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Tissue vs Liquid Biopsies for Cancer Detection: Ethical Issues


Cancer is the second leading cause of death in developed countries, making it a global public health problem. In this scenario, early detection is the key to successful treatment. Tissue biopsy, the current gold standard for cancer diagnosis, offers reliable results, but it is feasible only when the mass becomes detectable. On the other hand liquid biopsy, a promising experimental system, not yet implemented within clinical practice, allows early detection as its functioning relies on the analysis of body fluids. Yet, its results are less reliable if compared to those of tissue biopsy as, for instance, false positives and false negatives might occur. Despite technical features, the tradeoff between a reliable diagnosis available at a later time and a potentially less reliable diagnosis available at an early stage poses significant ethical challenges in the clinical scenario which involve, among other aspects, informed consent, communication, and patient-physician encounter.

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    For example, cancers of the mid-lung and retroperitoneum.

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    According to a study conducted at Anderson Cancer Center by Overman and colleagues (Overman et al. 2013), investigative biopsies registered complications rates of 17.1% for thoracic biopsies and 1.6% for abdominal/pelvic ones. This means that tissue biopsies are not free from adverse events and may jeopardize patients’ safety, for example, in cases of sampling of neoplastic masses surrounding important vessels or in specific locations of the brain. See also Diaz and Bardelli (2014). And Siravegna et al. (2017).

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    There are two sources of tumour DNA in the blood: one is ctDNA and the other is CTCs, namely circulating tumour cells. CTCs represent “intact, often viable, cells that can be purified from blood by virtue of physicochemical characteristics or cell surface molecules that distinguish them from normal blood cells” (Bettegowda et al. 2014, 224).

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    For example, low-grade in situ carcinomas (a possible precursor of carcinoma), are often treated as invasive tumours because diagnostic tools are not able to predict with reliable precision their further development. Actually, once the tumour (or prospective tumour) is detected, the only chance to know whether it had been overdiagnosed, would be to leave it untreated. Yet, this path entails several risks, because if the tumour had not been the object of overdiagnosis, treatment at an advanced stage would lessen the probability of positive outcome.


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Correspondence to Chiara Mannelli.

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Mannelli, C. Tissue vs Liquid Biopsies for Cancer Detection: Ethical Issues. Bioethical Inquiry 16, 551–557 (2019).

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  • Bioethics
  • Oncology Research
  • Liquid Biopsy
  • Informed consent