Authors: Sue‐Anne McLachlan (St Vincent's Hospital, Melbourne, Victoria, Australia; Department of Medicine, St Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia), Isabella Hall (St Vincent's Hospital, Melbourne, Victoria, Australia; Department of Medicine, St Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia), Anna Collins (St Vincent's Hospital, Melbourne, Victoria, Australia; Department of Medicine, St Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia), Jennifer Philip (St Vincent's Hospital, Melbourne, Victoria, Australia; Department of Medicine, St Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia), Peter Gibbs (Personalised Oncology Division, Walter and Eliza Hall Institute, Parkville, Australia; Western Health, Melbourne, Victoria, Australia), Jeanne Tie (Personalised Oncology Division, Walter and Eliza Hall Institute, Parkville, Australia; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia)
Categories: Original Article, adjuvant chemotherapy, circulating tumor DNA, colorectal cancer, fear of cancer recurrence, medical oncology, qualitative research
Source: Psycho-Oncology
Doi: 10.1002/pon.70464
Authors: Sue‐Anne McLachlan, Isabella Hall, Anna Collins, Jennifer Philip, Peter Gibbs, Jeanne Tie
Circulating tumor DNA (ctDNA) is a novel prognostic biomarker indicating minimal residual disease and high recurrence risk. In three randomised DYNAMIC trials, ctDNA was used to guide adjuvant chemotherapy (ACT) for early‐stage colorectal cancer. While clinical applications of ctDNA are being established, the psychosocial impact, particularly on fear of cancer recurrence (FCR), is less understood.
To explore the psychosocial impact, especially FCR, of ctDNA‐informed ACT decisions among a subset of DYNAMIC trial participants.
A qualitative study using semi‐structured interviews was conducted with English‐speaking, recurrence‐free patients from the DYNAMIC trials, across ctDNA‐guided and standard‐care groups. Interviews were audio‐recorded, transcribed, and thematically analyzed.
Twenty‐eight patients participated (median age 64 years; 64% male; equal numbers with early‐stage colon and rectal cancer). Eight received a positive ctDNA result, 11 a negative result, and 9 were blinded to their result. Three themes (1) Limited Understanding of ctDNA Results: Many patients had poor recall or understanding of the test and its prognostic meaning. (2) Trust in Clinician‐Led Decision‐Making: Strong reliance on clinicians to interpret results and guide ACT decisions. (3) FCR ‐ Episodic, Context Fear was intermittent, typically arising around scans, new symptoms, or others' diagnoses, and was not influenced by ctDNA knowledge.
In this cohort, on average 5 years from trial entry, ctDNA‐informed ACT decisions did not increase FCR or cause long term psychosocial harm. As ctDNA testing enters routine practice, clear communication strategies will be essential to ensure patients understand results while maintaining trust in clinician–patient decision‐making.
Colorectal cancer is the fourth most commonly diagnosed cancer in Australia, with approximately 15,000 new cases annually [1]. Advances in early detection and adjuvant treatments have improved 5‐year survival substantially over the past 3 decades, yet colorectal cancer remains the second leading cause of cancer‐related death nationwide [2].
Current guidelines recommend adjuvant chemotherapy (ACT) for all patients with stage III colon cancer and for rectal cancer with high‐risk clinico‐pathological features [3]. For stage II colon cancer, the benefit of ACT is limited, and treatment is generally reserved for patients with additional risk factors or strong preference [4]. While ACT can improve survival, side effects such as nausea, diarrhea, fatigue, and peripheral neuropathy may significantly affect quality of life during and after treatment [5].
Circulating tumor DNA (ctDNA) is a novel biomarker indicating minimal residual disease, and is strongly predictive of recurrence risk (> 80% in some tumor types) [6]. The DYNAMIC randomized trials in colon (DYNAMIC‐II, DYNAMIC‐III) and rectal cancer (DYNAMIC Rectal) tested ctDNA‐guided ACT strategies compared to standard care. In the standard care group, ctDNA results were not disclosed and adjuvant therapy determinations were based on patient and tumor characteristics. In contrast the experimental group was informed of their ctDNA results which were used to guide adjuvant therapy decisions; where patients with negative ctDNA results received no or reduced chemotherapy, and those with positive results received intensified regimens [7, 8, 9].
