Showing papers in "Prostate Cancer and Prostatic Diseases in 2018"

Prostate-specific antigen (PSA) density in the diagnostic algorithm of prostate cancer

Abstract: Screening for prostate cancer using prostate-specific antigen (PSA) alone leads to un-necessary biopsying and overdiagnosis. PSA density is easily accessible, but early evidence on its use for biopsy decisions was conflicting and use of PSA density is not commonly recommended in guidelines. We analyzed biopsy outcomes in 5291 men in the population-based STHLM3 study with PSA ≥ 3 ng/ml and ultrasound-guided prostate volume measurements by using percentages and regression models. PSA density was calculated as total PSA (ng/ml) divided by prostate volume (ml). Main endpoint was clinically significant cancer (csPCa) defined as Gleason Score ≥ 7. The median PSA-density was 0.10 ng/ml2 (IQR 0.075–0.14). PSA-density was associated with the risk of finding csPCa both with and without adjusting for the additional clinical information age, family history, previous biopsies, total PSA and free/total PSA (OR 1.06; 95% CI:1.05–1.07 and OR 1.07, 95% CI 1.06–1.08). Discrimination for csPCa was better when PSA density was added to a model with additional clinical information (AUC 0.75 vs. 0.73, P < 0.05). The proportion of men with Gleason Score 6 (ISUP 1) was similar across stratas of PSA-density. Omitting prostate biopsy for men with PSA-density ≤0.07 ng/ml2 would save 19.7% of biopsy procedures, while missing 6.9% of csPCa. PSA-density cutoffs of 0.10 ng/ml2 and 0.15 ng/ml2 resulted in detection of 77% (729/947) and 49% (461/947) of Gleason Score ≥7 tumors. PSA-density might inform biopsy decisions, and spare some men from the morbidity associated with a prostate biopsy and diagnosis of low-grade prostate cancer.

The microbiome in prostate inflammation and prostate cancer.

Abstract: The human microbiome may influence prostate cancer initiation and/or progression through both direct and indirect interactions. To date, the majority of studies have focused on direct interactions including the influence of prostate infections on prostate cancer risk and, more recently, on the composition of the urinary microbiome in relation to prostate cancer. Less well understood are indirect interactions of the microbiome with prostate cancer, such as the influence of the gastrointestinal or oral microbiota on pro- or anti-carcinogenic xenobiotic metabolism, and treatment response. We review the literature to date on direct and indirect interactions of the microbiome with prostate inflammation and prostate cancer. Emerging studies indicate that the microbiome can influence prostate inflammation in relation to benign prostate conditions such as prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia, as well as in prostate cancer. We provide evidence that the human microbiome present at multiple anatomic sites (urinary tract, gastrointestinal tract, oral cavity, etc.) may play an important role in prostate health and disease. In health, the microbiome encourages homeostasis and helps educate the immune system. In dysbiosis, a systemic inflammatory state may be induced, predisposing remote anatomical sites to disease, including cancer. The microbiome’s ability to affect systemic hormone levels may also be important, particularly in a disease such as prostate cancer that is dually affected by estrogen and androgen levels. Due to the complexity of the potential interconnectedness between prostate cancer and the microbiome, it is vital to further explore and understand the relationships that are involved.

Compositional differences in gastrointestinal microbiota in prostate cancer patients treated with androgen axis-targeted therapies.

