Diagnosis and Management of Rectal Cancer in Patients Younger Than 50 Years: Rising Global Incidence and Unique Challenges

Authors:
Daenielle LangDivision of Hematology/Oncology, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

Search for other papers by Daenielle Lang in
Current site
Google Scholar
PubMed
Close
 MD
and
Kristen K. CiomborDivision of Hematology/Oncology, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

Search for other papers by Kristen K. Ciombor in
Current site
Google Scholar
PubMed
Close
 MD, MSCI

The global incidence of colorectal adenocarcinoma is stable or decreasing overall; however, the incidence of colorectal cancer in patients aged <50 years is increasing. Although some of this increase is due to hereditary cancer syndromes, this is not the sole explanation. Patients with early-onset rectal cancer in particular have unique disease patterns and face distinct challenges in their treatment. Molecular patterns of disease in this patient cohort are noteworthy and often represent an opportunity to target these cancers more effectively. Recent and ongoing trials focusing on minimizing toxicities and necessary therapy modalities and maximizing response and patient outcome are of paramount importance in this patient population. Additional resources are needed for this patient population, including fertility counseling and preservation, financial guidance, genetic counseling, and psychosocial support.

Submitted April 18, 2022; final revision received July 8, 2022; accepted for publication July 27, 2022.

Disclosures: Dr. Ciombor has disclosed receiving institutional grant/research support from Inctye Corporation, Bristol-Myers Squibb Company, Merck & Co., Inc., Array BioPharma, Daiichi Sankyo, NuCana, Pfizer Inc., Genentech, Inc., and Calithera Biosciences; and serving as a consultant for Natera, Inc., Foundation Medicine, Inc., Taiho Pharmaceutical, Merck & Co., Inc., Eli Lilly and Company, Loxo Oncology, Replimune Group Inc., Personalis, Inc., and Array BioPharma. Dr. Lang has disclosed having no financial interest, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.

Correspondence: Kristen K. Ciombor, MD, MSCI, Division of Hematology/Oncology, Department of Internal Medicine, Vanderbilt University Medical Center, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, TN 37209. Email: kristen.k.ciombor@vumc.org
  • Collapse
  • Expand
  • 1.

    Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022. CA Cancer J Clin 2022;72:733.

  • 2.

    Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin 2020;70:145164.

  • 3.

    Islami F, Ward EM, Sung H, et al. Annual report to the nation on the status of cancer, part 1: national cancer statistics. J Natl Cancer Inst 2021;113:16481669.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Siegel RL, Torre LA, Soerjomataram I, et al. Global patterns and trends in colorectal cancer incidence in young adults. Gut 2019;68:21792185.

  • 5.

    American Cancer Society. Colorectal Cancer Facts & Figures 2020-2022. Atlanta, Georgia: American Cancer Society;2020.

  • 6.

    Bailey CE, Hu CY, You YN, et al. Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surg 2015;150:1722.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Eng C, Jácome AA, Agarwal R, et al. A comprehensive framework for early-onset colorectal cancer research. Lancet Oncol 2022;23:e116128.

  • 8.

    Stoffel EM, Mangu PB, Gruber SB, et al. Hereditary colorectal cancer syndromes: American Society of Clinical Oncology clinical practice guideline endorsement of the familial risk-colorectal cancer: European Society for Medical Oncology clinical practice guidelines. J Clin Oncol 2015;33:209217.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Patel SG, Murphy CC, Lieu CH, et al. Early age onset colorectal cancer. Adv Cancer Res 2021;151:137.

  • 10.

    Carvalho FA, Koren O, Goodrich JK, et al. Transient inability to manage proteobacteria promotes chronic gut inflammation in TLR5-deficient mice. Cell Host Microbe 2012;12:139152.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Gronbach K, Flade I, Holst O, et al. Endotoxicity of lipopolysaccharide as a determinant of T-cell-mediated colitis induction in mice. Gastroenterology 2014;146:765775.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Davidson KW, Barry MJ, Mangione CM, et al. Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. JAMA 2021;325:19651977.

  • 13.

