Suboptimal cancer-screening adherence in CLL/SLL patients

Abstract Background: Patients diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) have an increased risk of developing secondary primary malignancies. Several mechanisms have been proposed for this association which include genomic instability, impaired DNA repair and profound immune dysfunction. Studies estimate that the risk of secondary cancers in CLL/SLL patients may be as much as twice that of the general population. The current recommendation for the average-risk patient is to perform colorectal cancer screening with colonoscopy and mammogram screening for breast cancer. This study evaluates compliance with these recommended screening modalities in patients with CLL/SLL, a population that would theoretically benefit even more from early detection. To our knowledge, this is the first large-scale study to specifically assess adherence to routine cancer screenings among CLL/SLL patients following diagnosis. Methods: A retrospective analysis was conducted using the TriNetX Research Network, a federated database of de-identified electronic medical records from healthcare organizations (HCO) from the Global Collaborative Network. Patients aged 50–75 years with a diagnosis of CLL/SLL and at least one health encounter in this age range were included. Although current guidelines recommend mammography beginning at age 40 and colonoscopy at 45, our analysis focused on the 50–75 age group to capture individuals likely to have completed screenings under prior recommendations. To identify screening compliance, we queried terms such as “encounter for screening malignant neoplasm of colon,” “screening colonoscopy,” and “colonoscopy consultation,” all occurring after the index diagnosis of CLL/SLL. Similar logic was applied for breast cancer screening terms, including “screening mammogram,” “digital tomosynthesis,” and “computer-aided detection”. After balancing the cohorts, the survival outcomes were analyzed using Kaplan Meier curves and diagnosis of colon cancer or breast cancer was determined by measures of association. Results: A total of 90,847,151 women were screened from 139/151 HCO, with 36,475 cases with a diagnosis of CLL/SLL. Of these, only 7,158 had undergone a screening mammogram, corresponding to an approximate 20% compliance rate. Those patients who were doing mammograms had a 7.8% risk of being diagnosed with a malignant neoplasm of the breast compared to 6.2% in those who did not. Notably, the screening cohort had significantly better overall survival [p<0.0001], even after adjusting for confounding factors such as age, race and BMI. For those patients who were complaint with recommended screening, 61% had ≥5 mammograms, and 45% had ≥10. Similarly, from 142/151 HCO a total screened population of 170,009,536 patients, 92,728 with CLL/SLL were identified. Of these, 11,232 had undergone a colonoscopy, yielding a compliance rate of approximately 12%. The risk of developing colon cancer was noted to be 1.9% in those screened vs 1.3% in those who did not. Overall survival was again significantly better among those who underwent colonoscopy [p<0.0001], which remained statistical after balancing. Of those doing colonoscopies, 70% had ≥3 colonoscopies, and 50% had ≥5. Conclusion: Our findings highlight a concerning gap in compliance with age-appropriate cancer screening practices among patients with CLL/SLL, despite their increased risk for secondary malignancies. While the screened cohorts exhibited slightly higher cancer detection rates, this is likely due to lead-time bias as earlier identification had survival benefits for these patients. Although TriNetX relies on coding accuracy, this is the first study to evaluate real world data addressing this topic and highlighting a missed opportunity for these patients. The results emphasize the urgent need for increased awareness and adherence to these well-known and validated cancer screening methods, particularly for patients who are in more susceptible situations such as an underlying hematologic malignancy. Clinicians should prioritize comprehensive post-diagnosis care for CLL/SLL patients, including routine mammography, colonoscopy, and dermatologic evaluations, amongst others. Proactive screening is not only critical for early cancer detection but also strongly associated with improved long-term outcomes in CLL/SLL survivors.