PCaI patient conferences past and future

As a small not-for profit with limited funding, it can take Prostate Cancer International (PCaI) a little longer to do some things than we would like. However, … READ MORE …

Imaging studies for men with recurrent prostate cancer

We had previously reported on a presentation by Calais et al. earlier this year. … READ MORE …

PARP inhibitor has positive outcomes in Phase III trial in selected men with mCRPC

According to a media release issued jointly yesterday by AstraZeneca and Merck, treatment with the PARP inhibitor olaparib (Lynparza) has demonstrated “positive results from the Phase III PROfound trial … in [a subset of] men with metastatic castration-resistant prostate cancer (mCRPC).” … READ MORE …

Are “manograms” a viable option in prostate cancer screening and risk assessment?

For several years, Dr. Jelle Barentz in the Netherlands has been a prominent advocate for the idea that we might be able to use imaging methodologies (prostate “manograms”, like breast mammograms for women) to screen for risk of prostate cancer — either along with or instead of PSA testing. … READ MORE …

One large “zap” for painful bone metastases is enough

In 2011, the American Society for Radiation Oncology (ASTRO) issued a consensus statement as part of its “Choosing Wisely” campaign that found that 30 Gy in 10 fractions (treatments), 20 Gy in 5 fractions, and 8 Gy in 1 fraction all gave equivalent pain relief. … READ MORE …

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.

FDA approves darolutamide for treatment of nmCRPC

Bayer’s US pharmaceutical division has announced that the US Food and Drug Administration (FDA) has approved darolutamide — their formerly investigational androgen receptor inhibitor — for the treatment of men with non-metastatic, castration-resistant prostate cancer (nmCRPC). … READ MORE …