Association between prediagnostic prostate-specific antigen and prostate cancer probability in Black and non-Hispanic White men.

BACKGROUND: Although Black men are more likely than non-Hispanic White men to develop and die from prostate cancer, limited data exist to guide prostate-specific antigen (PSA) screening protocols in Black men. This study investigated whether the risk for prostate cancer was higher than expected among self-identified Black than White veterans based on prebiopsy PSA level. METHODS: Multivariable logistic regression models were estimated to predict the likelihood of prostate cancer diagnosis on first biopsy for 75,295 Black and 207,658 White male veterans. Self-identified race, age at first PSA test, prebiopsy PSA, age at first biopsy, smoking status, statin use, and socioeconomic factors were used as predictors. The adjusted predicted probabilities of cancer detection on first prostate biopsy from the logistic models at different PSA levels were calculated. RESULTS: After controlling for PSA and other covariates, Black veterans were 50% more likely to receive a prostate cancer diagnosis on their first prostate biopsy than White veterans (odds ratio [OR], 1.50; 95% CI, 1.47-1.53; p < .001). At a PSA level of 4.0 ng/mL, the probability of prostate cancer for a Black man was 49% compared with 39% for a White man. This model indicated that Black veterans with a PSA of 4.0 ng/mL have an equivalent risk of prostate cancer as White veterans with a PSA of 13.4 ng/mL. CONCLUSIONS: The findings indicate that, at any given PSA level, Black men are more likely to harbor prostate cancer than White men. Prospective studies are needed to better evaluate risks and benefits of PSA screening in Black men and other high-risk populations.

Understanding and Addressing Prostate Cancer Disparities in Diagnosis, Treatment, and Outcomes Among Black Men.

Despite advances in screening, diagnosis, and treatment for prostate cancer (PCa), Black men tend to be diagnosed at younger ages, have higher mortality rates, and are at increased risk of recurrence or metastasis compared to their White counterparts. PCa disparities among Black men are caused by a complex interaction of social, behavioral, and biological factors across the public policy, community, organizational, interpersonal, and individual levels. Key contributing factors include mistrust in the health care system, poor communication between patients and providers, low awareness of screening guidelines, and high medical costs. These disparities are further exacerbated by the low representation of Black men in clinical trials, which limits access to high-quality cancer care and generalizability for PCa treatments. In this narrative review of the existing literature, we examined the epidemiology and identified contributing factors, and propose multi-level strategies to address and mitigate disparities among Black men with PCa.

Clinical Outcomes of Prostate SBRT Using Non-adaptive MR-Guided Radiotherapy.

OBJECTIVES: Stereotactic body radiotherapy (SBRT) is widely used for localized prostate cancer and implementation of MR-guided radiotherapy has the advantage of tighter margins and improved sparing of organs at risk. Here we evaluate outcomes and time required to treat using non-adaptive MR-guided SBRT (MRgSBRT) for localized prostate cancer at our institution. METHODS: From 9/2019 to 11/2021 we conducted a retrospective review of 80 consecutive patients who were treated with MRgSBRT to the prostate. Patients included low (LR) (5%), favorable intermediate (FIR) (40%), unfavorable intermediate (UIR) (49%), and high risk (HR) (6%). Short-term androgen deprivation therapy was used in 32% of patients. Target volumes included prostate gland and proximal seminal vesicles with an isotropic 3 mm margin. Treatment was prescribed to 36.25 Gy in 5 fractions every other day with urethral sparing. Hydrogel spacer was used in 18% of patients. Time on the linac was recorded as beam on time (BOT) plus total treatment time (TTT) including gating. Analyzed outcomes included PSA response and patient reported outcomes scored by the American Urological Association (AUA) questionnaire and toxicity per CTCAE v5. General linear regression model was used to analyze factors affecting PSA and AUA in longitudinal follow up, and chi-square test was used to assess factors affecting toxicity. RESULTS: Median follow up was 19.3 months (3.8 - 36.6). Median BOT was 4.6 min (2.6 - 7.2) with a median TTT of 11 min (7.6 - 15.8). Pre-treatment vs post-RT median PSA was 6.36 (2.20 - 19.6) vs 0.85 (0.19 - 3.6), respectively (P < 0.001). PSA decrease differed significantly when patients were stratified by risk category, favoring LR/FIR vs UIF/HR group (P = 0.019). Four (5%) patients experienced a biochemical failure (BCF), with a median time to BCF of 20.4 months (7.9 - 34.5). Median biochemical failure free survival (BCFFS) was not reached, with 2-yr and 4-yr BCFFS of 97.1% and 72.1%, respectively. Patients with LR/FIR disease had 100% 2-yr and 4-yr BCFFS, whereas patients with UIF/HR had 95% and 41% 2-yr and 4-yr BCFFS (P = 0.05). Mean pre-treatment AUA was 7.3 (1 - 25) vs 11.3 (1 - 26) at first follow-up; however, AUA normalized to baseline over time. Urethral Dmax ≥35 Gy trended to lower AUA score at all follow-ups (P = 0.07). Forty-one (51%) patients reported grade 1-2 genitourinary toxicities at the 1 month follow up. Grade 3 toxicity (proctitis) was noted in 1 patient. There was no decrease in any grade rectal toxicity with use of hydrogel spacer (3 vs 6, P = 0.2). No grade ≥4 toxicities was observed. CONCLUSIONS: MRgSBRT has the potential for treatment adaptation but this comes at the cost of increased resource utilization. Our experience with non-adaptive MRgSBRT of the prostate highlights its short treatment times as well as efficacy with good PSA control and low toxicity profile.

