The Impact of Positron Emission Tomography Imaging and Tumor Molecular Profiling on Risk Stratification, Treatment Choice, and Oncological Outcomes of Patients with Primary or Relapsed Prostate Cancer: An International Collaborative Review of the Existing Literature.

CONTEXT: The clinical introduction of next-generation imaging methods and molecular biomarkers ("radiogenomics") has revolutionized the field of prostate cancer (PCa). While the clinical validity of these tests has thoroughly been vetted, their clinical utility remains a matter of investigation. OBJECTIVE: To systematically review the evidence to date on the impact of positron emission tomography (PET) imaging and tissue-based prognostic biomarkers, including Decipher, Prolaris, and Oncotype Dx, on the risk stratification, treatment choice, and oncological outcomes of men with newly diagnosed PCa or those with biochemical failure (BCF). EVIDENCE ACQUISITION: We performed a quantitative systematic review of the literature using the MEDLINE, EMBASE, and Web of Science databases (2010-2022) following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement guidelines. The validated Quality Assessment of Diagnostic Accuracy Studies 2 scoring system was used to assess the risk of bias. EVIDENCE SYNTHESIS: A total of 148 studies (130 on PET and 18 on biomarkers) were included. In the primary PCa setting, prostate-specific membrane antigen (PSMA) PET imaging was not useful in improving T staging, moderately useful in improving N staging, but consistently useful in improving M staging in patients with National Comprehensive Cancer Network (NCCN) unfavorable intermediate- to very-high-risk PCa. Its use led to a management change in 20-30% of patients. However, the effect of these treatment changes on survival outcomes was not clear. Similarly, biomarkers in the pretherapy primary PCa setting increased and decreased the risk, respectively, in 7-30% and 32-36% of NCCN low-risk and 31-65% and 4-15% of NCCN favorable intermediate-risk patients being considered for active surveillance. A change in management was noted in up to 65% of patients, with the change being in line with the molecular risk-based reclassification, but again, the impact of these changes on survival outcomes remained unclear. Notably, in the postsurgical primary PCa setting, biomarker-guided adjuvant radiation therapy (RT) was associated with improved oncological control: Δ↓ 2-yr BCF by 22% (level 2b). In the BCF setting, the data were more mature. PSMA PET was consistently useful in improving disease localization-Δ↑ detection for T, N, and M staging was 13-32%, 19-58%, and 9-29%, respectively. Between 29% and 73% of patients had a change in management. Most importantly, these management changes were associated with improved survival outcomes in three trials: Δ↑ 4-yr disease-free survival by 24.3%, Δ↑ 6-mo metastasis-free survival (MFS) by 46.7%, and Δ↑ androgen deprivation therapy-free survival by 8 mo in patients who received PET-concordant RT (level 1b-2b). Biomarker testing in these patients also appeared to be helpful in risk stratifying and guiding the use of early salvage RT (sRT) and concomitant hormonal therapy. Patients with high-genomic-risk scores benefitted from treatment intensification: Δ↑ 8-yr MFS by 20% with the use of early sRT and Δ↑ 12-yr MFS by 11.2% with the use of hormonal therapy alongside early sRT, while low-genomic-risk score patients did equally well with initial conservative management (level 3). CONCLUSIONS: Both PSMA PET imaging and tumor molecular profiling provide actionable information in the management of men with primary PCa and those with BCF. Emerging data suggest that radiogenomics-guided treatments translate into direct survival benefits for patients, however, additional prospective data are awaited. PATIENT SUMMARY: In this review, we evaluated the utility of prostate-specific membrane antigen positron emission tomography and tumor molecular profiling in guiding the care of men with prostate cancer (PCa). We found that these tests augmented risk stratification, altered management, and improved cancer control in men with a new diagnosis of PCa or for those experiencing a relapse.

Association Between Self-Reported Dyspnea and Depressive Symptoms in New Mexico Uranium Workers.

