When Tailoring Cancer Treatment, Biology Matters More than Age


Early-onset colorectal cancer (CRC) is likely clinically and genomically indistinguishable from average-onset cancer, according to a recent study published in the Journal of the National Cancer Institute by MSK investigators.The findings suggest that aggressive treatment for adolescent and young adult (AYA) patients based solely on their age at diagnosis is not warranted. (1)

Treating AYA Patients with an Adult Regimen

Lead study author Andrea Cercek, MD, is Section Head, Colorectal Cancer and Co-Director of the Center for Young Onset Colorectal and Gastrointestinal at MSK

Lead study author Andrea Cercek, MD, is Section Head, Colorectal Cancer and Co-Director of the Center for Young Onset Colorectal and Gastrointestinal at MSK

The increasing incidence of early-onset CRC in patients in their 20s and 30s has been a worrisome trend. (1) These patients have typically been treated with more aggressive chemotherapy regimens based on reports indicating early-onset CRC is more invasive than average-onset CRC. (2), (3), (4), (5), (6), (7), (8) However, this approach has not been associated with gains in survival. (9), (10)

In the largest and most comprehensive study of CRC across age groups to date, MSK researchers compared clinical, histopathologic, and genomic characteristics for 759 early-onset patients under the age of 50, including 151 under the age of 35, with 687 average-onset patients over the age of 50. They found no statistically significant difference in histopathologic tumor characteristics among patients with microsatellite stable (MSS) tumors. The investigators also identified some notable clinical differences between groups, with patients with early-onset CRC more likely to present with rectal bleeding and abdominal pain, and more than 80 percent of them had left-sided tumors. (1)

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This evidence affirms that the best treatment approach for AYA patients should be determined by disease biology rather than age at diagnosis. Some patients may benefit from less challenging regimens developed for adults, such as those with MSS early-onset CRC. However, the opposite can also be true, with improved outcomes observed in a recent study testing a less toxic pediatric regimen for leukemia in AYA and adult patients.

Treating AYA and Adult Patients with A Modified Pediatric Regimen

Treating AYA patients with a pediatric protocol matched to their type of acute lymphoblastic leukemia (ALL) has been MSK’s preferred approach for patients up to the age of 40 since several series published from 2003 to 2008 found pediatric-inspired regimens resulted in improved survival rates. (11)

MSK researchers recently tested a more tolerable pediatric protocol for ALL and lymphoblastic lymphoma in adults up to 60 and found that the revised protocol did not result in inferior outcomes compared to prior experience. (12)

Lead study author Mark Geyer, MD, hematologic oncologist and researcher at MSK, specializes in acute and chronic leukemias

Lead study author Mark Geyer, MD, hematologic oncologist and researcher at MSK, specializes in acute and chronic leukemias

In the phase II clinical trial, 39 adult patients up to the age of 60 with newly diagnosed ALL and lymphoblastic lymphoma were treated with a modified regimen inspired by the Children’s Cancer Group 1882 protocol. Protocol changes included omitting two intense, myelosuppressive courses of cytarabine/teniposide using a high dose of methotrexate rather than escalating doses, and careful monitoring and timed dosing of pegaspargase to avoid overlapping toxicity with other agents. A total of 97 percent of patients achieved a complete response with incomplete hematologic recovery post-induction. Rates of minimal residual disease were 33 percent (phase 1) and 83 percent (phase 2) after induction. Event-free and overall survival at three years were 68 percent and 76 percent, respectively, comparing favorably to other series. (12)

MSK treats cancer patients of all ages, including children, AYAs, and older adults. The Lisa and Scott Stuart Center for Adolescent and Young Adult Cancers was established at MSK to ensure young patients with cancer have access to treatment options that optimally address the biology of their disease. Physicians and researchers at the Stuart Center collaborate across MSK to extend learning, as appropriate, to improve outcomes and reduce the toxic effects of treatment in other age groups.

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  1. Cercek A, Chatila WK, Yaeger R, et al. A Comprehensive Comparison of Early-Onset and Average-Onset Colorectal Cancers [published online ahead of print, 2021 Aug 18]. J Natl Cancer Inst. 2021; djab124.
  2. Smith RA, Cokkinides V, Eyre HJ; for the American Cancer Society. American Cancer Society guidelines for the early detection of cancer, 2003. CA Cancer J Clin. 2003;53(1):27–43.
  3. Meyer JE, Narang T, Schnoll-Sussman FH, Pochapin MB, Christos PJ, Sherr DL. Increasing incidence of rectal cancer in patients aged younger than 40 years: an analysis of the surveillance, epidemiology, and end results database. Cancer. 2010;116(18):4354–4359.
  4. Howlader N, Noone AM, Krapcho M, et al., eds. National Cancer Institute Surveillance, Epidemiology, and End Results Program, Nov 2008 Sub (1975- 2016). National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch. https://seer.cancer.gov/csr/1975_2016/. Published 2019. Accessed October 01, 2020.
  5. Zhao L, Bao F, Yan J, et al. Poor prognosis of young patients with colorectal cancer: a retrospective study. Int J Colorectal Dis. 2017;32(8):1147–1156.
  6. Bleyer A, Barr R, Hayes-Lattin B, et al.; for the Biology and Clinical Trials Subgroups of the US National Cancer Institute Progress Review Group in Adolescent and Young Adult Oncology. The distinctive biology of cancer in adolescents and young adults. Nat Rev Cancer. 2008;8(4):288–298.
  7. Shida D, Ahiko Y, Tanabe T, et al. Shorter survival in adolescent and young adult patients, compared to adult patients, with stage IV colorectal cancer in Japan. BMC Cancer. 2018;18(1):334.
  8. Chiang J-M, Chen M-C, Changchien CR, et al. Favorable influence of age on tumor characteristics of sporadic colorectal adenocarcinoma: patients 30 years of age or younger may be a distinct patient group. Dis Colon Rectum. 2003; 46(7):904–910.
  9. Kneuertz PJ, Chang GJ, Hu C-Y, et al. Overtreatment of young adults with colon cancer: more intense treatments with unmatched survival gains. JAMA Surg. 2015;150(5):402–409.
  10. Manjelievskaia J, Brown D, McGlynn KA, Anderson W, Shriver CD, Zhu K. Chemotherapy use and survival among young and middle-aged patients with colon cancer. JAMA Surg. 2017;152(5):452–459.
  11. Dombret H, Cluzeau T, Huguet F, Boissel N. Pediatric-like therapy for adults with ALL. Curr Hematol Malig Rep. 2014;9(2):158-164.
  12. Geyer MB, Ritchie EK, Rao AV, et al. Pediatric-inspired chemotherapy incorporating pegaspargase is safe and results in high rates of minimal residual disease negativity in adults up to age 60 with Philadelphia chromosome-negative acute lymphoblastic leukemia. Haematologica. 2020;106(8):2086-2094.