Adaptation of the socioecological model to address disparities in engagement of Black men in prostate cancer genetic testing.

BACKGROUND: Black men consistently have higher rates of prostate cancer (PCA)- related mortality. Advances in PCA treatment, screening, and hereditary cancer assessment center around germline testing (GT). Of concern is the significant under-engagement of Black males in PCA GT, limiting the benefit of precision therapy and tailored cancer screening despite longstanding awareness of these disparities. To address these critical disparities, the Socioecological Model (SEM) was employed to develop comprehensive recommendations to overcome barriers and implement equitable strategies to engage Black males in PCA GT. METHODS: Clinical/research experts, national organization leaders, and community stakeholders spanning multiple regions in US and Africa participated in developing a framework for equity in PCA GT grounded in the SEM. A novel mixed-methods approach was employed to generate key areas to be addressed and informed statements for consensus consideration utilizing the modified Delphi model. Statements achieving strong consensus (> =75% agreement) were included in final equity frameworks addressing clinical/community engagement and research engagement. RESULTS: All societal levels of the SEM (interpersonal, institutional, community, and policy/advocacy) must deliver information about PCA GT to Black males that address benefits/limitations, clinical impact, hereditary cancer implications, with acknowledgment of mistrust (mean scores [MS] 4.57-5.00). Interpersonal strategies for information delivery included engagement of family/friends/peers/Black role models to improve education/awareness and overcome mistrust (MS 4.65-5.00). Institutional strategies included diversifying clinical, research, and educational programs and integrating community liaisons into healthcare institutions (MS 4.57-5.00). Community strategies included partnerships with healthcare institutions and visibility of healthcare providers/researchers at community events (MS 4.65-4.91). Policy/advocacy included improving partnerships between advocacy and healthcare/community organizations while protecting patient benefits (MS 4.57-5.00). Media strategies were endorsed for the first time at every level (MS 4.56-5.00). CONCLUSION: The SEM-based equity frameworks proposed provide the first multidisciplinary strategies dedicated to increase engagement of Black males in PCA GT, which are critical to reduce disparities in PCA-mortality through informing tailored screening, targeted therapy, and cascade testing in families.

Actionable Genomic Alterations in Prostate Cancer Among Black and White United States Veterans.

