Cancer tissue subtypes and prostate cancer prognosis

A newly published article in JAMA Oncology is asking whether there is a completely different way to look at how to classify prostate cancer tissue types and correlate such classification to responses to treatment using certainly classes of drugs.

This process is known as “molecular subtyping” and in the current study the research team classified the various patients’ tissue types into one of three subgroups:

  • Luminal A
  • Luminal B
  • Basal

which are analagous to three of the five molecular subtypes used in the molecular subtyping of breast cancer tissues (see here).

The research team (Zhao et al.) actually carried out two related studies by using retrospectively collected tissues from 1,567 patients who had been foll,owed for a median of 10 years from initial diagnosis and treatment, and prospectively collected tissues from another 2,215 prostate cancer patients.

Here is what they found:

  • For all 3,782 samples, the patients’ prostate cancer could be consistently segregated as follows:
    • Retrospective samples
      • Luminal A subtype: 538/1,567 (34.3 percent)
      • Luminal B subtype: 447/1,567 (28.5 percent)
      • Basal subtype: 582/1,567 (37.1 percent)
    • Prospective samples
      • Luminal subtype A: 737/2,215 (33.3 percent)
      • Luminal subtype B: 723/2,215 (32.6 percent)
      • Basal subtype: 755/2,215 (34.1 percent)
  • There was a clear connection between the different subtypes and prostate cancer biology:
    • Known luminal lineage markers were enriched in the luminal-like cancers.
    • The basal lineage CD49f signature was enriched in the basal-like cancers.
  • At 10 years of follow-up among the retrospective cohort of patients,
    • Patients with the luminal A subtype prostate cancers had
      • A 10-year biochemical recurrence-free survival [bRFS] of 41 percent
      • A distant metastasis-free survival [DMFS] of 73 percent
      • A prostate cancer-specific survival [PCSS] of 89 percent
      • An overall survival [OS] of 82 percent
    • Patients with the luminal B subtype prostate cancers had
      • A bRFS of 29 percent
      • A DMFS of 53 percent
      • A PCSS of 78 percent
      • An OS of 69 percent
    • Patients with the basal subtype prostate cancers had
      • A bRFS of 39 percent
      • A DMFS of 73 percent
      • A PCSS of 86 percent
      • An OS of 80 percent
  • Both luminal-like subtypes were associated with increased androgen receptor expression and signaling.
  • Only luminal B prostate cancers were significantly associated with postoperative response to androgen deprivation therapy (ADT).
  • Molecular subtyping by luminal and basal status in prostate cancer is prognostic for clinical outcomes and may be associated with response to postoperative ADT.

The authors conclude that

  • Luminal- and basal-like prostate cancers demonstrate divergent clinical behavior, and patients with luminal B tumors respond better to postoperative ADT than do patients with non-luminal B tumors. These findings contribute novel insight into prostate cancer biology, providing a potential clinical tool to personalize ADT treatment for prostate cancer by predicting which men may benefit from ADT after surgery.

It may take a while to work out just how important this all is in the practical treatment of men with higher-risk and progressive forms of prostate cancer, but in an invited commentary on this article by Abida and Scher, in the same issue of JAMA Oncology, these two commentators clearly seem to think that this set of findings of considerable potential import.

Findings like this may also have considerable relevance to other research, like that being initiated by van Allen and colleagues at The Broad Institute (the so-called Prostate Cancer Project that we discussed just the other day).

One Response

  1. The main point here looks quite interesting, but with a puzzling tangent.

    This tangent does not bear on the main point, but I was puzzled by the relatively low overall survival figures for the three categories at the 10-year point versus the figure published by the American Cancer Society for relative 10-year survival for US men (based on SEER data): 94% relative to their age-matched peers. The overall survival figures for the three groups above are:

    — Luminal A: 82%;
    — Luminal B: 69%; and
    — Basal: 80%.

    Perhaps the 10-year survival clock started at the date of RP instead of the date of diagnosis. Also, these men were all RP patients, and perhaps inclusion of men on active surveillance in the ACS figure boosts the average survival percentage a bit. On the other hand, this group would likely include few or none of the men diagnosed with distant metastases, men who have a median survival of 29% at 5 years per the latest ACS figures, and this fact would boost the average survival in a group such as the current study that effectively excluded such men. Perhaps the study group was treated many years ago where overall relative survival in the US was not as good.

    Any thoughts regarding this tangent?

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