Non-rising PSA but radiographic progression in men on treatment with enzalutamide

A recent presentation at the European Society of Medical Oncology (ESMO) annual meeting in Copenhagen, Denmark, has suggested that some men on treatment with enzalutamide (Xtandi) may have radiographic progression of their cancer even though there is no increase in their PSA levels. The details of this presentation by Bryce et al. have just been reported in Renal & Urology News.

Dr. Bryce and colleagues at the Mayo Clinic in Scottsdale, AZ, conducted a post-hoc analysis of data from the PREVAIL trial, in which 1,717 men with minimally symptomatic or asymptomatic,  chemotherapy-naive, metastatic, castration-resistant prostate cancer (mCRPC) were randomized to treatment with either enzalutamide or a placebo. Specifically, they looked at data from 265 patients who experienced radiographic disease progression while on treatment with enzalutamide. They found that:

  • 200/265 patients (75.5 percent) had rising PSA levels.
  • 65/265 patients (24.5 percent) had relaively stable PSA levels.

In other words, about a quarter of all the men progressing while on treatment with enzalutamide showed no sign of such progression based only on their PSA level.

This finding has clear implications for the monitoring of men with mCRPC who are receiving treatment with enzalutamide. It is clearly not sufficient to just monitor PSA levels in such patients — although many clinicians may have only been using this form of monitoring. These patients should also be receiving regular bone and CT scans to monitor for signs of radiographic progression.

Bryce et al. also reported that:

  • Patient characteristics at study entry were similar in the patient groups with rising and non-rising PSA levels.
  • Average (median) progression-free survival times were
    • 11.1 months among the patients with rising PSA levels
    • 8.3 months among the patients with non-rising PSA levels
  • Patients in the rising and non-rising groups had similar overall survival rates.
  • At the time of progression on enzalutamide,
    • 95/265 patients (35.8 percent) had bone-only progression.
    • 164/265 patients (61.9 percent) had soft-tissue-only progression
    • 6/265 patients (2.3 percent) had both bone and soft-tissue progression.
  • Among 77 patients with bone-only disease at study entry, 31 (40.3 percent) also experienced development of soft-tissue disease at progression.

Renal & Urology News quotes Dr. Bryce as stating that:

We feel that these results have practical implications for clinical practice, as well as being hypothesis generating from a research perspective. Whether the phenomenon of radiographic progression with non-rising PSA represents a form of tumor evolution requiring a distinct treatment paradigm is a question for future studies.

The original results of the PREVAIL trial were reported at the ASCO Genitourinary Cancers Symposium in 2014, and enzalutamide was approved later that year for the treatment of men with asymptomatic or minimally symptomatic,  chemotherapy-naive, mCRPC.

One Response

  1. This brief report certainly leaves me longing for more information. Were metastases that developed with non-rising PSA histologically distinct? Was there an association between non-rising PSA and the high rate of new soft-tissue metastases in this group? Neither the abstract nor the news article answers these questions.

    At least two speakers at the recent PCRI Conference in Los Angeles expressed concern about an apparent big jump in the incidence of neuroendocrine prostate cancer with use of Xtandi/Zytiga. I have to wonder if there is a tie-in here.

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