The accurate prognosis of recurrence- and metastasis-free survival

A company based on Northern Ireland called Almac Diagnostics has been working on the development of a 70-gene genetic assay (which they refer to as their Prostate Cancer Metastatic Assay) capable of projecting probability of metastasis-free survival in men treated for prostate cancer.

Earlier in the year, the company issued a media release announcing publication of assay validation data based on a total of 322 radical prostatectomy samples from men who had undergone first-line surgery as treatment for their prostate cancer. According to that media release, the 70-gene test was able to project increased risk for for biochemical recurrence and for metastatic prostate cancer on  its own, and it did so even better when the test results were combined with the patients’ CAPRA-S scores.

According to the company’s media release, this original paper was published in the “Journal of European Urology“. To date we haven’t been able to identify this paper and (as far as we know) there is no publication called the Journal of European Urology.

In a new and different media release, issued today, Queens University Belfast has indicated that the same Almac Diagnostics test has been used to assess risk for metastatic prostate cancer in a cohort of 248 patients with intermediate- or high-risk, locally advanced prostate cancer who were treated with radical radiotherapy + androgen deprivation therapy (ADT). In this case there is accurate information about the original publication (by Jain et al. in Annals of Oncology), so at least we have the abstract of the original research to look at.

In the new study, the authors report that, based on biopsy tissue taken from patients after completion of their radiation therapy:

  • Projected 10-year metastasis-free survival (MFS) was
    • 72 percent for patients who were positive for risk according to the Prostate Cancer Metastatic Assay
    • 94 percent for patients who were negative for risk according to the Prostate Cancer Metastatic Assay
  • The assay remained predictive for development of distant metastases on multivariable analysis
  • Combining the  test results with the patients’ CAPRA scores did not improve prognosis in this set of patient samples.

It would be extremely helpful to be able to give a patient some sort of test — after their first-line treatment — that could accurately project that patient’s individual risk for biochemical recurrence and metastasis-free survival at (say) 10 years post-treatment. But one would also need to know what — if anything — could be done to such a patient to see if one could improve his probability of long-term survival with high quality of life.

Is the Almac Diagnostics Prostate Cancer Metastatic Assay going to be able to meet that challenge? Frankly, we can’t tell from the available data. That is going to take some form of prospective trial in which patients will need to be followed closely for a number of years.

And then there is a second issue. … Let’s assume that the test can, accurately, project such risk for an individual patient with (say) 90 percent probability at 10 years of follow-up. Then what does this imply in terms of the treatment of any one individual patient? Yes we know he will have first a biochemical recurrence and then metastasis. But the test doesn’t tell us how long that is going to take for an individual patient. He might have recurrent disease within 6 months — which would imply the need early salvage therapy of some type. Alternatively, he might not have recurrent disease for 9 years — which would mean that one probably didn’t want to initiate any currently available form of therapy until that happened (because of the impact of such therapies on quality of life).

Sometimes the availability of risk data is not necessarily as useful as one might think. However, if we really could project, with accuracy, which patients were going to have metastatic disease 5 and 10 years after their initial treatment, what this would be important for is kn owing that these patients would be the ideal candidates for enrollment into clinical trials of new forms of salvage treatment as early as possible. We just need the new types of salvage therapy that might really work on a regular basis!


6 Responses

  1. Nice post..

  2. My opinion as being a prostate cancer survivor and having a complete radical prostatectomy 4 months ago, in regards to the time line of 5, 10 and 15 years of possible reoccurrence, large professional companies such as Thermo Fisher Scientific needs to be implemented to examine, proceed with research and offer possibilities of better accurate important varied findings how to deal with the outcomes of reoccurrence of cancer that was originally diagnosed as prostate cancer.

    I am not a researcher, pathologist, physician or employed by Thermo Fisher Scientific. I have mentioned Thermo Fisher Scientific because I have been researching about this company in their results of improving the outcomes of the many different cancer diseases. My feelings is that issues with general health, diet, exercise and change of life styles could help with the results of reoccurrence of cancer during the time line that is noted for survivors of the period of 5, 10 and 15 years of recovery.

