Prostate Cancer: In the Eye of the Storm

Prostate cancer has been described as the litmus test for healthcare spending reform. The disease, which strikes 240,000 men in the U.S. every year, is at the core of contentious clinical, economic and policy debates. As researchers, policymakers, physicians and payers attempt to revise the script for prostate cancer management, the process may offer lessons that can be applied across the healthcare continuum.

The U.S. Preventive Services Task Force (USPSTF) issued the most recent strike in the debate on May 21 when it delivered a Grade D rating for prostate-specific antigen (PSA)-based screening for prostate cancer. There is "moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits,” according to USPSTF. The demotion incited a flurry of activity among many urologists and radiation oncologists, who defended the test as the only widely available screening test for the disease, and referred to the 40 percent drop in mortality from prostate cancer in the last 20 years with the availability of PSA-based screening. At the same time, the American Urological Association acknowledged not all prostate cancers are life-threatening.

Active surveillance: A tough sell

There’s the rub. “Prostate cancer is different. It is one of the rare conditions where there are credible data which suggest certain patient groups are unlikely to benefit from screening or treatment,” says Cary P. Gross, MD, of Yale University School of Medicine in New Haven, Conn. Data suggest the value of prostate cancer screening and treatment decreases with age. Many men older than 65 years, and certainly older than 75 years, should not be screened, says Gross, who adds that some older men with less aggressive tumors are unlikely to benefit from treatment.

National Comprehensive Cancer Network guidelines recommend active surveillance as one option for men with low-risk of prostate cancer, i.e. a Gleason score of 6 on biopsy and a PSA of less than 10. However, research suggests active surveillance is not being used as often as it could be, according to Ronald C. Chen, MD, MPH, of the department of radiation oncology at University of North Carolina in Chapel Hill.

In fact, data, guidelines and clinical practice appear to be misaligned. In a research letter published Feb. 27 in Archives of Internal Medicine, Gross and colleagues reported “increasingly aggressive treatment of patients with a low likelihood of clinical benefit, without a commensurate increase in the treatment of patients with a high likelihood of clinical benefit.” They found the use of curative treatment (radical prostatectomy or radiation therapy) increased from 38 percent of men with moderate-risk disease and a life expectancy of less than five years in 1998 to 1999 to 52.1 percent in 2006 to 2007. Use of curative therapy also trended up for men with low-risk tumors and life expectancies less than five years and five to 10 years. But curative therapy dipped among men with moderate-risk tumors and a life expectancy of more than 10 years.

The View from Above: Effective Therapies Rise to the Top

Most men with prostate cancer want to know if treatment will cure the disease and if they will be cancer-free. The Prostate Cancer Results Study group has surveyed the evidence and compiled it in a format to share with patients and physicians. The chart on the right shows results of studies which included at least 100 men with low-risk disease (stage T1 or T2a or b, Gleason score </= 6, PSA </= 10 ng/ml). According to the chart, the brachytherapy cluster indicates more studies showing longer, progression-free survival.

Source: Prostate Cancer Center of Seattle,BJU Int, 2012, Vol. 109 (Supp. 1), 8/29/12

It’s likely that several forces are at play. Reimbursement for treatment is higher than for surveillance, which may incentivize physicians to treat some patients with lower-risk disease. Urologists who own a linear accelerator can earn $4,000 to $10,000 for referring a patient to their equipment and therefore may be incentivized to treat with only that modality, says Peter D. Grimm, DO, of the Prostate Cancer Treatment Center in Seattle.

Joseph C. Hodges, MD, MBA, of University of Texas Southwestern Medical Center in Dallas, agrees. “Overtreatment is a direct result of poorly designed healthcare policy. The [Stark Law] loophole that allows a urologist to own pathology labs, surgical centers, imaging equipment and radiation treatment facilities directly fuels the overdiagnosis and overtreatment of prostate cancer.”

The motivation to treat extends beyond the financial. “It may be patient-driven as some patients are not comfortable watching a cancer without doing anything,” notes Chen. Targeted marketing to patients also may be a factor, adds Gross. The last few decades have witnessed a proliferation of billboards, radio and television ads promoting various approaches to treating prostate cancer. “There is no counter-balance that recommends active surveillance,” says Gross.