    Bénard F, Barkun AN, Martel M, et al. Systematic review of colorectal cancer screening guidelines for average-risk adults: summarizing the current global recommendations. World J Gastroenterol 2018;24:124138.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Dharwadkar P, Greenan G, Singal AG, et al. Is colorectal cancer in patients younger than 50 years of age the same disease as in older patients? Clin Gastroenterol Hepatol 2021;19:192194.e3.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Cercek A, Chatila WK, Yaeger R, et al. A comprehensive comparison of early-onset and average-onset colorectal cancers. J Natl Cancer Inst 2021;113:16831692.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Khan SA, Morris M, Idrees K, et al. Colorectal cancer in the very young: a comparative study of tumor markers, pathology and survival in early onset and adult onset patients. J Pediatr Surg 2016;51:18121817.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Chang DT, Pai RK, Rybicki LA, et al. Clinicopathologic and molecular features of sporadic early-onset colorectal adenocarcinoma: an adenocarcinoma with frequent signet ring cell differentiation, rectal and sigmoid involvement, and adverse morphologic features. Mod Pathol 2012;25:11281139.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Holowatyj AN, Gigic B, Herpel E, et al. Distinct molecular phenotype of sporadic colorectal cancers among young patients based on multiomics analysis. Gastroenterology 2020;158:11551158.e2.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Willauer AN, Liu Y, Pereira AAL, et al. Clinical and molecular characterization of early-onset colorectal cancer. Cancer 2019;125:20022010.

  • 20.

    Lieu CH, Golemis EA, Serebriiskii IG, et al. Comprehensive genomic landscapes in early and later onset colorectal cancer. Clin Cancer Res 2019;25:58525858.

  • 21.

    Benson AB III, Venook AP, Al-Hawary MM, et al. NCCN Clinical Practice Guidelines in Oncology: Rectal Cancer. Version 1.2022. Accessed April 10, 2022. To view the most recent version, visit https://www.NCCN.org

    • Search Google Scholar
    • Export Citation
  • 22.

    Saltz LB, Clarke S, Díaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008;26:20132019.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:23352342.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Cunningham D, Lang I, Marcuello E, et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 2013;14:10771085.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Van Cutsem E, Köhne CH, Láng I, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol 2011;29:20112019.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Bokemeyer C, Bondarenko I, Hartmann JT, et al. Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann Oncol 2011;22:15351546.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Douillard JY, Siena S, Cassidy J, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 2010;28:46974705.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Kopetz S, Grothey A, Tabernero J. Encorafenib, binimetinib, and cetuximab in BRAF v600e–mutated colorectal cancer. Reply. N Engl J Med 2020;382:877878.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Siena S, Di Bartolomeo M, Raghav K, et al. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial. Lancet Oncol 2021;22:779789.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Pelosci A. Tucatinib plus trastuzumab yields positive topline data in phase 2 MOUNTAINEER trial for HER2+ mCRC. Accessed on July 5, 2022. Available at https://www.cancernetwork.com/view/tucatinib-plus-trastuzumab-yields-positive-topline-data-in-phase-2-mountaineer-trial-for-her2-mcrc

    • Search Google Scholar
    • Export Citation
  • 31.

    André T, Shiu KK, Kim TW, et al. Pembrolizumab in microsatellite- instability-high advanced colorectal cancer. N Engl J Med 2020;383:22072218.

  • 32.

    Fernández-Martos C, Pericay C, Aparicio J, et al. Phase II, randomized study of concomitant chemoradiotherapy followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiotherapy and surgery in magnetic resonance imaging-defined, locally advanced rectal cancer: Grupo Cancer de Recto 3 study. J Clin Oncol 2010;28:859865.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Bahadoer RR, Dijkstra EA, van Etten B, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol 2021;22:2942.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Garcia-Aguilar J, Patil S, Gollub MJ, et al. Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. J Clin Oncol 2022;40:25462556.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Conroy T, Bosset JF, Etienne PL, et al. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 2021;22:702715.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Cercek A, Lumish M, Sinopoli J, et al. PD-1 blockade in mismatch repair- deficient, locally advanced rectal cancer. N Engl J Med 2022;386:23632376.

  • 37.

    Salsman JM, Bingen K, Barr RD, et al. Understanding, measuring, and addressing the financial impact of cancer on adolescents and young adults. Pediatr Blood Cancer 2019;66:e27660.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38.

    Lu AD, Zheng Z, Han X, et al. Medical financial hardship in survivors of adolescent and young adult cancer in the United States. J Natl Cancer Inst 2021;113:9971004.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39.

    Daily K. The toxicity of time. J Clin Oncol 2018;36:300301.

  • 40.

    Fundytus A, Prasad V, Booth CM. Has the current oncology value paradigm forgotten patients’ time?: too little of a good thing. JAMA Oncol 2021;7:17571758.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Akimoto N, Ugai T, Zhong R, et al. Rising incidence of early-onset colorectal cancer - a call to action. Nat Rev Clin Oncol 2021;18:230243.

  • 42.

    Stupart D, Win AK, Winship IM, et al. Fertility after young-onset colorectal cancer: a study of subjects with Lynch syndrome. Colorectal Dis 2015;17:787793.

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 5218 5218 355
PDF Downloads 2639 2639 115
EPUB Downloads 0 0 0