Predicting Prostate Cancer Death with Different Pretreatment Risk Stratification Tools: A Head-to-head Comparison in a Nationwide Cohort Study

BackgroundNumerous pretreatment risk classification tools are available for prostate cancer. Which tool is best in predicting prostate cancer death is unclear.ObjectiveTo systematically compare the prognostic performance of the most commonly used pretreatment risk stratification tools for prostate cancer.Design, setting, and participantsA nationwide cohort study was conducted, including 154 811 men in Prostate Cancer data Base Sweden (PCBaSe) 4.0 diagnosed with nonmetastatic prostate cancer during 1998–2016 and followed through 2016.Outcome measurements and statistical analysisWe compared the D’Amico, National Institute for Health and Care Excellence (NICE), European Association of Urology (EAU), Genito-Urinary Radiation Oncologists of Canada (GUROC), American Urological Association (AUA), National Comprehensive Cancer Network (NCCN), and Cambridge Prognostic Groups (CPG) risk group systems; the Cancer of the Prostate Risk Assessment (CAPRA) score; and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram in predicting prostate cancer death by estimating the concordance index (C-index) and the observed versus predicted cumulative incidences at different follow-up times.Results and limitationsA total of 139 515 men were included in the main analysis, of whom 15 961 died from prostate cancer during follow-up. The C-index at 10 yr of follow-up ranged from 0.73 (95% confidence interval [CI]: 0.72–0.73) to 0.81 (95% CI: 0.80–0.81) across the compared tools. The MSKCC nomogram (C-index: 0.81, 95% CI: 0.80–0.81), CAPRA score (C-index: 0.80, 95% CI: 0.79–0.81), and CPG system (C-index: 0.78, 95% CI: 0.78–0.79) performed the best. The order of performance between the tools remained in analyses stratified by primary treatment and year of diagnosis. The predicted cumulative incidences were close to the observed ones, with some underestimation at 5 yr. It is a limitation that the study was conducted solely in a Swedish setting (ie, case mix).ConclusionsThe MSKCC nomogram, CAPRA score, and CPG risk grouping system performed better in discriminating prostate cancer death than the D’Amico and D’Amico-derived systems (NICE, GUROC, EAU, AUA, and NCCN). Use of these tools may improve clinical decision making.Patient summaryThere are numerous pretreatment risk classification tools that can aid treatment decision for prostate cancer. We systematically compared the prognostic performance of the most commonly used tools in a large cohort of Swedish men with prostate cancer. The Memorial Sloan Kettering Cancer Center nomogram, Cancer of the Prostate Risk Assessment score, and Cambridge Prognostic Groups performed best in predicting prostate cancer death. The use of these tools may improve treatment decisions.     

Prostate Cancer Risks for Male BRCA1 and BRCA2 Mutation Carriers: A Prospective Cohort Study

BackgroundBRCA1 and BRCA2 mutations have been associated with prostate cancer (PCa) risk but a wide range of risk estimates have been reported that are based on retrospective studies.ObjectiveTo estimate relative and absolute PCa risks associated with BRCA1/2 mutations and to assess risk modification by age, family history, and mutation location.Design, setting, and participantsThis was a prospective cohort study of male BRCA1 (n = 376) and BRCA2 carriers (n = 447) identified in clinical genetics centres in the UK and Ireland (median follow-up 5.9 and 5.3 yr, respectively).Outcome measurements and statistical analysisStandardised incidence/mortality ratios (SIRs/SMRs) relative to population incidences or mortality rates, absolute risks, and hazard ratios (HRs) were estimated using cohort and survival analysis methods.Results and limitationsSixteen BRCA1 and 26 BRCA2 carriers were diagnosed with PCa during follow-up. BRCA2 carriers had an SIR of 4.45 (95% confidence interval [CI] 2.99–6.61) and absolute PCa risk of 27% (95% CI 17–41%) and 60% (95% CI 43–78%) by ages 75 and 85 yr, respectively. For BRCA1 carriers, the overall SIR was 2.35 (95% CI 1.43–3.88); the corresponding SIR at age <65 yr was 3.57 (95% CI 1.68–7.58). However, the BRCA1 SIR varied between 0.74 and 2.83 in sensitivity analyses to assess potential screening effects. PCa risk for BRCA2 carriers increased with family history (HR per affected relative 1.68, 95% CI 0.99–2.85). BRCA2 mutations in the region bounded by positions c.2831 and c.6401 were associated with an SIR of 2.46 (95% CI 1.07–5.64) compared to population incidences, corresponding to lower PCa risk (HR 0.37, 95% CI 0.14–0.96) than for mutations outside the region. BRCA2 carriers had a stronger association with Gleason score ≥7 (SIR 5.07, 95% CI 3.20–8.02) than Gleason score ≤6 PCa (SIR 3.03, 95% CI 1.24–7.44), and a higher risk of death from PCa (SMR 3.85, 95% CI 1.44–10.3). Limitations include potential screening effects for these known mutation carriers; however, the BRCA2 results were robust to multiple sensitivity analyses.ConclusionsThe results substantiate PCa risk patterns indicated by retrospective analyses for BRCA2 carriers, including further evidence of association with aggressive PCa, and give some support for a weaker association in BRCA1 carriers.Patient summaryIn this study we followed unaffected men known to carry mutations in the BRCA1 and BRCA2 genes to investigate whether they are at higher risk of developing prostate cancer compared to the general population. We found that carriers of BRCA2 mutations have a high risk of developing prostate cancer, particularly more aggressive prostate cancer, and that this risk varies by family history of prostate cancer and the location of the mutation within the gene.     

