August's paper of the month looks at the effect of circulating tumor DNA analysis as a guide for adjuvant therapy in Stage II Colon Cancer.


What is known about the subject?

Circulating tumor DNA has been viewed a new diagnostic tool with the potential of identifying metastatic potential of Colon Cancer in peripheral blood samples (“liquid biopsy”). The presence of circulating tumor DNA after surgery predicts very poor recurrence-free survival [1].

As this technique is relatively new, results of ongoing trials investigating the impact of circulating tumor DNA analysis to guiding clinical decision making are eagerly awaited [2,3]. To date, the role of adjuvant chemotherapy on the oncological outcomes of patients with circulating tumor DNA after elective colorectal surgery remains uncertain.


What the study adds?

This clinical trial from 23 Australian centress [4] included 455 patients with stage II colon or rectal cancer who were randomized in a ratio of 2:1 to have circulating tumor DNA results guide treatment decisions (n=302) or standard clinicopathological variables (n=153). A circulating tumor DNA positive result at either 4/7 weeks postoperatively guided the patient towards oxaliplatin-based or fluoropyrimidine chemotherapy. Circulating tumor DNA-negative patients remained untreated. Adjuvant chemotherapy use was defined as a secondary end point.

Participants in both groups were generally balanced, except for a higher rate of right sided tumours in patients in the circulating tumour DNA-guided group (57%) compared to patients in the standard-management group (47%). Median follow-up was 37 months. Patients in the circulating tumour DNA-guided group received lower rates of adjuvant chemotherapy than in the standard-management group (15% vs. 28%; relative risk 1.82; 95% confidence interval [CI] 1.25-2.65). Circulating tumour DNA-guided management was noninferior to standard management for 2-year recurrence-free survival (93.5% and 92.4%, respectively; 95% CI, -4.1 to 6.2 [noninferiority margin, -8.5 percentage points]). Circulating tumour DNA-positive patients who received adjuvant chemotherapy had a 3-year recurrence-free survival of 86.4% versus 92.5% for circulating tumour DNA-negative patients.


Implications for colorectal practice

This trial showed that using circulating tumour DNA as a guide for the adjuvant treatment of stage II colon cancer was effective in reducing the use of adjuvant chemotherapy without a negative impact on 2 and 3 year recurrence-free survival. These study results call for a widespread evaluation of circulating tumour DNA analysis for the management of stage II colorectal cancer patients.



  1. Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, Silliman N, Tacey M, Wong HL, Christie M, Kosmider S, Skinner I, Wong R, Steel M, Tran B, Desai J, Jones I, Haydon A, Hayes T, Price TJ, Strausberg RL, Diaz Jr LA, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med 2016;8:346ra92.
  2. Schraa SJ, van Rooijen KL, van der Kruijssen DEW, Rubio Alarcon CR, Phallen J, Sausen M, Simmons J, Coupe VMH, van Grevenstein WMU, Elias S, Verkooijen M, Lacle MM, Bosch LJW, van den Broek D, Meijer GA, Velculescu VE, Fijneman RJA, Vink GR, Koopman M, PLCRC-MEDOCC group. Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study. BMC Cancer 2020 Aug 20;20(1):790.
  3. Taniguchi H, Nakamura Y, Kotani D, Yukami H, Mishima S, Sawada K, Shirasu H, Ebi H, Yamanaka T, Aleshin A, Billings PR, Rabinowitz M, Oki E, Takemasa I, Kato T, Mori M, Yoshino T. CIRCULATE-Japan: Circulating tumor DNA-guided adaptive platform trials to refine adjuvant therapy for colorectal cancer. Cancer Sci 2021 Jul;112(7):2915-2920.
  4. Tie J, Cohen JD, Lahouel K, Lo SN, Wang Y, Kosmider S, Wong R, Shapiro J, Lee M, Harris S, Khattak A, Burge M, Harris M, Lynam J, Nott L, Day F, Hayes T, McLachlan SA, Lee B, Ptak J, Silliman N, Dobbyn L, Popoli M, Hruban R, Lennon AM, Papadopoulos N, Kinzler KW, Vogelstein B, Tomasetti C, Gibbs P, DYNAMIC Investigators. Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer. New Engl J Med 2022 Jun 16;386(24):2261-2272.
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