EAU 2017: Intra-prostatic injection of PRX302 to focally ablate clinically significant prostate cancer: An open label, phase 2a study

London, England (UroToday.com) Novel techniques and therapies continue to be developed within the field of focal therapy. While early results seem to be promising, long-term outcomes result are still pending. However, in the meantime, newer agents and slight modifications continue to be developed to optimize this technology.

The authors of this abstract describe their experience with PRX302, a genetically modified pore-forming protein (aerolysin) activated intraprostatically only by enzymatically active PSA – thereby limiting activity to the prostate alone. This abstract describes their Phase II trial results – as such, the focus was toxicity, side effects and potential efficacy.

Eighteen patients with clinically significant localized cancer defined as either Gleason ≤ 4+3 with a maximum cancer core length (MCCL) ≤ 10mm, or Gleason 3+3 with MCCL ≥ 4mm. All patients had a single pre-identified lesion injected transperineally using MRI-ultrasound elastic image-fusion software (SmartTarget®), under general anaesthetic, with up to 5mL of a standard dosing solution of 20ug/mL PRX302. Follow-up occurred at 2 days (teleconsult) and at 2, 6, 12, 24 and 26 weeks. A mpMRI-targeted transperineal biopsy of the treated area was carried out at 24 weeks (6 months).

Median age and PSA were 66.50 years (IQR 13.00) and 6.25ng/ml (IQR 2.45), consistent with localized disease. Of the eighteen patients, 14 (78%) had Gleason 7 cancer with median lesion size of 0.3 cm (IQR 0.2-0.5), so all the lesions were quite small. No patients were lost to follow-up; all patients completed the study.

No serious adverse events were noted through the study. Summary of complications:

chart 9

In terms of efficacy and oncologic outcome, the follow-up was short. Biopsy data at 24 weeks following treatment showed that only 2 men (11%) had complete tumour ablation with no histological evidence of any cancer at 6 months. Seven (39%) had partial ablation defined as reductions in MCCL or Gleason grade; 9 men (50%) had no histological response and in some cases experienced an increase in MCCL or upgrading. Urinary and sexual function was preserved.

From an outcomes standpoint, I find these results to be underwhelming. While safe for the patient, a 50% insufficient treatment rate (with 39% having reduction but not resolution) is concerning. The authors felt the same way, and are considering dose adjustment and optimizing tumor delivery (as tissue saturation is required, they are considering continuous slow infusion).

Speaker: Y. Shanmugabavan

Co-Author(s): Bass E., Hulme A., Freeman A., Brew-Graves C., Potyka I., Ramachandran N., Emberton M., Ahmed H.U.

1. University College London, Division of Surgery and Interventional Sciences, London, United Kingdom
2. Sophiris, Sophiris Bio Corporation, California, United States of America
3. University College London Hospital, Dept. of Histopathology, London, United Kingdom
4. University College London Hospital, Dept. of Radiology, London, United Kingdom

Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto
Twitter: @tchandra_uromd

at the #EAU17 - March 24-28, 2017- London, England