Serum levels of 17-β-estradiol are not predictive of prostate cancer diagnosis and aggressiveness: Results from an Italian biopsy cohort

ObjectivesTo explore the association between serum levels of 17-β-estradiol (17BE) and prostate cancer (PCa) risk in men undergoing prostate biopsy.Methods and materialsBetween 2006 and 2012, we prospectively enrolled 894 patients, with no history of PCa, undergoing prostate biopsy. Before biopsy was performed, general data, digital rectal examination (DRE), body mass index, 17BE, and prostate-specific antigen (PSA) were recorded. The risk of detecting cancer and high-grade cancer was assessed as a function of 17BE using crude and adjusted logistic regressions.ResultsSerum levels of 17BE were not associated with an increased risk of PCa or high-grade disease. Age (odds ratio [OR] 1.05; 95% confidence interval [CI]: 1.03–1.07; P = 0.000), DRE(OR 2.81; 95% CI: 1.98–4.00; P = 0.000), and PSA(OR 1.07; 95% CI: 1.04–1.10; P = 0.000) were found to be independent predictors of PCa risk. Age (OR 1.05; 95% CI: 1.01–1.09; P = 0.007), DRE (OR 3.04; 95% CI: 1.79–5.17; P = 0.000), body mass index (OR 1.07; 95% CI: 1.01–1.150; P = 0.040), and PSA (OR 1.08; 95% CI: 1.03–1.12; P = 0.000) were found to be independent predictors of high-grade disease.ConclusionIn our cohort of patients, serum levels of 17BE are not predictive of PCa or high-grade disease. In patients at risk of PCa, 17BE should not be considered a reliable marker to predict poorly differentiated PCa in the setting of initial prostate biopsy.     

Mediterranean Diet and Prostate Cancer Risk and Mortality in the Health Professionals Follow-up Study

BackgroundProstate cancer (PCa) mortality rates are lower in the Mediterranean countries compared with northern Europe. Although specific components of the Mediterranean diet (Med-Diet) may influence PCa risk, few studies have assessed the traditional Med-Diet pattern with the risk of incident advanced or lethal PCa or with disease progression among men diagnosed with nonmetastatic PCa.ObjectiveTo determine whether the traditional Med-Diet pattern is associated with risk of incident advanced or lethal PCa and with PCa-specific and overall mortality among men with PCa.Design, setting, and participantsWe prospectively followed 47 867 men in the Health Professionals Follow-up Study followed from 1986 to 2010. The case-only analysis included 4538 men diagnosed with nonmetastatic PCa, followed from diagnosis to lethal outcome or to January 2010.Outcome measurements and statistical analysisWe used Cox proportional hazards models to examine traditional and alternative Med-Diet scores in relation to PCa incidence outcomes (advanced and lethal disease). In a case-only survival analysis, we examined postdiagnostic Med-Diet and risk of lethal (metastases or PCa death) and fatal PCa as well as overall mortality among men diagnosed with nonmetastatic disease.Results and limitationsBetween 1986 and 2010, 6220 PCa cases were confirmed. The Med-Diet was not associated with risk of advanced or lethal PCa. In the case-only analysis, there was no association between the Med-Diet after diagnosis and risk of lethal or fatal PCa. However, there was a 22% lower risk of overall mortality (hazard ratio: 0.78; 95% confidence interval, 0.67–0.90; p_trend = 0.0007) among men with greater adherence to the Med-Diet after PCa diagnosis. We found similar associations for the alternative score.ConclusionsA higher Med-Diet score was not associated with risk of advanced PCa or disease progression. Greater adherence to the Med-Diet after diagnosis of nonmetastatic PCa was associated with lower overall mortality.     

