Psychological Outcomes in Patients with Rare Cancers: A systematic Review and Meta-analysis

Background: Rare cancers are those that exhibit an incidence of less than six per 100,000 in a year. On average, the five-year relative survival for patients with rare cancers is worse than those with common cancers. The traumatic experience of cancer can be further intensified in patients with rare cancers due to the limited clinical evidence and the lack of empirical evidence for informed decision-making. With rare cancers cumulatively accounting for up to 25% of all cancers, coupled with the rising burden of rare cancers on societies globally, it is necessary to determine the psychological outcomes of patients with rare cancers.

Methods: This PRISMA-adherent systematic review (PROSPERO: CRD42023475748) involved a systematic search of PubMed, Embase, Cochrane and PsycINFO for all peer-reviewed English language studies published since 2000 to 30th January 2024 that evaluated the prevalence, incidence and risk of depression, anxiety, suicide, and post-traumatic stress disorder (PTSD) in patients with rare cancers. Two independent reviewers appraised and extracted the summary data from published studies. Random effects meta-analyses and meta-regression were used for primary analysis.

Findings: We included 32 studies with 57,470 patients with rare cancers. Meta-analyses indicated a statistically significant increased risk-ratio (RR) of depression (RR = 2.61, 95% CI: 1.43-4.77, I2 = 97%) and anxiety (RR = 2.66, 95% CI: 1.27-5.55, I2 = 92%) in patients with rare cancers compared to healthy controls. We identified a high suicide incidence (315 per 100,000 person-years, 95% CI: 162-609, I2 = 95%), prevalence of depression (17%, 95% CI: 14-22, I2 = 88%), anxiety (20%, 95% CI: 15-25, I2 = 96%) and PTSD (18%, 95% CI: 9-32, I2 = 25%). When compared to patients with common cancer types, suicide incidence, and PTSD prevalence were significantly higher in patients with rare cancers. Systematic review found that having advanced disease, chemotherapy treatment, lower income, and social status were risk factors for negative psychological outcomes.

Interpretation: We highlight the need for early identification of psychological maladjustment in patients with rare cancers. Additionally, studies to identify effective interventions are imperative.

Funding: This study was supported by the National Medical Research Council Transition Award, SingHealth Duke-NUS Oncology Academic Clinical Programme, the Khoo Pilot Collaborative Award, the National Medical Research Council Clinician Scientist-Individual Research Grant-New Investigator Grant, the Terry Fox Grant and the Khoo Bridge Funding Award.