Abstract: It is well known that the gastrointestinal (GI) microbiota can influence the metabolism, pharmacokinetics, and toxicity of cancer therapies. Conversely, the effect of cancer treatments on the composition of the GI microbiota is poorly understood. We hypothesized that oral androgen receptor axis-targeted therapies (ATT), including bicalutamide, enzalutamide, and abiraterone acetate, may be associated with compositional differences in the GI microbiota. We profiled the fecal microbiota in a cross-sectional study of 30 patients that included healthy male volunteers and men with different clinical states of prostate cancer (i.e., localized, biochemically recurrent, and metastatic disease) using 16S rDNA amplicon sequencing. Functional inference of identified taxa was performed using PICRUSt. We report a significant difference in alpha diversity in GI microbiota among men with versus without a prostate cancer diagnosis. Further analysis identified significant compositional differences in the GI microbiota of men taking ATT, including a greater abundance of species previously linked to response to anti-PD-1 immunotherapy such as Akkermansia muciniphila and Ruminococcaceae spp. In functional analyses, we found an enriched representation of bacterial gene pathways involved in steroid biosynthesis and steroid hormone biosynthesis in the fecal microbiota of men taking oral ATT. There are measurable differences in the GI microbiota of men receiving oral ATT. We speculate that oral hormonal therapies for prostate cancer may alter the GI microbiota, influence clinical responses to ATT, and/or potentially modulate the antitumor effects of future therapies including immunotherapy. Given our findings, larger, longitudinal studies are warranted.

68Ga-PSMA PET/CT vs. mpMRI for locoregional prostate cancer staging: correlation with final histopathology.

Abstract: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) can be used to locate lesions based on PSMA avidity, however guidelines on its use are limited by its infancy. We aimed to compare multiparametric magnetic resonance imaging (mpMRI) and PSMA PET/CT to prostatectomy histopathology. We conducted a chart review from February 2015 to January 2017 of 50 male patients staged for prostate cancer using PSMA PET/CT and mpMRI who then underwent radical prostatectomy. Pre-operative PSMA PET/CT and mpMRI were paired with corresponding histopathology. Correlations, sensitivity, and specificity were used for comparisons. A total of 81 lesions were confirmed by histopathology. Fifty index lesions were detected by histopathology, all of which were detected by PSMA PET/CT (100% detection), and 47 by mpMRI (94% detection). Thirty-one histologically confirmed secondary lesions were detected, 29 of which were detected by PSMA PET/CT (93.5% detection), and 16 by mpMRI (51.6% detection). PSMA had better sensitivity for index lesion localization than mpMRI (81.1 vs. 64.8%). Specificity was similar for PSMA PET/CT and mpMRI (84.6 vs. 82.7%). SUVmax of index lesions ranged from 2.9 to 39.6 (M = 9.27 ± 6.41). Index lesion SUVmax was positively correlated with PSA (rho = 0.48, p < 0.001) and ISUP grade (rho = 0.51, p < 0.001). PSMA-PET/CT provided superior detection of prostate cancer lesions with better sensitivity than mpMRI. PSMA-PET/CT can be used to enhance locoregional mpMRI to provide improved detection and characterization of lesions.

Serum cholesterol and risk of high-grade prostate cancer: results from the REDUCE study.

Abstract: Epidemiologic evidence for a serum cholesterol-prostate cancer link is mixed. Prostate-specific antigen (PSA) is positively correlated with cholesterol, potentially increasing PSA-driven biopsy recommendations in men with high cholesterol, though biopsy compliance may be lower in men with comorbid conditions. These potential biases may affect PSA-driven biopsy rates and subsequent prostate cancer detection in men with high serum cholesterol. Our objective was to test the association between serum cholesterol and prostate cancer risk in men receiving PSA independent, study-mandated prostate biopsies. We conducted a post hoc analysis of data from 4974 non-statin users in REDUCE, a randomized trial in men with elevated PSA and a negative baseline biopsy. Men underwent 2- and 4-year trial-mandated prostate biopsies. Associations between baseline serum levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and prostate cancer risk, overall and by Gleason grade ( 0.185). There was no association between serum LDL and overall, low- or high-grade prostate cancer risk (p-values >0.137). In contrast, elevated serum HDL was associated with increased risk of both overall (OR per 10 mg/dL 1.08; 95% CI 1.01–1.16; p = 0.033) and high-grade prostate cancer (OR per 10 mg/dL 1.14; 95% CI 1.01–1.28; p = 0.034). In REDUCE, where all men received PSA independent, trial-mandated biopsies thus ensuring complete prostate cancer ascertainment, high total serum cholesterol and high HDL were associated with increased risk of high-grade prostate cancer, supporting a cholesterol-prostate cancer link.

The use of PET/CT in prostate cancer.

