10-year Outcomes for Localized Prostate Cancer

SOURCE: Hamdy FC, Donovan JL, Lane JA, et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med 2016;375:1415-1424.

For the past three decades, the majority of prostate cancer (PRCA) detection has resulted from prostate-specific antigen (PSA) screening. As compared to pre-PSA modes of detection, the population of PSA screening-detected PRCA is predominantly comprised of earlier, prostate-localized disease. Is there a clear advantage to one path of long-term intervention than another in long-term management of localized PRCA?

From a population of 84,429 PSA-screened men in the United Kingdom, 2,664 were diagnosed with localized PRCA and randomized to active surveillance vs. radical prostatectomy vs. external beam radiation. Although prostatectomy and external beam radiation probably are self-explanatory, the method of “active surveillance” differs from the “watching waiting” in two other prostate cancer trials. That is, active surveillance entailed PSA measurement every three months for a year, and then every six to 12 months going forward. Any 12-month PSA increase of 50% or greater prompted a case review and reconsideration of intervention; ultimately, 56 men in the active surveillance group ended up receiving an intervention secondary to increases in PSA.

At 10 years of follow-up, there was no statistically significant difference in either PRCA-specific death or all-cause mortality between the three groups. Although these results are heartening in that the three methods demonstrated similar (and low) levels of mortality, the relatively younger age of these men (mean age = 62 years) and the fact that disease progression over 10 years was more common in the surveillance group indicates that even longer-term follow-up will be needed to fully inform men on how to make optimum choices.


Secondary Prevention of Stroke by Pioglitazone in Prediabetes

SOURCE: Inzucchi SE, Viscoli CM, Young LH, et al. Pioglitazone prevents diabetes in patients with insulin resistance and cerebrovascular disease. Diabetes Care 2016;39:1684-1692.

The Insulin Resistance After Stroke (IRIS) trial randomized patients with recent ischemic stroke or transient ischemic attack to pioglitazone (PIO) or placebo for approximately five years. The rationale for selecting PIO was that these patients were all prediabetic, as defined by the homeostatic model assessment-insulin resistance score, further supported by their mean A1c (5.8). To be clear: diabetics were excluded from the trial; only prediabetics were included.

The primary endpoint of the IRIS trial indicated a significant 24% reduction in new stroke with PIO. This follow-up report detailed the ability of PIO to prevent development of diabetes in this population of prediabetics.

Over a five-year interval, 7.7% of placebo recipients progressed from prediabetes to diabetes, compared with 3.8% of the PIO group (hazard ratio = 0.48). Predictably, those prediabetics with the greatest degree of fasting blood glucose perturbation and highest baseline A1c showed the greatest degree of benefit.

PIO reduces vascular events in insulin-resistant stroke victims, as well as reduces risk of progression from prediabetes to diabetes by > 50%.


Linking Psoriasis to Vascular Health

SOURCE: Chiu HY, Lo PC, Huang WF, et al. Increased risk of aortic aneurysm (AA) in relation to the severity of psoriasis: A national population-based matched-cohort study. J Am Acad Dermatol 2016;75:747-754.

Approximately 15,000 people per year die in the United States from ruptured abdominal aortic aneurysms (AAA). The commonly recognized risk factors for AAA include hypertension, smoking, male sex, and age. While the link between inflammatory disorders, such as rheumatoid arthritis and psoriasis, and coronary vascular disease has received increasing attention in the last decade, little cognizance exists of a relationship between psoriasis and AAA.

To define this relationship further, Chiu et al reviewed the medical records of 34,301 patients with psoriasis in a Taiwanese database. When age and sex matched with controls (n = 137,204), a surprisingly strong association between psoriasis and risk for AAA emerged.

Patients with psoriasis were almost twice as likely (hazard ratio = 1.8) to be diagnosed with AAA as controls. Further substantiating the relationship, psoriasis severity was associated linearly with increasing risk for AAA. The strong association was independent of the already recognized risk factors for vasculopathy such as hypertension, smoking, and dyslipidemia. The authors suggested consideration of screening for AAA in psoriasis patients because of increased risk. Current U.S. Preventive Services Task Force guidelines suggest a one-time ultrasound screening for men between 65-75 years of age who are ever smokers ( 100 lifetime cigarettes).