A new non-surgical treatment for low-risk prostate cancer can effectively kill cancer cells while preserving healthy tissue, reports a University College London-led phase III clinical trial in 413 patients.
The trial was funded by STEBA Biotech which holds the commercial licence for the treatment.
The new treatment, ‘vascular-targeted photodynamic therapy’ (VTP), involves injecting a light-sensitive drug into the bloodstream and then activating it with a laser to destroy tumour tissue in the prostate. The research found that around half (49%) of patients treated with VTP went into complete remission compared with 13.5% in the control group.
“These results are excellent news for men with early localised prostate cancer, offering a treatment that can kill cancer without removing or destroying the prostate,” says lead investigator Professor Mark Emberton, dean of UCL medical sciences and consultant urologist at UCLH. “This is truly a huge leap forward for prostate cancer treatment, which has previously lagged decades behind other solid cancers such as breast cancer. In 1975 almost everyone with breast cancer was given a radical mastectomy, but since then treatments have steady improved and we now rarely need to remove the whole breast. In prostate cancer we are still commonly removing or irradiating the whole prostate, so the success of this new tissue-preserving treatment is welcome news indeed.”
At the moment, men with low-risk prostate cancer are put under ‘active surveillance’ where the disease is monitored and only treated when it becomes more severe. Radical therapy, which involves surgically removing or irradiating the whole prostate, has significant long-term side effects so is only used to treat high-risk cancers.
Radical therapy causes lifelong erectile problems and around one in five patients also suffer from incontinence. By contrast, VTP only caused short-term urinary and erectile problems which resolved within three months, and no significant side-effects remained after two years.
In the trial only 6% of patients treated with VTP needed radical therapy compared with 30% of patients in the control arm who were under active surveillance. The chances of cancer progressing to a more dangerous stage were three times lower for patients on VTP, and the treatment doubled the average time to progression from 14 months to 28 months.
The trial involved 47 treatment sites from ten different European countries, most of which were performing VTP for the first time.
“The fact that the treatment was performed so successfully by non-specialist centres in various health systems is really remarkable,” says Emberton, who is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. “New procedures are generally associated with a learning curve, but the lack of complications in the trial suggests that the treatment protocol is safe, efficient and relatively easy to scale up. We would also expect the treatment to be far more precise if we repeated it today, as technology has come a long way since the study began in 2011.
“We can now pinpoint prostate cancers using MRI scans and targeted biopsies, allowing a much more targeted approach to diagnosis and treatment. This means we could accurately identify men who would benefit from VTP and deliver treatment more precisely to the tumour. With such an approach we should be able to achieve a significantly higher remission rate than in the trial and send nearly all low-risk localised prostate cancers into remission. We also hope that VTP will be effective against other types of cancer – the treatment was developed for prostate cancer because of the urgent need for new therapies, but it should be translatable to other solid cancers including breast and liver cancer.”
The VTP therapy approach was developed by scientists at the Weizmann Institute of Science in Israel in collaboration with STEBA Biotech, and the European phase I, II and III trials were all led by UCL. The drug used in the procedure, WST11, is derived from bacteria at the bottom of the ocean. To survive with very little sunlight, they have evolved to convert light into energy with incredible efficiency. This property has been exploited to develop WST11, a compound that releases free radicals to kill surrounding cells when activated by laser light.
The VTP treatment is currently being reviewed by the European Medicines Agency, so it is likely to be a number of years before it can be offered to patients more widely.
Background: Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial.
Methods: This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months’ follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov, number NCT01310894.
Findings: Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24–25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0·34, 95% CI 0·24–0·46; p<0·0001). 101 (49%) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 (14%) men in the active surveillance group (adjusted risk ratio 3·67, 95% CI 2·53–5·33; p<0·0001). Vascular-targeted photodynamic therapy was well tolerated. The most common grade 3–4 adverse events were prostatitis (three [2%] in the vascular-targeted photodynamic therapy group vs one [<1%] in the active surveillance group), acute urinary retention (three [2%] vs one [<1%]) and erectile dysfunction (two [1%] vs three [1%]). The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine (15 patients; severe in three); this event resolved within 2 months in all patients. The most common serious adverse event in the active surveillance group was myocardial infarction (three patients).
Interpretation: Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy.
Abdel-Rahmène Azzouzi, Sébastien Vincendeau, Eric Barret, Antony Cicco, François Kleinclauss, Henk G van der Poel, Christian G Stief, Jens Rassweiler, Georg Salomon, Eduardo Solsona, Antonio Alcaraz, Teuvo T Tammela, Derek J Rosario, Francisco Gomez-Veiga, Göran Ahlgren, Fawzi Benzaghou, Bertrand Gaillac, Billy Amzal, Frans M J Debruyne, Gaëlle Fromont, Christian Gratzke, Mark Emberton