Androgen-deprivation Therapy in Treatment of Prostate Cancer and Risk of Myocardial Infarction and Stroke: A Nationwide Danish Population-based Cohort Study

BackgroundAndrogen-deprivation therapy (ADT) has been suggested to increase the risk for cardiovascular diseases, including myocardial infarction (MI) and stroke, but data are inconsistent.ObjectivesTo investigate the association between ADT and risk for MI and stroke in Danish men with prostate cancer.Design, setting, and participantsA national cohort study of all patients with incident prostate cancer registered in the Danish Cancer Registry from January 1, 2002, through 2010 was conducted.Outcome measurements and statistical analysisWe used Cox regression analysis to estimate hazard ratios (HR) of MI and stroke for ADT users versus nonusers, adjusting for age, prostate cancer stage, comorbidity, and calendar period. Additionally, we stratified the analysis on preexisting MI/stroke status.Results and limitationsOf 31 571 prostate cancer patients, 9204 (29%) received medical endocrine therapy and 2060 (7%) were orchidectomized. Patients treated with medical endocrine therapy had an increased risk for MI and stroke with adjusted HRs of 1.31 (95% confidence interval [CI], 1.16–1.49) and 1.19 (95% CI, 1.06–1.35), respectively, compared with nonusers of ADT. We found no increased risk for MI (HR: 0.90; 95% CI, 0.83–1.29) or stroke (HR: 1.11; 95% CI, 0.90–1.36) after orchiectomy. One limitation of the study is that information on prognostic lifestyle factors was not included and might have further informed our estimates.ConclusionsIn this nationwide cohort study of >30 000 prostate cancer patients, we found that endocrine hormonal therapy was associated with increased risk for MI and stroke. In contrast, we did not find this association after orchiectomy.     

Radical Prostatectomy or Observation for Clinically Localized Prostate Cancer: Extended Follow-up of the Prostate Cancer Intervention Versus Observation Trial (PIVOT)

BackgroundVery long-term mortality in men with early prostate cancer treated with surgery versus observation is uncertain.ObjectiveTo determine long-term effects of surgery versus observation on all-cause mortality for men with early prostate cancer.Design, setting, and participantsThis study evaluated long-term follow-up of a randomized trial conducted at the US Department of Veterans Affairs and National Cancer Institute sites. The participants were men (n = 731) ≤75 yr of age with localized prostate cancer, prostate-specific antigen (PSA) <50 ng/ml, life expectancy ≥10 yr, and medically fit for surgery.InterventionRadical prostatectomy versus observation.Outcome measurements and statistical analysisAll-cause mortality was assessed in the entire cohort and patient and tumor subgroups. Intention-to-treat analysis was conducted using Kaplan-Meier methods with log-rank tests and Cox proportional hazard models; cumulative mortality incidence, between-group differences, and relative risks were also assessed at predefined time periods.Results and limitationsDuring 22.1 yr (median follow-up for survivors = 18.6 yr; interquartile range: 16.6–20.0), 515 men died; 246 of 346 men (68%) were assigned to surgery versus 269 of 367 (73%) assigned to observation (hazard ratio 0.84 [95% confidence interval {CI}: 0.70–1.00]; p =  0.044 [absolute risk reduction = 5.7 percentage points, 95% CI: –0.89 to 12%]; relative risk: 0.92 [95% CI: 0.84–1.01]). The restricted mean survival in the surgical group was 13.6 yr (95% CI: 12.9–14.3) versus 12.6 yr (95% CI: 11.8–13.3) in the observation group; a mean of 1 life-year was gained with surgery. Results did not significantly vary by patient or tumor characteristics, although differences were larger favoring surgery among men aged <65 yr, of white race, and having better health status, fewer comorbidities, ≥34% positive prostate biopsy cores, and intermediate-risk disease. Results were not adjusted for multiple comparisons, and we could not assess outcomes other than all-cause mortality.ConclusionsSurgery was associated with small very long-term reductions in all-cause mortality and increases in years of life gained. Absolute effects did not vary markedly by patient characteristics. Absolute effects and mean survival were much smaller in men with low-risk disease, but were greater in men with intermediate-risk disease although not in men with high-risk disease.Patient summaryIn this randomized study, we evaluated death from any cause in men with early prostate cancer treated with either surgery or observation. Overall, surgery may provide small very long-term reductions in death from any cause and increases in years of life gained. Absolute effects were much smaller in men with low-risk disease, but were greater in men with intermediate-risk disease although not in men with high-risk disease. Strategies are needed to identify men needing and benefitting from surgery while reducing ineffective treatment and overtreatment.     

