PROSTATE CANCER
What’s new in the exciting era of personalised medicine?
ONE OF the greatest dilemmas in diagnosing and treating men with early prostate cancer is attempting to determine which prostate cancers are lethal and, therefore, need to be treated and which are relatively innocuous and, therefore, ought to be left alone. This dilemma exists because prostate cancer is not a homogenous disease, but, instead, has a wide spectrum of biologic aggressive potential-ranging from rabidly malignant and aggressive forms on the one hand to innocuous and almost benign forms on the other hand. Differentiating between prostate cancers has always been very tricky because the tools at our disposal to make these distinctions were imprecise at best.
OVERDIAGNOSED
Failure to identify and separate out the bad actors from the fairly innocuous forms of prostate cancer because of the imprecision of currently available tools, caused many men with relatively innocuous prostate cancer to be overdiagnosed and overtreated. Since these men were unlikely to ever die or even suffer harm from prostate cancer, and since the treatments for prostate cancer may potentially leave a man impotent and incontinent of urine, many men suffered harm rather than derived any benefit from treatment. These men have had their quality of life adversely affected by treatment and were not happy. In rare cases, men have even died from unnecessary treatments.
Fortunately, there are now new tools that are becoming increasingly available which can help us to determine whether a particular patient’s prostate cancer is likely to kill him if left untreated or is likely never to cause harm or death if left alone. These new tools allow for an individually tailored or personalised approach to the treatment of a patient with prostate cancer, enabling us to correctly identify the best treatment for the patient that will maximise survival from prostate cancer while minimising the harms of treatment.
So what are these new tools? They are called molecular biologic markers, or biomarkers for short. They are genetic ‘fingerprints’ of a tumour that allow us to predict its future behaviour, thereby allowing us to better stratify patients according to the level of risk of death posed by a patient’s prostate cancer. Traditionally, tumour grade based on the microscopic appearance of a cancer was
the most robust
indicator of prognosis; new prostate cancer biomarkers have been outperforming tumour grade in early studies and have allowed more refined and accurate determinations of outcome. These biomarkers are, however, in their infancy where clinical use is concerned and need to be validated in large and diverse populations of men before they can be unreservedly recommended for routine clinical use.
While none of these biomarkers are yet available in Jamaica, they are, nevertheless, accessible in the USA where many Jamaicans travel to regularly. In selected patients with suspected or established early prostate cancer, the local treating urologist may recommend biomarker testing to be better able to advise the patient on whether a prostate biopsy should be done or which of several treatment alternatives is best; and in such cases it may be worth the expense to travel overseas to access these tests.
The commercially available biomarker and other tests accessible overseas, which allow us to be more discriminatory in investigation and treatment selection, include the 4Kscore Test, the Prostate Health Index, PCA3, Oncotype DX¨ and Prolaris. Hopefully, some of these tests will be available in Jamaica shortly after universal validation.
Another test which allows us to be more discriminatory and selective is a special
biopsy test called multi-parametric MRI-ultrasound fusion prostate biopsy. This special biopsy technique allows specific areas of the prostate which harbour aggressive prostate cancer cells to be selectively targeted while relatively indolent areas are left alone. It, therefore, preferentially identifies the ‘bad actors’ that are likely to cause death if left untreated, while not diagnosing prostate cancer in those men not likely to die from the disease. This is an improvement over the standard trans-rectal ultrasound guided prostate biopsy in which random biopsies are taken of the prostate based on an ultrasound image.
AGGRESIVE DISEASE
The multi-parametric MRI ultrasound fusion biopsy allows targeting of aggressive disease because it is not only giving anatomical information but also functional information. Since aggressive prostate cancer cells are more densely packed and have a greater blood vessel density, the diffusion of water through these malignant tissues is impeded and the blood flow into them is relatively greater. Special MRI techniques take advantage of these differences to give us functional ‘parameters’ which, along with anatomical information, is used to identify relatively more aggressive disease. This relatively new biopsy technique is not yet available in Jamaica and patients, therefore, have to be referred overseas by their urologists to access the technology.