The magic bullet for prostate cancer

Oklahoma City was not John Bell’s idea of a honeymoon spot. But somewhere between popping the question and setting a date came the difficult matter of his prostate cancer. Until the cancer reared its head, Bell was a fit 66-year-old who’d always boasted of remarkable health, provided he didn’t count an unfortunate dart to the eye in his college days. But then a biopsy in September 2009 revealed a tumour in his prostate. His doctors – and there would be many before he was done – recommended surgery. Bell didn’t like what he was hearing, though, about his prospects of impotence and incontinence.

Then his bride-to-be Sherry heard about something new: a treatment that zaps tumours with protons, subatomic particles that offer the promise of a cure with less collateral damage to healthy tissues. A little internet sleuthing and consultation with a successful proton-beam patient convinced Bell. “I was ready for something other than surgery,” he says. Even better, a new proton centre had just opened for business in Oklahoma City, right across the state line from his home near Dallas. The Bells were married in December 2009 and the following February he began treatment.

The newlyweds spent two months at the nearby Town Village Retirement Community – radiation in the morning, sightseeing in the afternoon – and the groom returned home cancer-free by all indications. Welcome to the atomic age for ailing prostates.

Proton therapy centres are now the object of technolust. Nine are operating in the US, with at least four more on the way. Here, the first proton therapy centre is due to open in Sydney within three years.

“I think people realise we have reached the limit on conventional radiation,” says Dr Sameer Keole, medical director of the Oklahoma City centre. “We haven’t even scratched the surface of what we can do with protons.”

There’s one problem, though: it isn’t certain that proton beams work better than conventional prostate-cancer treatments. And that bit of doubt has ignited one of the most contentious debates in modern prostate cancer treatment. With construction costs that can exceed $200 million, a proton-beam generator is the most expensive medical device ever made. In dramatic fashion, protons have raised a question most people find distasteful to ask and even more distasteful to answer: when is a lifesaving treatment worth its price?

But first things first: is this therapy even an improvement? “It’s very good treatment,” says Dr Anthony Zietman, from Massachusetts General Hospital in Boston, who is also president of the American Society for Radiation Oncology. “It just doesn’t appear to be superior treatment.” At least not for prostates, he says.

For tumours entrenched in exquisitely sensitive tissues, including the brain, eye and spinal cord, and for most malignancies in children, doctors are enthusiastic about the potential of protons. “I do not want to throw sand in the engine of proton-therapy development,” says Zietman. “I think it’s a game-changer in radiotherapy. But the risk is it will discredit itself by concentrating on prostate cancer, where there’s no obvious advantage, instead of concentrating on areas where a major advantage clearly exists.”

In an era when health care already consumes nearly 18 per cent of the US economy, cost is indeed an issue. At the University of Pennsylvania’s Roberts Proton Therapy Centre, US government health insurer Medicare will reimburse US$438 for a round of conventional radiation, but will pay US$1282 for a proton blast – 44 of which are required for a typical prostate cancer treatment. Private health insurers tend to follow Medicare’s lead. Who picks up the difference? Mostly US taxpayers and those with insurance, via their premiums.

Treatment is more expensive because protons are not easy to come by. The energy (and cancer-killing power) of traditional radiation comes when electrons are smashed into a metal plate, releasing their radioactive x-rays. The tumour-zapping energy of an electron can be harnessed by a device that fits easily into one treatment room. By contrast, the apparatus that beams the protons – which are stripped from hydrogen atoms and accelerated until they nearly reach the speed of light – weighs 200 tonnes. In its entirety, the machinery can take up more space than a football field.

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Protons were suggested as an option for cancer treatment in the Forties. Massachusetts General started collecting them from a Harvard cyclotron in the early Sixties. In the Eighties, Dr James Slater, a radiation oncologist at Loma Linda University Medical Centre in California, was so convinced of their potential that he envisioned building a cancer-fighting accelerator.

“I did not like the side-effects and the sickness we were producing with x-rays,” says Slater, now 82 and still on the Loma Linda faculty. After an almost two-decade mission beginning in the Seventies, Slater and the medical centre commissioned the Fermi National Accelerator Laboratory in Illinois to build a hospital-based proton accelerator, with part of the construction costs paid for by the US government. The first patient, a woman with melanoma on her eye, was treated in 1990.

What appealed to Slater – and what remains the main attraction of protons – is the idea that a stream of charged particles can be more easily controlled to match the irregular contours of a tumour. Traditional x-rays and proton treatments both disable a tumour’s genetic structure, which has less capacity for self-repair than healthy tissues do. But x-rays barrel through the body, affecting all tissue in their path.

One of Keole’s defining professional moments was the day in medical school when he saw hair loss in a child who was being treated for a brain tumour – on the opposite side of her head. A proton beam delivers most of its radiation when it hits a tumour, and then nearly stops dead. “These patients really do make it through treatment much better,” says Keole as he walks the halls of the Oklahoma centre. He’s one of roughly one per cent of radiation oncologists in the US with experience in proton therapy.

Protons may have a theoretical edge, but so far there is little convincing proof to back up the claim that they do a better job of eliminating prostate cancer. This is not entirely surprising, given that a scientific comparison is lacking for all prostate cancer treatments, says Zietman. No-one has compared the treatments – surgery, radiation and their incarnations – in a scientifically rigorous way. “Is surgery better than radiation? Who knows?” says Zietman, who calls prostate cancer “the bad boy of medicine” because of the scant data on which tumours are actually dangerous and which treatments work best.