Black Veterans have higher a incidence of localized and metastatic prostate cancer compared to White Veterans yet are underrepresented in reports of frequencies of somatic and germline alterations. This retrospective analysis of somatic and putative germline alterations was conducted in a large cohort of Veterans with prostate cancer (N = 835 Black, 1613 White) who underwent next generation sequencing through the VA Precision Oncology Program, which facilitates molecular testing for Veterans with metastatic cancer. No differences were observed in gene alterations for FDA approved targetable therapies (13.5% in Black Veterans vs. 15.5% in White Veterans, P = .21), nor in any potentially actionable alterations (25.5% vs. 28.7%, P =.1). Black Veterans had higher rates of BRAF (5.5% vs. 2.6%, P < .001) alterations, White Veterans TMPRSS2 fusions (27.2% vs. 11.7%, P < .0001). Putative germline alteration rates were higher in White Veterans (12.0% vs. 6.1%, P < .0001). Racial disparities in outcome are unlikely attributable to acquired somatic alterations in actionable pathways.

Sociocultural factors associated with physical activity in Black prostate cancer survivors.

PURPOSE: Prostate cancer disproportionately affects Black men. Physical activity protects long-term health and quality of life outcomes in prostate cancer survivors. This study aimed to identify sociocultural factors related to physical activity among Black prostate cancer survivors to inform culturally tailored intervention development. METHODS: This secondary analysis included data from 257 men who identified as Black or African American and were diagnosed with prostate cancer between 2013 and 2018. Participants completed validated self-report measures of perceived history of racial discrimination, religiosity, fatalism, sociodemographic (e.g., age, ethnicity, income) and clinical characteristics (e.g., years since diagnosis, comorbidity burden), and leisure-time physical activity. Regression analyses were conducted to examine the associations between sociocultural factors and mild, moderate, and vigorous physical activity. RESULTS: Participants were on average 68.7 years old (SD = 7.7), and most were non-Hispanic (97.3%), married (68.9%), reported an annual household income above $50,000 (57.1%), received at least some college education (74.1%), and were overweight or had obesity (78.5%). Participants reported on average 88.1 (SD = 208.6) min of weekly mild physical activity, and most did not meet guidelines for weekly moderate (80.5%) or vigorous (73.0%) physical activity. After adjusting for covariates, older age and greater religiosity were associated with mild physical activity (ps ≤ 0.05). Higher levels of fatalism were associated with lower odds of meeting guidelines for moderate physical activity (OR = 0.87, 95% CI = 0.77-0.99). CONCLUSIONS: Sociocultural factors such as religiosity and fatalism may be associated with some forms of physical activity in Black prostate cancer survivors. These findings suggest that incorporating faith-based practices into health behavior interventions may be appropriate for this population.

TMPRSS2-ERG fusion impacts anterior tumor location in men with prostate cancer.

BACKGROUND: In prostate cancer (PCa), lack of androgen receptor (AR) regulated TMPRSS2-ETS-related gene (ERG) gene fusion (ERGnegative ) status has been associated with African American race; however, the implications of ERG status for the location of dominant tumors within the prostate remains understudied. METHODS: An African American-enriched multiinstitutional cohort of 726 PCa patients consisting of both African American men (AAM; n = 254) and European American men (EAM; n = 472) was used in the analyses. Methods of categorical analysis were used. Messenger RNA (mRNA) expression differences between anterior and posterior tumor lesions were analyzed using Wilcoxon rank-sum tests with multiple comparison corrections. RESULTS: Anti-ERG immunohistochemistry staining showed that the association between ERG status and anterior tumors is independent of race and is consistently robust for both AAM (ERGnegative 81.4% vs. ERGpositive 18.6%; p = .005) and EAM (ERGnegative 60.4% vs. ERGpositive 39.6%; p < .001). In a multivariable model, anterior tumors were more likely to be IHC-ERGnegative (odds ratio [OR]: 3.20; 95% confidence interval [CI]: 2.14-4.78; p < .001). IHC-ERGnegative were also more likely to have high-grade tumors (OR: 1.73; 95% CI: 1.06-2.82; p = .02). In the exploratory genomic analysis, mRNA expression of location-dependent genes is highly influenced by ERG status and African American race. However, tumor location did not impact the expression of AR or the major canonical AR-target genes (KLK3, AMACR, and MYC). CONCLUSIONS: ERGnegative tumor status is the strongest predictor of anterior prostate tumors, regardless of race. Furthermore, AR expression and canonical AR signaling do not impact tumor location.

