Missing the Mark on Prostate-Specific Antigen Screening

Abstract

THE US PREVENTIVE SERVICES TASK FORCE RECENTLY issued a draft recommendation against prostatespecific antigen (PSA) screening for prostate cancer. After performing a rigorous review of the relevant empirical literature, the task force concluded with “moderate certainty” that the harms of PSA-based detection (eg, biopsy-related complications) and early intervention (eg, incontinence, erectile dysfunction) exceed the potential benefits. For this reason, the task force now proposes discouraging PSA screening among men who are free of symptoms suspicious for prostate cancer. Most clinicians are aware that PSA is an imperfect tool for the early detection of prostate cancer. First, rather than being focused on patients most likely to benefit from early detection, the use of PSA as a screening test is often undiscerning. Second, PSA-based screening can be inconclusive. As a consequence, for some patients this process can lead to a cycle of repeated venipuncture and biopsy, as well as psychological distress often referred to as “PSA anxiety.” Third, there can be collateral harm to patients in whom PSA screening detects a cancer that was never destined to cause death or morbidity. Fourth, the adverse effects of prostate cancer therapies remain too high, further justifying concerns about the balance of benefits and harms associated with PSA-based screening and early intervention. Even though the process undertaken by the US Preventive Services Task Force was rigorous and these issues were considered, it seems that their recommendations still miss the mark. Over the last 2 decades, and concurrent with the dissemination of PSA screening, there has been a significant decline in prostate cancer–specific mortality in the United States. However, this advance apparently was barely recognized in the deliberations and communications from the task force. This well-established epidemiological trend is difficult, if not impossible, to explain without accepting that early detection strategies built around PSA screening have allowed the identification and successful treatment of patients who would otherwise have died of biologically aggressive, clinically significant prostate cancers. Current evidence suggests that younger men (ie, 70 years) and those with higher-grade cancers benefit from PSA screening and early intervention. Two screening trials reviewed by the task force demonstrated a small—but significant—survival benefit associated with screening for men younger than age 70 years. In contrast, the United States Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial showed no mortality benefits from PSA screening. However, PSA testing in the study’s usual care group was quite high (up to 52%), raising concerns about the study’s ability to answer the question of interest. In terms of treatment, the only trial deemed of “good quality” by the US Preventive Services Task Force (ie, the Scandinavian Prostate Cancer Study Group No. 4) showed that—with 15 years of follow-up—prostate cancer–specific mortality and allcause mortality were 38% and 25% lower, respectively, among men treated surgically compared with men managed with watchful waiting. Subgroup analyses suggested that the survival benefits were greatest for men aged 65 years or younger. In addition, even the limited data currently available from the Prostate Cancer Intervention Versus Observation Trial, portrayed by the task force as a largely negative study, demonstrate a signal favoring treatment among men with higher-risk cancers. So, for PSA screening, is the glass half empty or half full? The answer may depend on clinical experience. Many clinicians involved in the care of men living with and dying of prostate cancer may consider that the data reviewed by the task force reveal potentially meaningful survival benefits for younger men, for those whose PSA level or Gleason score indicate a higher-risk cancer, or both groups (collectively representing tens of thousands of men diagnosed with prostate cancer each year in the United States). Accordingly, the US Preventive Services Task Force recommendation discouraging the use of PSA screening, however well-intentioned, cannot go uncontested. By emphasizing the centrality of avoiding harms associated with detection and treatment (without question a laudable goal), members of the task force—none of whom were urologists, medical oncologists, or radiation therapists—are in es-