RESPONSE: Colorectal Cancer Survivors' Follow-up Care - Now Digital and Need-based: A National Interventional Effectiveness Trial for Stage I and II Patients

Background:

Colorectal cancer (CRC) screening was implemented in Denmark in 2014 and has effectively shifted the CRC stage at the time of diagnosis from late stage (III and IV) to earlier stages (I and II)[1]. Consequently, more patients are offered curative intended treatment, which increases the number of survivors in postoperative follow-up care: In 2020, 65% of Danish patients with CRC, potentially eligible for follow-up care, had stage I-II disease[1].

The current follow-up for CRC survivors is recurrence-focused, with computed tomography (CT) imaging at 12 and 36 months[2] as early recurrence detection is critical to increase the possibility of curative treatment: The 5-year survival rate for patients treated for recurrence with curative intent is ~40% compared to <10% for patients managed with palliative or best supportive care[3-6]. However, the risk of recurrence strongly depends on the CRC stage: The 3-year cumulative recurrence rate is only 4.5%-7.9% for stage I and 10%-16% for stage II[7-9]. Consequently, the resources allocated to CRC follow-up in Denmark are primarily dissipated on patients who will never experience a recurrence. Hence, the challenge remains to distinguish between high- and low-risk patients, i.e., tailor the follow-up program to the personal risk of recurrence instead of "one-size-fits-all".

A promising and novel surveillance method for CRC recurrence is to screen longitudinally collected blood samples for the presence of circulating tumor DNA (ctDNA). Serial ctDNA analyses detect recurrence with high sensitivity (88%) and specificity (97%) independent of the stage (hazard ratio (HR)=40.7; 95% confidence interval (CI): 11.6-143) and with a median lead-time of 7-10 months compared to current standard-of-care follow-up[10-13]. Thus, serial ctDNA analyses have the potential to efficiently identify the 4.5%-16% of stage I-II patients, who should be offered CT imaging, whereas the remaining 84-95% of patients are spared unnecessary CT imaging.

CRC survivors with a low risk of recurrence may perceive other challenges than CRC recurrence as equally or more important in everyday life. Such challenges may include the psychological distress related to the CRC diagnosis, exaggerated fear of cancer recurrence (FCR) regardless of the actual risk of recurrence, and the presence of treatment-related organ-specific late effects, which may negatively impact their quality of life (QoL). Independently of stage, 13% of patients with CRC report persistently low QoL and/or high levels of psychological distress, e.g., impaired emotional well-being and/or high FCR[14].