Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer death around the world. According to 2025 data published by the International Agency for Research on Cancer (IARC), an estimated 1.9 million people will be diagnosed with the disease, and over 900,000 patients are expected to die as a result.* [1][2][3]
The incidence of colorectal cancer increases with age. While precise figures for people over 70 years of age may vary, estimates suggest that 40-50 people over 75 years of age per 100,000 will be diagnosed with the disease in the United States, compared to a much lower rate of 15-20 people per 100,000 for those 60–65 years of age.[2[[3]
A 2023 statistical analysis indicated that in France, the incidence rate for people between 70 and 74 years of age rose to 39.5-39.6 per 100,000. This analysis also considered that in this demographic of older people, there is a higher incidence of comorbidities and a higher risk of complications from treatment.[2][3]
Treatment of elderly patients
Although treatment with 5-FU, leucovorin, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPEOX) is considered the standard for stage III colon cancer,** the benefit of these treatment regimens in older patients is uncertain. [4]
While treatment options for elderly patients generally depend on their overall health, the inclusion of oxaliplatin (Eloxatin®; Sanofi), a third-generation platinum-based chemotherapy agent, in elderly patients is controversial due to conflicting data on its benefits and the possible increased risk of neurotoxicity. Although the safety profile of oxaliplatin shows only mild hematologic and gastrointestinal adverse effects, the dose-limiting toxicity (DLT) is a sensory neurotoxicity resembling that of cisplatin, with the important difference of a more rapid and complete reversibility.[5] This oxaliplatin-based sensory neurotoxicity depends on the cumulatively administered dose of the drug and generally peaks several months after the last oxaliplatin exposure. These toxic effects can be severe, potentially affecting patients’ health-related Quality of Life (hrQoL) and impacting their activities of daily living for the rest of their lives. [5][6]
Conflicting evidence
One of the complicating factors in recommending treatment options for elderly colorectal cancer patients is the fact that while guidelines recommend adjuvant chemotherapy, specific recommendations for elderly patients remain inconsistent. This is, in part, due to the fact that elderly patients are generally underrepresented in randomized (clinical) trials. This results in a gap between trial populations and the broader patient population, in turn making it more difficult to conclude the benefits of chemotherapy for older patients in clinical practice.[5][6]
A review of a population-based dataset from German clinical cancer registries (ADT), including 41,630 patients with stage III colon cancer, confirmed marked age-related disparities in the use of adjuvant chemotherapy in stage III colon cancer. The review showed that despite lower treatment rates, elderly patients derive substantial survival benefit. Based on this outcome, the researchers of this study concluded that the available data support careful consideration of adjuvant chemotherapy in patients aged 75 years and older. [7][11]
Subgroup analysis
Various subgroup analyses yielded diverse conclusions regarding the addition of oxaliplatin to the treatment of older patients. For example, the MOSAIC trial subgroup analysis did not show a substantial survival benefit for patients aged 65 years or older. [4] An analysis of the ACCENT database showed that elderly patients ≥ 70 years seemed to experience reduced benefit from adding oxaliplatin to fluoropyrimidines in the adjuvant setting.[8] However, an extensive retrospective study demonstrated improved overall survival (OS) with oxaliplatin administration in older patients (hazard ratio [HR], 0.6; 95% CI, 0.5-0.9). [9] Furthermore, a pooled analysis of randomized trials showed a reduced but substantial benefit in older patients, including those with comorbidities. [10][11]
Hence, one of the most urgent and fundamental clinical questions remains whether elderly patients should receive oxaliplatin as part of their treatment regimen.
To address this question, Jun Woo Bong, MD, Ph.D, from Korea University Guro Hospital, together with Hwamin Lee, Ph.D., and Seogsong Jeong, MD, Ph.D, from Korea University College of Medicine, conducted a large-scale population study, which was made available online on August 6, 2025, in JAMA Network Open. [12]
Health records
The team examined anonymized and aggregated health records from more than 8,500 patients with stage II or III colorectal cancer who underwent surgery followed by chemotherapy between 2014 and 2016. The population-based, retrospective cohort study used data from the Korea Health Insurance Review and Assessment Service (HIRA) National Quality Assessment (NQA) program. [12] In this study, patients were divided into two groups: those treated with oxaliplatin-based combinations and those given standard chemotherapy alone. Using advanced statistical methods, the researchers systematically tested whether an age threshold existed at which oxaliplatin ceased to provide survival benefits.
Decisive results
The results were decisive. In stage 3 patients aged 70 or younger, oxaliplatin reduced the risk of death by 41%, boosting five-year survival from 78% to nearly 85%. But in those older than 70, oxaliplatin did not improve survival and was linked to higher rates of treatment discontinuation.
In fact, almost 40% of older patients receiving oxaliplatin stopped chemotherapy early, often due to toxicity. For stage II patients of any age, oxaliplatin showed no added survival benefit.
“The most important point is that oxaliplatin improves survival only in patients with stage 3 colorectal cancer who are aged 70 years or younger. Beyond 70, the benefit disappears, and oxaliplatin is associated with higher discontinuation rates due to toxicity,” Bong explained.
These findings have immediate real-world applications.
“Oncologists can use this age threshold to make more precise, evidence-based choices about whether to add oxaliplatin, avoiding unnecessary toxicity in patients unlikely to benefit,” Jeong noted.
The broader significance extends to healthcare policy. Avoiding ineffective chemotherapy in older patients may help reduce costs, complications, and hospitalizations. Health systems could redirect resources to therapies and supportive care that make a greater difference in survival and quality of life. The research also sets the stage for longer-term changes in global cancer care.
