Brachytherapy: sowing the seeds for change

Prostate cancer is the most commonly diagnosed cancer in men and accounts for more than 10,000 deaths each year, yet men with prostate cancer report having a significantly worse experience of treatment and care than patients with other cancers.1

A group of leading healthcare professionals – the Prostate Brachytherapy Advisory Group – has been raising the profile of this issue and is also calling for the eradication of the postcode lottery system for patients seeking a form of treatment known as low dose rate (LDR) brachytherapy, which offers significant advantages for patients in terms of preserved quality of life.

Many men are not being given the information they need to make an informed choice, and the group says that one in six patients are being denied access to this treatment.2 This is despite its approval by the National Institute for Health and Clinical Excellence (NICE)3 and advice by the Department of Health supporting its increased usage.4 The group is calling for healthcare providers to improve access to LDR brachytherapy four-fold – in line with Government expectations.

This proven, cost-effective treatment is minimally invasive and carries less risk of impotence and incontinence after treatment compared to other options. Patients also have minimal discomfort, a rapid return to normal activity and can be back at work within a couple of days.5-7

An added advantage is the fact that it is possible to carry out the treatment as a single visit, day case procedure. “Despite the benefits for many patients, some clinicians are reluctant to recommend the procedure because they are relying on information that is 10 years out of date,” says Rick Popert – a member of the advisory group and consultant urological surgeon at Guy’s and St Thomas’ NHS Foundation Trust. “They may rule out brachytherapy, for example, because they consider the patient’s prostate to be too large, when this may not be a problem with modern techniques. Surgeons may also opt for conventional beam radiotherapy and radical surgery because there is more long-term data available on the outcomes.”

He points out that brachytherapy has data to support its use in the treatment of early, localised, prostate cancer with relapse-free survival rates of 85% at 10 years – which shows that outcomes are comparable to surgery. However, the absence of more long-term data, past this period, means there may be some small anxiety over outcomes for younger patients. There is no information on what will happen past 15 years time – although radical surgery can still be performed at a later date, should a relapse occur in the distant future. The Trust offers all types of therapy to ensure the patient gets the most appropriate treatment and Rick Popert believes the patient’s ability to make an informed choice is paramount. However, he is particularly keen to highlight the potential benefits of the modern “Potters Technique” – pioneered by Louis Potters, of the New York Prostate Institute, and describes his support of LDR brachytherapy as a “crusade”. He believes this treatment can be the best approach for many patients with early, localised, prostate cancer due to the reduced impact on quality of life. This therapy was first introduced at Guy’s and St Thomas’ NHS Foundation Trust in 2003 (followed by the Cromwell Hospital in 2005) and over 190 patients received treatment between December 2003 and March 2007.

THE PROCEDURE

The procedure itself involves implanting radioactive Iodine-125 titanium seeds (Oncura) directly into the prostate under ultrasound guidance to deliver a high dose of radiation to the prostate, through hollow needles. The Clinical Services Journal witnessed a procedure being carried out at Guy’s Hospital, by Rick Popert, which he said can take as little as 40 minutes to perform. The patient in this case was a 43-year-old, Afro-Caribbean patient, first diagnosed in 2003 with a slow growing cancer. Active surveillance was initially recommended, with follow-up biopsies, and his PSA remained stable to 2005. A biopsy later found that the abnormality had increased and the grade of the disease had become less favourable, which then required intervention.

There is an increased prevalence of prostate cancer at a younger age, in men from this patient’s ethnic profile, which presented him with a difficult choice. His age meant that he was not considered to be the ideal candidate for LDR brachytherapy, and radiotherapy and radical therapy were initially presented as the most suitable options (due to the uncertainty over long-term outcomes). However, the patient had good erectile function and he wanted to have more children, so the loss of fertility and risk of impotence were overriding issues. The patient decided LDR brachytherapy was therefore the most appropriate treatment for him. In addition, the use of the Potters Technique meant that the option remained to have radical surgery later on, which is not always possible with other forms of brachytherapy.

The patient was anaesthetised and placed in the extended dorsal lithotomy position and transrectal ultrasound used to visualise the prostate. Needles were then placed into the prostate through a template, to provide grid references, which Rick Popert described as being much “like battleships”. As each needle was inserted, its position on the grid was recorded manually and logged directly into the computer software program. Images of the prostate, the urethra, the rectum and the needles were “captured” from the base to the apex onto the computer. The prostate, urethra and rectum were outlined in red, green and blue to produce an accurate 3D interpretation of the patient’s prostatic, urethral and rectal anatomy in relation to the implanted needles. This is known as Inverse Planning and helps to reduce the risk of over-treatment to the urethra and rectum, while maximising the dose to the prostate, which may lead to less adverse side-effects in the long-term. However, Rick Popert explained that this part of the procedure was more challenging than usual as the patient’s prostate was rather small – resulting in closer proximity of these parts, so the software program was really helpful in this case.

