“NHS ban on pill to treat prostate cancer is lifted,” the Daily Express has said, while the Daily Mail has warned that a “prostate cancer wonder drug” was set for approval “south of border but turned down by Scotland”. The stories focus on the fact that the prostate cancer drug abiraterone may soon be available on the NHS in certain circumstances.

These stories are based on a revised decision on draft guidance published by The National Institute for Health and Clinical Excellence (NICE), which makes recommendations about which treatments should be available on the NHS in England and Wales. It recommends that abiraterone (brand name Zytiga) be made available for the treatment of advanced prostate cancer that has not responded to chemotherapy.

Previous draft NICE guidance published in February rejected the use of abiraterone, concluding that it was not cost-effective. The new draft guidance has reconsidered this decision following an offer from the drug manufacturer to make the drug available at a lower price to the NHS.

The Scottish Medicines Consortium (SMC), which advises NHS bodies in Scotland about the status of new treatments, published guidance in March that rejected making abiraterone available. The SMC is currently considering further evidence and is due to publish further guidance this summer.

What is abiraterone used for?

Abiraterone is a type of hormone therapy for cancer that has spread beyond the prostate to other parts of the body (metastatic prostate cancer). It is a tablet taken once a day in combination with a steroid drug (prednisolone or prednisone), which reduces inflammation.

Hormone treatments for prostate cancer aim to block the production of certain male hormones (androgens) that stimulate prostate cancers to grow. Although there are already hormone treatments for prostate cancer, the new drug works in a different way by blocking cytochrome P17, an enzyme that enables the body to make androgens.

Abiraterone was licensed by the European Medicines Agency (EMA) in September 2011. After price changes made the drug more affordable, NICE guidance recommended abiraterone for use within certain circumstances. NICE said it is suitable is for men with:

• metastatic prostate cancer that has not responded to castration (either surgical where the testes are removed, or where medical treatments are used to block male hormones); and
• metastatic prostate cancer that has not responded to a chemotherapy regimen that contains docetaxel (a chemotherapy drug licensed for hormone-resistant prostate cancer)

NICE added that abiraterone should be used in combination with the anti-inflammatory drug predisnolone (or prednisone) in both these cases.

Alternative treatment options for men with metastatic prostate cancer, whose disease still progresses after treatment with docetaxel, include a drug called mitoxantrone, supportive care and re-treatment with docetaxel (which is not recommended in current NICE guidance).

How effective is it?

NICE has concluded that abiraterone is an effective second-line treatment for advanced (metastatic) prostate cancer.

Evidence for its effectiveness comes from a large randomised controlled trial carried out in 13 countries including the UK, from May 2008 to April 2009. The trial aimed to find out how well abiraterone worked for men who had already had other types of hormone therapy and chemotherapy for advanced prostate cancer.

One group of men in the trial took abiraterone once a day together with prednisolone, while the other group took a placebo plus prednisolone.

A primary analysis of the results showed that, on average, men who had abiraterone survived about four months longer than those in the placebo group (14.8 months compared with 10.9 months, hazard ratio 0.65, 95% confidence interval 0.54 to 0.77). The trial was stopped early once the benefits of the drug became clear.

The study also included analysis of a subgroup that had received one course of chemotherapy only (as opposed to more than one). It found that in this group, men who took abiraterone lived significantly longer than men who took the placebo (17.0 months compared to 11.7 months, hazard ratio 0.71, 95% confidence interval 0.60 to 0.86). NICE said that this group is likely to be treated with abiraterone in clinical practice and would have better treatment outcomes because they had less advanced disease.

Experts also told NICE that the most important benefits were extension to life and improved quality of life, including less pain and improved mental and physical health. NICE also concluded that the drug has the benefit of being in tablet form, which means patients can take it at home. It added that abiraterone is generally safe and any adverse reactions were tolerable.

Why was the drug previously turned down by NICE?

NICE had previously said that abiraterone should not be made available on the NHS because it was not cost-effective. NICE uses a measure called the quality-adjusted life year (QALY) to assess the value for money of a medical intervention. QALY is based on the number of years of life that would be added to a patient’s life, as well as the improvement in the quality of their life in that time added by any treatment. Each year of life is assigned a value.

NICE had previously said that although the drug had survival benefits, it did not feel the drug provided enough benefit to patients to justify the price the NHS was being asked to pay, even with an (undisclosed) discount on the list price then offered by the manufacturer, Janssen. It concluded that the most plausible cost per quality adjusted life year would be at least £63,000.

