Research Needs for Understanding the Biology of Overdiagnosis in Cancer Screening

Abstract

Many cancers offer an extended window of opportunity for early detection and therapeutic intervention that could lead to a reduction in cause-specific mortality. The pursuit of early detection in screening settings has resulted in decreased incidence and mortality for some cancers (e.g., colon and cervical cancers), and increased incidence with only modest or no effect on cause-specific mortality in others (e.g., breast and prostate). Whereas highly sensitive screening technologies are better at detecting a number of suspected “cancers” that are indolent and likely to remain clinically unimportant in the lifetime of a patient, defined as overdiagnosis, they often miss cancers that are aggressive and tend to present clinically between screenings, known as interval cancers. Unrecognized overdiagnosis leads to overtreatment with its attendant (often long-lasting) side effects, anxiety, and substantial financial harm. Existing methods often cannot differentiate indolent lesions from aggressive ones or understand the dynamics of neoplastic progression. To correctly identify the population that would benefit the most from screening and identify the lesions that would benefit most from treatment, the evolving genomic and molecular profiles of individual cancers during the clinical course of progression or indolence must be investigated, while taking into account an individual’s genetic susceptibility, clinical and environmental risk factors, and the tumor microenvironment. Practical challenges lie not only in the lack of access to tissue specimens that are appropriate for the study of natural history, but also in the absence of targeted research strategies. This commentary summarizes the recommendations from a diverse group of scientists with expertise in basic biology, translational research, clinical research, statistics, and epidemiology and public health professionals convened to discuss research directions.

Risk Stratification System for Oral Cancer Screening

“…Overdiagnosis has been observed in breast, prostate and thyroid cancer screening (41). To avoid this, markers should identify aggressive forms of oral cancer rather than indolent cancers that will not cause significant problems during a patient’s lifetime (41).…”

“…To avoid this, markers should identify aggressive forms of oral cancer rather than indolent cancers that will not cause significant problems during a patient’s lifetime (41). We assessed marker association with prognostic factors and adjusted for confounders such as stage to determine whether the markers have potential to detect early, aggressive forms of the disease.…”

Squamous Cell Carcinoma Antigen-encoding Genes SERPINB3/B4 as Potentially Useful Markers for the Stratification of HNSCC Tumours

“…High SERPINB3 expression was negatively associated with tumour extension to lymph nodes and extracapsular spread, two essential pathological features that are used clinically to identify high risk HNSCC tumours that require adjuvant radiochemotherapy (3,4). Both facts suggest that SCCA might not be suited for diagnostic use (33). On the other hand, the SERPINB3/B4 status of HNSCC tumours could be helpful at the time of initial assesment of tumour agressiveness.…”

MicroRNA-433 targets AKT3 and inhibits cell proliferation and viability in breast cancer

“…Breast cancer is the second-leading cause of cancer-associated mortality in 2015, accounting for ~11% of the total cancer mortalities in women (2,3). Although substantial progress has been made in surgical management and chemotherapy treatment, the rate of relapse in patients with advanced breast cancer remains high (4)(5)(6).…”