AUA 2018: Four-year Follow-up of a Phase-3 Prospective Randomized Trial of Vascular-Targeted Phototherapy Versus Active Surveillance for Low-Risk Prostate Cancer

San Francisco, CA (UroToday.com) Dr. Inderbir Gill and colleagues presented four-year follow-up results from a phase III trial assessing vascular-targeted phototherapy (VTP) vs active surveillance for men with low-risk prostate cancer. Because of the well-known side effect profile of radical treatment for localized prostate cancer, there is an ever-present desire to be able to treat men with minimally invasive techniques without compromising the opportunity for cure. Furthermore, active surveillance fails 50% of the time and within 5-10 years 70% of patients will have radical therapy, thus lending clinical equipoise for pursuing other minimally invasive modalities according to Dr. Gill. Partial gland ablation for prostate cancer is one such modality. While safety has been reasonably established, there is limited, if any, Level I evidence of efficacy.

Dr. Gill’s group recently published their two-year follow-up data1 in 2017, which led the European Medicines Agency’s Committee for Medicinal Products for Human Use to approve (September 2017) VTP for unilateral low, but not very low, risk PCa. VTP’s mechanism of action is to generate reactive oxygen species and reactive nitrogen species at near-infrared illumination (753 nm), which causes instantaneous complete vascular occlusion within the tumor micro-vasculature. The objective of this presentation was to present four-year outcomes of this phase III trial. 

This prospective phase III trial (CLIN1001 PCM301) randomized (1:1) 413 men with low-risk prostate cancer to partial gland ablation with VTP (n=207) vs standard active surveillance (n=206) at 47 sites across Europe. Inclusion criteria included D’Amico low-risk prostate cancer (either 1 core 3-5 mm or 2-3 cores <= 5mm per core) and prostate volume 25-70cc. Key exclusion criteria included previous prostate cancer treatment, previous BPH treatment or life-expectancy <10 years. Baseline demographics and clinicopathologic variables were comparable between the two groups. The 2-year oncologic results [1] demonstrated that VTP increased the rate of negative biopsy (14% vs 49%), and decreased conversion to radical treatment (32% vs 6%). The four-year outcomes evaluated rates of crossover to radical therapy, and metastasis-free, cancer-specific and overall survival rates. Post-hoc analysis evaluated overall progression and spatial distribution of post-VTP biopsy findings.

There was 3- and 4-year follow-up available for 69% and 64% of men, respectively. VTP men had lower rates of crossover to radical therapy at 2 years (7% vs 33%), 3 years (14% vs 44%) and 4 years (24% vs 53%) (HR 0.31, 95%CI 0.21-0.45), yielding an absolute risk reduction for radical therapy at 2, 3 and 4 years in the VTP arm of 26%, 30% and 29%, respectively, compared to AS. The type of radical therapy was most commonly radical prostatectomy (80%) and external beam radiotherapy (14%). The four-year reasons for conversion to radical therapy are as follows:

The 4-year metastasis-free (99% vs 99%), cancer-specific (100% vs 100%) and overall survival (98% vs 99%) rates were, not unsurprisingly, similar between the two cohorts. After VTP treatment, negative biopsy rates were similar in the apex (72%), mid-gland (78%), and base (74%), indicating VTP’s ability to consistently ablate various spatial locations throughout the prostate.
As Dr. Gill notes, whole gland therapy is over treatment of localized prostate cancer and brings significant long-term toxicity. VTP is the only level 1 therapy that reduces over treatment of low risk prostate cancer. Dr. Gill feels that this trial changes the paradigm for treatment of low-risk prostate cancer, as follows:

Dr. Gill concluded by highlighting that VTP decreased conversion rate to radical therapy that lowers treatment related morbidity and improves cancer control compared active surveillance.

Reference:

1. Azzouzi AR, Vincendeau S, Barret E, et al. Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): An open-label, phase 3, randomized controlled trial. Lancet Oncol 2017;18(2):181-191.

Presented by: Inderbir Gill, USC Urology Institute, Los Angeles, CA

Co-Authors: Mark Emberton, London, United Kingdom, Abdel Azzouzi, Angers, France, Jonathan Coleman, Emmanuel Coeytaux, New York, NY, Avigdor Scherz, Rehovot, Israel, Peter Scardino, New York, NY

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre @zklaassen_md at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA
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