Quality of Life After Bladder Cancer: A Cross-sectional Survey of Patient-reported Outcomes

BackgroundLittle is known about health-related quality of life (HRQOL) following treatment for bladder cancer (BC).ObjectiveTo determine this, we undertook a cross-sectional survey covering 10% of the English population.Design, setting, and participantsParticipants 1–10 yr from diagnosis were identified through national cancer registration data.InterventionA postal survey was administered containing generic HRQOL and BC-specific outcome measures. Findings were compared with those of the general population and other pelvic cancer patients.Outcome measurements and statistical analysisGeneric HRQOL was measured using five-level EQ-5D (EQ-5D-5L) and European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ)-C30. BC-specific outcomes were derived from EORTC QLQ-BLM30 and EORTC QLQ-NMIBC24.Results and limitationsA total of 1796 surveys were completed (response rate 55%), including 868 (48%) patients with non–muscle-invasive BC, 893 (50%) patients who received radiotherapy or radical cystectomy, and 35 (1.9%) patients for whom treatment was unknown. Most (69%) of the participants reported at least one problem in any EQ-5D dimension. Age/sex-adjusted generic HRQOL outcomes were similar across all stages and treatment groups, whilst problems increased with age (problems in one or more EQ-5D dimensions: <65 yr [67% {95% confidence interval or CI: 61–74}] vs 85+ yr [84% {95% CI: 81–89}], p = 0.016) and long-term conditions (no conditions [53% {95% CI: 48–58}] vs more than four conditions [94% {95% CI: 90–97}], p < 0.001). Sexual problems were reported commonly in men, increasing with younger age and radical treatment. Younger participants (under 65 yr) reported more financial difficulties (mean score 20 [95% CI: 16–25]) than those aged 85+ yr (6.8 [4.5–9.2], p < 0.001). HRQOL for BC patients (for comparison, males with problems in one or more EQ-5D dimensions 69% [95% CI: 66–72]) was significantly worse than what has been found after colorectal and prostate cancers and in the general population (51% [95% CI: 48–53], all p < 0.05).ConclusionsHRQOL following BC appears to be relatively independent of disease stage, treatment, and multimodal care. Issues are reported with sexual function and financial toxicity. HRQOL after BC is worse than that after other pelvic cancers.Patient summaryPatients living with bladder cancer often have reduced quality of life, which may be worse than that for other common pelvic cancer patients. Age and other illnesses appear to be more important in determining this quality of life than the treatments received. Many men complain of sexual problems. Younger patients have financial worries.     

Comparisons of efficacy and complications between transrectal and transperineal prostate biopsy with or without antibiotic prophylaxis

Background and purposeWe aimed to determine the cancer detection rate and complications of transrectal prostate biopsy (TRBx) and transperineal prostate biopsy (TPBx) in the hospital. However, given the use of antibiotic prophylaxis in TPBx remains controversial according to the current guidelines, we also investigated the safety and side effects of TPBx with and without antibiotic prophylaxis.Materials and methodsA total of 777 patients who underwent prostate biopsy were enrolled in this study in accordance with the criteria. The primary outcome was pooled infectious complications (sepsis, fever, symptomatic urinary tract infection and urinary retention), and the secondary outcome was prostate cancer detection rate.ResultsFindings showed that TPBx and TRBx were equivalent in terms of prostate cancer detection rate (TPBx: 50.4% vs. TRBx: 47.3%; P = 0.424) and urinary retention (TPBx: 5% vs. TRBx: 6.3%; P = 0.451). However, TRBx had significantly higher incidences of sepsis (risk ratios, RR: 3.65, 95% confidence interval [CI]: 1.21–11.03; P = 0.014) and symptomatic urinary tract infection (RR: 3.04, 95% CI: 1.07–8.66; P = 0.029) than TPBx. Notably, for TPBx, patients who received a single dose of cephazolin prophylaxis were not associated with the risk of sepsis (RR: 0.78, 95% CI: 0.13–4.63; P = 0.783) and symptomatic urinary tract infection (RR: 1.17, 95% CI: 0.24–5.74; P = 0.848) in contrast to patients who did not receive any antibiotic prophylaxis. Meanwhile, no effects on prostate cancer detection rate and urinary retention were observed in the TPBx group.ConclusionsOur findings indicated that TPBx significantly reduced infectious complications compared with TRBx and should therefore be preferred. Importantly, we need to re-examine whether the antibiotic prophylaxis should be routinely applied before TPBx in consideration of increasing antibiotic resistance. This result complements the current national guidelines. Nevertheless, future studies on this topic with improved quality and increased sample size are still needed to minimise bacterial resistance.     

Associations of lower urinary tract symptoms with prostate-specific antigen levels, and screen-detected localized and advanced prostate cancer: a case-control study nested within the UK population-based ProtecT (Prostate testing for cancer and Treatment) study

OBJECTIVE

To determine associations of lower urinary tract symptoms (LUTS) with prostate‐specific antigen (PSA) levels and screen‐detected localized and advanced prostate cancer.

SUBJECTS AND METHODS

A case‐control study nested within the UK population‐based ProtecT (Prostate testing for cancer and Treatment) study. Men aged 50–69 years were invited for PSA testing and those with a PSA level of ≥3.0 ng/mL were invited for biopsy. We determined whether LUTS were associated with a PSA level of ≥3.0 ng/mL and prostate cancer using logistic regression models adjusted for age, family history of prostate cancer and PSA level as appropriate. Areas under receiver operating characteristic curves (AUC) were compared between models with and without symptoms.