The solution requires systemic change and practice evolution. “All members of the prostate cancer care community need to consider how we can put the interests of patients first and foremost, how we can best communicate the potential harms and benefits of treatment, as well as how we can contribute to redesigning the healthcare system,” says Gross. The optimal healthcare system would ensure patients who need treatment can easily access it, provide patients a variety of therapeutic options, generate evidence about which treatments are effective and allow patients for whom it is appropriate to choose active surveillance, Gross continues.

One of the first steps may be semantic, says Bruce L. Jacobs, MD, a fellow in urologic oncology, endourology and health services research at the University of Michigan in Ann Arbor. Some experts have suggested renaming low-risk prostate cancer and using a term that does not contain the word "cancer" to alleviate the stigma associated with it. “This might reduce patient anxiety.”

Dollars and sense

There is good news about prostate cancer. It’s a slow-growing disease, and an assortment of good treatment options is available. The bad news? It’s a common disease that strikes one in six men. Plus, costs are skyrocketing.

The economic trickle begins with PSA screening, which has negligible costs at the individual level. The population-level costs, however, have devolved into a torrent. Screening begets imaging and biopsies and ultimately, treatment.

During the last two decades, treatments have been approved and reimbursed without adequate population-based follow-up. This boom has occurred in both surgery and radiation therapy. In the last 10 years, robotic prostatectomy has nearly replaced open prostatectomy and intensity-modulated radiation therapy (IMRT) has inched from bleeding edge to standard of care. Medicare started reimbursing for IMRT in 2002, and reimbursement for IMRT is more than $14,000 more per patient than 3D conformal therapy.

Favorable reimbursement, coupled with purported clinical advantages of IMRT, fueled an uptick in utilization. The use of IMRT vs. conformal radiation therapy increased from 0.15 percent in 2000 to 95.9 percent in 2008, Chen and colleagues reported April 18 in Journal of the American Medical Association (JAMA).

The result is a fiscal fiasco. Prostate cancer accounts for more than $7 billion in annual healthcare spending, and spending growth averaged 11 percent a year in the last decade.

And as experts survey the horizon, they note a similar upgrade from IMRT to proton therapy seems to be percolating. There are 10 proton therapy centers in the U.S., which carry a price tag in the $150 to $200 million range, with another five under construction and at least two more planned. The Agency for Healthcare Research and Quality reported the number of Medicare beneficiaries receiving proton beam therapy nearly doubled from 2006 to 2009. Approximately 75 percent of these patients were diagnosed with prostate cancer.

However, the heightened scrutiny on healthcare spending may shed new light on the black hole of clinical research for prostate cancer treatment. “It’s unclear whether or not these newer and more costly treatments really offer benefits to patients. That’s what we are trying to determine with comparative effectiveness research,” explains Chen.

The Institute of Medicine designated localized prostate cancer as a first quartile priority in its top 100 topics for comparative effectiveness research, and the American Recovery and Reinvestment Act of 2009 allocated $1.1 billion to comparative effectiveness research.

A new direction

The IMRT saga illustrates the perils of U.S. healthcare policy. Researchers understood the theoretical advantages of IMRT, including its capability to reduce radiation to the rectum and bladder; however, until recently, researchers had not identified improved patient outcomes with IMRT.

That’s because there are numerous challenges associated with comparing various prostate cancer treatment modalities. “Eighty percent of low-risk patients do well no matter what treatment is used,” says Grimm. Furthermore, most results appear promising in the first five years after treatment, he notes. Prostate cancer has a relatively protracted clinical course, so it’s important for research to examine data for 10 years or longer after treatment.

Survival is not a good endpoint, Grimm explains. Two patients who undergo different treatments may both be alive after 10 years, which suggests 100 percent success. However, if patient A requires hormone therapy for five years, the treatment is not successful, according to Grimm. “There are different ways to define efficacy. My way is to ask how effective the treatment is in getting rid of cancer the first time.”

Other key factors to assess are quality of life, side effects and costs. More than one decade after its introduction, data about IMRT are starting to accrue. IMRT patients were less likely to undergo additional cancer treatments than 3D conformal patients, Chen et al reported in the April 18 issue of JAMA. The IMRT group also had fewer gastrointestinal morbidities and hip fractures than men undergoing 3D conformal therapy, but were more likely to receive a diagnosis of erectile dysfunction.

