Thursday, April 25, 2019

Very Brief Blog: Nature Reviews Cancer Publishes Go-To Review on "Cancer Over-Screening"

Screening for cancer is crucial to intercept cancers early and allow early successful treatment.  Some of the most successful screening methods are long-established (mammography, Pap smear, FIT or colonoscopy).   However, new methods are constantly coming on line (Exact Sciences ColoGuard, Epigenomics Epi proColon, low-dose CT for high risk lung cancer (LDCT), enhanced digital or MRI mammography, 4KScore, Prolaris, Decipher and others in prostate cancer, etc). 

Even with the oldest methods (mammography), the best rules and practices remain contentious (including start age, stop age, role of family history on practices, role of genetic risk burden, etc.)  Providing different screening rules based on risk or genetics seems especially murky.   Today in 2019, Medicare defines high-risk colon cancer screening solely by "family history" somewhere amongst your relatives, entirely ignoring whether or not you actually inherited the gene at risk or not (here).

New Review of (Over)-Screening:  Srivistava et al., 2019

Although it's not open access, Nature Review Cancer has published a comprehensive 10-page review that will probably be the go-to reference for the next couple years.   Find Srivistava et al., 2019, hereAuthors are from NIH, MD Anderson, Univ California, Hopkins.

I've clipped the abstract below the break.   Authors note that overdiagnosis rates vary a lot, they are not an issue in cervical or colon cancer, but rise to 25% in breast, 60% in prostate. 

In the conclusion, they view better molecular determinants as a path forward for better public healthcare in this area.

For a new article on budget impact modeling of cancer screening, Jahn et al. 2019, here.  For an article in Stat, tied to one in JAMA, on "excesssive use of testing," here. For an April 2019 article in The Economist on screening in lung cancer (and other purposes), here.

Cancer overdiagnosis: a biological challenge and clinical dilemma

Sudhir Srivastava, Eugene J. Koay, Alexander D. Borowsky, Angelo M. De Marzo, Sharmistha Ghosh, Paul D. Wagner & Barnett S. Kramer

Nature Reviews Cancer (2019)

For cancer screening to be successful, it should primarily detect cancers with lethal potential or their precursors early, leading to therapy that reduces mortality and morbidity. Screening programmes have been successful for colon and cervical cancers, where subsequent surgical removal of precursor lesions has resulted in a reduction in cancer incidence and mortality. However, many types of cancer exhibit a range of heterogeneous behaviours and variable likelihoods of progression and death.

Consequently, screening for some cancers may have minimal impact on mortality and may do more harm than good. Since the implementation of screening tests for certain cancers (for example, breast and prostate cancers), a spike in incidence of in situ and early-stage cancers has been observed, but a link to reduction in cancer-specific mortality has not been as clear. It is difficult to determine how many of these mortality reductions are due to screening and how many are due to improved treatments of tumours.

In cancers with lower incidence but high mortality (for example, pancreatic cancer), screening has focused on high-risk populations, but challenges similar to those for general population screening remain, particularly with regard to finding lesions with difficult-to-characterize malignant potential (for example, intraductal papillary mucinous neoplasms).

More sensitive screening methods are detecting smaller and smaller lesions, but this has not been accompanied by a comparable reduction in the incidence of invasive cancers.

In this Opinion article, we focus on the contribution of screening in general and high-risk populations to overdiagnosis, the effects of overdiagnosis on patients and emerging strategies to reduce overdiagnosis of indolent cancers through an understanding of tumour heterogeneity, the biology of how cancers evolve and progress, the molecular and cellular features of early neoplasia and the dynamics of the interactions of early lesions with their surrounding tissue microenvironment.

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