The list price of abiraterone is £2,930 for a 30-day supply of 120 tablets.

It also said that the drug did not meet its criteria for an end-of-life treatment as it did not consider the population for which the drug is licensed to be small.

What has changed now?

The manufacturer of abiraterone, Janssen, has offered the NHS a further undisclosed discount on the list price of the drug. Janssen also offered further information on which patients would benefit most (the subgroup who received only one course of chemotherapy), and clarified how many patients would receive the drug as an end-of-life treatment.

This has enabled NICE to conclude that the plausible cost per quality adjusted life year for this subgroup would be less than £50,000. In coming to this revised figure, NICE also took into account that abiraterone has other quality-of-life benefits, such as being an oral drug. It also meets the criteria for an end-of-life treatment which are:

• it would be used for men who would have a short life expectancy without treatment – less than 24 months 
• providing treatment would provide at least three months extension to life.

Is it definitely going to be made available?

NICE will now consult with interested parties on the new draft guidance recommending abiraterone, before it makes a final decision in June. Until then, NHS bodies are advised to make decisions locally on the funding of specific treatments.

Links To The Headlines

Prostate drug abiraterone ‘set for NHS use’. BBC News, May 16 2012

England benefits from NHS postcode lottery at long last – as prostate cancer wonder drug looks set for approval south of border but not in Scotland. Daily Mail, May 16 2012

Prostate cancer: health watchdog reverses NHS guidance on drug. The Guardian, May 16 2012

Nice ‘to reverse ban on prostate cancer drug’. The Daily Telegraph, May 16 2012

NHS ban on pill to treat prostate cancer is lifted. Daily Express, May 16 2012

Links To Science

NICE. Prostate cancer (metastatic, castration resistant) – abiraterone (following cytoxic therapy): final appraisal determination guidance. Published May 16 2012

Revolutionary surgery has given a paralysed man the ability to move his arms and hands again, it has been widely reported. The surgery, which made global news, has shown that rewiring nerves may allow surgeons to restore basic arm and hand control after serious spinal cord injuries.

A 71-year-old patient had been left paralysed from the neck down after the base of his neck was injured in a traffic accident. In a world first, surgeons were able to successfully bypass the injury site by grafting arm nerves from below the injury to nerves originating above the site of his injury. The surgery was given 23 months after his accident, and after several more months of therapy and training the man can handle objects, feed himself and even do basic writing.

This success story is clearly of massive significance to the man involved but also provides a blueprint for other surgeons around the country for how this technique may be applied in similar situations. Despite this fantastic success, it is important to bear in mind that this was an individual case, and it is not clear whether this technique will be equally successful in other patients with different types of spinal injuries or circumstances. The severity and location of the spinal cord injury are likely to be important factors in the success of this type of operation.

Where did the story come from?

The research was detailed in a report written by researchers from the Division of Plastic and Reconstructive Surgery and the Department of Neurological Surgery at Washington University School of Medicine in St. Louis, Missouri. The case report was published in the peer-reviewed Journal of Neurosurgery. The report does not specify any sources of funding for the research.

This story received widespread media coverage and many papers reported on the restoration of function in a previously paralysed man. The coverage of the story was generally well balanced and reflected the case report accurately.

What kind of research was this?

This case report described a surgical technique designed to restore nerve function to the hands of a 71-year-old man who had been injured in a road traffic incident and left paralysed. The patient had experienced severing of the spinal cord towards the top of his spine, causing him to be paralysed below the site of his injury. The site of his injury meant paralysis affected his arms, as the nerves that control the arms are situated below the site of his spinal cord damage. In this cutting-edge research surgeons were able to create a “nerve bypass” by grafting a working nerve originating in the spine above the injury site to the nerves in the lower arm originating below the injury site to restore some level of control lost following the injury.

Spinal cord injury (SCI) is devastating for the individuals affected and their families. Recovery from a complete SCI is rare, leaving most patients with significant permanent disability affecting the area below the site of the SCI. Despite advances in understanding the processes that occur in short- and long-term SCI, corresponding advances in surgical techniques or applications to repair them have so far lagged behind.

Case reports are often published that share interesting developments or new techniques in a particular medical field, in this case surgery. Case reports provide a detailed description of the background of a single person and the treatment they received, along with how effective the particular treatment course has been. They do not necessarily reflect what will be seen in all patients treated with the same techniques in the future, but still provide a good insight intonew or experimental techniques.