Jay P. Ciezki, MD, of the department of radiation oncology at the Cleveland Clinic, and colleagues took a slightly different approach and analyzed the costs of treating toxicities. The researchers analyzed 16 years of data on 137,000 men with prostate cancer in the Surveillance, Epidemiology and End Results (SEER) Medicare-linked database. They compared three primary treatment modalities: external beam radiation, brachytherapy and surgery. After factoring in initial costs, treatment costs and toxicity costs, external beam radiation, which resulted in the greatest number of toxicities, proved to be the most expensive treatment.

Not all of Ciezki’s colleagues have welcomed the findings. The researchers have been criticized for the length of the study, which fails to account for improvements in delivering external beam radiation. However, they attempted to quiet the critics with a substudy reviewing IMRT, which had less follow-up. “Interestingly, even with that limitation, which suggests less time to express side effects after treatment, IMRT patients expressed more side effects than those who underwent standard radiation therapy. This is particularly ominous because if they had the same follow-up as standard therapy, we would anticipate additional toxicities.”

In his attempt to provide physicians and patients with an apples-to-apples comparison of various treatments, Grimm has gathered a worldwide group of 25 prostate cancer experts representing different disciplines to analyze and consolidate the data.

The group has reviewed more than 21,000 articles published since 2000, with 917 meeting its inclusion criteria: publication in a peer-reviewed journal, at least 100 patients and a minimum five-year follow-up. Grimm and colleagues have created slides, available to patients and their physicians, which plot these data for low, intermediate and high-risk patients.

Proliferating Protons

The number of proton therapy centers in the U.S. continues to grow. Although prostate cancer treatment represents a primary revenue source for these centers, evidence has not yet demonstrated its superiority compared with other treatment options. In operation   Under construction   In development   Announced

Source: National Association for Proton Therapy

Toward a new model

As policymakers and politicians strive to bend the cost curve of prostate cancer costs, three prerequisites are essential. “To help control cancer costs, we need to align patient preference, clinical evidence and financial incentives of the healthcare system. All three arms need to be moving in the same direction,” says Gross.

Physicians need to have the data, structure and support to share evidence about the efficacy, potential harms and potential benefits of treatment with patients. As these researchers demonstrate, the studies are in progress and pioneers are attempting to make information accessible to physicians.

However, referring to mixed evidence about IMRT, Jacobs says it may be too late to change practice patterns given the dissemination of the treatment. “We may be able to apply what we’ve learned to newer treatments like proton beam therapy. If robust evidence supporting proton beam therapy's superiority over existing treatments is lacking, then adopting it will not be worth its added expense." Proton beam therapy center construction costs hover between $150 and $200 million. At the individual level, treatment costs for proton therapy can reach $50,000 per patient.

In fact, if research demonstrates proton beam therapy is not better than IMRT for prostate cancer, there may be excess capacity in existing centers as many centers are treating a large number of prostate cancer patients, according to Chen.

At the payment level, most experts agree that the fee-for-service model does not provide the optimal approach to recommend active surveillance to patients for whom it is appropriate and also to incentivize providers to treat patients who are likely benefit from treatment.

Value-based insurance, which links the amount of reimbursement or co-pay to the potential utility or benefit of treatment is one option. “Payers should reimburse less for treatments administered to patients for whom evidence suggests that harms of treatment clearly outweigh the benefits because there’s little value to those treatments,” says Gross. Thus, fewer resources would be allocated to low benefit or potentially harmful treatments. However, payers in the U.S. have not yet moved toward the model.

Other potential fixes have gained some traction. Accountable care organizations that share responsibility for patients at the population level may incentivize providers to employ cost-effective treatments. Similarly, bundled payments also may discourage less efficient use of resources by linking payment for all services related to a diagnosis.

Strategies that have proven successful in other arenas also may be translated into prostate cancer treatment. Prior authorization has helped curb advanced imaging utilization. However, employing the method in prostate cancer treatment “would require defining appropriate treatment, a controversial term,” Jacobs wrote in the April issue of Health Affairs. In addition, reduced Medicare reimbursement for prostate cancer treatment could impact practice patterns.

Jacobs also cited coverage with evidence development as a strategy to meet patient demand while acquiring evidence. Under this model, Medicare would cover new treatments as long as patients participate in research to evaluate the effectiveness of the treatment.

While treatment options continue to multiply, policymakers are attempting to apply the brakes and develop a more efficacious and cost-effective model. Others from across the healthcare continuum are watching as they forge new ground.