Prostate tumors of native men from West Africa show biologically distinct pathways-A comparative genomic study.

BACKGROUND: Native African men (NAM) experience a disproportionate burden of prostate cancer (PCa) and have higher mortality rates compared to European American men (EAM). While socioeconomic status has been implicated as a driver of this disparity, little is known about the genomic mechanisms and distinct biological pathways that are associated with PCa of native men of African origin. METHODS: To understand biological factors that contribute to this disparity we utilized a total of 406 multi-institutional localized PCa samples, collected by Men of African Descent and Carcinoma of the Prostate biospecimen network and Moffitt Cancer Center/University of Pennsylvania Health science system. We performed comparative genomics and immunohistochemistry to identify the biomarkers that are highly enriched in NAM from west Africa and compared them with African American Men (AAM) and EAM. Quantified messenger RNA expression and Median H scores based on immune reactivity of staining cells, were compared using Mann Whitney test. For gene expression analysis, p values were further adjusted for multiple comparisons using false discovery rates. RESULTS: Immunohistochemical analysis on selected biomarkers showed a consistent association between ETS related gene (ERG) status and race with 83% of NAM exhibiting tumors that lacked TMPRSS2-ERG translocation (ERGnegative ) as compared to AAM (71%) and EAM (52%). A higher proportion of NAM (29%) were also found to be double negative (ERGnegative and PTENLoss ) as compared to AAM (6%) and EAM (7%). NAM tumors had significantly higher immunoreactivity (H-score) for PSMA, and EZH2, whereas they have lower H-score for PTEN, MYC, AR, RB and Racemase, (all p < .05). Comparative genomics revealed that NAM had significant transcriptomic variability in AR-activity score. In pathways enrichment analysis NAM tumors exhibited the enrichment of proinflammatory pathways including cytokine, interleukins, inflammatory response, and nuclear factor kappa B signaling. CONCLUSIONS: Prostate tumors in NAM are genomically distinct and are characterized by the dysregulation of several biomarkers. Furthermore, these tumors are also highly enriched for the major proinflammatory pathways. These distinct biological features may have implications for diagnosis and response to targeted therapy among Black men, globally.

Outcomes of Black men with prostate cancer treated with radiation therapy in the Veterans Health Administration.

BACKGROUND: Population-based studies demonstrate that Black men in the United States have an increased risk of death from prostate cancer. Determinants of racial disparities are multifactorial, including socioeconomic and biologic factors. METHODS: The authors conducted a pooled analysis of patients derived from 152 centers within the Veterans Health Administration. The cohort included men who had nonmetastatic prostate diagnosed between 2001 and 2015 and received definitive radiation therapy. The primary endpoint was prostate cancer-specific mortality (PCSM). Secondary endpoints included all-cause mortality (ACM) and the time from a prostate-specific antigen level ≥4 ng/mL to biopsy and radiation therapy. A Cox regression model was performed to adjust for differences between clinical parameters. RESULTS: Among the 31,131 patients included in the cohort, 9584 (30.8%) were Black. The 10-year cumulative incidence of death from prostate cancer was lower in Black men compared with White men (4.0% vs 4.8%; P = .004). In a competing risk model, Black race was associated with a decreased risk of PCSM (subdistribution hazard ratio, 0.79; 95% CI, 0.69-0.92; P = .002). Similarly, the 10-year cumulative incidence of death from any cause was lower in Black men (27.6% vs 31.8%; P < .001). In multivariable analysis, Black men had a 10% decreased risk of ACM (hazard ratio, 0.90; 95% CI, 0.85-0.95; P < .001). CONCLUSIONS: The current results indicate relatively lower PCSM and ACM among Black men who were included in a large Veterans Health Administration cohort and received radiation therapy as primary treatment for nonmetastatic prostate cancer. There is an ongoing need to continue to understand and mitigate the factors associated with disparities in health care outcomes.

Effectiveness and Safety of Prostatic Artery Embolization for the Treatment of Lower Urinary Tract Symptoms from Benign Prostatic Hyperplasia in Men with Concurrent Localized Prostate Cancer.