RESULTS

In all, 65 871 men had a PSA test: 7251 had a PSA level of ≥3.0 ng/mL including 2467 subsequently diagnosed with prostate cancer (2119 localized, 348 advanced). LUTS were positively associated with a PSA level of ≥3.0 ng/mL: odds ratios (ORs) were 1.18 (95% confidence interval, CI 1.01–1.38), 1.69 (95% CI 1.32–2.16), and 1.60 (95% CI 1.33–1.93) for daytime urination frequency (hourly vs less frequent), urgency and hesitancy (most/all the time vs never), respectively. LUTS among men with a PSA level of ≥3 ng/mL were negatively associated with prostate cancer: ORs were 0.44 (95% CI 0.22–0.83), 0.74 (95% CI 0.63–0.87), and 0.83 (95% CI 0.73–0.94) for nocturia (4+ vs 0), leakage and hesitancy (occasionally/sometimes vs never), respectively. LUTS improved the prediction of a PSA level of ≥3.0 ng/mL (AUC 0.635 vs 0.606, P < 0.001) and prostate cancer (AUC 0.661 vs 0.638; P < 0.001).

CONCLUSIONS

A history of LUTS before PSA testing marginally improves the prediction of an individual’s risk for prostate cancer; men with a PSA level of ≥3 ng/mL and LUTS were more likely to be diagnosed with benign disease than prostate cancer.     

Mortality and Hospitalization Risk Following Oral Androgen Signaling Inhibitors Among Men with Advanced Prostate Cancer by Pre-existing Cardiovascular Comorbidities

BackgroundElderly patients (≥65 yr) with advanced prostate cancer and cardiovascular disease (CVD) conditions are often excluded from clinical trials of abiraterone acetate (AA) or enzalutamide (ENZ). Consequently, little is known about the effects of these medications on these vulnerable patients.ObjectiveTo assess the short-term outcomes of AA and ENZ in patients with pre-existing CVDs.Design, setting, and participantsA population-based retrospective study. The Surveillance, Epidemiology, and End Results-Medicare–linked database was used to identify prostate cancer patients using AA or ENZ.Outcome measurements and statistical analysisThe primary endpoint was 6-mo all-cause mortality, analyzed using modified Poisson regression modeling of relative risk (RR) adjusted for confounders and comorbidities.Results and limitationsAmong eligible patients (2845 with AA and 1031 with ENZ), 67% had at least one pre-existing CVD. Compared with those without pre-existing CVDs, having one to two pre-existing CVDs was associated with 16% higher 6-mo mortality (RR = 1.16, 95% confidence interval [CI]: 1.00–1.36), and the risk increased further among those having three or more CVDs (RR = 1.56, 95% CI: 1.29–1.88). Most of the differences in survival of patients with pre-existing CVD condition occurred within the first 6 mo of treatment.ConclusionsAfter treatment with AA or ENZ, elderly prostate cancer patients with pre-existing CVDs experienced higher short-term mortality than otherwise similar patients without CVDs. Mortality associated with CVDs did not depend on having received AA versus ENZ.Patient summaryPatients with pre-existing cardiovascular diseases (CVDs) experienced higher short-term mortality after abiraterone acetate or enzalutamide than those without pre-existing CVDs. It is recommended that a multidisciplinary team, including a cardiologist, evaluate patients having pre-existing CVDs in the process of making treatment decisions and monitoring potential side effects.     

Evaluation of the platelet-to-lymphocyte ratio as a prognostic indicator in a European cohort of patients with prostate cancer treated with radiotherapy

ObjectivesRecent evidence suggests that the presence of a systemic inflammatory response plays an important role in the progression of several solid tumors. The platelet-to-lymphocyte ratio (PLR) has been proposed as an easily assessable marker of systemic inflammation and has been shown to represent a prognostic marker in different cancer entities. To evaluate the prognostic value of the PLR in prostate cancer, we performed the present study.Methods and materialsData from 374 consecutive patients with prostate cancer, treated with 3D conformal radiotherapy from 1999 to 2007, were analyzed. Distant metastases–free survival (MFS), cancer-specific survival (CSS), overall survival (OS), biochemical disease–free survival, and time to salvage systemic therapy were assessed using the Kaplan-Meier method. Cox proportional hazards analysis was performed to calculate hazard ratio (HR) and 95% CI. Multivariate Cox regression analysis was performed to adjust for other covariates.ResultsUsing receiver operating characteristics analysis, the optimal cutoff level for the PLR was 190. Kaplan-Meier analyses revealed that PLR≥190 was a prognostic factor for decreased MFS (P = 0.004), CSS (P = 0.004), and OS (P = 0.024) whereas a significant association of an elevated PLR with biochemical disease–free survival (P = 0.740) and time to salvage systemic therapy (P = 0.063) was not detected. In multivariate analysis, an increased PLR remained a significant prognostic factor for poor MFS (HR = 2.24, 95% CI: 1.06–4.76, P = 0.036), CSS (HR = 3.99, 95% CI: 1.19–13.4, P = 0.025), and OS (HR = 1.87, 95% CI: 1.02–3.42, P = 0.044).ConclusionsOur findings indicate that the PLR may predict prognosis in patients with prostate cancer and may contribute to future individual risk assessment in them.     

