Intense androgen deprivation therapy tied to positive pathologic responses in prostate cancer

Intense neoadjuvant hormone therapy in high-risk localized prostate cancer is associated with favourable pathologic responses (tumour <5 mm) in nearly one of five patients, a phase II study has shown. In addition, pathologic responses are comparable between treatment groups.

The investigators included patients with a Gleason score ≥4+3=7, prostate specific antigen >20 ng/mL or T3 disease, and lymph nodes <20 mm. The first part of the study randomized participants 1:1 to apalutamide, abiraterone acetate, prednisone, and leuprolide (AAPL) or abiraterone, prednisone, leuprolide (APL) for six cycles (1 cycle=28 days) followed by radical prostatectomy. Surgical specimens underwent central review.

The rate of pathologic response or minimum residual disease (minimum residual disease, tumour ≤5 mm) was the primary outcome, and secondary ones included prostate-specific antigen response, positive margin rate, and safety. Finally, the investigators explored the magnetic resonance imaging (MRI) and tissue biomarkers of pathologic outcomes.

One hundred eighteen patients (median age 61 years) from four sites were enrolled in this study, of whom 94 percent had high-risk localized prostate cancer. The combined pathologic complete response or minimum residual disease rate was 22 percent and 20 percent in the AAPL and APL arms, respectively (difference, 1.5 percent, 95 percent confidence interval, –11 percent to 14 percent; p=0.4). There were no new safety signals noted.

Low concordance and correlation were noted between post-therapy MRI- and pathologically assessed tumour volume. Moreover, PTEN-loss, ERG positivity, and presence of intraductal carcinoma correlated with extensive residual tumour.

The second part of this phase II trial will examine the effect of adjuvant hormone therapy on biochemical recurrence, according to the investigators.