Highlights
– A therapist‑guided online intervention (TG‑iConquerFear) produced large, clinically meaningful reductions in overall fear of cancer recurrence (FCR) among colorectal cancer survivors with clinical FCR.
– At 3 months postintervention the between‑group difference in FCRI total score was 19.1 points (95% CI, 10.0–28.3; P < .001) with a standardized effect size (Cohen d) of 0.62.
– 81% of TG‑iConquerFear participants fell below the clinical FCR cutoff on the FCRI‑SF versus 43% with augmented self‑help (number needed to treat = 3).
Background
Fear of cancer recurrence (FCR) is one of the most common and persistent concerns among cancer survivors. High FCR is associated with impaired quality of life, increased healthcare use, and greater psychological distress. Although face‑to‑face cognitive behavioral interventions and targeted psychological therapies (including the ConquerFear model) have demonstrated efficacy in reducing FCR, access barriers persist: limited specialist resources, geographic constraints, and survivor preference for remote or flexible care. Digitally delivered interventions with therapist guidance have the potential to expand access while retaining treatment fidelity and clinician oversight, but randomized evidence in population‑based survivorship cohorts is limited.
Study design
This single‑site, population‑based randomized clinical trial (Denmark) tested the efficacy of TG‑iConquerFear, a 10‑week therapist‑guided e‑health program adapted for colorectal cancer (CRC) survivors. The trial enrolled cancer‑free adult CRC survivors (≥18 years) with clinically significant FCR, defined as FCRI‑SF score ≥22, who had completed curative‑intent treatment between March 1, 2014, and December 31, 2018. Recruitment ran from May 8, 2023, to April 8, 2024. Participants were randomized 1:1 (stratified by age and sex) to TG‑iConquerFear or an augmented control.
Interventions
– TG‑iConquerFear: Six modules delivered remotely over 10 weeks, with written therapist guidance provided individually and asynchronously as needed. Participants could progress through modules at their own pace; mean completion was 4.5 of 6 modules (SD 1.9).
– Augmented control: Diagnostic interview plus referral to an online webpage containing self‑help mindfulness exercises.
Primary endpoint
– Change in Fear of Cancer Recurrence Inventory (FCRI) total score at 3 months postintervention (intention‑to‑treat analysis).
Follow‑up was 6 months overall; the primary outcome was assessed at 3 months postintervention.
Key findings
Participants and retention
– From 9,946 eligible CRC survivors identified, 103 met inclusion and were randomized. Two participants were later excluded due to recurrent cancer; six dropped out before intervention start, leaving 95 analyzed (median age 63 years [IQR 57–72]; 60 [63%] female; median time since diagnosis 7 years [IQR 6–9]). Of those, 42 participants were included in the TG‑iConquerFear arm and 53 in the augmented control arm for primary outcome analyses.
Primary outcome
– TG‑iConquerFear group: mean change in FCRI total score from baseline to 3 months = −21.7 points (95% CI, −30.1 to −13.3).
– Augmented control group: mean change = −2.6 points (95% CI, −7.8 to 2.6).
– Between‑group difference = 19.1 points (95% CI, 10.0–28.3; P < .001).
– Standardized effect size (Cohen d) = 0.62 (95% CI, 0.13–1.10), indicating a moderate effect.
Categorical outcome: clinically meaningful remission
– At 3 months postintervention, 22 of 27 (81%) TG‑iConquerFear participants had FCRI‑SF scores below the clinical cutoff (<22), compared with 18 of 42 (43%) in the augmented control group (P = .002). Number needed to treat (NNT) = 3.
Adherence and engagement
– Mean modules completed: 4.5 of 6 (SD 1.9). Asynchronous written therapist guidance was the primary mode of clinician contact. The study reports feasibility in a population‑based sample with sustained engagement over 10 weeks for many participants.
Safety and adverse events
– The published abstract and trial report do not indicate serious adverse events attributable to the intervention. No signal of harm is reported; however, detailed safety tables and event rates should be consulted in the full manuscript for completeness.
Clinical interpretation
– The magnitude of reduction in FCRI total score in the TG‑iConquerFear arm is large and likely clinically meaningful. The between‑group difference and the NNT of 3 both suggest that therapist‑guided online programs can produce robust, rapid improvements in FCR when deployed in a community survivorship population.
