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Enhanced knowledge base is fundamental to personalised medicine


08-01-2013      1512 views

By Prof. Bernard Malavaud et al.

Personalised medicine is often understood as a new era of “molecular medicine and targeted therapies” following the empirical approaches of medical care until the second half of the 20th century. However attractive this may appear, this new paradigm warrants a critical analysis to determine the probability of personalised medicine becoming the new standard of modern healthcare or whether more down-to-earth approaches can be developed with more immediate benefits to the population and healthcare providers.

From the classical 19th century studies on peas and fruit flies, in 1905 the Danish scientist Wilhelm Johannsen coined the term "gene" from the Greek word "genea" or "race" to solidify the relationship between parents and offspring’s characteristics. In 1953, Watson & Crick, who were awarded the Nobel Prize of Medicine and Physiology in 1962 already for this achievement, unveiled the DNA double strand helix and the dynamic of its duplication between sister cells, thereby opening the era of modern genetics.

The paths from genes to messenger RNAs and then proteins and cell functions are now taught in high school although the discovery of the intricate mechanisms supporting the infinite variation in cells and tissues physiology still continues at a higher level of complexity until this day and age. These pathways result from inherited or acquired variations (e.g. single nucleotide polymorphism, mutations) in the genetic material or result from alterations in the ways it is processed (epigenetic regulation) into proteins that then interact with other moieties to regulate one, or multiple, cellular functions.

Human medicine

However, such a chain of event can rarely be demonstrated in human medicine. The first instance was in a rare blood cancer -chronic myeloid leukaemia- where a select chromosomal aberration brings together two normal genes into a fusion gene that (unrestrictedly) activates a cascade of molecular events that support the disease. Targeting the fusion gene can then abrogate the clinical expression of the disease until therapeutic escape ultimately results from the genetic instability of cancer stem cells.

Perfect coherence from gene equipment or genotype" to the expression of the disease or "phenotype" is extremely rare in human medicine although some fragments of it can be found in most diseases which are now being used to develop diagnostic tools or targeted treatments, but also as prognostic factors.

Urology, which deals with the diseases of the genitourinary system in the male and the urinary tract system in the female, addresses a wide scope of age-related benign diseases (e.g. lower urinary tract symptoms, stress incontinence) and cancers. It is the main objective of urologists to provide the best care; balancing the worries and desires of their patients and the natural course of the disease.

A working definition

The EAU acknowledges the working definition proposed by the European Alliance for Personalised Medicine (EAPM) "The right treatment for the right patient at the right time" as it encompasses the three principles of modern urological care: adaptation of treatment protocol to disease characteristics, acknowledgement of patients’ personal history and choices, and a balanced analysis of the benefits and risks linked to a given treatment. Two separate examples may be helpful to illustrate how standard urological practice effectively promotes personalised medicine. In the European male population the estimated prevalence of lower urinary tract symptoms related to benign prostatic hyperplasia is considerable (30%).

Depending on their impact on micturition and quality of life, they can be alleviated by drugs, minimally invasive treatments or surgery, all with different pros and cons. Since Male LUTS are most often age-related, concurrent diseases and treatments will also have to be taken into account, as well as addressing a patient’s concerns about potential interference of treatment on his sex life.

Characterisation of the disease in an individual patient will therefore be based on a complex combination of the degree of bother (validated IPPS self-administered questionnaires are available in all European languages, prostate volume characteristics assessed clinically by digital rectal examination and prostate specific antigen serum levels, assessed by laboratory testing and, if needed, by imaging and functional studies). Therefore, the urologist has to master many layers of information before a treatment recommendation can be made.

Second example would relate to renal cell cancer, the incidence of which has increased within the European Union to 63,000 new cases with approximately 26,400 deaths observed in 2006. Due to the increase of abdominal imaging studies (ultrasounds, CT scans), mostly for unrelated complaints, the number of kidney tumours detected rose significantly but most of these tumours were small when identified.

Treatments that address the cancer, but spare the normal tissue of the diseased kidney have been developed since, in view of the strong relationship that exists between altered renal function, as possibly induced by kidney ablation, and the increased risks of cardiovascular diseases and even death. However, those treatments are much more complex than the ablation of the entire kidney and generally tend to be underused, as shown by a recent US study.

Here, personalised medicine would amount to the use of nephron-sparing strategies (partial nephrectomy, radiofrequency ablation, cryoablation) while taking into account the level of anatomical complexity of the tumour and a patient’s health status (comorbidities). This was indeed one of the objectives in the latest release of the EAU guidelines on RCC.

In 1996 the EAU established a HealthCare Office, incorporating specialty groups consisting of key opinion leaders in urology, to build a corpus of data on how to provide balanced management of urological care to the European population.

Optimal care

Of note, promoting optimal care in urology across the European Union requires that a common body of knowledge be built amongst physicians, starting with initial medical training and further enhanced through continuous medical education. Since 1999 the EAU, through the European School of Urology, provided courses, lectures and hands-on training to students and urologists aiming to enhance and solidify their knowledge. “Molecular medicine” may play a more prominent role in the future of urology. Meanwhile, the EAU has structured urological care along the principles of personalised medicine “The right treatment to the right patient at the right time” with the constant objective of delivering the best urological care across Europe and worldwide.

This article, including references, was published in the October-Novebmer 2012 issue of EUT >



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