New Mexico has the largest number of former uranium workers, mostly racial/ethnic minorities. Uranium workers are at risk for dyspnea secondary to mine dust exposure. The association between dyspnea and depressive symptoms has not been well examined in occupational minority cohorts. This study evaluated the associations between dyspnea (measured by the modified Medical Research Council Questionnaire) and depressive symptoms (measured by the Patient Health Questionnaire-2) in former uranium workers screened by the New Mexico Radiation Exposure Screening & Education Program. The subjects were mostly elderly, rural-residing, minority males. Dyspnea was commonly reported; however, depressive symptoms were uncommon. At baseline, former workers experiencing higher levels of dyspnea were more than 3 times likely to endorse depressive symptoms than those with no or mild dyspnea. Longitudinal analysis failed to determine an association between change in dyspnea and concomitant change in depressive symptoms. Dyspnea and depressive symptoms were associated cross-sectionally in former uranium workers.

Greater Odds for Angina in Uranium Miners Than Nonuranium Miners in New Mexico.

OBJECTIVE: The aim of this study was to test the hypothesis that uranium miners in New Mexico (NM) have a greater prevalence of cardiovascular disease than miners who extracted the nonuranium ore. METHODS: NM-based current and former uranium miners were compared with nonuranium miners by using cross-sectional standardized questionnaire data from the Mining Dust in the United States (MiDUS) study from 1989 to 2016. RESULTS: Of the 7215 eligible miners, most were men (96.3%). Uranium miners (n = 3151, 43.7%) were older and diabetic, but less likely to currently smoke or use snuff (P ≤ 0.001 for all). After adjustment for covariates, uranium miners were more likely to report angina (odds ratio 1.51, 95% confidence interval 1.23 to 1.85) than nonuranium miners. CONCLUSION: Our data suggest that along with screening for pulmonary diseases, uranium industry workers should be screened for cardiovascular diseases.

Morbidity and Health Risk Factors Among New Mexico Miners: A Comparison Across Mining Sectors.

OBJECTIVE: This study examines differences in chronic health outcomes between coal, uranium, metal, and nonmetal miners. METHODS: In a cross-sectional study using data from a health screening program for current and former New Mexico miners, log-binomial logistic regression models were used to estimate relative risks of respiratory and heart disease, cancer, osteoarthritis, and back pain associated with mining in each sector as compared with coal, adjusting for other relevant risk factors. RESULTS: Differential risks in angina, pulmonary symptoms, asthma, cancer, osteoarthritis, and back pain between mining sectors were found. CONCLUSIONS: New Mexico miners experience different chronic health challenges across sectors. These results demonstrate the importance of using comparable data to understand how health risks differ across mining sectors. Further investigation among a broader geographic population of miners will help identify the health priorities and needs in each sector.

Variation in Locoregional Prostate Cancer Care and Treatment Trends at Commission on Cancer Designated Facilities: A National Cancer Data Base Analysis 2004 to 2013.

BACKGROUND: Contemporary treatment trends for prostate cancer show increased rates of active surveillance. However, nationwide applicability of these reports is limited. Additionally, the effect of Commission on Cancer facility type on prostate cancer treatment patterns is unknown. PATIENTS AND METHODS: We used the National Cancer Data Base to identify men diagnosed with prostate cancer, between 2004 and 2013. Our cohort was stratified on the basis of the National Comprehensive Cancer Network prostate cancer risk classes. Cochran-Armitage tests were used to evaluate temporal trends. Random effects hierarchical logit models were used to assess treatment variation at Commission on Cancer facility and institution level. RESULTS: In 825,707 men, utilization of radiation therapy declined and utilization of radical prostatectomy increased for all prostate cancer risk groups between 2004 and 2013 (P < .0001). Observation for low-risk prostate cancer increased from 16.3% in 2004 to 2005 to 32.0% in 2012 to 2013 (P < .0001). Significant treatment variation was observed on the basis of Commission on Cancer facility type. Across all risk groups, the lowest rates of radical prostatectomy and highest rates of external beam radiation therapy were observed in community cancer programs. The highest rates of observation for low-risk disease were observed in academic centers. Treatment variation according to institution ranged from 14% (95% confidence interval, 0.12-0.15) for androgen deprivation therapy up to 59% (95% confidence interval, 0.45-0.73) for cryotherapy. CONCLUSION: The increased utilization of observation in low-risk prostate cancer is an encouraging finding, which appears to be mainly derived by a decrease in radiotherapy utilization in this risk group. Regardless of tumor characteristics, significant variations in treatment modality exist among different facility types and institutions.

