THE "NEW" PROSTATE CANCER INFOLINK

• 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.