Initial conservative management for men with low-risk prostate cancer (PCa), a strategy recommended in guidelines from major urology and oncology organizations, is increasing in the United States, but the extent to which this approach is used varies widely among urologists, practices, and facilities.1-4 Investigators cite multiple factors to explain the unequal uptake of such monitoring approaches as active surveillance (AS) and the less intensive watchful waiting (WW).

“Ethnicity, race, socioeconomic status, geography, educational background, and personal patient experiences all, in my opinion, have a significant impact on selection of primary treatment for prostate cancer,” said Udit Singhal, MD, of the University of Michigan in Ann Arbor, Michigan. “There are substantial provider-dependent factors as well, including physician background and level of training, payer/reimbursement status in a given region, availability of resources, or even ambiguity of clinical guidelines.”

In a recent study, Dr Singhal and colleagues documented wide variation in the use of WW for men with low-risk PCa in Michigan. The investigators examined data from the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry. MUSIC is a physician-led partnership of community and academic urology practices in Michigan. The study included 2393 men with PCa who had a life expectancy of less than 10 years at the time of their cancer diagnosis. Among the 358 men with low-risk PCa as defined by National Comprehensive Cancer Network (NCCN) criteria, 69.3% and 15.1% underwent AS and WW, respectively, and 15.6% received definitive treatment, according to study findings published in Urology.1 Rates varied widely among practices: 44% to 81% for AS, 6% to 35% for WW, and 0% to 30% for definitive treatment.

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“Integration of AS into practice requires navigation of numerous different criteria, and these are often institution- or practice-dependent,” Dr Singhal said. “In this sense I think it is difficult to achieve uniformity in AS for patients across practices. At the same time, urologists like to say that ‘no 2 prostate cancers are the same’ due to the clinical heterogeneity inherent in the disease, and therefore shared decision-making guides individual decisions.”

He said he believes a drive towards more uniform AS protocols would benefit both providers and patients. Current protocols have varying inclusion criteria and disparate outcomes, and this can lead to difficulties in comparing groups. “Developing a uniform AS protocol would standardize this approach for treating prostate cancer, similar to standard dosing of radiation or standard techniques for prostatectomy,” Dr Singhal said. 

Wide variation in AS use also emerged in a study of 2250 men diagnosed with PCa from January 2015 to November 2017 and who received care at facilities belonging to the Pennsylvania Urologic Regional Collaborative (PURC), a cooperative effort of urology practices in southeastern Pennsylvania and New Jersey.2 Overall, 57.4% of patients with very low- or low-risk PCa according to NCCN criteria received AS for initial management of their cancer. The AS rate, however, for these men varied widely among practitioners, ranging from 10% to 100%, investigators led by Adam C. Reese, MD, of Temple University School of Medicine in Philadelphia, Pennsylvania, reported in The Journal of Urology.2

In addition, a study of 20,597 men with low-risk PCa receiving care in the Veterans Affairs healthcare system found that although overall use of conservative management — either AS or WW — for low-risk PCa rose from 51% in 2010 to 76% in 2016, the proportion among facilities varied from 35% to 100%. The study also revealed geographical differences. Men receiving care at facilities in the Midwest and West had 23% and 36% increased odds, respectively, of undergoing conservative management compared with those receiving care at Northeast facilities.

The authors, led by Stacy Loeb, MD, of New York University in New York City, published their findings in European Urology, where they concluded that “even within an integrated health care system, there remains significant heterogeneity in the uptake of conservative management for low-risk prostate cancer.”3

Socioeconomic status (SES) might be among the reasons for heterogeneity in the uptake of AS or WW. A study led by Brandon A. Mahal, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, demonstrated that although use of these conservative approaches increased from 2010 to 2015 in the United States, their use varied by SES.4 AS or WW use for patients in the lowest, middle, and highest SES tertiles increased from 11.2% to 37.3%, 14.1% to 45.8%, and 17.6% to 46.4%, respectively, the investigators reported in Prostate Cancer and Prostatic Diseases. By 2015, patients in the lowest tertile had 27% decreased odds of being managed with AS or WW compared with those in the highest tertile.

Dr Reese, who led the PURC study, said the disparity in the use of AS among institutions could stem in part from significant variability in criteria used to identify patients who are eligible for AS. “Furthermore, the fact that some criteria are much more strict than others has significant implications on the percentage of men eligible for AS,” said Dr Reese, chief of urologic oncology and director of the urology resident program at Temple University. “Very stringent AS eligibility criteria will result in relatively few men eligible for AS and many men potentially undergoing unnecessary treatment. In contrast, lenient eligibility criteria will allow more men to pursue AS, but potentially with an increased risk of developing progressive or metastatic disease.”

Dr Reese said he believes provider-related factors play a large role in the use of AS in contemporary practice. “When providers believe in the efficacy of AS and provide patients with honest and objective data regarding the pros and cons of AS, I think that a large percentage of patients will be willing to accept AS as an initial management strategy.” Another factor potentially contributing to the variation in AS use is patients’ anxiety over their cancer diagnosis, he said.