Abstract: Positron emission tomography/computed tomography (PET/CT) has recently emerged as a promising diagnostic imaging platform for prostate cancer. Several radiolabelled tracers have demonstrated efficacy for cancer detection in various clinical settings. In this review, we aim to illustrate the diverse use of PET/CT with different tracers for the detection of prostate cancer. We searched MEDLINE using the terms ‘prostate cancer’, ‘PET’, ‘PET/CT’ and ‘PET/MR’). The current review was limited to 18F-NaF PET/CT, choline-based PET/CT, fluciclovine PET/CT and PSMA-targeted PET/CT, as these modalities have been the most widely adopted. NaF PET/CT has shown efficacy in detecting bone metastases with high sensitivity, but relatively low specificity. Currently, choline PET/CT has been the most extensively studied modality. Although having superior specificity, choline PET/CT suffers from low sensitivity, especially at low PSA levels. Nevertheless, choline PET/CT was found to significantly improve upon conventional imaging modalities (CIM) in the detection of metastatic lesions at biochemical recurrence (BCR). Newer methods using fluciclovine and PSMA-targeted radiotracers have preliminarily demonstrated great promise in primary and recurrent staging of prostate cancer. However, their superior efficacy awaits confirmation in larger series. PET/CT has emerged as a promising staging modality for both primary and recurrent prostate cancer. Newer tracers have increased detection accuracies for small, incipient metastatic foci. The clinical implications of these occult PET/CT detected disease foci require organized evaluation. Efforts should be aimed at defining their natural history as well as responsiveness and impact of metastasis-directed therapy.

Current approaches to incorporation of radium-223 in clinical practice.

Abstract: Treatment options for metastatic castration-resistant prostate cancer (mCRPC) have expanded in recent years and include cytotoxic agents (e.g., docetaxel and cabazitaxel), immunotherapy (e.g., sipuleucel-T), oral hormonal therapies targeting the androgen receptor axis (e.g., enzalutamide and abiraterone), and targeted alpha therapy (e.g., radium-223 dichloride (radium-223)). Although treatment guidelines have been updated to reflect the availability of new agents, it is not easy to apply them in daily clinical practice because recommendations vary depending on patient comorbidities and disease characteristics. Furthermore, therapeutic accessibility, clinical judgment, and experience affect the selection of treatment options. In this review, we provide practical guidance for the integration of radium-223 into the management of patients with mCRPC based on our collective clinical experience, as well as the available clinical trial data. Radium-223 is a targeted alpha therapy; as a bone-seeking calcium mimetic, it accumulates in hydroxyapatite areas surrounding tumor lesions and selectively binds to the areas of increased bone turnover. Radium-223 prolongs overall survival and delays time to the first symptomatic skeletal events in men with mCRPC, and is indicated for the treatment of patients with CRPC, symptomatic bone metastases, and no known visceral metastases. We review its clinical efficacy and safety, practical guidance on identifying the appropriate patient, and recommendations for how best to educate and inform prospective patients regarding their treatment decision making. In addition, we review recent evidence for sequential and combination therapies with radium-223, provide our experiences with these treatment approaches, and discuss their implications for the future treatment of patients with mCRPC. Based on our clinical experience, radium-223 should be considered relatively early in the treatment course in patients with mCRPC with bone metastases. Coordination of care among multidisciplinary team members, patients, and caregivers is essential for optimizing safe and effective treatment with all CRPC therapies.

The molecular biology of prostate cancer: current understanding and clinical implications.

