Phase III Results Support Novel Focal Therapy for Low-Risk Prostate Cancer

Mark Emberton, MD

Padeliporfin vascular-targeted photodynamic therapy, a novel tissue-preserving treatment, may offer men with low-risk prostate cancer a safe and effective alternative to either active surveillance or radical therapy, according to the results of a phase III trial published in The Lancet Oncology.

Among treatment-naïve patients with low-risk, localized prostate cancer, disease progression at 24 months was 28% among patients receiving padeliporfin vascular-targeted photodynamic therapy versus 58% in those receiving active surveillance (HR, 0.34; 95% CI, 0.24-0.46; P <.0001). The median time to progression was 28.3 months (95% CI, 26.0-30.6) versus 14.1 months (95% CI, 12.9-23.8; P <.0001), respectively.

“Our study has shown that partial-gland ablation by vascular-targeted photodynamic therapy influences the course of prostate cancer in the short-to-medium term,” study author Mark Emberton, MD, UCL Faculty of Medical Sciences, London, and colleagues wrote.

Emberton et al randomly assigned 206 patients with low-risk, localized prostate cancer to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Padeliporfin was administered at 4 mg/kg intravenously over 10 minutes in the vascular-targeted photodynamic group, optical fibers were then inserted into the prostate to cover the intended treatment zone and were activated by laser light 753 nm with a fixed power of 150 mW/cm for 22 minutes and 15 seconds.

Active surveillance consisted of a protocol-directed biopsy at 12-month intervals and PSA measurement, as well as a digital rectal examination at intervals of 3 months.

The coprimary efficacy endpoints were treatment failure and absence of definite cancer. Secondary objectives were total number of positive patient core samples, proportion of patients that underwent radical therapy, frequency of severe prostate cancer-related events and frequency of adverse events (AEs).

In the vascular-targeted photodynamic therapy group, 49% of patients had negative prostate biopsy results at 24 months, compared with 14% of patients in the active surveillance group (adjusted risk ratio, 3.67; 95% CI, 2.53-5.33; P <.0001).

“The proportion of men with transition from a cancer status to a cancer-free status was increased in the vascular-targeted photodynamic therapy group compared with the active surveillance group…The proportion of men who progressed from a histologically defined

low-risk status to a high risk status was diminished. As a result, fewer men in the vascular-targeted photodynamic therapy group chose to undergo radical therapy during the study period. Moreover, these benefits were achieved safely, efficiently, and without compromising genitourinary function when assessed at 12 and 24 months after the procedure,” Emberton et al wrote.

Both frequency and severity of AEs were higher in the vascular-targeted photodynamic therapy group. The AEs were usually mild or moderate in severity and occurred during the procedure or in the days following. This was thought to be related to the transcutaneous needle placement or the swelling of the prostate following the procedure.

The most common grade 3/4 AEs in the padeliporfin arm were prostatitis (2% vs 1% in the active surveillance arm), acute urinary retention (2% vs 1%), and erectile dysfunction (1% in each arm). Urinary retention was the most common serious AE in the vascular-targeted photodynamic group (n = 15; all resolved within 2 months). The most serious AE in the active surveillance group was myocardial infarction (n = 3).

According to the authors, this is the first known trial to evaluate the efficacy of vascular-targeted photodynamic therapy in comparison to active surveillance. Although it showed safe and tolerable results, the authors stressed that the methodological considerations that were inherent in its design and conduct must be considered.

The authors noted that more research must be done, as there are unanswered questions of the long-term effect of tissue-preserving treatment on control rates of prostate cancer, as well as tissue that lies beyond the treatment zone. A long-term follow-up has been initiated within the patients who participated in this study.

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, randomised controlled trial [published online December 19, 2016]. Lancet Oncol. doi: 10.1016/S1470-2045(16)30661-1.