  3. Dear William:

    I think I should be clear that dozens of companies (including major companies like Beckman Coulter and a whole bunch of biotech companies) and thousands of researchers have spent much of the past 30 years trying to find better tests that can accurately predict prostate cancer progression over time. I know of no reason that Thermo Fisher would be any better qualified to do this than anyone else.

    The fundamental problem is that no one has been able to identify either one molecule or a set of molecules that are: (a) measurable in the body and (b) accurately associated with the progression of prostate cancer. Part of the reason that no one such molecule or set of molecules has been identified is that prostate cancer is very definitely not one singular disorder. Even within the most common type of prostate cancer, adenocarcinoma of the prostate, there is a wide spectrum of subtypes that come with greater of lesser degrees of aggressiveness, and we are only now beginning to understand how to assess the risks associated with these specific subtypes based on genomic databases.

    In addition, you are absolutely correct in thinking that a whole spectrum of other issues (general health, diet, exercise, and life style) can impact the progression of prostate cancer in individual patients. This means that even if we could find a specific molecule or set of molecules that could be used to measure risk for progression with greater accuracy, these underlying issues would affect prognosis as well, making the accuracy of prognosis in individual patients extremely difficult.

  4. Thanks for your returned email and the information you have provided.

    After reading the response the research I mentioned was about Thermo Fisher. I then remembered that I had first researched several months ago about the research of a new blood test called IsoPSA. I decided to pull out what I had copied about IsoPSA and I realized that these two subjects of research were very different.

    When I began to researched about IsoPSA, what was on my mind, I did not like having my biopsy with the 12 needle samples along with (layman terms) the insertion of a probe into the rectum. The information I had read was that if research proved to be complete and accepted that this IsoPSA could substantially reduce the need for the invasive biopsy such as I had back in Jan. 2017. I had talked to several men and they expressed about they were on “Active Wait & Watch and any changes in the regular PSA readings could create more biopsies. I had a close friend tell me he has had several of the invasive biopsies because “no cancer found” or negative results even with the PSA showing to be elevated.

    One thing that has helped me now is the explanation of reoccurrence and metastasis-free survival which was also in my mind since I had surgery in the removal of my prostate.

  5. Dear William:

    There has been and is extensive ongoing research into how best we can re-test men who are on active surveillance (what you refer to as “Active Watch & Wait”) in order to minimize the number of re-biopsies that might be necessary over time. It is well understood that frequent re-biopsies are not exactly a good idea (for all sorts of reasons). It is becoming apparent that regular multiparametric MRI scans can reduce the need for frequent re-biopsies, and other tests are also being explored.

    Also … almost everyone would prefer to be able to accurately diagnose prostate cancer without the need for transrectal or transurethral biopsies. However, at present this remains the only accurate way to be able to confirm the presence of prostate cancer in a man with localized disease. And an equally important goal for all concerned is not to be giving radical surgery or radiation therapy to men who do not need such treatment (because the risk for side effects of treatment in such men far outweighs any benefit in terms of extending survival or even avoiding metastatic disease).

  6. Thanks for the continued information which adds to my knowledge. I am not in the medical profession but I have found when people I know find out I had prostate cancer and had a complete radical prostatectomy, they will begin to ask questions. Many who also have this disease find out you really must do the research — just as I did back in January 2017. Having the ability to read blogs helps to explain some of the issues with this complicated disease, as the information comes from men who have dealt with or are just beginning just get involved in their own disease.

    I think that it is important that people think about donating to help research for fighting cancer. It takes many years to have success, and my wife and I currently have been donating to lung and lymphoma research as her brother died from lung cancer (Agent Orange) and her dad died from lymphoma. Her brother only survived for 18 monthsand he died at the age of 66 years. Her dad had just turned 81 and was in perfect health and he passed away in about maybe the same time as her brother. We are looking to change our plans to add donating to prostate cancer research. Both of us are in our 70s, and we are retired.

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