Once the computer was given the position of the needles within the prostate, the computer software was able to generate a treatment plan. Having placed the needles into the correct position, a specially designed instrument, called the Mick Applicator, was used to push the seeds into position. Between 50 and 105 seeds are normally implanted depending on the size of the prostate.

The technique used by Rick Popert has a number of advantages over the traditional Seattle approach, in his view: “It is a single stage day case, catheterless procedure with no dosimetric learning curve assuring high quality implants from the outset.8 The procedure may take slightly longer, but can be used to treat larger prostates because pubic arch interference is less important.” Many urologists and oncologists have concerns recommending brachytherapy to patients with larger prostates (> 50 cc) because of a perceived risk of acute urinary retention and a worse side-effect profile. Work at Guy’s and St Thomas’ NHS Foundation Trust has shown that these fears are not justified.9With their approach they have been able to treat larger prostates (>50 cc) without any increased risk of retention (as long as the patient has no significant urinary symptoms). Most experienced brachytherapy centres will often be able to treat prostates of up to 70 cc but are likely to recommend a period of three months hormone treatment to downsize the gland.

“This has been unnecessary in our experience and is known to increase the risk of urinary retention,” Rick Popert explained. “The larger the prostate the more likely patients will suffer from voiding symptoms but retention of urine remains uncommon.”

He worries that some patients will be advised against or not referred for brachytherapy because of the size of their prostate.

Retention of urine is considered to be one of the most significant potential complications of brachytherapy, but Rick Popert believes the dynamic, real-time approach used at the Trust may reduce the risk by better targeting of the prostate with avoidance of the urethra. The retention rate is low, under 5%, (lower than most published series of 10% and no difference is seen between small and large prostates). Only one patient with a very large prostate (over 80 cc), had significant retention. He required catheterisation but has been successfully treated with a limited transurethral resection one year after treatment with an excellent symptomatic outcome.

Rick Popert said his department was more fortunate than others in the fact that it offered a comprehensive range of treatments – as well as LDR brachytherapy – and added: “In some respects, this makes it harder to advise patients when the choice is so broad, but I would rather that my patients were well informed on their options. Most often, it is not which treatment would be best for an individual but why one particular choice would be a bad idea,” he commented. “It would be even harder to tell patients they couldn’t have a particular treatment because it’s not available, however.”

A PATIENT’S VIEW

Bruce Lucas, from Glasgow, opted for LDR brachytherapy in November 2006 – despite laparoscopic surgery initially being advised. The procedure was carried out by Stephen Langley, Professor of Urology at St Luke’s Cancer Centre, Guildford, who is also the chair of the Prostate Brachytherapy Advisory Group. Prof Langley advised Bruce Lucas against “watchful waiting” due to his rising PSA. He had preliminary mapping, then received the treatment a month later.

“Having studied the options, it came down to surgery or brachytherapy – so I opted for the later. I had a medical friend who advised me not to go for surgery unless I was absolutely desperate. In addition to that, the statistics for success seemed to be similar. There was also minimal disruption to normal life.

“I had the operation at 3 pm on a Wednesday afternoon, in Guildford, and my wife drove me back to Glasgow on the Thursday afternoon. I took a couple of weeks off, because I didn’t know how I was going to feel, but I needn’t have done so – in fact, I played golf on the following Saturday with very satisfactory results. I think it slowed down my swing a bit!” he joked. Bruce Lucas added that he has had a PSA test every three months which has shown a decrease from 10, just before he had the operation, to just 0.8 at his latest check. “For me, the treatment was perfect. It was simple, painless, didn’t cause me to miss any work and I haven’t had any side-effects,” he concluded.

Bruce Lucas underwent a two-stage technique, in which the patient has an ultrasound scan before the treatment – either as a day case procedure under general anaesthetic, or in the clinic setting when the patient is assessed. However, around a quarter of patients receive both the planning and treatment in one visit – in much the same way as patients at Guy’s and St Thomas’. Both approaches show equally high quality results at the Guildford unit.

“There are a whole host of different techniques for brachytherapy, but ultimately the aim is to implant the seeds in the prostate in a planned approach to deliver the right dose of radiation to the prostate gland. There is no data to indicate one technique is more superior to another. What is important is the fact that the end result is the same and the procedure is carried out by a unit that is well trained and practiced in the technique,” Prof Langley commented.

