Prostate cancer is the second most common cancer among men in the United States, as well as the third leading cause of cancer-related death.1 More than 160,000 men are diagnosed with prostate cancer annually, and approximately 25,000 men die of the disease per year.2 Despite its prevalence, a level of uncertainty continues to persist about the most appropriate treatment methods for men diagnosed with the disease.3
For men with aggressive or high-risk disease, radical prostatectomy and radiation serve as recommended treatments. Performed as an open or robotic surgery, prostatectomy involves the removal of the prostate gland and select surrounding nerves, after which the bladder is reconnected to the urethra.4 Although these procedures can functionally cure prostate cancer, the potentially associated adverse events—including urinary and bowel incontinence, urinary dribbling, erectile dysfunction, and sterility—can lead to a sharp decline in quality of life.5 Because the effects of treatment can possibly outweigh its therapeutic value, many in the urologic oncology community have suggested active surveillance—defined as the watchful observation of a patient’s condition, with treatment withheld until signs of disease progression—for men with indolent, low-grade, or low-risk prostate cancer.6
Much of the debate surrounding the diagnosis and treatment of prostate cancer centers around a 2012 United States Preventive Services Task Force (USPSTF) recommendation against prostate-specific antigen (PSA) screening for men of all ages.7 This recommendation built upon guidelines issued in 2008 that discouraged PSA screenings among men aged 75 years or older, or men with a life expectancy of less than 10 years.8 The USPSTF cited the high rate of false positive results seen in PSA tests—which measure the levels of proteins produced by the prostate in the bloodstream of asymptomatic men9—coupled with the frequent inability to differentiate between indolent and aggressive prostate tumors as a rationale for their recommendations. In contrast, the American Urological Association continues to recommend PSA screening in men aged between 55 and 69 years, with screening recommendations extended to younger men (aged 40-54 years) with risk factors for prostate cancer, such as positive family history or African American race.10
The differing recommendations between general and specialized organizations have led to a debate as to whether men should or should not receive PSA testing, as well as the appropriate level of treatment among men who have been diagnosed with prostate cancer. A study published in Health Affairs found that population-based treatment rates for prostate cancer declined by 42% in the period during which the USPSTF first issued its screening recommendations; however, among men with prostate cancer, treatment declined by only 8%.11 In order to better understand the sharp divide in treatment receipt, Journal of Clinical Pathways spoke with Tudor Borza, MD, clinical lecturer in urology at University of Michigan Medical School (Ann Arbor, MI), the study’s lead researcher.
The appropriate screening measures for prostate cancer has been a frequent topic of discussion in the oncology world. Why is that?
After skin cancer, prostate cancer is the most common cancer in men, and the degrees of severity in prostate cancer can range from low-risk—which does not cause harm—to high-risk, which is a deadly cancer. The difference in severity is not something that was necessarily recognized when the PSA test was developed in the early 1990s, and it was not until the late 2000s when we began getting data from randomized trials evaluating whether or not screening for prostate cancer saved lives. Urologists and other doctors began to understand that some patients do not benefit from screening, and that some harms are associated with the screening, diagnosis, and treatment of prostate cancer. In the wake of those trials, the USPSTF initially recommended against screening in men older than 75 years; subsequently, they revised their recommendation against screening for all men.
However, the second recommendation from the USPSTF was based on these randomized trials, which were eventually judged to be less credible than initially thought. This was due to really high rates of PSA testing in men who were randomly assigned not to receive screening. The primary care doctors—who are really the target for the USPSTF recommendations—see the recommendations and largely bought into the idea of decreased screening rather quickly. Urologists and treating specialists really have not bought into the recommendations all that much, and are more likely to follow screening guidelines from their own professional societies, like the American Urological Association, which still recommends screening for patients at the highest risk for cancer.
Would you say that the divide between primary care physicians and urologists is one of the reasons you decided to conduct your study in a twofold manner, focusing on both the general population and men diagnosed with prostate cancer?
That’s exactly right. We wanted to see if screening was really changing treatment rates—which would be apparent from looking at the overall population—or if it came down to differences in who was being treated. Over the period of time when these screening recommendations were being disseminated, treating specialists also began to use surveillance more frequently. That decision was made using data from trials showing that active surveillance and watchful waiting were safe options for appropriately selected men. Active surveillance can delay treatment until a patient becomes symptomatic or disease becomes more advanced. By studying treatment rates in the overall population, then looking just at men who were diagnosed, we were able to see how much of a component in the decrease could be attributed to screening, and how much could be attributed to surveillance. Both are intended to decrease overdiagnosis and overtreatment, which we know is occurring in prostate cancer.
Your paper found that the lowest treatment rates occurred among men with the highest risk for noncancer mortality, but that there was no change in treatment within this population. Could you explain why that is?
