New laser therapy for low-risk prostate cancer shows promise

Tuesday December 20 2016

The new technique spares healthy prostate tissue

“A drug activated by laser light successfully destroys early prostate cancer while avoiding side effects … results have shown,” The Guardian reports.

This new technique may offer an alternative treatment to the current “wait and see” approach, also known as active surveillance.

The main challenge of treating prostate cancer judged to be low risk is that it’s difficult to predict if it will spread far enough to pose a threat to health. 

A study we looked at in 2014 found around half of predictions about the likely outcome of “low-risk” cases of prostate cancer were incorrect.

Many men are reluctant to have prostate cancer surgery unless they really have to, as it carries the risk of causing erectile dysfunction and urinary incontinence.

In this study, researchers compared active surveillance with a new technique known as vascular-targeted photodynamic therapy.

This involves injecting a light-sensitive drug into the prostate and activating it with a laser when it reaches cancer cells.

The benefit of this approach is damage to healthy prostate tissue is minimised, reducing the risk of side effects.

Two years after having this treatment, almost half of the men in the treatment group were cancer-free and only 6% of patients needed further treatment, compared with 14% being cancer-free and 30% needing further treatment in the active surveillance group. Side effects were mostly mild.

Overall, these are promising results, but it’s not possible to say when, and indeed if, this treatment will become widely available.

Where did the story come from?

The study was carried out by researchers from hospitals across 10 European countries, including the UK, France, the Netherlands, Germany and Spain.

It was published in the peer-reviewed journal, The Lancet Oncology.

The study was funded by Steba Biotech, a company focused on targeting cancer in a minimally invasive way, which holds the commercial license for the treatment.

Many of the study’s authors were employed by or had financial links to Steba. The authors also declared receiving payment from various other pharmaceutical companies.

The UK media generally reported the story accurately, with The Daily Telegraph highlighting that the treatment brought about complete remission in around half of the patients who had it.

The Daily Mail also made it clear that this treatment was for early-stage prostate cancer and the study did not look at later stages. 

What kind of research was this?

This randomised controlled trial (RCT) aimed to compare the safety and effectiveness of vascular-targeted photodynamic therapy with active surveillance in men with low-risk prostate cancer.

The likely outcome for prostate cancer is assessed using a well-validated scoring system known as the Gleason grade.

This can range from 1 to 5 – the higher the grade, the more likely the cancer is to spread outside the prostate.

All men in this study had a Gleason grade of 3. This means that the cancer had not spread outside the prostate and was expected to grow slowly.

Men with this early-stage prostate cancer may have a number of treatment options, depending on their individual circumstances.

This may involve active surveillance, where the potential spread of the cancer is assessed on a regular basis. Many men only opt for treatment when the tumour grows more aggressively.

Active treatment options for localised prostate cancer may include surgery or radiotherapy, but these carry a risk of side effects like erectile problems and incontinence.

An RCT is the best way of investigating the effects of this new intervention, as the randomisation process should balance out other confounding variables that may differ between the men.

What did the research involve?

This multicentre trial was carried out in 47 centres across Europe, including the UK.

Researchers included 413 men (age 44-85) with low-risk prostate cancer who had not received treatment previously and had no contraindications.

They were randomly assigned to the vascular-targeted photodynamic therapy (206 men) group or active surveillance (207 men).

The new treatment first involved the men having an MRI scan to determine the number, length and position of optical fibres to be inserted.

Fibreoptic laser fibres were then positioned in the target positions in the prostate under general anaesthetic.

The men then received an intravenous infusion of a drug called padeliporfin. This drug is made from bacteria living in almost complete darkness at the bottom of the sea, which only become toxic in the presence of light.

When the laser is switched on, the drug becomes activated and kills the cancer, but leaves healthy tissue unharmed.

Both the treatment group and the active surveillance group had a PSA test (a measurement of a protein linked to prostate enlargement) and a rectal examination every three months. They were also given a prostate biopsy every year.

If the biopsy still showed prostate cancer at one year, those in the treatment group were offered further treatment.

The two main outcomes of interest in both groups were treatment failure at 24 months (progression of cancer from low-to-moderate to high risk) and the absence of cancer at 24 months (the proportion of men with negative prostate biopsy results).

Adverse side effects were also assessed from the point of treatment until the end of the study.

What were the basic results?

Vascular-targeted photodynamic therapy was found to reduce the risk of further more invasive treatment being required, which was reported as the photodynamic therapy failing.

Cancer had progressed at 24 months in 58 out of 206 (28%) men in the treatment group, compared with 120 out of 207 (58%) in the active surveillance group.

This gave a 66% reduced risk of treatment failure (adjusted hazard ratio 0.34, 95% confidence interval [CI] 0.24 to 0.46).

Vascular-targeted photodynamic treatment also increased the likelihood of being cancer-free at 24 months.

In the treatment group, 101 out of 206 (49%) men had a negative prostate biopsy at 24 months, compared with 28 out of 207 (14%) men in the active surveillance group.

This was equivalent to a more than tripled increased chance of cancer clearance (adjusted risk ratio 3.67, 95% CI 2.53 to 5.33).

Looking at other outcomes, fewer men in the vascular-targeted photodynamic group (12 of 206, 6%) needed subsequent radical therapy in the form of surgery or radiotherapy compared with the active surveillance group (60 of 207 men, 29%).

However, the frequency and severity of adverse side effects were higher in the vascular-targeted photodynamic therapy group. Most of these were mild and did not last very long.

The most common treatment-related serious adverse event in the treatment group was difficulty passing urine. All 15 cases resolved within two months. 

How did the researchers interpret the results?

The researchers concluded that, “Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer.”

They added that, “This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy.” 

Conclusion

This large randomised controlled trial indicates that the new treatment vascular-targeted photodynamic therapy for men with low-risk prostate cancer results in a greater chance of being declared cancer-free, and slows the progress of the disease.

The treatment also reduced the number of men who needed to have further surgery or radiotherapy to 6%, compared with 29% in the active surveillance group.

This is a well-designed trial conducted in several countries that followed men for a reasonably long period of time.

It also analysed all men included in the study, regardless of whether they completed treatment or follow-up.

However, there are some points to note to put the study in context. Researchers only included men with a very low-risk localised prostate cancer.

The results cannot be generalised to men with more advanced cancers – it’s not known whether it would be safe and effective in other groups.

The results also may not apply to all men defined as “low risk”, only those defined as such when the study began in 2011.

Despite including a fairly large sample, the population was almost entirely white men, with only 5 out of 413 belonging to other racial backgrounds. This means results may not apply to other demographics.

The comparator used was active surveillance. The researchers did not compare treatment with other active treatment options, such as surgery or radiotherapy.

As the researchers say, surgery could not have been a suitable comparator as the prostate would be removed, so they couldn’t compare biopsy results.

And they couldn’t compare with radiotherapy because of the need to administer hormone treatments before and after radiotherapy.

But this doesn’t mean to say that this new treatment is better than surgery or radiotherapy in terms of curing the person, preventing progression or prolonging survival.

Early active treatment with surgery or radiotherapy may give more favourable outcomes than active surveillance and even this new treatment.

Follow-up has also only continued for two years. Information on progression and survival outcomes at 5 and 10 years would be valuable.

Overall, these are promising results for a potential new treatment, but it’s not possible to say at the current time when and if it will become available, or who for.

As far as we know, there is no 100% guaranteed way to prevent prostate cancer, other than having your prostate removed.

But maintaining a healthy weight and regular exercise may help reduce the risk. 

Read more about prostate health.