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.

Computer modeling, genomics, and prostate cancer prognosis

A newly published paper on the development of prostate cancer in patients of ≤ 55 years of age claims to have shown that

Using a newly-developed computer model, it is now possible to predict the course of the disease in individual patients. … 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 …

Commercially available liquid biopsy data may be misleading

A newly published research letter in JAMA Oncology is entitled “Patient-paired sample congruence between 2 commercial liquid biopsy tests”. The two tests are both said — by the companies that market them — to have high clinical sensitivity and specificity in the identification of specific genetic markers associated with high-risk forms of prostate cancer. … READ MORE …

Alternative medicine in the treatment of cancer (prostate cancer included)

There are very few good and thorough clinical studies on the use and the long-term effectiveness or efficacy of alternative forms of medicine in the treatment of cancer (let alone the treatment of prostate cancer specifically). … 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 …

More in the new Everyday Urology-Oncology Insights

Last week we had let readers know about a new, straightforward, on-line review journal called Everyday Urology-Oncology Insights. … READ MORE …