PURPOSE: To assess the effectiveness and safety of prostatic artery embolization (PAE) on lower urinary tract symptoms (LUTS) in the setting of localized prostate cancer (PCa). MATERIALS AND METHODS: This was a retrospective, single-center, institutional review board-approved study from December 2016 to June 2020 of 21 patients (median age, 72; range, 63-83 years) with moderate LUTS and localized PCa. Clinical effectiveness was evaluated at 6 and 12 weeks using International Prostate Symptom Score (IPSS) and quality of life (QoL) improvement. Seventeen patients were scheduled to receive definitive radiotherapy (RT) after PAE; 13 patients completed RT. Short-term imaging signs of oncologic progression were evaluated at 6 and 12 weeks defined by at least one of the following on magnetic resonance imaging: increased Prostate Imaging-Reporting and Data System score of index lesion(s) to at least 4, new extracapsular extension, seminal vesicle involvement, or pelvic lymphadenopathy. Nonparametric Wilcoxon signed-rank test was used for analysis. RESULTS: IPSS improved by a median of 12 (n = 19, P < .0001) and 14 (n = 14, P < .0001) at 6 and 12 weeks, respectively. QoL improved by a median of 2 (n = 19, P < .0001) and 3 (n = 3, P < .0001) at 6 and 12 weeks. Prostate volume decreased by a median of 24% (n = 19, P < .0001) and 36% (n = 12, P = .015) at 6 and 12 weeks. No patients demonstrated disease progression at 6 (n = 16) or 12 (n = 8) weeks by imaging. No patients experienced increased prostate-specific antigen after RT, grade ≥3 adverse events, or greater genitourinary toxicity. CONCLUSIONS: PAE is effective and safe for the treatment of men with LUTS from benign prostatic hyperplasia in the setting of concomitant, localized, non-obstructive PCa.

Phase I dose escalation trial of stereotactic radiotherapy prior to robotic prostatectomy in high risk prostate cancer.

BACKGROUND: The aim of the study was to investigate the safety of combining preoperative stereotactic body radiotherapy (SBRT) with robotic radical prostatectomy (RP) for high risk prostate cancer (HRCaP). Many patients with HRCaP will require adjuvant or salvage radiotherapy after RP. The addition of preoperative SBRT before RP may spare patients from subsequent prolonged courses of RT. MATERIALS AND METHODS: Eligible patients had NCC N HRCaP and received a total of 25 Gy or 30 Gy in five daily fractions of SBRT to the prostate and seminal vesicles followed by robotic RP with pelvic lymphadenectomy 31-45 days later. The primary endpoint was prevalence of acute genitourinary (GU) and gastrointestinal (GI) toxicity. Secondary endpoints were patient-reported quality of life (QOL) and biochemical recurrence (BcR). RESULTS: Three patients received preoperative SBRT to 25 Gy and four received 30 Gy. Median follow-up was 18 months. Highest toxicity was grade 2 and 3 in six (85.7%) and one (14.3%) patients, respectively. All patients developed grade 2 erectile dysfunction and 4 of 7 (57%) developed grade 2 urinary incontinence (UI) within a month after surgery. One patient developed acute grade 3 UI, but there was no grade ≥ 4 toxicity. One patient experienced acute grade 2 hemorrhoidal bleeding. On QOL, acute GU complaints were common and peaked within 3 months. Bowel symptoms were mild. Two patients with pN+ experienced BcR. CONCLUSIONS: Preoperative SBRT before robotic RP in HRCaP is feasible and safe. The severity of acute GU toxicity with preoperative SBRT may be worse than RP alone, while bowel toxicity was mild.

African American Specific Gene Panel Predictive of Poor Prostate Cancer Outcome.

