In recent years, patients with cancer have had the benefit of much high technology: proton-beam radiotherapy, intensity-modulated radiation therapy, various minimally invasive surgery techniques, and robots in the operating room. They all receive hype in the professional and public press, and patients and physicians demand their use. They are all more expensive—many wildly so—than the techniques they replace. In light of this trend, a recent National Cancer Policy Forum workshop titled “Appropriate Use of Advanced Technologies for Radiation Therapy and Surgery in Oncology” sought to examine the clinical benefits and comparative effectiveness of emerging advanced technologies for cancer treatment in radiotherapy and surgery.
“The increased cost of novel treatments without adequate assessment on patient outcomes warrants further discussion,” said Ralph R. Weichselbaum, MD, Chair of Radiation and Cellular Oncology at the University of Chicago Medicine and Planning Committee Co-Chair of the workshop. “We need a critical assessment of the clinical [efficacy] and cost-effectiveness of emerging technologies in radiation and surgery.”
In addition, new technology often dominates discussions of value in health care, said Ya-Chen Tina Shih, PhD, Planning Committee Co-Chair. The goal, she said, is to find the best treatments that patients and the health-care system can afford. However, evaluating the clinical benefit of new devices is more difficult than testing new drugs due to the difference in regulatory oversights. Unlike new drugs that require clinical trials for U.S. Food and Drug Administration approval, devices often proliferate the market without evidence established in clinical trials.
Advances in Radiotherapy
Radiation technology has been burgeoning of late, with intensity-modulated radiation therapy, various forms of stereotactic radiotherapy, particle beam therapy, and proton-beam radiotherapy. They all have the potential for better clinical outcomes and reduced treatment-related morbidity, but they are all significantly more expensive than older techniques. Moreover, some do not necessarily confer extra benefit.
Some of the “sexy” new machinery may be better than its older counterparts, and although there is some evidence to that effect, there is insufficient comparative research. This is especially troubling, because about half of all patients with cancer receive radiotherapy.
“There are three basic principles underlying radiotherapy,” said Anthony Zietman, MD, Associate Director, Harvard Radiation Oncology and Director, Genitourinary Service, Massachusetts General Hospital: direct radiation-related complications do not occur in nonirradiated tissue; irradiating normal tissue does not benefit patients; and the therapeutic ratio can be optimized by maximizing the radiation dose to the tumor and minimizing the normal tissue dose.
Although these principles appear to clearly obvious, until recently, radiation oncologists have not been able to fully protect normal tissue, even as they did a good job irradiating tumors. Now there is proton-beam radiotherapy, the “point of the arrow,” as Dr. Zietman called it.
Traditional x-rays (photons) attenuate progressively with the depth of tissue, but they continue to deposit radiation beyond the tumor target, thus bathing normal tissue in unwanted radiation. However, proton therapy has a precisely defined range with no radiation delivered beyond a specified point. Hence, there is no damage to normal tissue.
Although using proton-beam radiotherapy may seem like a no-brainer in theory, it may not necessarily be the case in practice. The technology is complicated, the machinery is enormous and tremendously heavy (requiring its own real estate), and the cost ranges in the hundreds of millions for its initial installation and many millions each year for its use and maintenance. Very few cancer centers have the required resources.
Proton beams are generated by a cyclotron, which accelerates hydrogen protons to two-thirds the speed of light. The hydrogen protons are then shot through and focused by magnets toward a gantry that can rotate 360° around the patient. Inside the gantry is a nozzle that weighs 21,000 pounds. This nozzle guides the beam to the patient who, in schematic depictions, appears no bigger than a bug amid the gigantic machinery.
There are currently 14 of these behemoths in the United States, 11 are under construction, and more are in the offing.
Proton-beam radiotherapy has clinical advantages, said Dr. Zietman. The integral dose of radiation is smaller, and there is no exit dose. Therefore, it improves acute treatment tolerance, allows delivery of higher doses of radiation, and can be integrated with systemic chemotherapy. It also reduces late effects.
It is thought that children have the most to gain from proton therapy because of the profoundly negative effects of any type of radiation on growth and development as well as a substantial risk of radiation-induced cancers over the remainder of their lives. There is, however, no classic comparative effectiveness research to prove this claims because most physicians would be uncomfortable randomizing their pediatric patients is such a trial in which the conventional radiation arm is very likely to prove inferior.
Adult indications for protons include tumors of the skull base, eyes, spine, and sacrum. “It’s not so much that the evidence is strong for these indications but rather that the alternatives are unacceptable,” said Dr. Zietman.