A Pragmatic Randomized Controlled Trial Examining the Impact of the Retzius-sparing Approach on Early Urinary Continence Recovery After Robot-assisted Radical Prostatectomy.

BACKGROUND: Retzius-sparing (posterior) robot-assisted radical prostatectomy (RARP) may expedite postoperative urinary continence recovery. OBJECTIVE: To compare the short-term (≤3 mo) urinary continence (UC), urinary function (UF), and UF-related bother outcomes of posterior RARP compared with standard anterior approach RARP. DESIGN, SETTING, AND PARTICIPANTS: A total of 120 patients aged 40-75 yr with low-intermediate-risk prostate cancer (per the National Comprehensive Cancer Network guidelines) underwent primary RARP at a tertiary care institution. INTERVENTION: Eligible men were randomized to receive either posterior (n=60) or anterior (n=60) RARP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Primary outcome was UC (defined as 0 pads/one security liner per day) 1 week after catheter removal. Secondary outcomes were short-term (≤3 mo) UC recovery, and UF and UF-related bother scores (measured by the International Prostate Symptom Score [IPSS] and IPSS quality-of-life scores, respectively) assessed at 1 and 2 wk, and 1 and 3 mo following catheter removal. Continence outcomes were objectively verified using 24-hr pad weights. UC recovery was analyzed using Kaplan-Meier method and Cox proportional hazards regression; UF and UF-related bother outcomes were compared using linear generalized estimating equations (GEEs). Perioperative complications, positive surgical margin, and biochemical recurrence-free survival (BCRFS) represent secondary outcomes reported in the study. RESULTS AND LIMITATIONS: Compared with 48% in the anterior arm, 71% men undergoing posterior RARP were continent 1 wk after catheter removal (p=0.01); corresponding median 24-h pad weights were 25 and 5g (p=0.001). Median time to continence in posterior versus anterior RARP was 2 and 8 d postcatheter removal, respectively (log-rank p=0.02); results were confirmed on multivariable regression analyses. GEE analyses showed that UF-related bother (but not UF) scores were significantly lower in the posterior versus anterior RARP group at 1 wk, 2 wk, and 1 mo on GEE analyses. Incidence of postoperative complications (12% anterior vs 18% posterior) and probability of BCRFS (0.91 vs 0.91) were comparable in the two arms. CONCLUSIONS: In this single-center randomized study, the Retzius-sparing approach of RARP resulted in earlier recovery of UC and lower UF-related bother compared with standard RARP. These results require long-term validation and reproduction by other centers, as well as studies on men with high-risk localized disease. PATIENT SUMMARY: In our hands, men with low-intermediate-risk prostate cancer undergoing Retzius-sparing robot-assisted radical prostatectomy (RARP) had earlier recovery of urinary continence and lower urinary function-related bother than those undergoing standard RARP.

Uranium Workers Demonstrate Lower Lobe Predominant Irregular Pneumoconiotic Opacities on Chest Radiographs.

BACKGROUND: There is a paucity of literature on the chest radiographic findings in uranium workers. OBJECTIVE: To characterize the chest radiographic findings of pneumoconiosis in a New Mexican cohort of uranium workers. METHODS: The most recent results from chest radiographs were abstracted in this cross-sectional study. RESULTS: Radiographs showed small pneumoconiotic opacities of profusion score of ≥ 1/0 in 155/429 (36.1%) uranium workers. The most common shape/size of the primary and secondary opacities was s (90.3%) and t (83.7%) types, respectively. Lower lung zones were the most affected. American Indians were the population group at greatest odds for having profusion score ≥ 1/0 (O.R. 2.65, 95% C.I. 1.61, 4.36). CONCLUSIONS: Uranium workers' pneumoconiosis is associated with predominantly lower lobe, irregular, and small opacities. Clinical providers and policymakers must consider uranium workers' pneumoconiosis in the differential diagnosis for lower lobe-predominant interstitial lung disease, in the appropriate exposure setting.

Morbidity and mortality after benign prostatic hyperplasia surgery: data from the American College of Surgeons national surgical quality improvement program.