Early results show that ctDNA‐guided management in stage II colon cancer reduced chemotherapy use without compromising survival or recurresnce rates [10].
Fear of cancer recurrence (FCR) ‐ the worry that cancer could return or progress ‐ is common, affecting up to 60% of survivors [11, 12]. It can impair daily functioning, limit future planning, and reduce quality of life [13]. Higher FCR is associated with younger age, chemotherapy, and triggers such as medical appointments or new symptoms [12, 13]. Conversely, information‐seeking, positive attitudes, and emotional support may reduce FCR [14, 15].
As biomarker tests like ctDNA enter clinical care, they offer opportunities to personalise treatment, avoid unnecessary toxicity, and target therapy to those at highest risk [16]. However, little is known about their psychosocial impact, particularly whether receiving ctDNA results influences FCR [17]. Two prospective quantitative studies in patients with early‐stage colorectal cancer, recently presented suggest that knowledge of ctDNA status, whether positive or negative, did not significantly impact FCR [18]. In the BESPOKE study, 414 patients underwent serial ctDNA testing over a 24‐month period. Patients with ctDNA‐positive results reported slightly higher anxiety levels regarding colorectal cancer recurrence, while those with ctDNA‐negative results experienced reduced anxiety. However, the differences in FCR scores between the ctDNA‐positive and ctDNA‐negative groups were marginal. Our group conducted a FCR substudy involving 317 patients enrolled in the three DYNAMIC randomized trials. FCR levels were highest in the immediate postoperative period and decreased over 12 months. Notably, the reduction in FCR was more pronounced among patients receiving ctDNA‐guided treatment, with no evidence of increased psychological distress, including among those who were ctDNA‐positive [19]. To further investigate these interesting findings we conducted a qualitative study exploring colorectal cancer survivors' experiences with ctDNA‐guided care and its impact on FCR.
This exploratory qualitative study, underpinned by a social constructivist epistemology was conducted with patients from nine trial centers participating in the DYNAMIC studies across Australia [20]. Ethical approval was obtained from the Melbourne Health Human Research Ethics Committee (HREC) [HREC/17/MH/235, HREC/16/MH/388, HREC/14/MH/355] and the study was conducted in accordance with the COREQ guidelines [21].
At the time of consenting to participate in the main DYNAMIC randomized controlled trials a subset of patients was invited to join the Fear of Cancer Recurrence substudy. It was approved at selected sites and only 428 of the 1687 participants across all the trials took part. It involved an opt‐in semi‐structured interview at a later date.
Eligible participants for interview met the following at least 12 months from trial entry; no evidence of cancer recurrence; proficient in English; and contactable by study site personnel.
In this qualitative study, rather than aiming for a representative sample we applied purposive sampling to intentionally select patients who were most likely to provide rich, relevant and diverse data related to our research question. We ensured there was representation from both the control arm (standard care) and the experimental arm (circulating tumor DNA [ctDNA]–informed ctDNA‐positive and ctDNA‐negative groups).
Potential participants were contacted via telephone to confirm interest and availability (IH). A semi‐structured interview schedule was developed by the research team to explore patients' experiences with biomarker‐informed adjuvant chemotherapy and their fear of cancer recurrence (see Table 1).
Recruitment continued until data saturation was reached. Codes and themes were reviewed after each interview to determine whether new concepts were emerging. Twenty‐eight patients were interviewed via telephone or telehealth by a researcher independent of the DYNAMIC trials (IH). All interviews were audio‐recorded and transcribed verbatim. Transcripts were not returned to participants for comment.
De‐identified transcripts were analyzed using NVivo (v15.1.1; Lumivero) by one author (IH) following a framework analysis approach [22]. Codes were generated inductively from the data, grouped into categories, and iteratively mapped to establish thematic relationships. Themes were refined through an iterative analytic process.
Data collection and analysis were conducted concurrently, with systematic refinement of categories and themes. Interim findings were regularly presented to the investigator group (SAM, JP, AC) for discussion, resolution of discrepancies, and consensus on the final thematic structure, including determination of data saturation.
A total of 292 patients from the FCR substudy (conducted at 9 study sites) agreed to be contacted for a future interview; however, only 48 were re‐contacted for potential participation in this qualitative study. We had initially anticipated that this number would be sufficient to reach data saturation. In fact, data saturation was achieved after interviewing 28 patients. On average, 3 patients were recruited per site.
