Aggressive, neoadjuvant androgen ablation prior to surgery in higher risk prostate cancer patients

The development of drugs like abiraterone acetate and enzalutamide has stimulated new research into the use of such agents early on, in combination with first-line therapy, to see if it can affect the outcomes for men with high-risk and unfavorable intermediate-risk prostate cancer.

In a recent paper by Montgomery et al., clinical researchers have reported data from a study in which 52 patients with either intermediate- or high-risk forms of prostate cancer were assigned to receive one or other of two types of neoadjuvant therapy prior to treatment by radical prostatectomy:

  • The 25 evaluable patients in Group A were treated with neoadjuvant enzalutamide alone for 6 months prior to surgery.
  • The 23 evaluable patients in Group B were treated with neoadjuvant enzalutamide + an LHRH agonist + dutasteride for 6 months prior to surgery.

The objective was to see whether such treatments had significant but differing impact on a variety of measurable outcomes at time of surgery, including:

  • The complete absence of any cancer in the prostate on post-surgical pathology, referred to as a pathologic complete response or pCR (compared to historical control data of 5 percent based on older studies in which neoadjuvant flutamide + an LHRH agonist had been given prior to surgery)
  • “Minimal residual disease” in the prostate (MRD), which meant residual cancer in the prostate with a diameter of ≤ 3 mm
  • “Residual cancer burden” in the prostate (RCD), i.e., the total volume of cancer found in the prostate post-surgery
  • PSA level
  • Concentrations of androgens like dihydrotestosterone in the prostate tissue and in the patients’ bloodstream

Here are the basic study findings:

  • Among the patients in Group A
    • 0/25 patients achieved either a pCR or MRD.
    • Average (median) RCB = 0.41 cm3
  • Among the patients in Group B
    • 1/23 patients (4.3 percent) achieved a pCR.
    • 3/23 patients (13.0 percent) achieved MRD.
    • Average (median) RCB = 0.06 cm3
  • Prostate tissue levels of testosterone and dihydrotestosterone correlated with the levels of RCB.
  • There were no drug discontinuations as a consequence of adverse events to the drugs used in the study.

Montgomery et al. conclude that the combination of enzalutamide + dutasteride + an LHRH agonist produced rates of pCR and MRD that were comparable to historical controls with flutamide + an LHRH agonist.

The implication is that this type of aggressive neoadjuvant therapy prior to surgery is unable to eliminate risk for disease progression in  men with intermediate- and high-risk forms of prostate cancer, which was also found to be the case years ago when this was tried with the combination of an antiandrogen (flutamide) and an LRHR agonist.

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