Expert commentary and contextualization
How this trial fits into the evidence base
– Face‑to‑face ConquerFear and other structured psychological interventions have previously shown benefit for FCR, but access barriers have limited their population impact. This trial demonstrates that an adapted, therapist‑guided e‑health format can replicate clinically relevant outcomes in colorectal cancer survivors with persistent, clinically significant FCR.
Mechanisms and therapeutic content
– iConquerFear adapts core techniques from evidence‑based FCR treatments: cognitive strategies to reframe worry and threat appraisals, behavioral experiments to test catastrophic predictions, metacognitive and acceptance‑based techniques to shift the relationship to worry, and relapse prevention. Asynchronous therapist input likely helped maintain accountability, troubleshoot module content, and tailor recommendations, balancing scalability with personalization.
Generalizability and limitations
– Strengths: population‑based sampling, randomized design, validated outcome measures, and active augmented control (diagnostic interview plus self‑help resources) that improves trial rigor over waitlist controls.
– Limitations: single‑site Danish sample may limit cross‑cultural generalizability; the analyzed numbers (42 vs 53) are modest and differential numbers analyzed between arms merit careful inspection; mean module completion was below full completion, raising questions about dose–response and optimal engagement strategies; longer‑term outcomes (beyond 6 months) and effects on downstream healthcare utilization, quality of life, and cost‑effectiveness require further study.
– The trial excluded survivors with recurrent disease, so applicability to those with ongoing active cancer care is not established.
Implementation considerations
– For healthcare systems: therapist‑guided digital programs require initial adaptation, training for therapists in asynchronous written guidance and digital therapeutic skills, and integration into survivorship care pathways.
– For clinicians: screening for FCR (for example, using the FCRI‑SF) is crucial to identify candidates for stepped care. TG‑iConquerFear may be positioned as an intermediate intensity intervention—more intensive than unguided self‑help but less resource‑intensive than weekly face‑to‑face therapy.
Comparison with unguided digital interventions
– The magnitude of effect here (Cohen d 0.62) supports prior findings that guidance—whether therapist or coach—enhances outcomes in digital psychological interventions compared with unguided approaches, particularly for conditions requiring individualized cognitive restructuring or complex behavioral strategies.
Conclusion and practice implications
This randomized clinical trial demonstrates that TG‑iConquerFear, a 10‑week therapist‑guided e‑health program, produced clinically meaningful reductions in fear of cancer recurrence among colorectal cancer survivors with clinically significant baseline FCR. The observed effect size and high proportion of participants falling below the clinical FCR threshold support the intervention as a viable, scalable option within survivorship care frameworks. Health systems and survivorship programs should consider integrating therapist‑guided digital therapies as part of a stepped‑care model for FCR, accompanied by routine screening and protocols for escalation to face‑to‑face or specialist mental health care for nonresponders.
Research and policy priorities
– Replication in larger, multi‑center and cross‑cultural samples is needed, together with head‑to‑head comparisons versus face‑to‑face interventions.
– Longer follow‑up is required to assess durability, relapse rates, and impacts on healthcare utilization and quality of life.
– Economic evaluations will inform cost‑effectiveness and resource allocation decisions.
Funding and clinicaltrials.gov
Trial registration: ClinicalTrials.gov Identifier: NCT04287218. Funding sources and detailed trial conduct statements are reported in the original publication: Lyhne JD et al., JAMA Network Open. Please consult the full paper (Lyhne et al., 2025) for funding declarations, conflict of interest statements, and full methodological appendices.
References
Lyhne JD, Smith AB, Timm S, Klein B, Thewes B, Girgis A, Bamgboje‑Ayodele A, Beatty L, Fardell J, Fink P, Butow P, Frostholm L, Jensen LH. E‑Health Intervention for Fear of Cancer Recurrence: A Randomized Clinical Trial. JAMA Netw Open. 2025 Nov 3;8(11):e2542112. doi: 10.1001/jamanetworkopen.2025.42112. PMID: 41217757; PMCID: PMC12606383.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Distress Management. Available at: https://www.nccn.org (accessed 2025). The NCCN guidelines provide a framework for screening and managing distress, including cancer‑related anxiety and FCR, within survivorship care.
(Readers are encouraged to consult the full JAMA Network Open manuscript for comprehensive methodologic and supplementary data.)