**Background:** Despite advances in cancer treatment and survival, many oncological patients lack adequate information and psycho-social support. The PIKKO program (German acronym for 'Patient information, communication and competence empowerment in oncology') was designed to address these gaps by combining a patient navigator (PN), specialized psycho-oncological and socio-legal counseling, supportive courses, and a web-based knowledge database. The study hypothesized that PIKKO would improve health-related quality of life (HRQoL), self-efficacy, and health literacy while reducing depression and anxiety.
**Methods:** This non-randomized, controlled, multicenter longitudinal study was conducted in Saarland, Germany, across 38 medical institutions in 19 cities. The control group (CG, n=424) was recruited first (Nov 2017–Oct 2018) and received treatment as usual (TAU). The intervention group (IG, n=580) was recruited subsequently (Nov 2018–Mar 2020) and received TAU plus full access to PIKKO modules. Randomization was not possible for ethical and service reasons. Eligibility included age 18–90 years, any cancer diagnosis (ICD-10 C00-C97 or D45-D48), no guardianship, sufficient German language, no severe sensory or cognitive impairment. The PN (n=15, 14 women) were non-physicians with medical backgrounds and ≥2 years oncological experience, trained via a two-week German Cancer Society course. SCS offered psycho-social and socio-legal counseling plus courses (nutrition, art, music therapy, Nordic walking, QiGong, yoga). The knowledge database provided evidence-based cancer and socio-legal information with 24/7 access. Outcomes were measured at baseline, 3, 6, 9, and 12 months using SF-12 (HRQoL), PHQ-9 (depression), GAD-7 (anxiety), GSE (self-efficacy), and HLS-EU-Q47 (health literacy). The target sample was 1,014 patients (507 per group), calculated for d=0.25 effect, α=0.05, power 0.9, with 33.3% expected dropout. Imputation used MissForest (19 iterations, NRMSE=0.245, PFC=0.065). Propensity score weighting (stabilized weights) adjusted for baseline differences. Dose-effect analyses used growth curve models.
**Key Results:** No significant differences favoring the IG were found on any primary or secondary outcome. At the primary endpoint (6 months), mental HRQoL was 44.92 (SD 6.45) in IG vs 46.38 (SD 8.01) in CG (Hedges' g = -0.226, p<0.05 favoring CG). Depression scores at 6 months were 8.08 (SD 2.58) in IG vs 7.24 (SD 3.18) in CG (g=0.326, p<0.001 favoring CG). These differences diminished by 12 months. Physical HRQoL, anxiety, self-efficacy, and health literacy showed no significant between-group differences. However, module utilization was high: 87.6% (382/436) of IG patients contacted the PN (mean 5.07 contacts, SD 5.73); 39.8% (231/580) used SCS offers; 65.9% (413/627) accessed the knowledge database (mean 2.28 visits, SD 2.61). Patient ratings were positive: PN rated 1.96 (SD 0.81), SCS counseling 1.39 (SD 0.77), knowledge database 2.16 (SD 0.74) on a 1–6 German school scale (1=very good). Dose-response analyses showed that under non-COVID-19 lockdown conditions, more frequent database use was associated with greater health literacy improvement, particularly among patients with high baseline health literacy. More frequent SCS counseling was associated with improved mental HRQoL among patients with high baseline mental HRQoL. Dropout rates at 6 months were 25.5% (CG) and 34.5% (IG); by 12 months, 43.6% (CG) and 70.0% (IG) had dropped out.
**Clinical Implications:** The PIKKO study did not demonstrate statistically significant improvements in HRQoL, depression, anxiety, self-efficacy, or health literacy in the overall sample, despite high patient satisfaction and module utilization. The authors attribute null findings primarily to study limitations: lack of randomization, sequential group allocation creating selection bias, heterogeneous sample, insufficient dosage of psycho-social counseling (only 6.9% of documented counseling users had ≥7 sessions), and COVID-19 lockdown disruptions. The dose-response trends suggest that patients with higher baseline health literacy may benefit more from educational eHealth tools, and those with higher baseline mental HRQoL may benefit more from counseling. The authors recommend initial needs screening to target interventions to appropriate patients and note that psycho-social counseling may be more relevant later in the cancer trajectory (average 21 months post-diagnosis per prior literature). The knowledge database remains available post-study as a recommended eHealth element. The study provides structural insights relevant to Germany's planned nationwide introduction of patient navigators.