THE "NEW" PROSTATE CANCER INFOLINK

According to an article to appear in the September issue of The Lancet Oncology, some patients with aggressive prostate cancer are more likely to die earlier from their disease if they carry a specific testosterone-related genetic abnormality.

Details about this new finding can be found in a media release issued by the Cleveland Clinic as well as in the actual paper by Hearn et al. Additional editorial comment on the paper (by Antonarakis) is also available on line, but only to subscribers to the journal.

The new finding was the result of work by a collaborative research team at the Cleveland Clinic and at the Mayo Clinic. The researchers suggest that a specific, inherited polymorphism known as 1245C (an inherited genetic mutation) in the HSD3B1 gene seems to make standard androgen deprivation therapy (ADT) for metastatic prostate cancer significantly less effective.

Basically Hearn et al. have shown that, in a primary study cohort of 118 men who had a radical prostatectomy as first-line treatment,

• Median progression-free survival diminished as a function of the number of variant alleles inherited:
  • 6.6 years in men with a “normal” homozygous wild-type genotype
  • 4.1 years in men with a heterozygous variant genotype (i.e., just one copy of the mutant HSD3B1 gene)
  • 2.5 years in men with a homozygous variant genotype (i.e., two copies of the mutant HSD3B1 gene).
• By comparison to men with the homozygous wild-type genotype,
  • Inheritance of two copies of the variant allele was predictive of decreased progression-free survival (hazard ratio [HR] = 2.4).
  • Inheritance of one copy of the variant allele predicted a slightly longer but still decreased propgression-free survival (HR = 1.7).
• Similar findings were apparent for distant metastasis-free survival and overall survival.
• The effect of the HSD3B1 genotype was independently confirmed in the 137 patients in a post-prostatectomy validation cohort, and 188 patients in a metastatic validation cohort.

The authors state that

Inheritance of the HSD3B1 (1245C) allele that enhances dihydrotestosterone synthesis is associated with prostate cancer resistance to ADT. HSD3B1 could therefore potentially be a powerful genetic biomarker capable of distinguishing men who are [inherently less likely to respond well to ADT].

According to the media release:

The researchers anticipate that the findings will lead to a simple blood test to detect the presence of the polymorphism, personalizing cancer treatment and indicating which patients may need more aggressive treatment.

However, it may take a while to develop this blood test and to make it widely available to prostate cancer patients … and then there will be the question of who should be given this test, and how should we most appropriately treat patients who have a positive response to the test.

Filed under: Diagnosis, Living with Prostate Cancer, Management, Risk, Treatment | Tagged: ADT, aggressive, gene, HSD3BI, LESS, responsive |