Disease-a-Month 60 (2014) 150–154

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A review of the current epidemiology and treatment options for prostate cancer Daniel M. Saman, DrPH, MPH, CPH, Andrine M. Lemieux, PhD, May Nawal Lutfiyya, PhD, FACE, Martin S. Lipsky, MD

Introduction Prostate cancer—the 2nd leading cause of cancer death among US men—affects 1 in 7 men at some point in their lifetime.1 Nearly 1 in 36 men die from prostate cancer in the US annually. The American Cancer Society estimates that in 2013 there will be about 239,000 new cases of diagnosed prostate cancer, and about 30,000 deaths due to prostate cancer.2 The overall ageadjusted annual incidence rate is 152 per 100,000 men, but the incidence varies widely across different race and ethnicity categories. For example, the annual incidence rate for Caucasian men is 144.9 per 100,000 men, while for African-American men it is 228.5 per 100,000.1 Native American/Alaska Native men have the lowest annual incidence rate at 77.8 per 100,000 men. Prostate cancer mostly affects older men, with about 60% of cases diagnosed in men 65 years or older and with 67 years being the average age at diagnosis.2 Relative to stage of diagnosis, local and regional stages have a 100% 5-year survival rate. However, distant-stage prostate cancer (which has spread to distant lymph nodes, bones, or other organs) has a 28% 5-year survival rate.2 The purpose of this review is to explain the most important issues surrounding prostate cancer and to offer primary care providers up-to-date information on guidelines and recommendations. The ultimate intention of this review is that it will assist primary care providers in the informed decision-making process that we advise should take place between physician and patient.

Risk factors Several risk factors have been identified regarding the development of prostate cancer. Most notable is age; it is rare for men younger than 40 years to develop prostate cancer.2 A recent study examining data from the Health Professionals Follow-Up Study found that smoking history, taller height, higher BMI, family history, high caloric intakes, calcium, and alphalinolenic acid, all significantly increased risk for fatal prostate cancer.3 This study also found that higher physical activity levels were associated with lowered prostate cancer risk,3 which appears http://dx.doi.org/10.1016/j.disamonth.2014.02.003 0011-5029 & 2014 Elsevier Inc. All rights reserved.

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to apply to Caucasian but not African-American men.4 This indicates that the mechanisms behind prostate cancer are complex and that risk factors are still being understood. Furthermore, Singh et al.4 demonstrated that future research is still needed to identify risk factors. Recent research has also suggested that patients living in rural communities are less likely to receive definitive surgery for early-stage prostate cancer for reasons that were not related to either travel burden to seek treatment or use of active surveillance.5 This rural–urban disparity in care is variable across states.6 Although it has been noted that the majority of patients in rural states receive definitive treatment of their cancer, the source of this rural/urban variability in care is uncertain.5

Screening Prostate cancer is a slow-growing tumor with very few symptoms, particularly early in the development of the disease. The development of the prostate-specific antigen test (PSA) in the 1980s and FDA approval of screening with PSA in the mid-1990s led to cancer diagnoses with increasingly lower PSA levels (PSA o 4 ng/ml) at increasingly younger ages.7 With the use of serial PSA screening, identification of men at low risk of dying from prostate cancer is possible, though annual PSA screening is currently considered controversial. The incidence of men diagnosed with prostate cancer and at low risk for aggressive disease, as defined by a combination of PSA levels ( o 10 ng/ml), Gleason biopsy scores (o 6), and early clinical staging, has increased 85% between 2004 and 2008.8 Despite being categorized as low risk of death from prostate cancer, the use of advanced treatment technologies continues to rise.8 This use of advanced techniques has been called into question and described as an overuse of treatment.9 Annual screening of average-risk men for prostate cancer with PSA is no longer recommended by the United States Preventive Services Task Force (USPSTF),10 a decision that has been controversial.7,9 The ultimate rationale for preventive screening measures is to detect cancers early and reduce mortality. Digital rectal exams were the screening test of choice for many years but usually detected prostate cancers at advanced stages.11 The PSA test was widely available as a screening option in the late 1980s, and by 2001 about 75% of men 50 years or older had undergone PSA testing.12 The controversy surrounding the PSA is that there has yet to be evidence that PSA testing reduces mortality from prostate cancer. In fact, a normal PSA value does not mean the nonexistence of prostate cancer. The Prostate Cancer Prevention Trial found that 15% of men with normal PSA values actually had prostate cancer.13 In addition, there are serious potential harms of PSA screening, with an estimated 23–42% of PSA-detected cancers overdiagnosed and not expected to cause clinical problems during the life of the diagnosed patient.14 An additional problem annual screening presents is that of managing an early-stage diagnosis. The main concern is that there is a level of uncertainty about treatment options of early-stage identification of prostate cancer,15 with the dilemma of trying to avoid both undertreatment and overtreatment of the disease.