PURPOSE: Most prostate cancer in African American men lacks the ETS (E26 transforming specific) family fusion event (ETS-). We aimed to establish clinically relevant biomarkers in African American men by studying ETS dependent gene expression patterns to identified race specific genes predictive of outcomes. MATERIALS AND METHODS: Two multicenter cohorts of a total of 1,427 men were used for the discovery and validation (635 and 792 men, respectively) of race specific predictive biomarkers. We used false discovery rate adjusted q values to identify race and ETS dependent genes which were differentially expressed in African American men who experienced biochemical recurrence within 5 years. Principal component modeling along with survival analysis was done to assess the accuracy of the gene panel in predicting recurrence. RESULTS: We identified 3,047 genes which were differentially expressed based on ETS status. Of these genes 362 were differentially expressed in a race specific manner (false discovery rate 0.025 or less). A total of 81 genes were race specific and over expressed in African American men who experienced biochemical recurrence. The final gene panel included APOD, BCL6, EMP1, MYADM, SRGN and TIMP3. These genes were associated with 5-year biochemical recurrence (HR 1.97, 95% CI 1.27-3.06, p = 0.002) and they improved the predictive accuracy of clinicopathological variables only in African American men (60-month time dependent AUC 0.72). CONCLUSIONS: In an effort to elucidate biological features associated with prostate cancer aggressiveness in African American men we identified ETS dependent biomarkers predicting early onset biochemical recurrence only in African American men. Thus, these ETS dependent biomarkers representing ideal candidates for biomarkers of aggressive disease in this patient population.

Testicular Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

Testicular cancer is relatively uncommon and accounts for <1% of all male tumors. However, it is the most common solid tumor in men between the ages of 20 and 34 years, and the global incidence has been steadily rising over the past several decades. Several risk factors for testicular cancer have been identified, including personal or family history of testicular cancer and cryptorchidism. Testicular germ cell tumors (GCTs) comprise 95% of malignant tumors arising in the testes and are categorized into 2 main histologic subtypes: seminoma and nonseminoma. Although nonseminoma is the more clinically aggressive tumor subtype, 5-year survival rates exceed 70% with current treatment options, even in patients with advanced or metastatic disease. Radical inguinal orchiectomy is the primary treatment for most patients with testicular GCTs. Postorchiectomy management is dictated by stage, histology, and risk classification; treatment options for nonseminoma include surveillance, systemic therapy, and nerve-sparing retroperitoneal lymph node dissection. Although rarely occurring, prognosis for patients with brain metastases remains poor, with >50% of patients dying within 1 year of diagnosis. This selection from the NCCN Guidelines for Testicular Cancer focuses on recommendations for the management of adult patients with nonseminomatous GCTs.

Interrelationship Between Health Insurance Status and Prostate Cancer Grade Can Have Critical Impact on Prostate Cancer Disease Control: A Retrospective Cohort Study.

The extent to which prostate cancer (PCa) pathology interacts with health insurance to predict PCa outcomes remains unclear. This study will assess the overall association of health insurance on PCa disease control and analyze its interrelationship PCa pathology. A total of 674 PCa patients, treated with prostatectomy from 1987 to 2015, were included in the study. Freedom from biochemical failure (FFbF) was used as a measure of PCa disease control. Methods of categorical and survival analysis were used to analyze the relationships between health insurance, PCa pathology, and FFbF. A total of 63.3% patients were privately insured, 27.1% were publicly insured, and 9.5% were uninsured. In a multivariable model, privately (hazard ratio [HR] = 0.64, 95% confidence interval [CI]: 0.42-0.97, P = .03) and publicly (HR = 0.65, 95% CI: 0.41-1.04, P = .07) insured patients showed improvement in FFbF compared to uninsured patients. The association of health insurance was significantly stronger for the patients with pathologically low grade PCa (pathologic Gleason Score 3+3 & preoperative prostate-specific antigen ≤10 ng/mL), likelihood ratio P = .009. Privately (HR = 0.22, 95% CI: 0.10-0.46) or publicly (HR = 0.26, 95% CI: 0.11-0.60) insured patients with low grade PCa demonstrated favorable association with FFbF. Patients with private and public insurance were more likely to experience favorable treatment. The association of health insurance on PCa disease control is significantly stronger among patients with pathologically low grade PCa. This study identifies health insurance status as pretreatment surrogate for PCa disease control.

Sequence of hormonal therapy and radiotherapy field size in unfavourable, localised prostate cancer (NRG/RTOG 9413): long-term results of a randomised, phase 3 trial.