Differences in the way physicians frame AS when counseling patients are probably the single biggest cause of variation in AS use, said Michael S. Leapman, MD, assistant professor of urology at the Yale School of Medicine in New Haven, Connecticut.

Patients’ perceptions about PCa, which might be influenced by personal experiences such as knowing somebody who suffered or died from PCa, can be an important factor in the care they choose, he said. A common first instinct for patients is to be treated right away rather than undergo monitoring, and physicians may also feel reluctant to encourage them to be monitored due to their own perceptions about the risk. Although there has been significant uptake of AS, many patients who are candidates for this approach still are treated for low-grade PCa. “One of many approaches needed to bridge the gap is to keep physicians updated about clinical guidelines, and also to understand values, preferences, and biases that the patient may enter the discussion with,” Dr Leapman said.

Clinical guidelines that recommend AS for low-risk PCa, such as those from the NCCN and American Urological Association, “do a very good job representing the current state of evidence” in support of AS and present clear recommendations, Dr Leapman said. Still, it is unclear whether physicians consult the guidelines or how much weight they place on the recommendations.

A potential way to address variation in AS use is to identify parts of the country with relatively high levels of definitive treatment for low-risk PCa and then ferret out the barriers to wider AS use, he said.

Urologist age and training environment also may influence their use of conservative measures. Most newly graduated urologists receive their training at academic medical centers, where AS is more likely to be used, Dr Leapman said. Thus, urologists emerging from academic medical centers could be more comfortable recommending surveillance, particularly if this approach was part of their training, he said.

Meanwhile, investigators believe there is room for improvement in the current conservative management strategies for low-risk PCa. For example, a subset of patients with relatively short life expectancies because of their age and comorbidities might not need the intense monitoring of AS and can instead be managed with WW. “There are certainly some patients for whom doing close monitoring and biopsies and PSA testing is probably unlikely to make a difference in what we do [as physicians],” said Dr Leapman, who coauthored a 2020 paper in European Urology Focus titled “When and How Should Active Surveillance for Prostate Cancer be De-Escalated?”5

Physicians err on the side of being overly cautious, “which is probably a good thing, but may expose patients who are older or who have other medical problems to needless invasive diagnostic testing to find small changes in their prostate,” he said.

A major challenge in identifying these patients is making accurate assessments of life expectancy, and then bringing that into discussions with patients, he said. “It’s always difficult when we have a patient in front us, to tell them, ‘We don’t think you’re going to be alive in 3 years, so we’re not going to follow [the cancer]. That’s a hard message to give, and one that we probably underperform in doing.”

Some patients start on AS but then reach an age at which findings from PSA tests, imaging studies, and biopsies would not affect their clinical management, Dr Leapman said. In such cases, it makes sense to considering transitioning patients to less intensive monitoring, he said.

Dr Reese agrees. “I certainly think it is appropriate to de-escalate the intensity of surveillance and transition towards a more watchful waiting approach as men age, or in those men with significant comorbidities.” he said. Prostate biopsies can result in complications, and therefore should be used judiciously in men with limited life expectancies.

Individual treatment decisions should be based on shared decision-making, “but as urologists, we must do a better job of offering WW as a reasonable alternative for the appropriately selected patient,” Dr Singhal said. AS is not without potential harm, and this can be avoided in men who may not necessarily benefit from this approach. For men with low-risk PCa and a life expectancy less than 10 years, he said, WW should be the preferred management strategy.

References

  1. Singhal U, Tosoian JJ, Qi J, et al. Overtreatment and underutilization of watchful waiting in men with limited life expectancy: An analysis of the Michigan Urological Surgery Improvement Collaborative registry. Urology. 2020;145:190-196. doi:10.1016/j.urology.2020.07.047
  2. Botejue M, Abbott D, Danella J, et al. Active surveillance as initial management of newly diagnosed prostate cancer: Data from the PURC. J Urol. 2019;201:929-936. doi:10.1016/j.juro.2018.10.018
  3. Loeb S, Byrne NK, Wang B, et al. Exploring variation in the use of conservative management for low-risk prostate cancer in the Veterans Affairs healthcare system. Eur Urol. 2020;77:683-686. doi:10.1016/j.eururo.2020.02.004
  4. Butler SS, Loeb S, Cole AP, et al. United States trends in active surveillance or watchful waiting across patient socioeconomic status from 2010 to 2015. Prostate Cancer Prostatic Dis. 2020;23:179-183. doi:10.1038/s41391-019-0175-9
  5. Rajwa P, Sprenkle PC, Leapman MS. When and how should active surveillance for prostate cancer be de-escalated? Published online February 1, 2020. Eur Urol Focus. doi:10.1016/j.euf.2020.01.001