Precision medicine and primary Gleason pattern 5 prostate cancer

Patients who are initially diagnosed with primary Gleason pattern 5 localized prostate cancer (i.e., having Gleason scores of 5 + 5 = 10 and 5 + 4 = 9) are well understood to have very high-risk disease.

A group of researchers at Johns Hopkins (see Velho et al.) have recently published data on the molecular characterization of a consecutive set of 60 such patients, all of whom underwent a radical prostatectomy as first-line therapy for their cancer between 2005 and 2015.

Now this was a retrospective analysis of the available data, and so we need to be cautious about how much to “read into” these data, but here are some of their key findings:

  • 49/60 patients had somatic sequencing data (i.e., genetic sequencing data on their actual tumor cells) and clinical follow-up.
  • Of these 49 patients,
    • 17/49 (34 percent) had DNA repair gene mutations, including
      • 11/49 (22 percent) with homologous recombination mutations (of which 9 turned out to also be germline mutations)
      • 6/49 (12 percent) with mismatch repair gene alterations
  • 16/49 (33 percent) of patients had TP53 mutations.
  • 29/57 patients (51 percent) had PTEN loss.
  • 29/60 patients (43 percent) went on to develop metastasis, with a time to castration resistance of 12 months.
  • On multivariable analysis of clinicopathologic variables, only two such variables were associated with risk for metastasis
    • Ductal/intraductal histology (hazard ratio [HR] = 4.43; P = 0.002)
    • Seminal vesicle invasion (HR = 5.14; P = 0.002)
  • Among genomic alterations, only TP53 mutation and PTEN loss were associated with metastasis on univariable analysis, and neither remained significant in multivariable analyses.

The authors are very clear that, at best, “These data are retrospective and hypothesis generating.” They go on to conlude that

Potentially actionable homologous recombination and mismatch repair alterations are observed in a significant proportion of patients with very high-risk [prostate cancer] at the time of radical prostatectomy. These findings could inform the design of prospective trials in this patient population.

The important thing that this study shows us is that it is becoming a great deal easier to describe and identify very specific subsets of prostate cancer patients based on genetic/genomic data along with older, “classical” data such as PSA levels, Gleason scores, clinical and pathological stages of disease, etc. As we become better at identifying these very specific subsets of patient and applying the evolving forms of treatment that are now available, it is reasonable to believe that we will also become better at managing and treating many of the patients whose disease, historically, was aggressive and difficult to treat well.

MRI-guided biopsy in the diagnosis of prostate cancer (again)

The results of the so-called PRECISION trial were just published in the New England Journal of Medicine this morning. … READ MORE …

How many men are really benefiting from genome-targeted prostate cancer treatment?

The answer to that question, at present, is that we don’t know — but it’s probably very few indeed compared to all the men who have progressive forms of prostate cancer. … READ MORE …

Experts create guidelines for screening prostate cancer patients for inherited cancer risk genes

Knowing whether you carry inherited cancer risk genes can help you to make the best decisions for your treatment and for your family. … READ MORE …

How close are we really to “precision medicine” for cancer care?

A newly published paper in the journal JCO Precision Oncology confirms what many of us may have suspected — that the practical application of somatic tissue testing to clinical decision-making was low prior to 2015 . … READ MORE …

CureTalk on genomic testing and precision medicine

For interested readers, there will be a CureTalk this evening on precision medicine and the role of genetic/genomic testing in the selection of appropriate forms of treatment. It will not be prostate cancer-specific, but its role in prostate cancer will be addressed. … READ MORE …

Of moonshots, precision medicine, and progress in the management of cancer

As your sitemaster, let me be very clear about a couple of my most basic beliefs about prostate cancer and prostate cancer research. I want to do this because of all the recent media discussion about Vice President Byden’s “Moonshot” and the possible wonders of precision medicine. … READ MORE …