BRCA1 and BRCA2 pathogenic variants and prostate cancer risk: systematic review and meta-analysis

Background BRCA1 and BRCA2 pathogenic variants (PVs) are associated with prostate cancer (PCa) risk, but a wide range of relative risks (RRs) has been reported.Methods We systematically searched PubMed, Embase, MEDLINE and Cochrane Library in June 2021 for studies that estimated PCa RRs for male BRCA1/2 carriers, with no time or language restrictions. The literature search identified 27 studies (BRCA1: n = 20, BRCA2: n = 21).Results The heterogeneity between the published estimates was high (BRCA1: I² = 30%, BRCA2: I² = 83%); this could partly be explained by selection for age, family history or aggressive disease, and study-level differences in ethnicity composition, use of historical controls, and location of PVs within BRCA2. The pooled RRs were 2.08 (95% CI 1.38–3.12) for Ashkenazi Jewish BRCA2 carriers, 4.35 (95% CI 3.50–5.41) for non-Ashkenazi European ancestry BRCA2 carriers, and 1.18 (95% CI 0.95–1.47) for BRCA1 carriers. At ages <65 years, the RRs were 7.14 (95% CI 5.33–9.56) for non-Ashkenazi European ancestry BRCA2 and 1.78 (95% CI 1.09–2.91) for BRCA1 carriers.Conclusions These PCa risk estimates will assist in guiding clinical management. The study-level subgroup analyses indicate that risks may be modified by age and ethnicity, and for BRCA2 carriers by PV location within the gene, which may guide future risk-estimation studies.Subject terms: Cancer epidemiology, Cancer epigenetics, Prostate cancer, Risk factors     

Individualized norms of optimal fetal growth: fetal growth potential

OBJECTIVE: To demonstrate that individualized optimal fetal growth norms, accounting for physiologic and pathologic determinants of fetal growth, better identify normal and abnormal outcomes of pregnancy than existing methods. METHODS: In a prospective cohort of 38,033 singleton pregnancies, we identified 9,818 women with a completely normal outcome of pregnancy and characterized the physiologic factors affecting birth weight using multivariable regression. We used those physiologic factors to individually predict optimal growth trajectory and its variation, growth potential, for each fetus in the entire cohort. By comparing actual birth weight with growth potential, population, ultrasound, and customized norms, we calculated for each fetus achieved percentiles, by each norm. We then compared proportions of pregnancies classified as normally grown, between 10th and 90th percentile, or aberrantly grown, outside this interval, by growth potential and traditional norms, in 14,229 complicated pregnancies, 1,518 pregnancies with diabetes or hypertensive disorders, and 1,347 pregnancies with neonatal complications. RESULTS: Nineteen physiologic factors, associated with maternal characteristics and early placental function, were identified. Growth potential norms correctly classified significantly more pregnancies than population, ultrasound, or customized norms in complicated pregnancies (26.4% compared with 18.3%, 18.7%, 22.8%, respectively, all P<.05), pregnancies with diabetes or hypertensive disorders (37.3% compared with 23.0%, 28.0%, 34.0%, respectively, all P<.05) and neonatal complications (33.3% compared with 19.7%, 24.9%, 29.8%, respectively, all P<.05). CONCLUSION: Growth potential norms based on the physiologic determinants of birth weight are a better discriminator of aberrations of fetal growth than traditional norms. LEVEL OF EVIDENCE: II.     

Robot-assisted Radical Cystectomy: Description of an Evolved Approach to Radical Cystectomy

Background

Although open radical cystectomy (ORC) remains the gold standard of care for muscle-invasive bladder cancer, robot-assisted radical cystectomy (RARC) continues to gain wider acceptance. In this article, we focus on the steps of RARC, describing our approach, which has been developed over the past 10 yr. Totally intracorporeal RARC aims to offer the benefits of a complete minimally invasive approach while replicating the oncologic outcomes of open surgery.

Objective

We report our outcomes of a totally intracorporeal RARC procedure, describing step by step our technique and highlighting the variations on this standard template of nerve-sparing and female organ–preserving approaches in men and women.

Design, setting, and participants

Between December 2003 and October 2012, a total of 113 patients (94 male and 19 female) underwent totally intracorporeal RARC.

Surgical procedure

We performed RARC, extended pelvic lymph node dissection, and a totally intracorporeal urinary diversion (UD) in all patients. In the accompanying video, we focus on the standard template for RARC, also describing nerve-sparing and female organ–preserving approaches.

Outcome measurements and statistical analysis

Complications and oncologic outcomes are reported, including overall survival (OS) and cancer-specific survival (CSS) using Kaplan-Meier analysis.

Results and limitations

RARC with intracorporeal UD was performed in 113 patients. Mean age was 64 yr (range: 37–84). Forty-three patients underwent intracorporeal ileal conduit, and 70 had intracorporeal neobladder. On surgical pathology, 48% of patients had ≤pT1 disease, 27% had pT2 disease, 13% had pT3 disease, and 12% had pT4 disease. The mean number of lymph nodes removed was 21 (range: 0–57). Twenty percent of patients had lymph node–positive disease. Positive surgical margins occurred in six cases (5.3%). Median follow-up was 25 mo (range: 3–107). We recorded a total of 70 early complications (0–30 d) in 54 patients (47.8%), with 37 patients (32.7%) having Clavien grade ≥3. Thirty-six late complications (>30 d) were recorded in 30 patients (26.5%), with 20 patients (17.7%) having Clavien grade ≥3. One patient (0.9%) died within 90 days of operation from pulmonary embolism. Using Kaplan-Meier analysis, CSS was 81% at 3 yr and 67% at 5 yr.

Conclusions

Our structured approach to RARC has enabled us to develop this complex service while maintaining patient outcomes and complication rates comparable with ORC series. Our results demonstrate acceptable oncologic outcomes and encouraging long-term CSS rates.