HR: 2.2, p=0.01), cancer antigen 19-9 (HR: 1.7, p=0.03), and mucinous histology (HR: 1.9, p=0.02) were independent risk factors for OS. Conclusion: This study revealed the prognostic value of mucinous histology in mCRC patients treated with regorafenib. Consideration of histologic features may be helpful in selecting patients for regorafenib therapy.
  1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49. [Crossref]  [PubMed] 
  2. Siegel RL, Miller KD, Fedewa SA, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017;67(3):177-93. [Crossref]  [PubMed] 
  3. Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386-422. [Crossref]  [PubMed] 
  4. Grothey A, Cutsem E Van, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303-12. [Crossref]  [PubMed] 
  5. Li J, Qin S, Xu R, et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015;16(6):619-29. [Crossref]  [PubMed] 
  6. Wilhelm SM, Dumas J, Adnane L, et al. Regorafenib (BAY 73-4506): A new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer. 2011;129(1):245-55. [Crossref]  [PubMed] 
  7. Adenis A, de la Fouchardiere C, Paule B, et al. Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBECCA) nested within a compassionate use program. BMC Cancer. 2016;16(1):412. [Crossref] 
  8. Yoon SE, Lee SJ, Lee J, et al. The Impact of Primary Tumor Sidedness on the Effect of Regorafenib in Refractory Metastatic Colorectal Cancer. J Cancer. 2019;10(7):1611-1615. [Crossref]  [PubMed]  [PMC] 
  9. UNSELD M, FILIP M, SEIRL S, et al. Regorafenib therapy in metastatic colorectal cancer patients: markers and outcome in an actual clinical setting. Neoplasma. 2018;65(04):599-603. [Crossref]  [PubMed] 
  10. World Health Organization. Classification of Tumours of the Digestive System Fourth Edition-WHO-OMS, Vol. 3. press, Geneva, Switzerland: WHO; 2010.
  11. Catalano V, Bergamo F, Cremolini C, et al. Clinical impact of first-line bevacizumab plus chemotherapy in metastatic colorectal cancer of mucinous histology: a multicenter, retrospective analysis on 685 patients. J Cancer Res Clin Oncol. 2020;146(2):493-501. [Crossref]  [PubMed] 
  12. Moretto R, Morano F, Ongaro E, et al. Lack of Benefit From Anti-EGFR Treatment in RAS and BRAF Wild-type Metastatic Colorectal Cancer With Mucinous Histology or Mucinous Component. Clin Colorectal Cancer. 2019;18(2):116-24. [Crossref]  [PubMed] 
  13. Zhou Y, Long Y, Chen Y, et al. First‐line therapy of bevacizumab plus chemotherapy versus cetuximab plus chemotherapy for metastatic colorectal cancer patients with mucinous adenocarcinoma or mucinous component. Cancer Med. 2021;10(10):3388-402. [Crossref]  [PubMed]  [PMC] 
  14. Ott C, Gerken M, Hirsch D, et al. Advanced Mucinous Colorectal Cancer: Epidemiology, Prognosis and Efficacy of Chemotherapeutic Treatment. Digestion. 2018;98(3):143-52. [Crossref]  [PubMed] 
  15. Verhulst J, Ferdinande L, Demetter P, Ceelen W. Mucinous subtype as prognostic factor in colorectal cancer: a systematic review and meta-analysis. J Clin Pathol. 2012;65(5):381-8. [Crossref]  [PubMed] 
  16. Ayhan M, Turan N, Köstek O, et al. Does the efficacy of regorafenib differ in chemotherapy refractory metastatic colorectal cancer patients who had mucinous pathology compared to those who had non-mucinous pathology? Curr Probl Cancer. 2021;45(3):100670. [Crossref]  [PubMed] 
  17. Hsu H-C, Huang K-C, Chen W-S, et al. Preference criteria for regorafenib in treating refractory metastatic colorectal cancer are the small tumor burden, slow growth and poor/scanty spread. Sci Rep. 2021;11(1):15370. [Crossref]  [PubMed]  [PMC] 
  18. Washington K. Excisional biopsy (polypectomy), local excision (transanal disk excision), colectomy (total, partial, or segmental resection), rectal resection (low anterior resection or abdominoperineal resection). College of American Pathologists, 2012.
  19. Huang A, Yang Y, Shi J-Y, et al. Mucinous adenocarcinoma: A unique clinicopathological subtype in colorectal cancer. World J Gastrointest Surg. 2021;13(12):1567-83. [Crossref]  [PubMed]  [PMC] 
  20. Miyakawa T, Kawamura H, Honda M, et al. Impact of histological subtype on prognosis in stage IV colorectal cancer: A population-based cohort study. Chou W-C, ed. PLoS One. 2022;17(3):e0264652. [Crossref]  [PubMed]  [PMC] 
  21. Catalano V, Loupakis F, Graziano F, et al. Mucinous histology predicts for poor response rate and overall survival of patients with colorectal cancer and treated with first-line oxaliplatin- and/or irinotecan-based chemotherapy. Br J Cancer. 2009;100(6):881-7. [Crossref]  [PubMed]  [PMC] 
  22. Maisano R, Azzarello D, Maisano M, et al. Mucinous histology of colon cancer predicts poor outcomes with FOLFOX regimen in metastatic colon cancer. J Chemother. 2012;24(4):212-6. [Crossref]  [PubMed] 
  23. Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70(3):145-64. [Crossref]  [PubMed] 
  24. Chiu JW, Krzyzanowska MK, Serra S, et al. Molecular Profiling of Patients With Advanced Colorectal Cancer: Princess Margaret Cancer Centre Experience. Clin Colorectal Cancer. 2018;17(1):73-9. [Crossref]  [PubMed] 
  25. Seligmann JF, Fisher D, Smith CG, et al. Investigating the poor outcomes ofBRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials. Ann Oncol. 2017;28(3):562-8. [Crossref]  [PubMed]