What did the research involve?

The right-handed 71-year-old man presented to a surgical department 22 months after he was injured in a motor vehicle accident. He had sustained a spinal injury to the lower part of his neck, called the C7 vertebra. This caused extensive paralysis below the injury site. The strength and mobility of his limbs were extensively assessed to see if surgery might be able to help. Before surgery, he could flex his right wrists only weakly and could not pinch or grip with either hand. He could also not move his fingers on either hand.

A month after his initial assessment, the patient had surgery on both arms in a bid to restore some of the function of his hands. This was based on the concept that a working nerve originating in the spine above the injury site could be grafted onto the nerves in the lower arm to restore some of the control lost after the injury.  The “nerve transfer” surgical technique involved taking a working nerve in the upper arm that originates from the C6 vertebral level (above the site of the injury), and joining it to the nerve system in the arm that originates from the C7 vertebra (the site of the injury). This “nerve rewiring” allowed working nerves above the spinal injury site to artificially connect with nerves below the injury site, which were previously unable to receive a signal due to the injury. Nerve transfer for spinal injuries is not new, but its application has so far been relatively limited.

After the surgery, the patient received continued hand physiotherapy to aid recovery and rehabilitation of the wasted hand muscles due to the injury.

What were the basic results?

During the operation, the surgeons stimulated the newly rewired nerves to check they were working and found that the nerve responses were essentially normal for the rewired nerves feeding the hand.

Eight months after the operation, the patient was able to move his left thumb and perform a pinching motion with his fingers and thumb in his left hand. The same increase in movement was achieved in the right hand after 10 months.

The authors report that he can now use his right hand to perform simple “hand to mouth movements”, and with his left hand he can feed himself and perform rudimentary writing activities. Recovery in the right hand has been slower than in the left.

Videos made available by the study group show that the man is now able to handle a ball with both hands, touch his fingers against his thumb in a pinching motion and feed himself. These were all activities he could not do before the surgery.

How did the researchers interpret the results?

The researchers said that, to their knowledge, this is the first reported case of restored nerve control of the thumb and finger flexing movement after a spinal cord injury.

They also said that the patient’s “function has improved significantly with his ability to feed himself”.

Conclusion

This case report represents the positive experience of a paralysed 71-year-old man who has been granted some manual control after a serious spinal injury to his neck. Before surgery, he could only make minimal arm movements controlled by the nerves above his injury site, but no lifting or fine hand movements as they are controlled by nerves joined lower down the spine, below the site of his injury.

While the nerve transfer technique given to this patient is not new, its application is not widespread and the authors say this is the first time it has been used to successfully rewire the nerves supplying a hand. Furthermore, these gains occurred after surgery that was carried out 23 months after the injury was sustained. This suggests that surgery does not have to be performed immediately, and that it may be possible to carry out the technique in people who have been paralysed for some time.

In addition to the hugely significant benefits to the man involved, this success story has also created a blueprint for other surgeons around the country for how this technique may be applied in similar cases.

However, it is important to bear in mind the limitations of the surgery and the evidence of its effectiveness. This case report represents the experience of just one individual. Therefore, it is not clear whether this technique will be equally successful in other patients with different types of injuries or circumstances. The severity and location of the spinal cord injury are likely to be important in determining the relative success of this type of operation. Also, the level of strength and control achieved in this case did not appear to represent a complete restoration of arm function, although it was clearly still a massive improvement.

Analysis by Bazian. Edited by NHS Choices.

Links To The Headlines

Prostate drug abiraterone ‘set for NHS use’. BBC News, May 16 2012

For once England benefits from NHS divide as Nice set to approve prostate cancer drug turned down by Scotland. Daily Express, May 16 2012

Prostate cancer: health watchdog reverses NHS guidance on drug. The Guardian, May 16 2012

Prostate drug u-turn by NICE. The Daily Telegraph, May 16 2012

Nice ‘to reverse ban on prostate cancer drug’. The Daily Telegraph, May 16 2012

NHS ban on pill to treat prostate cancer is lifted. Daily Express, May 16 2012

Links To Science

Mackinnon SE, Yee A, Ray WZ. Nerve transfers for the restoration of hand function after spinal cord injury. Journal of Neurosurgery, Published online May 15 2012.