BACKGROUND: The NRG/RTOG 9413 study showed that whole pelvic radiotherapy (WPRT) plus neoadjuvant hormonal therapy (NHT) improved progression-free survival in patients with intermediate-risk or high-risk localised prostate cancer compared with prostate only radiotherapy (PORT) plus NHT, WPRT plus adjuvant hormonal therapy (AHT), and PORT plus AHT. We provide a long-term update after 10 years of follow-up of the primary endpoint (progression-free survival) and report on the late toxicities of treatment. METHODS: The trial was designed as a 2 × 2 factorial study with hormonal sequencing as one stratification factor and radiation field as the other factor and tested whether NHT improved progression-free survival versus AHT, and NHT plus WPRT versus NHT plus PORT. Eligible patients had histologically confirmed, clinically localised adenocarcinoma of the prostate, an estimated risk of lymph node involvement of more than 15% and a Karnofsky performance status of more than 70, with no age limitations. Patients were randomly assigned (1:1:1:1) by permuted block randomisation to receive either NHT 2 months before and during WPRT followed by a prostate boost to 70 Gy (NHT plus WPRT group), NHT 2 months before and during PORT to 70 Gy (NHT plus PORT group), WPRT followed by 4 months of AHT (WPRT plus AHT group), or PORT followed by 4 months of AHT (PORT plus AHT group). Hormonal therapy was combined androgen suppression, consisting of goserelin acetate 3·6 mg once a month subcutaneously or leuprolide acetate 7·5 mg once a month intramuscularly, and flutamide 250 mg twice a day orally for 4 months. Randomisation was stratified by T stage, Gleason Score, and prostate-specific antigen concentration. NHT was given 2 months before radiotherapy and was continued until radiotherapy completion; AHT was given at the completion of radiotherapy for 4 months. The primary endpoint progression-free survival was analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769548. The trial has been terminated to additional follow-up collection and this is the final analysis for this trial. FINDINGS: Between April 1, 1995, and June 1, 1999, 1322 patients were enrolled from 53 centres and randomly assigned to the four treatment groups. With a median follow-up of 8·8 years (IQR 5·07-13·84) for all patients and 14·8 years (7·18-17·4) for living patients (n=346), progression-free survival across all timepoints continued to differ significantly across the four treatment groups (p=0·002). The 10-year estimates of progression-free survival were 28·4% (95% CI 23·3-33·6) in the NHT plus WPRT group, 23·5% (18·7-28·3) in the NHT plus PORT group, 19·4% (14·9-24·0) in the WPRT plus AHT group, and 30·2% (25·0-35·4) in the PORT plus AHT group. Bladder toxicity was the most common grade 3 or worse late toxicity, affecting 18 (6%) of 316 patients in the NHT plus WPRT group, 17 (5%) of 313 in the NHT plus PORT group, 22 (7%) of 317 in the WPRT plus AHT group, and 14 (4%) of 315 in the PORT plus AHT group. Late grade 3 or worse gastrointestinal adverse events occurred in 22 (7%) of 316 patients in the NHT plus WPRT group, five (2%) of 313 in the NHT plus PORT group, ten (3%) of 317 in the WPRT plus AHT group, and seven (2%) of 315 in the PORT plus AHT group. INTERPRETATION: In this cohort of patients with intermediate-risk and high-risk localised prostate cancer, NHT plus WPRT improved progression-free survival compared with NHT plus PORT and WPRT plus AHT at long-term follow-up albeit increased risk of grade 3 or worse intestinal toxicity. Interactions between radiotherapy and hormonal therapy suggests that WPRT should be avoided without NHT. FUNDING: National Cancer Institute.

Predicting Prostate Cancer Recurrence After Radical Prostatectomy.

