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Understanding Early Onset Colorectal Cancer: Challenges and Strategies

Updated: 6 days ago

By Alessandro Mannucci, MD Communications Committee Member



The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing, and it appears that this trend shows no signs of slowing down. Recent reports confirmed that EOCRC has officially become the leading cause of cancer death among young men and the second leading cause among young women (Siegel RL, et al).

Despite ongoing research efforts, there is still much that is unknown about EOCRC, with the primary concern being the underlying cause of this alarming trend (Patel SG, et al).


While various hypotheses have been proposed, ranging from microbiota changes to lifestyle factors such as diet and smoking, the overall understanding remains unclear. Ultimately, the daunting reality is that we are witnessing a birth-cohort effect, wherein populations born after a specific time are disproportionately affected.


However, CGA-IGC is actively collaborating with clinicians and researchers to address this patient population's unique challenges and requirements.


Some of the unique challenges where CGA-IGC is urging research include the following: 

  1. Risk Factor Assessment: Obtaining a comprehensive family history is the first and most important step in preventing EOCRC. However, it is challenging at times, necessitating innovative risk assessment tools and dedicated resources. For other non-familial risk factors, further research is needed to elucidate their precise contributions to EOCRC and effectively inform screening guidelines.

  2. Diagnostic Modalities: EOCRC assessment primarily relies on three tests: fecal immunochemical test (FIT), colonoscopy, and sigmoidoscopy. Patients presenting with high-risk symptoms should be offered an expedited assessment, particularly if they report iron-deficiency anemia, hematochezia, and unexplained weight loss. However, other more vague gastrointestinal symptoms such as abdominal pain, dyspepsia, or altered bowel patterns, are very common in the general population, and it may not be feasible to offer colonoscopy to all of these individuals (Fritz CDL, et al; Yen T, et al). FIT has the potential to evaluate patients who present with these low-risk symptoms, but FIT usage still poses challenges such as cost-effectiveness, false negatives, and potentially, diagnostic delays after a FIT result. It should be emphasized that most scientific societies now recommend endoscopy-based screening starting from the age of 45.  Regarding sigmoidoscopy versus colonoscopy, each modality offers distinct advantages, underscoring the importance of tailored approaches based on individual patient characteristics.

  3. Oncological Treatment Strategies: Tailoring treatment regimens to EOCRC patients' needs remains a challenge. Some pre-clinical studies have suggested that younger individuals have cancers that are more biologically aggressive. This supposedly higher aggressiveness, coupled with the better fitness of these patients, has led some investigators to offer more aggressive or more prolonged therapeutic strategies. Unfortunately, these measures have not improved survival outcomes compared to standard treatments. However, there have been reports of potentially higher toxicity. Therefore, more aggressive therapies, if offered exclusively based on age,  are currently discouraged. In this regard, the inclusion of patients with EOCRC in clinical trials emerges as a novel imperative, underscoring the importance of dedicated research endeavors. Additionally, younger patients often have needs that differ from older patients. These include, among others, a desire to preserve fertility. Several fertility preservation techniques can be pursued in treatment administration, including both surgical and pharmacological strategies. However, several reports have indicated that patients with EOCRC often do not have a chance to discuss these issues with their caregivers (Stal J, et al; Rogers JE, et al). In this respect, the recently published DIRECT guidelines, endorsed by CGA-IGC (Cavestro GM, et al) advocate for a significant improvement in fertility preservation (before treatments start) and infertility treatment (at treatment completion). Conversations on fertility may seem difficult, but are necessary to offer patients the best possible care.

  4. Post-Treatment Management: Post-treatment surveillance presents a unique challenge for this patient population following curative intent treatment. Indeed, higher rates of recurrence have been observed compared to traditional onset CRC, yet it remains unclear how this elevated risk may be effectively managed. The optimal surveillance protocol for EOCRC patients remains to be determined, perhaps necessitating a more nuanced and personalized approach. This underscores the imperative for further investigation into recurrence risk and long-term outcomes to inform tailored surveillance strategies.

  5. Supportive Care: Chemotherapy-induced side effects and nutritional support are of paramount importance to young patients, particularly given their unique desire to preserve fertility. Therefore, further research on supportive care is warranted to mitigate treatment-related morbidity and enhance patient well-being.