We know that men who have a life expectancy of less than 10 years are not likely to benefit from aggressive initial prostate cancer therapy. That has been shown by multiple studies, and is generally a well-accepted fact by most doctors. These men are the ones for whom we like to use what we call “watchful waiting,” which is not intended to provide upfront curative treatment. So, we expected that over our study period, we expected to see the greatest decline in treatment rates in this population. We actually didn’t—we found no change in the treatment rate for this group of men. One of the limitations of our study is that we didn’t have cancer severity data, so we do not know if these men were diagnosed with highly aggressive cancers that warranted initial treatment. But simply based on general population trends, we wouldn’t expect that to be the case.
You did find the largest changes occurred in the treatment periods concurrent with recommendation issuances. Is that an important distinction?
Definitely. It bolsters our hypothesis that screening recommendations are what drove down population-level treatment rates. We found the biggest changes occurred in 2009, when the screening recommendations against men older than 75 years came out; and from 2011 to 2012, coinciding with the USPSTF final recommendation against screening in all men. Both of those findings suggest that recommendations are responsible for the bulk of decreases in treatment rates.
It seems that there still remains a lot of misconceptions around screening and treatment. How best can doctors explain the state of the science?
The amount of lay media coverage of this topic has contributed to a lot of confusion among men in the general population. Further, the presence of opposing national-level recommendations from multiple medical bodies can be a cause for concern. As a urologist, I tend to lean towards the recommendations issued by our professional society, the American Urological Association. We know that there are men who are at risk for developing lethal prostate cancer. There are harms associated with PSA screening, but there are also potential harms when we do not screen.
I would encourage a patient to speak with his primary care doctor or his urologist about what it really means to have a PSA. By that I mean that if you have a PSA test, and that test is above a certain threshold, it will lead to a biopsy and a potential diagnosis of cancer, leading to treatment. So if you are not inclined to ever receive prostate cancer treatment—whether because of age or poor health—then you really should not get this test. Having an informed discussion with a physician is definitely a first step. That is what I tell my patients, and what I would tell any other man who is weighing this question.
What do you think is next for health services research in prostate cancer?
I think there are a couple of next steps. Really, we need to continue to see how the trends in diagnosis and treatment have changed over an even more recent period. We now know that active surveillance is gaining more buy-in among urologists, so there might be a sharp increase in surveillance over the last year or two. But we just do not have those data yet.
Another area of research should be defining who constitutes a low-risk patient, which has proven somewhat difficult in the past. We have PSA tests, prostate biopsies, prostate MRIs [magnetic resonance imaging], and genetic testing, but none of that has provided us with the ability to say to a man that he is not going to die of prostate cancer. This creates a lot of fear, and it can produce enough uncertainty that a lot of patients will choose to be treated for the disease, even when there might be a 75% to 90% chance that they wouldn’t need to be. That uncertainty is just too much for them. If we figure out what combination of current tests can really identify low-risk patients with a much higher certainty, that would be a huge asset. And if new tests become available, we will need to determine how they should be implemented, and for which patients.
References
1. Prostate cancer. American Cancer Society website. https://www.cancer.org/cancer/prostate-cancer.html. Accessed February 27, 2017.
2. Prostate cancer: causes, risks, and preventions. American Cancer Society website. https://www.cancer.org/cancer/prostate-cancer/causes-risks-prevention.html. Accessed February 27, 2017.
3. Treatment options. Prostate Cancer Foundation website. https://www.pcf.org/c/treatment-options/. Accessed February 27, 2017.
4. What is a radical prostatectomy? Prostate Cancer Foundation website. https://www.pcf.org/c/prostatectomy-surgery/. Accessed February 27, 2017.
5. Radical prostatectomy. Johns Hopkins Health Library website. https://www.hopkinsmedicine.org/healthlibrary/test_procedures/urology/radical_prostatectomy_92,P09111/. Accessed February 27, 2017.
6. Active surveillance. National Cancer Institute website. https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=616060. Accessed February 27, 2017.
7. Final recommendation statement: prostate cancer: screening. United States Preventive Services Task Force website. https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/prostate-cancer-screening#update-of-previous-uspstf-recommendation. Published May 22, 2012. Accessed February 27, 2017.
8. U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149(3):185-191.
9. Prostate-specific antigen (PSA) test. National Cancer Institute website. https://www.cancer.gov/types/prostate/psa-fact-sheet#q1. Accessed February 27, 2017.
10. Early detection of prostate cancer: AUA guideline. American Urological Association website. https://www.auanet.org/education/guidelines/prostate-cancer-detection.cfm. Published May 3, 2013. Accessed February 27, 2017.
11. Borza T, Kaufman SR, Shahinian VB, et al. Sharp decline in prostate cancer treatment among men in the general population, but not among diagnosed men. Health Aff (Millwood). 2017;36(10):108-115.
