Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer

Abstract

Despite standard-of-care treatment, more than 30% of patients with resectable colorectal cancer (CRC) relapse. Circulating tumor DNA (ctDNA) analysis may enable postsurgical risk stratification and adjuvant chemotherapy (ACT) treatment decision-making. We report results from GALAXY, which is an observational arm of the ongoing CIRCULATE-Japan study (UMIN000039205) that analyzed presurgical and postsurgical ctDNA in patients with stage II–IV resectable CRC (n = 1,039). In this cohort, with a median follow-up of 16.74 months (range 0.49–24.83 months), postsurgical ctDNA positivity (at 4 weeks after surgery) was associated with higher recurrence risk (hazard ratio (HR) 10.0, P < 0.0001) and was the most significant prognostic factor associated with recurrence risk in patients with stage II or III CRC (HR 10.82, P < 0.001). Furthermore, postsurgical ctDNA positivity identified patients with stage II or III CRC who derived benefit from ACT (HR 6.59, P < 0.0001). The results of our study, a large and comprehensive prospective analysis of ctDNA in resectable CRC, support the use of ctDNA testing to identify patients who are at increased risk of recurrence and are likely to benefit from ACT.

Liquid Biopsy Assessment of Molecular Residual Disease in Localized Colorectal Cancer

“…Based on the results of the present study and previous work published by others, Mo and colleagues proposed potential clinical scenarios in which ColonAiQ could help guide the management of patients with localized CRC. Such clinical scenarios include adjuvant treatment escalation or intensification in molecular residual disease-positive patients and de-escalation of treatment in those patients with undetectable molecular residual disease after surgery with curative intention.…”

GLUT-1 may predict metastases and death in patients with locally advanced rectal cancer

“…Meanwhile, circulating tumor DNA (ctDNA) is an emerging biomarker that has gained popularity nowadays. ctDNA can be a prognostic and predictive biomarker in gastrointestinal cancers ( 26 – 28 ). Recently, Kotani et al.…”

“…Meanwhile, circulating tumor DNA (ctDNA) is an emerging biomarker that has gained popularity nowadays. ctDNA can be a prognostic and predictive biomarker in gastrointestinal cancers (26)(27)(28). Recently, Kotani et al have reported results from GALAXY, which is an observational arm of the ongoing CIRCULATE-Japan study (UMIN000039205) that analyzed preoperative and postoperative ctDNA in patients with stage II-IV resectable colorectal cancer (28).…”

“…ctDNA can be a prognostic and predictive biomarker in gastrointestinal cancers (26)(27)(28). Recently, Kotani et al have reported results from GALAXY, which is an observational arm of the ongoing CIRCULATE-Japan study (UMIN000039205) that analyzed preoperative and postoperative ctDNA in patients with stage II-IV resectable colorectal cancer (28). In the multivariate analysis for recurrence in patients with pathologic stage II-III, ctDNA positivity (at 4 weeks after surgery) was the most significant prognostic factor for recurrence (HR 10.82, 95% CI 7.07-16.6, p<0.001).…”

The Current State and Future of Plasma Cell-Free DNA Analysis in Urologic Malignancies

“…In addition to CGP, cfDNA analysis has been applied for the early diagnosis and detection of MRD in other types of cancer [27]. However, the barrier to clinical application in these areas is high in prostate cancer, because prostatespecific antigen (PSA), a remarkably sensitive and inexpensive biomarker, is already available.…”