Purpose of Review and Prior USPSTF Recommendation

Screening with prostate-specific antigen (PSA) testing can detect prostate cancer in earlier, asymptomatic stages, when treatments might be more effective. In 2008, based on an earlier systematic review that focused on studies of PSA-based screening versus no screening,¹ the U.S. Preventive Services Task Force (USPSTF) found insufficient evidence to determine the balance of benefits and harms associated with prostate cancer screening in men younger than age 75 years (I statement), and recommended against screening in men ages 75 years or older (grade D recommendation).² See Appendix A for a list of all abbreviations included in this report.

Once prostate cancer has been detected by screening, treatments are frequently initiated. Understanding the benefits and harms associated with such treatments is therefore critical for informing screening decisions. Evidence on benefits and harms of treatments for localized prostate cancer was last reviewed by the USPSTF in 2002.³ This report summarizes the evidence on benefits and harms of treatment for screen-detected or early-stage prostate cancer, with an emphasis on studies published since 2002.

Condition Definition

Prostate cancer is the most commonly diagnosed cancer in American men.^4–6 Adenocarcinoma accounts for over 95% of all prostate cancer cases. Prostate cancer is typically staged according to the American Joint Committee on Cancer’s tumor, node, metastasis (TNM) system, in which the tumor stage (T) is based on the extent of penetration or invasion beyond the prostatic capsule into adjacent structures (Table 1). Localized prostate cancer is classified as stages T1 (non-palpable) and T2 (palpable) and is confined within the prostatic capsule. The likelihood of progression to invasive cancer is associated with the presence of more poorly differentiated cells and other histopathologic features.

Table 1

Prostate Cancer Tumor Staging.

This review focuses on the benefits and harms of treatments for screen-detected prostate cancer. However, many studies do not report how prostate cancer was initially detected. Therefore, we also included studies of treatments for localized (stages T1 and T2) prostate cancer, which is far more frequently detected by screening than more advanced cancer. Among newly diagnosed patients in 2004–2005, 94% had clinically localized prostate cancer.⁷

Prevalence and Burden of Disease

Within the era of PSA testing, an estimated 16% of men will receive a diagnosis of prostate cancer sometime during their lifetime,⁵ and about 2.2 million American men are estimated to be living with prostate cancer.⁸ In 2010, approximately 217,000 prostate cancer diagnoses and 32,000 prostate cancer deaths were expected in U.S. men.⁴ The likelihood of prostate cancer increases with age, particularly starting at around age 45 years.

Prostate cancer is the second leading cause of cancer-related death in American men.⁶ Despite an increase in prostate cancer diagnoses since the start of the prostate cancer screening era, the risk of dying from prostate cancer has remained relatively stable at around 3%.⁹ Since the adoption of PSA-based screening in the early 1990s, prostate cancer is being detected and treated earlier. Approximately 80% to 90% of men with prostate cancer have clinically localized disease.¹⁰ Survival following a diagnosis of localized prostate cancer has improved in the prostate cancer screening era.⁹ This may be due to advances in medical care or earlier detection, but could also be spurious due to additional lead time, overdiagnosis related to PSA testing, grade migration, or other factors.¹¹

Etiology and Natural History

The natural history of clinically localized disease varies. The tumor grade, often assessed using the Gleason score, is an important marker of tumor aggressiveness. Tumors that remain localized to the prostate are often asymptomatic, but may cause symptoms of bladder outlet obstruction. Such types of cancer generally do not affect survival. On the other hand, tumors that spread beyond the prostate to invade local structures or metastasize can have severe negative impacts on quality of life and mortality.¹²

The etiology of prostate cancer is not completely understood. Men with 5-alpha-reductase deficiency do not develop prostate cancer, suggesting that androgenic hormones play some role in pathogenesis.¹³

Risk Factors

Age, race, and family history are well-established risk factors for prostate cancer. Age is the strongest risk factor, with over 80% of prostate cancer diagnoses occurring in men older than age 65 years.¹⁴ The degree to which the incidence of prostate cancer increases exponentially with age is greater than with any other cancer.¹⁴ Autopsy studies found that as many as 75% of men older than age 85 years have prostate cancer at the time of death.¹⁵

Among U.S. men, black men have the highest incidence rates of prostate cancer, at 226 cases per 100,000 person-years.⁶ White men have an incidence of 145 per 100,000, Hispanic men have an incidence of 122 per 100,000, and Asian/Pacific Islander and Native American men have incidence rates of 78 and 72 per 100,000, respectively.

Family history is another risk factor for prostate cancer. Having a first-degree relative with a history of prostate cancer increases the risk two- to three-fold.^14,15 Data from studies of twins suggest that 42% of the risk of prostate cancer may be accounted for by genetic factors.¹⁴ However, the exact genes responsible for the development of prostate cancer are not known.¹⁴

Other potential risk factors such as endogenous levels of androgens and other hormones (vitamin D levels, insulin-like growth factors), differences in diet and use of vitamin supplements, obesity, inflammation, and vasectomy status may also be associated with prostate cancer risk, but evidence is less consistent, or associations are less strong.¹⁴

Rationale for Screening

The primary rationale for screening with PSA testing is to identify high-grade, localized prostate cancer at earlier, asymptomatic stages, in order to enhance the chances of a cure. Screening also identifies lower-grade, localized prostate cancer, for which benefits of earlier treatment are less clear.

Interventions/Treatment

This systematic evidence review evaluates common treatment options for men with localized prostate cancer, including radical prostatectomy (retropubic, perineal, and laparoscopic [with or without robotic assistance]), radiation therapy (external beam radiation therapy [EBRT] and brachytherapy), and, less commonly, androgen deprivation therapy (ADT), cryoablation, and high-intensity focused ultrasonography (HIFU) (Table 2). Other treatments for localized prostate cancer are watchful waiting and active surveillance. Although these terms are not well defined in the published literature and have sometimes been used interchangeably, active surveillance implies a higher degree of monitoring (including PSA levels and prostatic biopsies) in order to guide the decision of when to intervene, whereas watchful waiting implies a more passive approach focused on treatment of symptoms associated with disease progression.¹⁶ The choice of therapy depends on a number of factors, including cancer stage, histologic grade, presence of comorbidities, and patient preferences.

Table 2

Treatments for Localized Prostate Cancer.

Recommendations of Other Groups

Prostate cancer screening recommendations from other groups are summarized in Table 3. The American Urological Association,¹⁷ National Comprehensive Cancer Network,¹⁸ and Prostate Cancer Canada¹⁹ recommend that clinicians consider screening (or offering screening) for prostate cancer with PSA testing beginning at age 40 years. Other groups, such as the American Cancer Society,²⁰ European Association of Urologists,²¹ American Academy of Preventive Medicine,²² American Academy of Family Physicians,²³ United Kingdom National Health Service,²⁴ National Health Committee of New Zealand,²⁵ and Cancer Council of Australia²⁶ do not recommend prostate cancer screening, though many suggest that clinicians provide information about the potential benefits and harms of screening in order to help patients make an informed screening decision.

Table 3

Recommendations of Other Groups.