“In this absence of knowledge, anything goes,” he says. “Surgeons recommend their favourite surgery. Radiation oncologists recommend their favourite form of radiation.” The least expensive option, which also happens to have the fewest side-effects, is largely unused: active surveillance (also known as “watchful waiting”), in which a patient is closely monitored and receives treatment only when his cancer shows signs of growing.

To truly know whether proton therapy works best, large numbers of men would have to participate in a randomised trial, a study in which volunteers are randomly assigned to a treatment and followed for a decade or so to see who fares better. In a climate where web-savvy men are already hooked on the promise of protons, such a study is proving difficult to launch. Zietman and Dr Stephen Hahn, chairman of radiation oncology at the University of Pennsylvania, are trying. “Most men are coming to us convinced that protons are absolutely better,” says Hahn. “The challenge is to discuss the available data and why many of us feel as if we don’t know whether it’s better.”

Another challenge of conducting a study: even men who have unexpected side-effects won’t let go of the idea that protons are superior, says Zietman. They are so convinced they received the best treatment, “they imagine the situation would have been even worse had they had another treatment”, he says.

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Oncologists have already learned a hard lesson about assumptions. In the Eighties, doctors began giving women with breast cancer colossal doses of chemotherapy to annihilate their tumours, then replacing their bone marrow (which was also wiped out in the treatment) with a transplant. Preliminary study findings appeared so promising that scientists struggled to recruit trial volunteers who had not received the treatment. But randomised trials finally revealed that women who received chemo and a transplant didn’t live any longer and suffered more adverse effects.

Prostate experts are in much the same position with proton therapy today, comparing the outcomes of proton treatment with the historical experience of standard radiation treatments. It’s inexact science, but so far protons haven’t outshone their competitors, either for treatment effectiveness or for side-effects.

In September 2009, the US Agency for Healthcare Research and Quality pronounced proton-beam treatment for cancer “promising but unproven”. One of the largest proton studies, which appeared in the Journal of the American Medical Association, compared two groups of men who had received conformal, or targeted, doses of x-ray radiation followed by either a standard dose or a high dose of proton therapy.

As part of the analysis, the researchers compared outcomes for these proton-beam patients with those for a group of men who had received only x-rays. They found the latter group’s quality of life was similar to the proton group’s. Zietman cites the increased precision of conventional x-rays as a reason the difference between the two has become so much harder to detect.

Keole points to recent study data, presented at the American Society for Radiation Oncology’s 2010 meeting. In that study, 94 per cent of men younger than 55 who’d had proton therapy at the University of Florida were sexually active 18 months later. (The study didn’t provide a comparison for men under 55 who’d had surgery or x-ray treatments. Also, men under 55 may more easily recover their sexual mojo than older men can, so the study may have had some inherent bias.)

To say that nothing supports the use of protons, says Keole, “is simply false”. Given the early data and the known physical properties of protons, he says, “I firmly believe they are superior to targeted x-ray treatments for prostate cancer”.

It is that kind of endorsement that men like John Bell find when they start googling. One of the biggest resources is protonbob.com, founded by Bob Marckini, a retired manufacturing executive from Massachusetts who was treated at Loma Linda in 2000, and who has a missionary zeal in promoting protons through his website and self-published book You Can Beat Prostate Cancer: And You Don’t Need Surgery to Do It. “You can’t argue with the laws of physics,” says Marckini.

He was like most men with early prostate cancer – the threat of death was secondary to the threat of side-effects. “There aren’t too many things more important to a man than sexual function and bladder control,” he says. His own treatments were so exact that he hit the golf course every afternoon. “My friends were sending flowers and get-well cards, and I was feeling guilty.”

Testimonials on Marckini’s website often run along these lines: “I played golf and swam at the beach during my treatment,” says one. The National Association for Proton Therapy assures patients that they can “play golf, tennis, swim, walk, run, work out in a gym, or go on a ‘radiation vacation’” – which has actually become part of the appeal, in Zietman’s view. That’s because until recently, access to the treatment had been limited to men with the time and means to relocate, so patients felt as if they were joining a privileged club. “It’s acquired a very high-end following,” he says.

But that sense of exclusivity will probably fade as more centres open. The cost may drop, too, which is a point that proton advocates make – as if a proton-beam generator were just another mobile phone or flatscreen TV. But this rationale (ie, we need more units to make the treatment affordable) bothers people like Dr Elliott Fisher, who, as director of the Centre for Population Health at the Dartmouth Institute for Health Policy and Clinical Practice, spends a lot of time contemplating the cost of health care. “I believe in technological progress,” he says. Nonetheless, “how many proton-beam accelerators do we need in a given city? How many in a given country? I want these decisions to be made thoughtfully.”

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Above all, says Bob Hill, the author of the self-published Dead Men Don’t Have Sex: A Guy’s Guide to Surviving Prostate Cancer, men shouldn’t be so eager for protons that they ignore other options. Hill was diagnosed with prostate cancer in 2004, aged 47, and underwent surgery. Even if proton therapy didn’t have lofty claims, men would be attracted to it because it represents the latest technology, he says. “What do you think sells the newest plasma TV or GPS system?”

He also says that a man who has a positive experience wants to convert others. “Once they go through this, guys almost become evangelists telling other guys this is the way to go. I had the same experience with laparoscopic surgery,” he says. “The downside to that, for some guys, is that it makes them think they don’t have any other options. Prostate cancer is typically a slow-growing cancer. I want men to take the time to make their own decisions.”

For his part, John Bell remains happy with his choice of protons. He’s had no side-effects from the treatment. He sometimes has to enlist a little blue friend when he’s ready for action – but he did before protons, too. (“The way it goes” at his age, he laments.) He is unwavering in his belief that he received the best treatment. Maybe one day, researchers will know for certain whether he’s right.