BACKGROUND: Prostate cancer prognosis is variable, and management decisions involve balancing patients' risks of recurrence and recurrence-free death. Moreover, the roles of body mass index (BMI) and race in risk of recurrence are controversial [1,2]. To address these issues, we developed and cross-validated RAPS (Risks After Prostate Surgery), a personal prediction model for biochemical recurrence (BCR) within 10 years of radical prostatectomy (RP) that includes BMI and race as possible predictors, and recurrence-free death as a competing risk. METHODS: RAPS uses a patient's risk factors at surgery to assign him a recurrence probability based on statistical learning methods applied to a cohort of 1,276 patients undergoing RP at the University of Pennsylvania. We compared the performance of RAPS to that of an existing model with respect to calibration (by comparing observed and predicted outcomes), and discrimination (using the area under the receiver operating characteristic curve (AUC)). RESULTS: RAPS' cross-validated BCR predictions provided better calibration than those of an existing model that underestimated patients' risks. Discrimination was similar for the two models, with BCR AUCs of 0.793, 95% confidence interval (0.766-0.820) for RAPS, and 0.780 (0.745-0.815) for the existing model. RAPS' most important BCR predictors were tumor grade, preoperative prostate-specific antigen (PSA) level and BMI; race was less important [3]. RAPS' predictions can be obtained online at https://predict.shinyapps.io/raps. CONCLUSION: RAPS' cross-validated BCR predictions were better calibrated than those of an existing model, and BMI information contributed substantially to these predictions. RAPS predictions for recurrence-free death were limited by lack of co-morbidity data; however the model provides a simple framework for extension to include such data. Its use and extension should facilitate decision strategies for post-RP prostate cancer management. Prostate 77:291-298, 2017. © 2016 Wiley Periodicals, Inc.

Transcriptome evaluation of the relation between body mass index and prostate cancer outcomes.

BACKGROUND: Large epidemiological studies indicate that an increased body mass index (BMI) is associated with increased prostate cancer (PCa) mortality. Data indicate that there is no association between elevated metabolic pathway proteins and PCa mortality. There are no published studies evaluating the relation between BMI and metabolic pathways with respect to PCa outcomes with a genomics approach. METHODS: The Decipher Genomic Resource Information Database was queried for patients who had undergone prostatectomy and had BMI information available. These patients came from Thomas Jefferson University (TJU) and Johns Hopkins Medical Institution (JHMI); the latter provided 2 cohorts (I and II). A high-BMI group (≥30 kg/m2 ) and a low-BMI group (<25 kg/m2 ) were identified, and genomic data were interrogated for differentially expressed genes with an interquartile range filter and a Wilcoxon test. P values were adjusted for multiple testing with the Benjamini-Hochberg false-discovery rate method. RESULTS: A total of 477 patients with a median follow-up of 108 months had BMI information available. Two genes were found to interact with BMI in both the JHMI I cohort and the TJU cohort, but there was no statistical significance after adjustments for multiple comparisons. Aberrant metabolic gene expression was significantly correlated with distant metastases (P < .05). No relation was found between BMI and metastases or overall survival (both P values > .05). CONCLUSIONS: In a genomic analysis of prostatectomy specimens, metabolic gene expression, but not BMI, was associated with PCa metastases. Cancer 2017;123:2240-2247. © 2017 American Cancer Society.

miRNAs associated with prostate cancer risk and progression.

Prostate cancer is the most common malignancy among men in the US. Though considerable improvement in the diagnosis of prostate cancer has been achieved in the past decade, predicting disease outcome remains a major clinical challenge. Recent expression profiling studies in prostate cancer suggest microRNAs (miRNAs) may serve as potential biomarkers for prostate cancer risk and disease progression. miRNAs comprise a large family of about 22-nucleotide-long non-protein coding RNAs, regulate gene expression post-transcriptionally and participate in the regulation of numerous cellular processes. In this review, we discuss the current status of miRNA in studies evaluating the disease progression of prostate cancer. The discussion highlights key findings from previous studies, which reported the role of miRNAs in risk and progression of prostate cancer, providing an understanding of the influence of miRNA on prostate cancer. Our review indicates that somewhat consistent results exist between these studies and reports on several prostate cancer related miRNAs. Present promising candidates are miR-1, -21, 106b, 141, -145, -205, -221, and -375, which are the most frequently studied and seem to be the most promising for diagnosis and prognosis for prostate cancer. Nevertheless, the findings from previous studies suggest miRNAs may play an important role in the risk and progression of prostate cancer as promising biomarkers.