Genomic testing and management of low-/intermediate-risk prostate cancer

A new paper has provided us with data on the ability of genomic testing to predict adverse pathology in a man undergoing a multiparametric MRI (mpMRI) and subsequent biopsy for risk of prostate cancer.

This new paper by Salmasi et al. looked at the ability of mpMRI and biopsy-based molecular tests — in this case the Oncotype DX® Genomic Prostate Score™ (GPS) assay — to improve risk stratification in men with clinically localized prostate cancer.

Specifically, Salmasi et al. studied data from a cohort of patients diagnosed with very low-, low-, or intermediate-risk prostate cancer who were all given an mpMRI scan followed by a simultaneous mpMRI fusion-targeted and a systematic prostate biopsy, a GPS assay, and who were then treated by radical prostatectomy within the next 6 months.

In all patients, the GPS testing was performed on the biopsy tissue with the highest Gleason score. The primary study outcome was adverse pathology after surgery (i.e., a Gleason score of 4 + 3 or higher and/or a pathological stage pT3+ based on the post-surgical pathology examination of the prostate).

Here is the brief summary of the results of their study:

  • 134 patients were eligible for primary analysis.
  • Based on univariable analysis, the following were specific predictors of adverse pathology:
    • UCLA MRI score (similar to but not quite the same as the PI-RADs v2 score)
    • GPS assay result
    • Gleason score on biopsy
  • Based on subsequent multivariable analysis
    • GPS values remained a significant predictor of adverse pathology (OR for GPS per 20 units  = 3.28).
    • A wide and overlapping distribution of GPS results were seen across PI-RADs v2 scores.

The authors conclude that

The GPS result is an independent predictor of [adverse pathology] in patients who were diagnosed with very low/low/intermediate-risk [prostate cancer] in the setting of mpMRI-fusion prostate biopsy. This assay can be useful as an independent or adjunct technology to mpMRI for individualizing risk stratification in low and intermediate risk [prostate cancer].

Now we should be clear that this study was funded by the developers of the Oncotype DX GPS assay and that some of the authors of the paper work for that company. On the other hand, the senior and corresponding author of this paper (Dr. Robert Reiter of the University of California, Los Angeles) is a physician  with an extremely high reputation as a researcher who would be highly unlikely to want to be associated with any research that wasn’t of what he considered to be an appropriate and sufficient degree of independence and accuracy.

It is becoming increasingly clear that genomic testing with the Oncotype DX GPS assay and similar genomic assays can be used to help to predict outcomes of first-line treatment as well as in predicting which patients may be good candidates for active surveillance. What we do not know yet, however, if whether any one of these commercial tests is significantly better than any other.

8 Responses

  1. Thanks and clarification needed

    Thank you for featuring this promising paper!

    That odds ratio is impressive, but could you clarify the meaning of “GPS per 20 units” in the sentence “GPS values remained a significant predictor of adverse pathology (OR for GPS per 20 units = 3.28)”? That is not covered in the abstract, and the complete paper is not readily available. (I found their web site helpful, but it did not cover “per 20 units”. I’m thinking this means a GPS score of 20; if so, my impression is that such a score would be consistent with “low-risk” disease as compared with “very-low risk” or “favorable-intermediate risk” disease. I have called the company and may get an answer back today or tomorrow.

  2. Jim:

    Then when you get the answer I suggest you let readers know. I have no more idea than you do. I have also only seen the abstract.

  3. Are there any data regarding GPS for reoccurring prostate cancer with Gleason score “6”? Is watchful waiting a reasonable option for the second time around with low-risk cancer? First time, I had Gleason 6s and 7s. Had HIFU 7 years ago and now six-needle biopsy only showed Gleason 6s in three samples (6%, 5%, and 35%).

    My entire prostate and seminal vesicles were ablated by HIFU. My PSA after HIFU went to 0.20 — now it is 1.39 ng/ml.

  4. Dear Frank:

    This is something you really need to discuss with your doctors. There are no “standard practices” for the management of a slowly rising PSA with a recurrent form of prostate cancer like this that is Gleason 6 only. However, there are a number of issues that would be relevant to the appropriate decision:

    — Your age is an issue; the younger you are, the wiser it may be to consider “doing something”.
    — Your recent PSA doubling time is an issue; you can calculate this by using your most recent three PSA levels and the exact dates on which blood was drawn for those tests by using this calculator on the Memorial Sloan-Kettering Cancer Center’s web site. The longer the PSA doubling time the less urgency there may be to do anything.
    — You could ask your doctors about having an MRI scan followed by a repeat but MRI/TRUS fusion targeted biopsy to make sure you really do only have the three areas of risk that are all Gleason 6. You’d have to wait a while before this could be done, however, so that any effects of the most recent biopsy had resolved and a high-quality MRI scan could be taken.
    — You could ask you doctors about having the tissue samples from the most recent biopsy sent for genomic testing to see if that forms of testing confirms that you are low risk.

    In the end, however, you are the person who is going to have to determine what works best for you and to some extent that may depend on what forms of additional test are available to you and covered by whatever form of health insurance coverage you have.

    If you were to need to have treatment, it is likely that some form of radiation therapy would be the most appropriate option.

  5. Thank you for your prompt response! I have been reading the site’s info for 7 years and it never occurred to me that one day I would have a contribution. I cannot believe that I left out my age (67) as that does significantly factor into the decision matrix. I also forgot to mention that my biopsies have been sent out for DNA analysis. I do not know what specific test at this time. I have two urologists — both recommended retreatment with HIFU — schedule of such procedure to be determined by DNA results. Obviously, if the test shows fast-growing cancer then HIFU will be scheduled ASAP. Given my age, I will have retreatment to insure that I do not encounter a much larger issue in later life.

    For the record, I had whole gland and seminal vesicle HIFU ablation, 7 years ago. The procedure was easy to recover from and I had no negative issues at all. My potency and continence were not compromised. Unfortunately, I was told by my HIFU doctor that I had only a 2% chance of re-occurring cancer. He has performed over 3,000 first-line procedures and over 250 retreats.

  6. I have not yet heard back from the company on the meaning of “per 20 units” in my 3/16 1:26 pm comment. I’m going to try again via a different route.

  7. Frank,

    You might want to get an opinion from a radiation oncologist or a urologist who would remove the prostate. While HIFU theoretically could work, you would be using the same technology that failed the first time to achieve success on the second try. The US FDA has not approved HIFU for treatment of prostate cancer. (I was at one of the hearings, making a statement against HIFU because of poor evidence of success, essentially.) Several trials around the world have not had long-term success with HIFU, with results around the 4- or 5-year point looking non-competitive with surgery and radiation. Dr. Mark Emberton, an eminent HIFU pioneer from the UK, gave up on whole-gland HIFU about 9 years ago.

  8. Dear Jim (and Frank):

    Surgical removal of the prostate after a man has been given first-line HIFU comes with the same spectrum of complications and side effects as are seen in most men who have surgery after first-line radiation therapy. I don’t think this is a particularly good idea for the majority of former HIFU patients.

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