Predictors of risk for metastatic disease

Patients who develop metastatic, castration-resistant prostate cancer (CRPC) have historically had an estimated survival of 24 to 36 months from failure of hormone therapy, and although progress has been made in developing drugs for the treatment of CRPC, these drugs have, on average, only added a few months to the overall survival of men who cease to respond to hormonal or androgen deprivation therapy (ADT).

A new study by Abouassaly et al. set out to identify predictors of clinical disease progression in patients with prostate cancer who were already receiving ADT.

This study analyzed data on 4,003 men enrolled in the Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) database, all of whom had been treated with ADT after diagnosis but who had no evidence of metastases at initiation of treatment. The primary endpoint of the study was the development of bone metastasis.

The results of this study showed that:

  • The mean age of the men in the cohort was 70 years (but range from 39 to 94 years).
  • 191/4,003 patients (4.8 percent) progressed to metastatic disease at a median of 18 months from the initiation of ADT (but again, the range was from 1 month to 11.6 years).
  • Four factors were shown to be significantly associated with the development of metastatic disease after initiation of ADT:
    • Prostate cancer risk category at diagnosis
    • Percentage of biopsies positive >33 percent at diagnosis
    • Age ≤ 65 years at diagnosis
    • PSA velocity while on treatment with ADT

The authors concluded that, “Younger men with high-risk disease appear to have worse prognosis than older men with similar disease.” This would appear to make perfect sense, since younger men with high-risk disease have more time available to progress to metastatic disease and therefore a greater chance to do so. It may also be the case that the type of prostate cancer that is most common in younger men tends to be more aggressive by nature — but we do not have specific evidence for this possibility as yet.

Having said this, it should also be noted that the CaPSURE database contains data on a total of 13,740 prostate cancer patients, accumulated over the 13 years from 1995 to 2007. If only 191 of the 4,003 patients were treated with ADT prior to any evidence of metastatic prostate cancer, one is tempted to wonder just how many patients in the CaPSURE database EVER progressed to having visible evidence of metastatic disease. We already that about 3 percent of prostate cancer patients actually die of their disease. Do only about 5 percent of patients today actually progress to having metastatic disease at all?

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