Have You Read? August 2021

By: Daniel A. Shoskes, MD | Posted on: 06 Aug 2021

Cullen A, Lynch JA, Klein EA et al: Multicenter comparison of 17-gene genomic prostate score as a predictor of outcomes in African American and Caucasian American men with clinically localized prostate cancer. J Urol 2021; 205: 1047–1054.

There are now several tissue-based prostate cancer diagnostic assays for risk stratification, but their utility for an individual patient is only as good as the genetic representation of that patient’s tumor behavior in the original training sets. This is particularly important for groups such as African Americans whose differential outcomes in prostate cancer are well documented. In this study, the authors assessed the performance of the Oncotype DX® Genomic Prostate Score® test in African American and Caucasian American men with surgically treated prostate cancer. They compared the assay results (scale 0–100) and the 4 gene group scores in biopsy specimens from 201 African American and 1,144 Caucasian American men with clinically localized prostate cancer in 6 cohorts. Adverse pathology was defined as high grade (primary Gleason pattern 4 or any pattern 5) and/or nonorgan-confined disease (≥pT3). Biochemical recurrence was defined as 2 successive prostate specific antigen levels >0.2 ng/ml or initiation of salvage therapy after radical prostatectomy.

Each cohort had different clinical risk distributions and percentages of African Americans, although median and interquartile ranges of the assay results and gene group scores were similar between both racial groups. In a multivariable model with the assay and pathological/clinical features including race, the assay was significantly associated with adverse pathology (p≤0.004) and biochemical recurrence (p<0.001). Race was not a significant predictor of either end point.

The authors conclude that the assay is similarly predictive of outcomes in African American and Caucasian American patients, and improves risk stratification in men with newly diagnosed prostate cancer from both racial groups.

Kuhlmann PK, Fischer SC, Howard LE et al: Dutasteride improves nocturia but does not lead to better sleep: results from the REDUCE Clinical Trial. J Urol 2021; 205: 1733–1739.

Nocturia is a highly bothersome and impactful symptom in men and women, but commonly used anticholinergics and benign prostatic hyperplasia interventions may not target the underlying pathophysiology. In this study the authors assessed whether treating lower urinary tract symptoms with dutasteride altered either nocturia or sleep quality using data from REDUCE.

REDUCE was a 4-year randomized, multicenter trial comparing dutasteride 0.5 mg/day vs placebo for prostate cancer chemoprevention. At baseline, 2 years and 4 years, men completed the International Prostate Symptom Score and Medical Outcomes Study Sleep Scale, a 6-item scale assessing sleep. To test differences in nocturia and Medical Outcomes Study Sleep Scale over time, they used linear mixed models adjusted for baseline confounders. Subanalyses were conducted in men symptomatic from lower urinary tract symptoms, nocturia, poor sleep or combinations thereof.

Of 6,914 men with complete baseline data, 80% and 59% were assessed at 2-year and 4-year followup, respectively. Baseline characteristics were balanced between treatment arms. Dutasteride improved nocturia at 2 (–0.15, 95% CI –0.21, –0.09) and 4 years (–0.24, 95% CI –0.31, –0.18) but did not improve sleep. When limited to men symptomatic from lower urinary tract symptoms, nocturia, poor sleep or combinations thereof, results mirrored findings from the full cohort.

The authors conclude that in men with poor sleep who complain of nocturia, treatment of lower urinary tract symptoms with dutasteride modestly improves nocturia but has no effect on sleep. These results suggest men with poor sleep who complain of nocturia may not benefit from oral benign prostatic hyperplasia treatment.

Cusimano MC, Baxter NN, Sutradhar R et al: Delay of pregnancy among physicians vs nonphysicians. JAMA Intern Med 2021; doi: 10.1001/jamainternmed.2021.1635.

Medical training is difficult, parenting is difficult and trying to combine the 2 can introduce unique challenges and may lead to delay of pregnancy until later in life. The purpose of this study was to compare patterns of childbirth between physicians and nonphysicians in Ontario, Canada. This was a population-based retrospective cohort study of reproductive-aged women (15–50 years) accrued from 1995 to 2018 and observed to March 31, 2019. Outcomes of 5,238 licensed physicians of the College of Physicians and Surgeons of Ontario were compared with those of 26,640 nonphysicians (sampled in a 1:5 ratio). Physicians and nonphysicians were observed from age 15 years onward. The primary outcome was childbirth at gestational age of 20 weeks or greater.

All physicians (5,238) and nonphysicians (26,640) were aged 15 years at baseline. Median followup was 15.2 years after age 15 years. Physicians were less likely to experience childbirth at younger ages (HR for childbirth at 15–28 years, 0.15; 95% CI 0.14–0.18; p<0 .001) and initiated childbearing significantly later than nonphysicians; the cumulative incidence of childbirth was 5% at 28.6 years in physicians and 19.4 years in nonphysicians. However, physicians were more likely to experience childbirth at older ages (HR for 29–36 years, 1.35; 95% CI 1.28–1.43; p<0.001; HR for ≥37 years, 2.62; 95% CI 2.00–3.43; p<0.001), and ultimately achieved a similar cumulative probability of childbirth as nonphysicians overall. Median age at first childbirth was 32 years in physicians and 27 years in nonphysicians (p<0.001). After stratifying by specialty, the cumulative incidence of childbirth was higher in family physicians than in both surgical and nonsurgical specialists at all observed ages.

The authors conclude that women physicians appear to delay childbearing compared with nonphysicians, and this phenomenon is most pronounced among specialists. Physicians ultimately appear to catch up to nonphysicians by initiating reproduction at older ages and may be at increased risk of resulting adverse reproductive outcomes. System-level interventions should be considered to support women physicians who wish to have children at all career stages.

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