Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.

Quality-of-life Effects of PSA Screening

Source: Heijnsdijk EA, et al. Quality-of-life effects of prostate-specific antigen screening. N Engl J Med 2012;367:595-605.

The european randomized study of Screening for Prostate Cancer (ERSPC) is a clinical trial in which adult men (n = 162,243) were randomized to prostate-specific antigen (PSA) screening or no screening. While this trial did find a statistically significant reduction in prostate cancer deaths, overall mortality was not affected, supporting the current recommendations by the United States Preventive Services Task Force (USPSTF) that PSA screening be abandoned. Although the USPSTF decision was based on the "hard" data about mortality, there is likely also substantial quality-of-life (QOL) burden engendered from PSA screening, since many — indeed, the vast majority of — men diagnosed with prostate cancer through PSA screening will die with, not from, their prostate cancer. Additionally, adverse effects of intervention for (the mostly) early prostate cancer detected through screening are not uncommon, and include erectile dysfunction and incontinence. Finally, even in men who elect not to have a surgical intervention in response to prostate cancer detected as a result of PSA screening, it would take little imagination to envision substantial ongoing concerns/anxieties referable to that diagnosis.

Heijnsdijk et al report that per 1000 men screened by PSA, nine fewer prostate-cancer related deaths would occur and 73 life-years would be gained. After adjustment for overdiagnosis and overtreatment of prostate cancer subsequent to PSA screening, these benefits were reduced by almost one-fourth. In an era when PSA screening is no longer supported because of an insufficiently favorable risk:benefit ratio, recognition of the negative QOL impact of PSA screening may help clinicians (and their patients) better come to terms with the now well-recognized limitations of PSA screening.

 

Secondary Prevention of Lacunar Stroke

Source: SPS3 Investigators. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med 2012;367:817-825.

Lacunar strokes (l-cva) are small subcortical brain infarctions that may comprise as many as 25% of ischemic strokes. Aspirin (ASA) monotherapy is already established as appropriate treatment for secondary prevention of ischemic stroke, as is clopidogrel (CLOP) monotherapy. In the CAPRIE trial, CLOP provided a marginal advantage over ASA for major adverse cardiovascular events (absolute risk reduction = 0.5%) in the overall study population, leading some to advocate clopidogrel routinely over ASA. It is often under-recognized that in the CAPRIE trial, study subjects who enrolled specifically because of previous stroke did not experience any statistically significant stroke reduction with CLOP compared to ASA; the outcomes were the same.

The Secondary Prevention of Small Subcortical Strokes (SPS3) trial is the first published trial to compare the efficacy of ASA monotherapy vs ASA + CLOP in reference to L-CVA. The study population included more than 30% Hispanics, concordant with the observation that L-CVA is more common in Hispanics.

At the conclusion of the trial (3.4 years mean), ASA + CLOP was not more effective than ASA alone in preventing L-CVA. Among the study population (n = 3020 adults with prior L-CVA), most new strokes were L-CVA (71%).

Unfortunately, as has been seen in other studies of combined ASA + CLOP, bleeding risk was significantly increased compared to ASA alone, as was all-cause mortality. Two prior trials in vasculopathic populations (MATCH, CHARISMA) have arrived at similar conclusions: For persons with stable non-acute vascular disease, ASA + CLOP is not more beneficial than ASA alone, but incurs greater bleeding risk.

 

PSA Elevations After Prostate Cancer Radiotherapy

Source: Crook JM, et al. Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med 2012;367:895-903.

Since prostate cancer (pca) is often an-drogen-dependent, PCA recurrences after radiotherapy are often treated with androgen deprivation by means of regimens consisting of continuous luteinizing hormone-releasing hormone agonists (LHRHa) combined with antiandrogens. Unfortunately, such treatment is associated with hot flashes, decreased libido, urinary symptoms, and fatigue. Might intermittent androgen deprivation be equally effective, but less problematic as far as adverse effects?

Crook et al randomized patients who had undergone radiation treatment for PCA but had a post-treatment PSA > 3.0 ng/dL to continuous or intermittent androgen deprivation.

For overall mortality, intermittent androgen deprivation was non-inferior to continuous treatment. The time to development of castration-resistant disease (the stage at which androgen deprivation no longer represses disease progression) was significantly longer for intermittent treatment. Similarly, the adverse effects of hot flashes, libido, and urinary symptoms were all significantly fewer in the intermittent treatment group. In addition to necessitating a substantially reduced amount of medication (and of course, expense), intermittent androgen deprivation regimens are non-inferior for overall mortality, and are associated with superior quality of life.