Feasibility,Acceptability, and Behavioral Outcomes from a Technology-enhanced Behavioral Change Intervention (Prostate 8): A Pilot Randomized Controlled Trial in Men with Prostate Cancer

BackgroundIncreasing evidence suggests that lifestyle factors may decrease the risk of prostate cancer progression. Lifestyle guidelines and tools may support lifestyle modification after diagnosis.ObjectiveTo determine the feasibility and acceptability of a digital lifestyle intervention among men with prostate cancer.Design, setting, and participantsA 12-wk pilot randomized controlled trial among 76 men with clinical stage T1–T3a prostate cancer. Eligibility included Internet access, no contraindications to aerobic exercise, and engaging in four or fewer of eight targeted behaviors at baseline.InterventionWebsite, Fitbit One, and text messaging to facilitate adoption of eight behaviors: vigorous activity, smoking cessation, and six diet improvements.Outcome measurements and statistical analysisOur primary outcomes were feasibility and acceptability based on recruitment and user data, and surveys, respectively. Secondarily, we evaluated the change in eight lifestyle behaviors, and also objective physical activity. Each factor was assigned one point, for an overall “P8 score” (range 0–8). Analysis of covariance (ANCOVA) was conducted. Exploratory outcomes included quality of life, anthropometrics, and circulating biomarkers after 12 wk, and behaviors after 1 yr.Results and limitationsAt baseline, men in both arms met a median of three targeted behaviors. Sixty-four men (n = 32 per arm) completed the study; 88% completed 12-wk assessments (intervention, 94%; control, 82%). Intervention participants wore their Fitbits a median of 82 d (interquartile range [IQR]: 72–83), replied to a median of 71% of text messages (IQR: 57–89%), and visited the website a median of 3 d (IQR: 2–5) over 12 wk. Median (IQR) absolute changes in the P8 score from baseline to 12 wk were 2 (1, 3) for the intervention and 0 (?1, 1) for the control arm. The estimated mean score of the intervention arm was 1.5 (95% confidence interval: 0.7, 2.3) higher than that of the control arm at 12 wk (ANCOVA p < 0.001). Changes were driven by diet rather than exercise. Limitations include self-reported diet and exercise data.ConclusionsOverall, in this novel pilot trial, the intervention was feasible and acceptable to men with prostate cancer. Next steps include improving the intervention to better meet individuals’ needs and focusing on increasing physical activity in men not meeting nationally recommended physical activity levels.Patient summaryTailored print materials combined with technology integration, including the use of a website, text messaging, and physical activity trackers, helped men with prostate cancer adopt healthy lifestyle habits, in particular recommended dietary changes, in the Prostate 8 pilot trial.     

Local Failure and Survival After Definitive Radiotherapy for Aggressive Prostate Cancer: An Individual Patient-level Meta-analysis of Six Randomized Trials

BackgroundThe importance of local failure (LF) after treatment of high-grade prostate cancer (PCa) with definitive radiotherapy (RT) remains unknown.ObjectiveTo evaluate the clinical implications of LF after definitive RT.Design, setting, and participantsIndividual patient data meta-analysis of 992 patients (593 Gleason grade group [GG] 4 and 399 GG 5) enrolled in six randomized clinical trials.Outcome measurements and statistical analysisMultivariable Cox proportional hazard models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), and distant metastasis (DM)-free survival (DMFS) and LF as a time-dependent covariate. Markov proportional hazard models were developed to evaluate the impact of specific transitions between disease states on these endpoints.Results and limitationsMedian follow-up was 6.4 yr overall and 7.2 yr for surviving patients. LF was significantly associated with OS (hazard ratio [HR] 1.70 [95% confidence interval {CI} 1.37–2.10]), PCSS (3.10 [95% CI 2.33–4.12]), and DMFS (HR 1.92 [95% CI 1.54–2.39]), p < 0.001 for all). Patients who had not transitioned to the LF state had a significantly lower hazard of transitioning to a PCa-specific death state than those who transitioned to the LF state (HR 0.13 [95% CI 0.04–0.41], p < 0.001). Additionally, patients who transitioned to the LF state had a greater hazard of DM or death (HR 2.46 [95% CI 1.22–4.93], p = 0.01) than those who did not.ConclusionsLF is an independent prognosticator of OS, PCSS, and DMFS in high-grade localized PCa and a subset of DM events that are anteceded by LF events. LF events warrant consideration for intervention, potentially suggesting a rationale for upfront treatment intensification. However, whether these findings apply to all men or just those without significant comorbidity remains to be determined.Patient summaryMen who experience a local recurrence of high-grade prostate cancer after receiving upfront radiation therapy are at significantly increased risks of developing metastases and dying of prostate cancer.     