Abstract: With continuous progress over the past few decades in understanding diagnosis, treatment, and genetics, much has been learned about the prostate cancer-diagnosed genome. A comprehensive MEDLINE® and Google scholar literature search was conducted using keyword variations relating to the genetics of prostate cancer such as chromosomal alterations, androgen receptor, castration-resistant, inheritance, polymorphisms, oncogenes, metastasis, biomarkers, and immunotherapy. Traditionally, androgen receptors (AR) have been the focus of research. Recently, identification of recurrent chromosomal alterations that lead to either multiplication of regions (gain-of-function) or deletion of regions (loss-of-function) has opened the door to greater genetic accessibility. These chromosomal aberrations lead to variation in copy number and gene expression. Some of these chromosomal alterations are inherited, while others undergo somatic mutations during disease progression. Inherited gene mutations that make one susceptible to prostate cancer have been identified with familial-linked studies. Somatic genes that progress tumorigenesis have also been identified. Research on the molecular biology of prostate cancer has characterized these genes into tumor suppressor genes or oncogenes. Additionally, genome-wide assay studies have identified many high-risk single-nucleotide polymorphisms recurrent throughout the prostate cancer-diagnosed genome. Castration-resistant prostate cancer is the most aggressive form of prostate cancer, and its research has elucidated many types of mutations associated with AR itself, including enhanced expression and amplification, point mutations, and alternative splicing. Understanding the molecular biology of prostate cancer has permitted more accurate identification using advanced biomarkers and therapy for aggressive forms using immunotherapy. An age-related disease, prostate cancer commands profound attention. With increasing life expectancy and the continuous pursuit of it, prostate cancer is a powerful obstacle best defeated using targeted therapies specifically designed for the unique molecular profile of the malignancy.

Convective radiofrequency water vapor thermal therapy for benign prostatic hyperplasia: a single office experience

Abstract: Convective radiofrequency water vapor thermal therapy with the Rezūm system is a relatively new treatment for benign prostatic hyperplasia (BPH). We present results from a single surgeon in an office setting. A retrospective review of 129 patients from a single surgeon who underwent the Rezūm procedure was performed. All patients were at least 4 months out from treatment. International prostate symptom scores (IPSS), maximum flow rates (Qmax), residual urine volumes, medication usage, and adverse events were monitored. Data were analyzed at baseline, 15–45 days, 46–90 days, and 91–180 days after treatment. A scripted patient questionnaire was attempted over the phone to all patients. It was administered by a resident and medical student who do not work in the provider’s office. Maximal effects were noted at the 91–180 day interval. IPSS improved from a baseline of 18.3 to 6.9 and Qmax from 10.5 to 16.8 mL/s. Improvements were independent of starting symptom score, median lobe treatment, and prostate size. There was a 17% prostate volume reduction based on TRUS and 14% based on PSA. The most common adverse events were urinary tract infections (17%) and transient urinary retention (14%). In total 90% of patients were able to come off their BPH medications and 86% of patients would recommend the procedure to a friend. Rezūm radiofrequency water vapor thermal therapy offers a minimally invasive option for BPH management with moderate improvement in symptoms and flow rate. The results appear to be independent of prostate size or presence of a median lobe, and have now been replicated in a single office setting.

Processed and raw tomato consumption and risk of prostate cancer: a systematic review and dose-response meta-analysis.

Abstract: Prostate cancer (PCa) is the second most frequently diagnosed cancer among men worldwide. Many epidemiological studies have found an inverse association between increased tomato consumption and PCa risk. This study aims to determine the associations between consumption of various types of tomato products and PCa risk and to investigate potential dose–response relationships. We conducted a systematic review and dose–response meta-analysis of dietary tomato in relation to PCa. Eligible studies were published before April 10, 2017 and were identified from PubMed, Web of Science, and the Cochrane Library. We estimated pooled risk ratios (RRs) and 95% confidence intervals (CI) using random and fixed effects models. Linear and nonlinear dose–response relationships were also evaluated for PCa risk. Thirty studies related to tomato consumption and PCa risk were included in the meta-analysis, which summarized data from 24,222 cases and 260,461 participants. Higher total tomato consumption was associated with a reduced risk of PCa (RR = 0.81, 95% CI: 0.71–0.92, p = 0.001). Specifically, tomato foods (RR = 0.84, 95% CI: 0.72–0.98, p = 0.030) and cooked tomatoes and sauces (RR = 0.84, 95% CI: 0.73–0.98, p = 0.029) were associated with a reduced risk of PCa. However, no associations were found for raw tomatoes (RR = 0.96, 95% CI: 0.84–1.09, p = 0.487). There was a significant dose–response association observed for total tomato consumption (p = 0.040), cooked tomatoes and sauces (p < 0.001), and raw tomatoes (p = 0.037), but there was not a significant association with tomato foods (plinear = 0.511, pnonlinear = 0.289). Our data demonstrate that increased tomato consumption is inversely associated with PCa risk. These findings were accompanied with dose–response relationships for total tomato consumption and for cooked tomatoes and sauces. Further studies are required to determine the underlying mechanisms of these associations.

