Prostate Cancer Screening: Have Clinicians Been Listening?

SOURCE: Jemal A, et al. Prostate cancer incidence and PSA testing patterns in relation to USPSTF screening recommendations. JAMA 2015;314:2054-2061.

Prostate cancer screening has been an embattled topic for more than a decade. While intuitively appealing to both the clinician population and mid-life males, outcomes from large clinical trials could not confirm improvements in overall survival subsequent to screening, and, with the exception of one large trial with contentious results, data were similarly unsupportive of even reduced mortality related to prostate cancer itself. Showing how the same data can be perceived differently by different experts, the U.S. Preventive Services Task Force (USPSTF) recommends against prostate-specific antigen (PSA) screening. The American Cancer Society endorses it in men > 50 years of age with at least a 10-year life expectancy. The American Urologic Association recommends PSA screening in men 55-59 years of age.

In 2008, the USPSTF recommended against PSA screening in men > 75 years of age, after which there was a minimal decline. Did clinicians heed the 2012 USPSTF advice to cease screening in asymptomatic men regardless of age?

Jemal et al reviewed data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) population (n = 446,000) to compare PSA screening rates between 2005 and 2013. They found an 18% decline in prostate cancer screening between 2010-2013, which was independent of age and included both younger men and men > 75 years of age. Modeling methods have been published that suggest we might experience an increase in prostate cancer mortality by omission of universal screening; to date, that has not been the case, but it may require a longer window of observation before reaching definitive conclusions.

Potential Benefits of Down Titration Through Inhaled Steroid Discontinuation

SOURCE: Suissa S, et al. Discontinuation of inhaled corticosteroids in COPD and the risk reduction of pneumonia. Chest 2015;148:1177-1183.

For patients with moderate to severe chronic obstructive pulmonary disease (COPD), combination treatment often includes anticholinergics, long-acting beta-agonists, and inhaled corticosteroids (ICS), the latter two treatments most commonly combined into a single inhalation device. As many as 85% of COPD patients are prescribed ICS, though many may fall below the threshold for ICS treatment recommended by FDA labeling or guidelines. Observational data have reported an increased incidence of pneumonia in COPD patients who used ICS, which prompts the question of whether discontinuation of ICS reduces the likelihood of pneumonia. Suissa et al used the Quebec health insurance database to evaluate a population of COPD patients who had been prescribed ICS (n = 103,386). Among this population, a comparison was made of the incidence of pneumonia in patients who continued to be treated with ICS vs those COPD patients who had discontinued ICS. The period of observation was approximately 5 years.

They found that the likelihood of serious pneumonia was reduced by 37% in patients who discontinued ICS vs those who remained on ICS. Risk reduction was demonstrated as quickly as the first month post-ICS cessation. Among ICS treatments, risk reduction was more dramatic with fluticasone cessation (42%) than budesonide (13%), but omitting either ICS was beneficial for pneumonia risk reduction. The authors suggested that ICS may be currently over-prescribed, and that limiting their use could reduce the risk for pneumonia without compromising quality of care.

Expanding Safe Prescribing for Metformin

SOURCE: Tuot DS, et al. Potential impact of prescribing metformin according to eGFR rather than serum creatinine. Diabetes Care 2015;38:2059-2067.

Metformin is the pharmacologic foundation of most guidelines for management of type 2 diabetes (T2DM), based on its efficacy, safety record, and the availability of favorable clinical trial outcomes data. Although serious adverse effects from metformin are rare, significant renal insufficiency increases the risk for lactic acidosis, which can be fatal. Original FDA labeling suggested renal safety boundaries based on serum creatinine (sCR), but when first devised, the boundaries (sCR < 1.4 for women, < 1.5 for men) were based on doses of metformin up to 3000 mg/d. Currently, the maximum approved dose (2550 mg/d) is not thought to be meaningfully more efficacious than 2000 mg/d, hence the commonplace prescription of metformin 1000 mg twice a day.

Recent recommendations suggest that metformin is safe when eGFR is > 45 mL/min, but the risk rises significantly when eGFR < 30 mL/min (30 mL/min to 45 mL/min eGFR is an “indeterminate” zone). Using data from the National Health and Nutrition Examination Survey (NHANES) population (n = 3902), the investigators determined that as many as 15% of patients who were excluded from metformin based on sCR would have been eligible for metformin based on a eGFR of > 45 mL/min.

In an era of progressively more expensive interventions for T2DM, clinicians may wish to re-evaluate the boundaries of safe prescribing for metformin.