Randomized controlled trials of proton-beam radiotherapy in both children and adults are problematic. There are ethical objections; trials need to be very large and very long, and the advantages are small and arrive late; and the initial investment for the technology is huge—perhaps too big for a treatment that may have limited advantages. Despite these considerations, Dr. Zietman said proton-beam radiotherapy is here to stay for a number of reasons. The treatment can be accurate, effective, and perhaps the best choice for pediatric solid tumors and some adult tumors. It rides the current minimally invasive popularity wave. Its technical and biologic advances create a “personalized” dose. New centers are quickly being established around the world.
Money Still Matters
Even if clinical research indicated that proton-beam therapy is an unequivocally good thing, cost remains a problem. James Yu, MD, Associate Professor of Therapeutic Radiology, Yale University, said that cost has always been problematic, just not as dramatic as it is now. He noted that in 1979, the National Research Council reported expenditures of $4 billion for new technology, and no one knew whether it did any good. That sum now seems downright paltry.
The personal “financial toxicity” of health care is staggering now, he said, and the burden affects the quality of life of patients with cancer, so even though a treatment is physically safe, it can have an ultimately negative affect. “Therefore, rejecting low value or overly expensive treatments should be a top priority.”
What about Medicare, which pays for most of it? Reimbursement for intensity-modulated radiation therapy and proton-beam radiotherapy has surpassed older technologies, and the cost is passed on to taxpayers and patients. For example, in prostate cancer in 2005, three-dimensional radiotherapy costs $20,588; intensity-modulated radiation therapy costs $31,574; and in 2008 the price tag for proton-beam radiotherapy is $13,753 more than intensity-modulated radiation therapy. In 2005, intensity-modulated radiation therapy cost Medicare $282 million more than three-dimensional radiotherapy for prostate cancer, though reimbursement has steadily declined over the past decade. In its place, proton-beam radiotherapy has the potential to cost Medicare hundreds of millions of dollars more than intensity-modulated radiation therapy —for prostate cancer alone.
Dr. Yu said that although about 50% of all patients with cancer require radiotherapy, only 1.6% of all National Institutes of Health cancer funding went to radiation research in 2013. This amount should be significantly increased, he added. Moreover, insurance coverage with development of evidence is not applied evenly; therefore, all patients undergoing treatment with a new technology should be enrolled in a study.
Deciding on coverage of any device or technology requires review of high-quality studies that provide direct evidence of positive outcomes. The problem is that many, probably most, have not benefited from such studies. Although there is intense public interest in covering high-tech devices, published evidence has been suggestive of benefit but insufficient. In addition, clinical trials usually do not have enough subjects representative of the Medicare population.
Advances in Surgery
The challenge in surgery, said David C. Miller, MD, Associate Professor of Urology, University of Michigan Medical School, Ann Arbor, is to enhance accessibility to minimally invasive procedures.
One such avenue is the popular, but not necessarily always better, da Vinci Surgical System for robotic-assisted laparoscopic surgery, cleared by the U.S. Food and Drug Administration in 2000. It carries a number of advantages:
- Better visualization of the operative field: three-dimensional, high-definition, and 10x magnification.
- Greater flexibility of the robot arm’s “wrist” than a natural wrist.
- More precise movements and dampening of hand tremors.
- Improved ergonomics.
- Facilitation of laparoscopic surgery, which carries the advantages of smaller incisions, shorter hospital stay, and easier short-term recovery.
The da Vinci Surgical System enjoyed widespread and almost immediate success. For example, of the 111 surgeons in Michigan who performed 3,730 prostatectomies between March 2012 and June 2015, 93% used this system over open surgery. The robot is also used for cancer of the bladder, kidneys, uterus, cervix, ovaries, colon, pancreas, thyroid, lung, esophagus, tonsil, and tongue base.
It’s popular, but is it really better? No one knows for sure because although there are observational studies about its advantages, except for cystectomy, rectal excision, and radical prostatectomy, there are few randomized controlled trials. And there is no obvious reason to believe it is better for cancer control or that it provides better functional outcomes such as urinary control and erectile function, said Dr. Miller. In addition, current data are somewhat mixed regarding the benefits of robotic surgery for functional outcomes such as urinary control and erectile function.
Like proton-beam radiotherapy, the da Vinci Surgical System is often more expensive than open surgery. Each unit costs more than $1 million; annual service costs at least $150,000; the instruments are disposable and cost about $2,000 per case. At least one study estimated that this adds up to an average of $3,200 more per case than open surgery.
Is it worth it? “We don’t know yet,” said Dr. Miller. “The da Vinci has definite benefits and some unintended adverse consequences, including higher cost. Comparative clinical [efficacy] and cost-effectiveness has not been fully defined, so we need to make a greater effort to improve its performance and outcomes.” ■
Disclosure: Drs. Weichselbaum, Shih, Zietman, and Miller reported no potential conflicts of interest. Dr. Yu has received research funding from 21st Century Oncology LLC.
