We are clearly getting closer to being able to make accurate projections about which forms of castration-resistant prostate cancer (CRPC) are really aggressive and need immediate, aggressive therapeutic intervention and which are likely to progress more slowly (over a period of years). However, this is only the beginning of the story.
In a Reuters.com article today we find information about two newly published studies (both in Lancet Oncology) focused on genetic ?signatures? for aggressive subtypes of prostate cancer. Unfortunately, this Reuters article fails to note that the research studies it refers to are exclusively focused on men with CRPC!
In the first of these two studies, Ross et al., describe a six-gene, whole blood-based test that was able to separate men with castration-resistant prostate cancer (CRPC) into two risk groups:
- A low-risk group with a survival of more than 34.9 months (average [median] survival was not reached for this group of patients)
- A high-risk group with a median survival of just 7.8 months
This six-gene model was based on identification of the expression of the ABL2, SEMA4D, ITGAL, and C1QA, TIMP1, CDKN1A genes.
In the second paper, Olmos et al. were able to use a a nine-gene, blood-based test that could categorize men with metastatic CRPC into four groups:
- Men in their so-called LDP1 group had a median overall survival of just 10.7 months (range 4.1 to 17.1 months)
- Men in the LDP2, LDP3, and LDP4 subgroups? had a collective median overall survival of? 25.6 months (range 18.0 to 33.4 months)
It is not clear from the abstracts of the two papers how many of the genes used by Ross et al. were also being used by Olmost et al.
The ability to project short-term risk for death in men with differing forms of CRPC is clearly going to be important to our ability to treat these men with the highest possible levels of effectiveness and safety compared to their risk for death and the potential side effects of treatment. However, the degree to which knowing this information can be used on a routine basis to make decisions about men in these subcategories is still not known. The most likely place for the immediate utility of tests like this will, in fact, be for stratification of patients by risk group in late stage clinical trials of new drugs.
In contrast, the ability to use tests like these to be able to make decisions about whether men could be managed with active surveillance as opposed to immediate therapeutic intervention would be huge ? if we can generate the data to prove the hypothesis. Whether this will all help us to better treat the men who really do have high-risk prostate cancer is still moot. Until we have a test that we think can discriminate with accuracy between less aggressive and more aggressive forms of adenocarcinoma of the prostate, it is impossible to carry out therapy and compare the long-term outcomes in men with gene profiles suggesting different levels of risk (regardless of the patients? Gleason score, PSA level, and other current prognostic factors).
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Filed under: Diagnosis, Drugs in development, Living with Prostate Cancer, Management, Risk, Treatment Tagged: | gene, profile, prognosis, risk, signature
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