Combining intratumoral Treg depletion with androgen deprivation therapy (ADT): preclinical activity in the Myc-CaP model.

Abstract: Immune checkpoint blockade has shown promising antitumor activity against a variety of tumor types. However, responses in castration-resistant prostate cancer remain relatively rare—potentially due to low baseline levels of infiltration. Using an immunocompetent cMyc-driven model (Myc-CaP), we sought to understand the immune infiltrate induced by androgen deprivation therapy (ADT) and to leverage that infiltration toward therapeutic benefit. Using flow cytometry, qPCR and IHC, we quantified ADT-induced immune infiltration in terms of cell type and function. Preclinical treatment studies tested the combinatorial effects of ADT and immune checkpoint blockade using tumor outgrowth and overall survival as end points. ADT induces a complex pro-inflammatory infiltrate. This pro-inflammatory infiltrate was apparent in the early postcastration period but diminished as castration resistance emerged. Combining ADT with tumor-infiltrating regulatory T cell (Treg) depletion using a depleting anti-CTLA-4 antibody significantly delayed the development of castration resistance and prolonged survival of a fraction of tumor-bearing mice. Immunotherapy as a monotherapy failed to provide a survival benefit and was ineffective if not administered in the peri-castration period. The immune infiltrate induced by ADT is diverse and varies over time. Therapeutic strategies focusing on depleting Tregs in the peri-castration period are of particular interest.

p53 status in the primary tumor predicts efficacy of subsequent abiraterone and enzalutamide in castration-resistant prostate cancer

Abstract: We tested whether tissue-based analysis of p53 and PTEN genomic status in primary tumors is predictive for subsequent sensitivity to abiraterone and enzalutamide in castration-resistant prostate cancer (CRPC). We performed a retrospective analysis of 309 consecutive patients with CRPC treated with abiraterone or enzalutamide. Of these, 101 men (33%) had available primary tumor tissue for analysis. We screened for deleterious TP53 missense mutations and PTEN deletions using genetically validated immunohistochemical assays for nuclear accumulation of p53 protein and PTEN protein loss, with sequencing confirmation of TP53 mutations in a subset. Overall survival (OS) and progression-free survival (PFS) were compared between patients with and without p53 and/or PTEN alterations. Forty-eight percent of the evaluable cases had PTEN loss and 27% had p53 nuclear accumulation. OS and PFS did not differ according to PTEN status, but were significantly associated with p53 status. Median OS was 16.7 months (95% CI, 14–21.9 months) and 31.2 months (95% CI, 24.5–43.4) for men with and without p53 nuclear accumulation, respectively (HR 2.32; 95% CI 1.19–4.51; P = 0.0018). Similarly, median PFS was 5.5 months (95% CI, 3.2–9.9 months) and 10.9 months (95% CI, 8–15.2 months) in men with and without p53 nuclear accumulation, respectively (HR 2.14, 95%CI 1.20–3.81; P = 0.0008). In multivariable analyses, p53 status was independently associated with PFS (HR 2.15; 95% CI 1.03–4.49; P = 0.04) and a HR of 2.19 for OS (95% CI 0.89–5.40; P = 0.087). p53 inactivation in the primary tumor (but not PTEN loss) may be predictive of inferior outcomes to novel hormonal therapies in CRPC.

Clinical utility of the Prostate Health Index (phi) for biopsy decision management in a large group urology practice setting.