Two hundred and ninety two patients from the main FCR substudy (conducted at 9 study sites) consented to be contacted about a future interview however we only re‐contacted 48 of these for potential participation in this qualitative study. We anticipated that this number would be required to reach data saturation. In fact, data saturation occurred after interviewing 28 patients. A median of 3 patients were recruited per site. The 9 study sites were a mixture of metropolitan, regional, public and private centers. Interviews ranged from 11 to 80 min and were conducted between January and April 2025, on average 59 months (range 32–82) after trial entry. Median participant age was 64 years (range 50–84), and 64% were male. Fourteen participants had early‐stage colon cancer and 14 had rectal cancer. Eight received a positive ctDNA result, 11 a negative result, and nine were blinded to their result at the time of adjuvant chemotherapy decision‐making.
Many participants had poor recall or understanding of their ctDNA result, despite having consented to receive it. Half could not accurately recall their result; some remembered it incorrectly, while others could not remember it at all. As one participant explained, “I can't remember… I can't recall any of it” (P11). For some, medical terminology was a barrier ‐ “Because you're not a medical person, some of this stuff goes over your head” (P5)‐ and in a few cases, ctDNA was misinterpreted as relating to hereditary cancer “The DNA… does that mean whether it will be passed on to your children?” (P14).
Even when recall was limited, this generally did not cause distress. One participant reflected, “Not a great deal that I can remember. But I wasn't concerned about it” (P1). Some were unsure whether ctDNA testing was a standard part of bowel cancer care ‐ “Is that a normal test undertaken in bowel cancer?” (P19) ‐ and several described trial participation as motivated by altruism rather than personal “Didn't know what it was… but if it's going to benefit somebody, do it” (P25).
A smaller group accurately recalled their result and its impact on treatment. For example, one participant reported, “They told me there were no cancer cells in my blood, and that changed my treatment ‐ I only had one chemo drug after that” (P5).
Participants expressed strong trust in their treating clinicians, viewing ctDNA as one of many inputs to guide decision‐making. As one noted, “The tests were only there to provide them with certainty… the specialist was always in control” (P16). This trust often fostered reassurance, particularly for those with negative results ‐ “The fact that there were no other cancer cells in my body made me happy with the results. I was relieved” (P5).
Even for those who received a positive result, trust in the care team supported acceptance of more intensive treatment. One participant recalled, “I found out mine was positive and as a result I had the longer chemotherapy… and I ended up being cleared of cancer” (P23). Another described the personal confidence this “He [the clinician] exuded confidence… that gave me so much great feeling about it” (P16).
Trust in clinicians also extended beyond individual care to participation in research. Many participants reported agreeing to enroll in the study when approached by hospital staff, reflecting both confidence in the treating team and an altruistic desire to help others. Overall, 23 of the 28 participants expressed motivation to contribute to research and improve outcomes for future patients with colorectal cancer ‐ “If it's going to help someone, why wouldn't you” (P2).
Participants reported varied experiences of fear of cancer recurrence (FCR). Half the patients described acceptance of the possibility of recurrence, viewing it as largely uncontrollable and best managed through adherence to medical advice. Most participants reported no or low levels of FCR, describing recurrence as something they rarely considered ‐ “If it does come back, I've just got to live with it” (P 20).
When prompted, participants identified specific concerns related to recurrence, including undergoing treatment again, loss of independence, death, and the emotional impact on family members ‐ “Having to go through chemo again… I don't think I'd want to” (P8).
Only one participant reported that FCR significantly affected their daily life, limiting future plans such as overseas travel.
Although recall of ctDNA results was limited, among those who remembered, FCR varied according to ctDNA status, particularly at result disclosure. ctDNA‐negative results were generally associated with reassurance ‐ “I was happy to know that there were no cancers…” (P5). In contrast, ctDNA‐positive results elicited more varied responses, including distress, behavioral responses, and treatment affirmation ‐ “It stressed me out…” (P21); “I had the longer chemotherapy… and ended up being cleared of cancer.” (P23).
Fear of Cancer recurrence was mostly intermittent, arising at specific triggers such as surveillance scans ‐ “I always got quite nervous when I would go for my six‐monthly check.” (P13) ‐ the onset of new symptoms ‐ “Sometimes you just think, I have a pain somewhere‐is the cancer coming back?” (P8) or hearing of another person's cancer diagnosis ‐ “If I hear someone else has a cancer, that brings it back” (P12).