Association of 5-alpha-reductase inhibitor and prostate cancer incidence and mortality: a meta-analysis

Background5-Alpha-reductase inhibitors (5-ARIs) have been suggested as potential chemopreventive agents for prostate cancer (PCa). This study was conducted to evaluate the effect of 5-ARIs on the incidence and mortality of PCa.MethodsThe PubMed, Embase and Cochrane Library databases were searched comprehensively from database inception to October 2019. The clinical outcomes included the incidence of overall PCa, high-grade (Gleason8-10) PCa, metastatic PCa, overall survival (OS), and cancer-specific survival (CSS).ResultsOverall, 23 studies were included in the present study, representing 11 cohort studies, 5 case-control studies, and 8 randomized controlled trials. The use of 5-ARIs was associated with a decreased risk of overall PCa [relative risk (RR) =0.77; 95% CI: 0.67–0.88; P<0.001] and increased risk of Gleason 8–10 PCa (RR=1.19; 95% CI: 1.01–1.40; P=0.036). In terms of metastatic PCa, there were no significant between-group differences (RR=1.23; 95% CI: 0.69–2.18; P=0.487). Furthermore, we found that prediagnostic 5-ARI usage was not associated with an increased risk of overall or prostate cancer mortality, with HRs of 1.00 (95% CI: 0.92–1.08; P=0.938) and 0.98 (95% CI: 0.80–1.21; P=0.881), respectively.ConclusionsIn conclusion, while male 5-ARI users were associated with a decreased risk of overall prostate cancer and increased risk of high-grade prostate cancer (Gleason 8–10), they were not associated with an increased risk of overall or prostate cancer mortality. 5-ARIs should be recommended carefully for use as chemopreventive agents.     

Screening for Prostate Cancer Starting at Age 50–54 Years. A Population-based Cohort Study

Background

Current prostate cancer screening guidelines conflict with respect to the age at which to initiate screening.

Psychological morbidity associated with prostate cancer: Rates and predictors of depression in the RADICAL PC study

IntroductionAcross all cancer sites and stages, prostate cancer has one of the greatest median five-year survival rates, highlighting the important focus on survivorship issues following diagnosis and treatment. In the current study, we sought to evaluate the prevalence and predictors of depression in a large, multicenter, contemporary, prospectively collected sample of men with prostate cancer.MethodsData from the current study were drawn from the baseline visit of men enrolled in the RADICAL PC study. Men with a new diagnosis of prostate cancer or patients initiating androgen deprivation therapy for prostate cancer for the first time were recruited. Depressive symptoms were evaluated using the nine-item version of the Patient Health Questionnaire (PHQ-9). To evaluate factors associated with depression, a multivariable logistic regression model was constructed, including biological, psychological, and social predictor variables.ResultsData from 2445 patients were analyzed. Of these, 201 (8.2%) endorsed clinically significant depression. Younger age (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.16–1.60 per 10-year decrease), being a current smoker (OR 2.77, 95% CI 1.66–4.58), former alcohol use (OR 2.63, 95% CI 1.33–5.20), poorer performance status (OR 5.01, 95% CI 3.49–7.20), having a pre-existing clinical diagnosis of depression or anxiety (OR 3.64, 95% CI 2.42–5.48), and having high-risk prostate cancer (OR 1.49, 95% CI 1.05–2.12) all conferred independent risk for depression.ConclusionsClinically significant depression is common in men with prostate cancer. Depression risk is associated with a host of biopsychosocial variables. Clinicians should be vigilant to screen for depression in those patients with poor social determinants of health, concomitant disability, and advanced disease.     

Aspirin use and the risk of prostate cancer: a meta-analysis of 24 epidemiologic studies

Purpose

Several epidemiologic studies were performed to clarify the protective effect of regular aspirin use on prostate cancer risk; however, the results remain controversial. Therefore, we conducted this meta-analysis to assess the association between regular aspirin use and risk of prostate cancer.

Methods

Electronic databases including PubMed, EMBASE and Cochrane Library were searched between January 1966 and April 2013 to identify eligible studies. Pooled relative ratios (RRs) and 95 % confidence intervals (CIs) were computed to assess the influence of aspirin use on prostate cancer risk. All statistical tests were two-sided.