“We have now treated over 1,000 patients at Guildford and published our five year results, which show a 93% PSAfree cure rate.10We believe pre-planning can make the procedure more efficient and reduce the time under anaesthetic, but there are pros and cons to both approaches and we frequently use a new second generation real-time technique here in Guildford as well. It is most important to use a technique that works in one’s hands that shows good outcomes.”

FUNDING ISSUES

Brachytherapy was first introduced at Guildford in 1999, but funding proved to be a complex issue for the centre, as well as many other hospitals across the UK at this time. When the system changed from Extra Contractual Referrals (ECRs) to Out of Area Transfers (OATs), the decision was made to base funding on the previous year’s ECRs. Therefore, if a treatment had not previously existed there was no funding allocated.

“We started the wrong side of that year,” Prof Langley explained. In his view, this resulted in a divide. The Cookridge Hospital in Leeds had started offering brachytherapy a year earlier and, as such, patients in the North of England had better access to brachytherapy on the NHS than those in the South, where Guildford was initially the only centre offering the treatment.

“It was virtually impossible to get funding in the South from any health authority,” he commented.

St Luke’s did not want to offer the treatment just to private patients, so it agreed with its Trust that the revenue generated by private cases would be spent on funding NHS patients. As the technique became more popular, the centre’s catchment area grew larger and larger, so the Trust decided that patients outside the Guildford area would then have to obtain funding from their own PCT. However, Prof Langley said he is appalled by the inequality that patients face when trying to obtain treatment.

“Many PCTs are now funding brachytherapy, but it is still patchy. Faced with the agony of trying to persuade a PCT to provide funding, many clinicians simply won’t mention the treatment to their patient. They play the down the benefits because they know their patients will be disappointed if they choose this option. “We have seen patients from Wales, for example, where the PCT funded brachytherapy one year, then decided they could not afford it the next. One patient used most of his life savings to pay for the treatment, only to find that six months later the PCT had decided to fund it again. Meanwhile, he had been treated and they would not refund his money. It is a nonsense way to deliver cancer services across the UK.”

Some PCTs also wait to see if patients are going to appeal, he said. This raises concerns that while the most erudite patients are capable of embarking on such a campaign, those who do not have the same skills simply get “washed along”.

“There should be equity in access to brachytherapy – we all pay the same taxes. If the NHS provides a service it is supposed to provide it to all – irrespective of the patient’s postcode address,” he concluded.

REFERENCES

1 Comptroller and Auditor General. Tackling Cancer: Improving the patient journey. HC 288 2004-2005. 2005. London, National Audit Office.

2 http://www.channel4.com/news/ dispatches/health/health_lottery

3 Interventional Procedures Overview of Low Dose Rate Brachytherapy for Localised Prostate Cancer (NICE Overview 251, January 2005).

4 Department of Health Advice on the Development of Low Dose Rate (Permanent Seed Implant) Brachytherapy Services for Localised Prostate Cancer in England. (Gateway Reference 7385, November 2006).

5 Kupelian P.A., Potters L., Khuntia D. et al. Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy ³72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. International Journal of Radiation Oncology Biology and Physics 2004;58:25-33.

6 Buron C., Vu B.L., Cosset J.O.M. et al. Brachytherapy versus prostatectomy in localised prostate cancer: Results of a French multicenter prospective medicoeconomic study. International Journal of Radiation Oncology Biology and Physics 2007;67:812-822.

7 Frank S., Pisters L., Davis J. et al. An Assessment of Quality of Life Following Radical Prostatectomy, High Dose External Beam Radiation Therapy and Brachytherapy Iodine Implantation as Monotherapies for Localised Prostate Cancer. The Journal of Urology 2007; 177: 2151-2156.

8 Acher P.L., Popert R., Nichol J., Potters L., Morris S., Beaney R. Permanent Prostate Brachytherapy: Dosimetric Results & Analysis of a Learning Curve with a Dynamic Dose Feedback Technique. IJROBP 2006; 65: 694-8.

9 Acher P., Popert R., Morris S,. Potters L., Austin-Smith S., Johnston U., Beaney R. Dynamic Dose Feedback Prostate Brachytherapy in Patients with Large Prostates and/or Planned Transurethral Surgery before Implantation. BJU Int 2007; 99 (5): 1066-71.

10 Khaksar S.J., Laing R.W., Henderson A., Sooriakumaran P., Lovett D., Langley S.E.M. Biochemical (PSA) relapse-free survival and toxicity after 125-I low dose rate prostate brachytherapy. BJU Int 2006. 98:1210-1215.

USEFUL WEBSITES

www.prostatebrachytherapyinfo.net

www.prostatecancercentre.com