Participants described using cognitive and behavioral strategies to manage FCR, including distraction, maintaining a positive outlook, and engaging in healthy lifestyle behaviors ‐ “There's nothing I can control about it, apart from following the best advice offered to me” (P3). Reassurance from cancer‐free follow‐up results and trust in the healthcare team further reduced FCR ‐ “I just find something else to occupy my mind and stop thinking about it.” (P20).
This study is the first to qualitatively examine how ctDNA biomarker results influence psychological wellbeing, particularly fear of cancer recurrence, among colorectal cancer survivors. Our findings suggest that ctDNA‐guided ACT decisions do not exacerbate FCR or cause long term psychosocial harm, regardless of whether patients receive a positive or negative result.
Most participants demonstrated limited recall or understanding of ctDNA testing. For many, the test was perceived as one of several tools used by their care team, rather than a pivotal determinant of prognosis. This gap may reflect the complexity of biomarker science, the cognitive demands of treatment, or fading recall over several years. It underscores the need for communication strategies tailored to patient preferences and health literacy, particularly when results carry significant prognostic weight.
Trust in clinicians emerged as central to treatment acceptance. Patients relied on their medical team to interpret results, integrate multiple clinical factors, and recommend the best course of action. This trust‐based model may explain why ctDNA knowledge did not increase FCR, and in some cases provided reassurance.
FCR in this cohort of colorectal cancer survivors who remained recurrence‐free at 5 years, was episodic and trigger‐based consistent with findings from previous studies [23].
Several study limitations should be acknowledged. The sample size reflects the qualitative methodological approach that prioritizes depth of understanding over breadth. Purposive sampling, was employed to intentionally select participants most likely to provide rich in‐depth data. Participants were chosen based on the researchers' judgment of their specific experiences, characteristics, or knowledge, with the aim of capturing variation in perspectives rather than achieving statistical generalizability. Nevertheless, the limited number of participants may have constrained the range of perspectives represented. Although efforts were made to include variation in participant characteristics through purposive sampling, the sample may not fully reflect the diversity of patient experiences. For example, the older age of participants may not be fully generalisable to younger survivors, who often report higher and more persistent FCR. Given that little is known about this topic our data provides preliminary insights which may be the foundation for future research.
In addition, participants were interviewed on average 5 years after their initial study participation, and ctDNA testing. Retrospective recall may not fully capture emotional responses at the time of testing and treatment decision‐making. Nevertheless, participants who took part in ctDNA‐guided trials whose cancer had not recurred, and were interviewed did not appear to experience ongoing or long‐term adverse psychological outcomes related to ctDNA testing. While this finding should be interpreted cautiously, it provides preliminary reassurance regarding the psychological safety of ctDNA‐informed care.
Future research could prioritize the integration of prospective qualitative designs within ongoing and emerging ctDNA clinical trials across diverse tumor streams. Embedding longitudinal qualitative components within these trials would facilitate the collection of temporally sensitive data at multiple time points, from testing through result disclosure and subsequent treatment decisions. This would allow for a more comprehensive examination of how ctDNA results influence psychological outcomes, decision making processes and engagement with care over time.
Finally, all patients in our study underwent ctDNA testing within the context of a clinical trial, where information was provided in a standardized manner and supported by a formal informed consent process, which included clear details about the adverse prognostic implications of a positive ctDNA result. This structured approach may not fully reflect everyday clinical practice, where the provision of information can vary and often depends on the treating team. As a result, the generalizability of these findings to routine care may be limited.
Taken together with the quantitative studies recently reported, these findings suggest that personalized ctDNA‐guided approaches are not likely to be associated with long‐term adverse psychological outcomes. The themes identified in this study contribute to the existing literature and offer valuable insights to inform the integration of ctDNA testing into routine clinical practice. These findings may also serve as a foundation for future research in this area. Clinicians must balance delivering precise prognostic information with assessing individual patient readiness for detailed discussions. Structured approaches designed to enhance patient education and understanding of precision oncology and its impacts may help facilitate informed, patient‐centered conversations. As patient understanding of ctDNA testing and its prognostic significance improves, psychosocial outcomes such as FCR should be closely monitored and continue to be a focus of future research.
Open Access funding enabled and organized by Projekt DEAL.