EOCRC represents a complex clinical entity characterized by distinct challenges across diagnostic, genetic, therapeutic, and supportive care domains. Collaborative efforts among clinicians, researchers, and advocacy groups are essential to unraveling its underlying mechanisms and improving patient outcomes. By embracing multidisciplinary approaches and fostering research innovation, we can navigate the evolving landscape of EOCRC and enhance the quality of care.


CGA-IGC has actively participated in the development of the first international guidelines for the management and care of these patients, recently published on Clinical Gastroenterology and Hepatology and available HERE. The Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) group was founded with the mission to determine a change in the clinical approach to EOCRC, leading the entire scientific community toward a future where EOCRC is less common, lethal, and burdensome. With many of our CGA-IGC members participating in this initiative, these guidelines currently offer the highest level of knowledge on EOCRC. This is crucial for the benefit of patients.  The DIRECt group offered several key insights into EOCRC, spanning several clinical realms, including diagnostics, therapeutic decisions, surgical planning, fertility issues, best supportive care, genetics, family history, and many other areas of clinical interest. 


The CGA-IGC has dedicated research and efforts towards bringing EOCRC to a wider audience, both in the scientific world and in the lay world. To learn more about EOCRC and how CGA-IGC is actively promoting research on this topic, please see our dedicated toolkit and the research grants currently supported by CGA-IGC.


REFERENCES

Cavestro GM, Mannucci A, Balaguer F, Hampel H, Kupfer SS, Repici A, Sartore-Bianchi A, Seppälä TT, Valentini V, Boland CR, Brand RE, Buffart TE, Burke CA, Caccialanza R, Cannizzaro R, Cascinu S, Cercek A, Crosbie EJ, Danese S, Dekker E, Daca-Alvarez M, Deni F, Dominguez-Valentin M, Eng C, Goel A, Guillem JG, Houwen BBSL, Kahi C, Kalady MF, Kastrinos F, Kühn F, Laghi L, Latchford A, Liska D, Lynch P, Malesci A, Mauri G, Meldolesi E, Møller P, Monahan KJ, Möslein G, Murphy CC, Nass K, Ng K, Oliani C, Papaleo E, Patel SG, Puzzono M, Remo A, Ricciardiello L, Ripamonti CI, Siena S, Singh SK, Stadler ZK, Stanich PP, Syngal S, Turi S, Urso ED, Valle L, Vanni VS, Vilar E, Vitellaro M, You YN, Yurgelun MB, Zuppardo RA, Stoffel EM; Associazione Italiana Familiarità Ereditarietà Tumori; Collaborative Group of the Americas on Inherited Gastrointestinal Cancer; European Hereditary Tumour Group, and the International Society for Gastrointestinal Hereditary Tumours. Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines. Clin Gastroenterol Hepatol. 2023 Mar;21(3):581-603.e33

Fritz CDL, Otegbeye EE, Zong X, Demb J, Nickel KB, Olsen MA, Mutch M, Davidson NO, Gupta S, Cao Y. Red-flag signs and symptoms for earlier diagnosis of early-onset colorectal cancer. J Natl Cancer Inst. 2023 Aug 8;115(8):909-916.

Patel SG, Karlitz JJ, Yen T, Lieu CH, Boland CR. The rising tide of early-onset colorectal cancer: a comprehensive review of epidemiology, clinical features, biology, risk factors, prevention, and early detection. Lancet Gastroenterol Hepatol. 2022 Mar;7(3):262-274

Rogers JE, Woodard TL, Dasari A, Kee B, Das P, Bednarski BK, Skibber JM, Rodriguez-Bigas MA, Eng C. Fertility discussions in young adult stage III colorectal cancer population: a single-center institution experience. Support Care Cancer. 2021 Dec;29(12):7351-7354

Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024 Jan-Feb;74(1):12-49.

Stal J, Yi SY, Cohen-Cutler S, Gallagher P, Barzi A, Freyer DR, Milam JE, Lenz HJ, Miller KA. Fertility Preservation Discussions Between Young Adult Rectal Cancer Survivors and Their Providers: Sex-Specific Prevalence and Correlates. Oncologist. 2022 Jul 5;27(7):579-586

Yen T, Patel SG. Symptoms and early-onset colorectal cancer: red flags are common flags! J Natl Cancer Inst. 2023 Aug 8;115(8):883-885


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