“Clinical practice guidelines may adopt age 70 as a critical factor in recommending oxaliplatin, laying the foundation for precision oncology and future research focused on safer, more effective treatments for older patients,” Lee concluded.
Study limitations
The authors note some limitations, including the retrospective design and lack of molecular marker data. Even so, the sheer size of the national dataset lends strong weight to the findings, which are likely to influence both clinical guidelines and everyday oncology practice.
As cancer treatment increasingly moves toward personalization, this retrospective cohort study underscores the importance of tailoring care not only to tumor stage but also to patient age and resilience.
For younger patients with stage III disease, oxaliplatin remains a crucial treatment option. However, for patients beyond 70, it may be time to reconsider and focus on therapies that preserve both survival and health-related Quality of Life (hrQoL).[12]
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Note:* The American Cancer Society (ACS) estimates that 154,270 people in the United States will be diagnosed with colon and rectal cancer in 2025, and 52,900 will die from the disease. [2]
** Based on the results of three adjuvant studies, including MOSAIC, NSABP-C-07, and XELOXA, oxaliplatin-based combination chemotherapy is considered to be a standard of care in the treatment of patients diagnosed with stage III colon cancer. [4]
Highlights of prescribing information
Oxaliplatin (eloxatin®; Sanofi)[Prescribing Information]
Reference
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[2] Colorectum Cancer Statistics at a glance. Cancer Statistics Center. American Cancer Society (ACS). Online. Last accessed on September 20, 2025.
[3] International Agency for Research on Cancer. Cancer Fact Sheets. Online. Last accessed on September 20, 2025.
[4] André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A; Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004 Jun 3;350(23):2343-51. doi: 10.1056/NEJMoa032709. PMID: 15175436.
[5] Grothey A. Oxaliplatin-safety profile: neurotoxicity. Semin Oncol. 2003 Aug;30(4 Suppl 15):5-13. doi: 10.1016/s0093-7754(03)00399-3. PMID: 14523789.
[6] Papamichael D, Audisio RA, Glimelius B, de Gramont A, Glynne-Jones R, Haller D, Köhne CH, Rostoft S, Lemmens V, Mitry E, Rutten H, Sargent D, Sastre J, Seymour M, Starling N, Van Cutsem E, Aapro M. Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013. Ann Oncol. 2015 Mar;26(3):463-76. doi: 10.1093/annonc/mdu253. Epub 2014 Jul 11. PMID: 25015334.
[7] Langheinrich M, Gerken M, Robers G, Hansinger J, Franke B, Lacruz ME, Mueller-Nordhorn J, Schneider C, Reinwald F, Stang A, Sackmann A, Zeissig SR, Klinkhammer-Schalke M, Kersting S, Völkel V, Benz S. Survival benefit of adjuvant chemotherapy in elderly patients with UICC stage III colon carcinoma: A 20-year population-based German cohort study. Eur J Cancer. 2025 Sep 9;227:115583. doi: 10.1016/j.ejca.2025.115583. Epub 2025 Jun 18. PMID: 40749415.
[8] McCleary NJ, Meyerhardt JA, Green E, Yothers G, de Gramont A, Van Cutsem E, O’Connell M, Twelves CJ, Saltz LB, Haller DG, Sargent DJ. Impact of age on the efficacy of newer adjuvant therapies in patients with stage II/III colon cancer: findings from the ACCENT database. J Clin Oncol. 2013 Jul 10;31(20):2600-6. doi: 10.1200/JCO.2013.49.6638. Epub 2013 Jun 3. PMID: 23733765; PMCID: PMC3699725.
[9] Brungs D, Aghmesheh M, de Souza P, Carolan M, Clingan P, Rose J, Ranson M. Safety and Efficacy of Oxaliplatin Doublet Adjuvant Chemotherapy in Elderly Patients With Stage III Colon Cancer. Clin Colorectal Cancer. 2018 Sep;17(3):e549-e555. doi: 10.1016/j.clcc.2018.05.004. Epub 2018 May 31. PMID: 29861156.
[10] Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, Souglakos J, Shi Q, Kerr R, Labianca R, Meyerhardt JA, Vernerey D, Yamanaka T, Boukovinas I, Meyers JP, Renfro LA, Niedzwiecki D, Watanabe T, Torri V, Saunders M, Sargent DJ, Andre T, Iveson T. Duration of Adjuvant Chemotherapy for Stage III Colon Cancer. N Engl J Med. 2018 Mar 29;378(13):1177-1188. doi: 10.1056/NEJMoa1713709. PMID: 29590544; PMCID: PMC6426127.
[11] Lim BL, Park IJ, Ro JS, Kim YI, Lim SB, Yu CS. Oncologic outcomes and associated factors of colon cancer patients aged 70 years and older. Ann Coloproctol. 2025 Jun;41(3):198-206. doi: 10.3393/ac.2023.00367.0052. Epub 2024 Aug 5. PMID: 39107230; PMCID: PMC12215319.
[12] Bong JW, Lee H, Jeong S, Kang S. Older Age Threshold for Oxaliplatin Benefit in Stage II to III Colorectal Cancer. JAMA Netw Open. 2025 Aug 1;8(8):e2525660. doi: 10.1001/jamanetworkopen.2025.25660. PMID: 40768144; PMCID: PMC12329608.
Feature image licensed under the Unsplash+ License
DOI: 10.14229/onco.2025.09.22.001
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