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Objectives To evaluate the optimal treatment conditions and effects of TOOKAD® Soluble vascular-targeted photodynamic (VTP) therapy in patients with localised prostate cancer. To evaluate the safety and quality of life after TOOKAD® Soluble VTP treatment in patients with localised prostate cancer. Patients and Methods Men (aged >18 years) diagnosed with localised prostate cancer, who were suitable for active surveillance, were invited to take part in the study. Patients who had received prior or current treatment for their cancer were excluded. There were two parts to the study: in part one, patients were assigned to one of two treatment groups based on the size of their prostates (patients with prostate size 80% of patients treated with this regimen having a negative biopsy at 6 months. Overall, the treatment was well tolerated and exhibited early signs of efficacy for minimally invasive focal treatment of localised prostate cancer.

To evaluate the optimal treatment conditions and effects of TOOKAD(®) Soluble vascular-targeted photodynamic (VTP) therapy in patients with localised prostate cancer. To evaluate the safety and quality of life after TOOKAD(®) Soluble VTP treatment in patients with localised prostate cancer.Men (aged18 years) diagnosed with localised prostate cancer, who were suitable for active surveillance, were invited to take part in the study. Patients who had received prior or current treatment for their cancer were excluded. There were two parts to the study: in part one, patients were assigned to one of two treatment groups based on the size of their prostates (patients with prostate size60 mL would receive 4 mg/kg TOOKAD(®) Soluble and patients with prostate size ≥60 mL would receive 6 mg/kg TOOKAD(®) Soluble both activated with 200 J/cm light). In part two, patients were assigned to one of two treatment groups based on predefined criteria and received either 4 or 6 mg/kg TOOKAD(®) Soluble and 200 or 300 J/cm light. VTP was conducted under general anaesthesia using TOOKAD(®) Soluble administered intravenously and activated by light-diffusing fibres within the prostate via the perineum. Follow-up was conducted for 6 months. Magnetic resonance imaging (MRI) carried out at 1 week after VTP and transrectal prostate biopsy at 6 months were the key endpoints. Adverse event (AE) recording and patient-reported outcome measures were collected.In all, 86 patients were enrolled in the study and 85 patients received treatment. Of the 85 treated patients, one patient discontinued (due to withdrawal of consent). At 6 months, 61/83 (74%) patients who underwent prostate biopsy had histopathology that was negative for prostate cancer (95% confidence interval (CI) 62.7-82.6%). Considering patients who received 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light (unilateral), which are considered optimal treatment parameters, 38/46 (83%) patients had histopathology from the biopsies that was negative for prostate cancer at 6 months (95% CI 68.6-92.2%; P0.001). The mean percentage of necrosis of the targeted prostate tissue at 7 days after VTP was 78% overall (83 patients) with extraprostatic necrosis reported in 76% (63/83) of patients. Considering patients who received 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light (unilateral), the mean 7-day necrosis percentage was 88% (46 patients) with extraprostatic necrosis reported in 72% (33/46) of patients. All occurrences of extraprostatic necrosis were considered clinically acceptable and none were associated with any clinical sequelae. The mean percentage prostate necrosis at 7 days was statistically significantly higher (P0.001) in patients treated with a therapeutic light density index (LDI) of ≥1 than those treated with a LDI of1. The percentage of patients with negative biopsies at 6 months was also higher in patients treated with a therapeutic LDI of ≥1 than those treated with a LDI of1 (78.6% and 63.0%, respectively). In all, 87% (75/86) of patients reported at least one treatment-emergent AE during the study. Most AEs were mild or moderate in intensity and considered related to the technical procedures of the study. No treated patients had hypotension or discontinued due to AEs. Eight patients (9.3%) had serious AEs; none resulted in discontinuation from the study.Biopsy data, post-treatment dynamic contrast-enhancement MRI at 1 week after VTP and analysis of the safety data have shown that 4 mg/kg TOOKAD(®) Soluble and 200 J/cm light are the optimal treatment conditions for the VTP procedure resulting in80% of patients treated with this regimen having a negative biopsy at 6 months. Overall, the treatment was well tolerated and exhibited early signs of efficacy for minimally invasive focal treatment of localised prostate cancer.

Prostate cancer is the most common neoplasm in men. Encouraging results are emerging in prostate cancer risk reduction with 5alpha-reductase (5AR) inhibitors. The Prostate Cancer Prevention Trial (PCPT) showed that prostate cancer risk is reduced by finasteride. However, there was an increase in the incidence of high-grade prostate cancer with finasteride treatment vs placebo. The number of cases should have increased during the study in the finasteride group with the length of exposure to the drug. But, in fact the ratio between the two groups was lower during the fourth year. This therefore favours the hypothesis of a bias in the results. There are many hypotheses to explain the increase in the prevalence of high-grade tumours with finasteride therapy. The effects of finasteride on prostate volume rather than on the tumour's morphology and a selective inhibition of low-grade cancers may have contributed to the increase the number of high-grade cancers with finasteride in the PCPT. Despite the current trend to explain the increase of high-grade tumours with finasteride therapy by a detection bias, other studies underline the potential role of low levels of dihydrotestosterone in the genesis of high-grade tumours. In May 2008, a re-analysis of the PCPT results showed a significant decrease of 30% in the overall risk of prostate cancer in the finasteride group vs the placebo group, but it also found a statistically non-significant and less important increase of the prevalence of high-grade cancers in the finasteride group. However, the 5AR isoenzyme type 1 is present at higher rates than type 2 in high-grade cancers. Thus, finasteride is probably not the ideal drug to prevent high-grade cancers.