BACKGROUND AND PURPOSE: With the aging population, it is becoming increasingly important to identify patients at risk for postsurgical complications who might be more suited for conservative treatment. We sought to identify predictors of morbidity after surgical treatment of benign prostatic hyperplasia (BPH) using a large national contemporary population-based cohort. METHODS: Relying on the American College of Surgeons National Surgical-Quality Improvement Program (ACS-NSQIP; 2006-2011) database, we evaluated outcomes after transurethral resection of the prostate (TURP), laser vaporization of the prostate (LVP), and laser enucleation of the prostate (LEP). Outcomes included blood-transfusion rates, length of stay, complications, reintervention rates, and perioperative mortality. Multivariable logistic-regression analysis evaluated the predictors of perioperative morbidity and mortality. RESULTS: Overall, 4794 (65.2%), 2439 (33.1%), and 126 (1.7%) patients underwent TURP, LVP, and LEP, respectively. No significant difference in overall complications (P=0.3) or perioperative mortality (P=0.5) between the three surgical groups was found. LVP was found to be associated with decreased blood transfusions (odds ratio [OR]=0.21; P=0.001), length of stay (OR=0.12; P<0.001) and reintervention rates (OR=0.63; P=0.02). LEP was found to be associated with decreased prolonged length of stay (OR=0.35; P=0.01). Men with advanced age at surgery and non-Caucasians were at increased risk of morbidity and mortality. In contrast, normal preoperative albumin and higher preoperative hematocrit (>30%) levels were the only predictors of lower overall complications and perioperative mortality. CONCLUSIONS: All three surgical modalities for BPH management were found to be safe. Advanced age and non-Caucasian race were independent predictors of adverse outcomes after BPH surgery. In patients with these attributes, conservative treatment might be a reasonable alternative. Also, preoperative hematocrit and albumin levels represent reliable predictors of adverse outcomes, suggesting that these markers should be evaluated before BPH surgery.

Robotic kidney transplantation with intraoperative regional hypothermia.

OBJECTIVE: To describe a novel and reproducible technique of robotic kidney transplantation (RKT) that requires no repositioning, and permits intraoperative regional hypothermia. PATIENTS AND METHODS: A GelPOINT™ (Applied Medical, Santa Ranchero, CA, USA) access port was used for delivery of ice-slush and introduction of the graft kidney. The new RKT technique using ice-slush has been performed in 39 patients. RESULTS: At a mean follow-up of 3 months all of the grafts functioned. There was a marked reduction in pain and analgesic requirement compared with patients undergoing open KT, with a propensity towards quicker graft recovery and lower complication rate. CONCLUSION: RKT has been shown to be safe and feasible in patients undergoing living-donor related KT. A prospective trial is underway to assess outcomes definitively.

Intakes of long-chain omega-3 (n-3) PUFAs and fish in relation to incidence of asthma among American young adults: the CARDIA study.

BACKGROUND: Although long-chain ω-3 (n-3) PUFAs (LCω3PUFAs) have been linked to the prevention of some inflammatory disorders, little is known about the association between these fatty acids and incidence of asthma. OBJECTIVE: The objective was to prospectively investigate the association between LCω3PUFAs and fish intake and incidence of asthma among American young adults. DESIGN: A 20-y follow-up longitudinal analysis was conducted in a biracial cohort of 4162 Americans, aged 18-30 y, with a history of asthma at baseline in 1985. Diet was assessed by a validated interviewer-administered quantitative food-frequency questionnaire at the examinations in 1985, 1992, and 2005. Incident self-reported asthma was defined as having a physician diagnosis of asthma and/or the use of asthma medications between 1985 and 2005. RESULTS: During the 20-y follow-up, 446 incident cases of asthma were identified. LCω3PUFA intake was significantly inversely associated with incidence of asthma after adjustment for sociodemographic, major lifestyle, and dietary confounders. The multivariable-adjusted HR for the highest quintile of LCω3PUFA intake as compared with the lowest quintile was 0.46 (95% CI: 0.33, 0.64; P-trend < 0.01). However, a higher frequency of nonfried fish consumption was not significantly associated with the risk of asthma. DHA showed a greater inverse association than did EPA. The association between LCω3PUFAs and incident asthma was not appreciably modified by sex, race, BMI, smoking status, or atopic status. CONCLUSION: This study showed that intakes of LCω3PUFAs are inversely longitudinally associated with the incidence of asthma in American young adults.