Results

A total of 24 observational studies including 14 case–control studies and 10 cohort studies were eligible for this meta-analysis. Regular aspirin use was associated with reduction in overall and advanced prostate cancer risk (pooled RR 0.86, 95 % CI 0.81–0.92; pooled RR 0.83, 95 % CI 0.75–0.91, respectively). When we restricted our analyses to studies with long-time regular aspirin use (equal or more than 4 years), reverse association became stronger (pooled RR 0.82, 95 % CI 0.72–0.93; pooled RR 0.70, 95 % CI 0.55–0.90, respectively).

Conclusions

Our findings suggest that regular, especially long-time regular aspirin use may reduce the risk of overall and advanced prostate cancer. Considering the limitation of included studies, further well-designed large-scaled cohort studies and RCTs are required to draw more definitive conclusions.     

Patient-reported Quality of Life in Patients with Primary Metastatic Prostate Cancer Treated with Androgen Deprivation Therapy with and Without Concurrent Radiation Therapy to the Prostate in a Prospective Randomised Clinical Trial; Data from the HORRAD Trial

BackgroundA survival benefit was demonstrated for patients with low-volume metastatic prostate cancer (mPCa) when local radiotherapy was added to androgen deprivation therapy (ADT).ObjectiveTo determine the effect of ADT combined with external beam radiotherapy (EBRT) to the prostate on health-related quality of life (HRQoL) of patients with primary bone mPCa.Design, setting, and participantsThe HORRAD trial is a multicentre randomised controlled trial recruiting 432patients with primary bone mPCa between 2004 and 2014.InterventionPatients were randomised to ADT with EBRT or to ADT alone.Outcome measurements and statistical analysisPatients completed two validated HRQoL questionnaires (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire Core Module (QLQ-C30) and EORTC Quality of Life Questionnaire Prostate Module [QLQ-PR25]) at baseline and at 3, 6, 12, and24 mo after the initiation of treatment. The effect of both treatments was evaluated based on mixed-effect models.Results and limitationsPatient characteristics and HRQoL scores at baseline were similar in both arms. At baseline, 98% of patients completed the questionnaires, compared with 58% at 24 mo. Patients reported significantly more diarrhoea (difference between the groups 10.8; 95% confidence interval [CI] 7.3–14.2), bowel symptoms (4.5; 95% CI 2.1–6.8), and urinary symptoms (11.9; 95% CI 8.9–14.8) after EBRT and ADT compared with ADT alone (all between-arm difference p < 0.001). Urinary complaints levelled at 6 mo. At 2 yr, only bowel symptom scores were significantly different (8.0; 95% CI 4.8–11.1, p ≤ 0.001), but 68% of patients in the radiotherapy group did not report clinically relevant worsening of their bowel symptom scores.ConclusionsPatients with bone mPCa reported temporary modest urinary and bowel symptoms after combined treatment with EBRT of the prostate and ADT compared with ADT alone. For some patients (22%), deterioration of bowel functions remains at 2 yr, whereas general HRQoL does not deteriorate..Patient summaryThis study investigated the effect of radiotherapy to the prostate added to hormonal therapy on patient-reported health-related quality of life (HRQoL) in patients with primary bone metastatic prostate cancer. Most patients reported only temporary urinary and bowel symptoms. In 22% of patients, bowel symptoms remained at 2 yr, whereas general HRQoL did not deteriorate.     

Radical prostatectomy readmissions: Causes,risk factors,national rates, & costs

IntroductionReadmissions have substantial clinical and financial impacts on the healthcare system. Radical prostatectomy (RP) is considered a standard treatment in the management of clinically localized prostate cancer. Yet, there is a paucity of research evaluating readmissions for RP in a national dataset.Patients and methodsPatients with histologically confirmed prostate cancer managed with RP were identified within the 2016 to 2018 Nationwide Readmissions Database. Patient factors, facility factors, and surgical characteristics were evaluated for associations with readmission using univariable and multivariable analyses.ResultsA total of 133,727 patients receiving RP were identified. Early (30-day) and late (31–90-day) readmission rates were 4.2% and 1.8% respectively. The most common cause of early readmission was postoperative digestive system complication (10%) and the most common cause of late readmission was septicemia (13%). On multivariable logistic regression, factors associated with both early and late readmission include nonroutine discharge at index (early: OR 1.877, 95% CI 1.667–2.113; late: OR 1.801, 95% CI 1.490–2.183), and circulatory system comorbidity (early: OR 1.29, 95% CI 1.082–1.538); late: OR 1.515, 95% CI 1.157–1.984).ConclusionsOur findings regarding factors associated with readmission provide insight for RP counseling and may inform postoperative care pathways. Elucidation of readmission trends may allow the identification and proactive management of patients at higher risk for readmission.