Psychological and physical burden of prostate cancer With increasingly earlier diagnoses of low-risk prostate cancer, it is clear that men are more likely to die with the cancer than from the cancer. Diagnosis of a localized or regional cancer (lymph nodes only) carries a 100% 5-year survival rate and 3% decline in mortality from more severe disease from 2004 to 2010.1 As of January 1, 2010 there were over 2.5 million men living with prostate cancer.1 Living with the disease, however, has significant impacts on quality of life including mental health. Decreased sexual functioning, urinary incontinence, and changes in bowel function may occur prior to treatment.7 Treatment itself may also further diminish quality of life.16 Psychologically, the majority of men experience negative, intrusive thoughts about their cancer diagnosis prior to surgical intervention, which nearly quadruples the chance of postsurgical anxiety symptoms and doubles the likelihood of depressed mood.17 There is evidence,

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however, that overall quality of life for patients has improved from 1999 to 2011.7 With the proscription against the use of universal screening, watchful waiting or active surveillance has become increasingly preferred for younger men and those at low risk of dying from prostate cancer. This change in recommendations was not initially accepted by both clinicians and patients, but a study of online patient communications suggests that both providers and patients are increasingly accepting of active surveillance rather than aggressive treatment.18

Recommendations As primary care providers work with patients, several recommendations can be made. First, receiving the diagnosis of cancer is a frightening experience that can, for some patients, increase the risk of clinically significant anxiety and depression. Screening patients for either is strongly recommended. The Patient Health Questionnaire-9 (PHQ-9) is a frequently used depression screen.19 How a provider interacts with patients may depend upon the geographic location of the practice and the patients seen in that practice. Within rural communities, patients place a higher degree of trust, and therefore social influence, in their providers and will use this trust on which to base their decisions to participate in cancer screening.20 This is not surprising but places heavy responsibility on the provider practicing in rural communities. Patients report confusion over the usefulness of screening, frustration over physician uncertainty, and a desire to see a new medical specialty specific to active surveillance.18,20 In addition, reviewing the complex options for treatment can be distressing and patients are increasingly asking for more specific information about options. Research has shown that patients want to understand the changes in recommended treatment (in particular, active surveillance for low-risk cancers) and, more importantly, the opportunity to review patient-friendly data behind preference for watchful waiting and active surveillance as viable options to more aggressive and potentially negative medical procedures.18 Several additional recommendations can be made to primary care providers to improve clinical practice related to prostate cancer and screening. First, providers and patients should discuss the risks and benefits of PSA screening. PSA screening is complex and men considering it should receive some support when making their decisions, ultimately leading to informed, shared decision making.21 Such ideal informed decision making with patient and physician discussing the harms and benefits is currently not the norm.22 Though clinical demands on a provider's time make informed decision making difficult to achieve, certain tools such as “decision aids” (e.g., video, internet materials, and written materials) have been shown to significantly increase patients' knowledge of prostate cancer and screening and decrease PSA screening.23 In addition to assisting patients navigate through the wealth of data related to screening for prostate cancer and providing follow-up screening for negative emotional reactions to the diagnosis and treatment of prostate cancer for those diagnosed, primary care providers can provide patients with support, information, treatment, and referral for the decreased quality of life that can occur with aggressive treatment of prostate cancer. Once positively screened, careful monitoring and follow-up evaluation with the PHQ-9 or other mental health screening tools will be important. Careful attention to suicidal ideation is also warranted.24 For those demonstrating increased anxiety and depression secondary to these issues, pharmacotherapy may be necessary. Issues such as incontinence and erectile dysfunction can be addressed with education, referral to ancillary therapies, medication, and support. Establishing and maintaining good working relationships with community-based marriage and family therapists, primary care embedded behavioral health care coordinators, or health psychologists as a source of referrals will be important for patients where incontinence and erectile dysfunction negatively impacts marital relationships. Despite increased acceptance of mental health care in the media and popular press, patients still continue to seek advice from their primary care provider and “social permission” to access mental health services related to sexual recovery following treatment for prostate cancer.25,26

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Conclusions The complexity of prostate cancer and screening necessitates shared informed decision making between health care providers and patients. Though there is a real difficulty to understanding PSA screening and prostate cancer for both providers and patients, there are also clear take-away messages that should be understood and incorporated in practice: 1. Prostate cancer occurs mostly among men older than 60 years. 2. Digital rectal exams and PSA screenings have not been shown to reduce mortality from prostate cancer. 3. PSA screening comes with risks, including overdiagnosis and can lead to biopsy that can cause psychological (depression) and physical distress (incontinence and erectile dysfunction). 4. There are currently no hard guidelines for treatment of early-stage prostate cancer. 5. Informed decision making should take place between physician and patient.

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24. Andrine M. Lemieux, Daniel M. Saman, M. Nawal Lutfiyya. Men and suicide in primary care. Dis Mon. in this issue. 25. Nelson CJ, Kenowitz J. Communication and intimacy-enhancing interventions for men diagnosed with prostate cancer and their partners. J Sex Med. 2013;10(suppl 1):127–132. 26. Wittman D, Northouse L, Foley S, et al. The psychosocial aspects of sexual recovery after prostate cancer treatment. Int J Impot Res. 2009;21(2):99–106.

A review of the current epidemiology and treatment options for prostate cancer.

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