Abstract: Deciding when to biopsy a man with non-suspicious DRE findings and tPSA in the 4–10 ng/ml range can be challenging, because two-thirds of such biopsies are typically found to be benign. The Prostate Health Index (phi) exhibits significantly improved diagnostic accuracy for prostate cancer detection when compared to tPSA and %fPSA, however only one published study to date has investigated its impact on biopsy decisions in clinical practice. An IRB approved observational study was conducted at four large urology group practices using a physician reported two-part questionnaire. Physician recommendations were recorded before and after receiving the phi test result. A historical control group was queried from each site's electronic medical records for eligible men who were seen by the same participating urologists prior to the implementation of the phi test in their practice. 506 men receiving a phi test were prospectively enrolled and 683 men were identified for the historical control group (without phi). Biopsy and pathological findings were also recorded for both groups. Men receiving a phi test showed a significant reduction in biopsy procedures performed when compared to the historical control group (36.4% vs. 60.3%, respectively, P < 0.0001). Based on questionnaire responses, the phi score impacted the physician’s patient management plan in 73% of cases, including biopsy deferrals when the phi score was low, and decisions to perform biopsies when the phi score indicated an intermediate or high probability of prostate cancer (phi ≥36). phi testing significantly impacted the physician’s biopsy decision for men with tPSA in the 4–10 ng/ml range and non-suspicious DRE findings. Appropriate utilization of phi resulted in a significant reduction in biopsy procedures performed compared to historical patients seen by the same participating urologists who would have met enrollment eligibility but did not receive a phi test.

Post prostatectomy outcomes of patients with high-risk prostate cancer treated with neoadjuvant androgen blockade

Abstract: Patients with high-risk prostate cancer have an increased likelihood of experiencing a relapse following radical prostatectomy (RP). We previously conducted three neoadjuvant androgen-deprivation therapy (ADT) trials prior to RP in unfavorable intermediate and high-risk disease. In this analysis, we report on the post-RP outcomes of a subset of patients enrolled on these studies. We conducted a pooled analysis of patients with available follow-up data treated on three neoadjuvant trials at three institutions. All patients received intense ADT prior to RP. The primary endpoint was time to biochemical recurrence (BCR). BCR was defined as a PSA ≥ 0.2 ng/mL or treatment with radiation or androgen-deprivation therapy for a rising PSA < 0.2 ng/mL. Overall, 72 patients were included of whom the majority had a Gleason score ≥ 8 (n = 46, 63.9%). Following neoadjuvant therapy, 55.7% of patients (n = 39/70) had pT3 disease, 40% (n = 28) had seminal vesicle invasion, 12.9% (n = 9) had positive margins, and 11.4% (n = 8) had lymph node involvement. Overall, 11 (15.7%) had tumor measuring ≤ 0.5 cm, which included four patients (5.7%) with a pathologic complete response and seven (10.0%) with residual tumor measuring 0.1–0.5 cm. Compared to pretreatment clinical staging, 10 patients (14.3%) had pathologic T downstaging at RP. The median follow-up was 3.4 years. Overall, the 3-year BCR-free rate was 70% (95% CI 57%, 90%). Of the 15 patients with either residual tumor ≤ 0.5 cm or pathologic T downstaging, no patient experienced a recurrence. In this exploratory pooled clinical trials analysis, we highlight that neoadjuvant therapy prior to RP in unfavorable intermediate and high-risk patients may potentially have a positive impact on recurrence rates. Larger studies with longer follow-up periods are warranted to evaluate the impact of neoadjuvant hormone therapy on pathologic and long-term outcomes.

MRI in prostate cancer diagnosis: do we need to add standard sampling? A review of the last 5 years

Abstract: In recent years, evidence has accrued to support the introduction of multiparametric magnetic resonance imaging (mpMRI) in the prostate cancer diagnostic pathway. The exact role of mpMRI in different settings is not widely agreed. In this review, we look at the use of MRI in three groups of men: biopsy naive men, those with a previous negative biopsy and those with a previous positive biopsy suitable for active surveillance. An electronic MEDLINE/PubMed search up to 24th January 2018 was performed, using the search terms (prostate cancer OR prostate adenocarcinoma) AND (MRI OR magnetic resonance) AND (biopsy naive OR active surveillance OR prior negative biopsy OR no prior biopsy). Only those studies which reported detection rates of standard biopsy and MRI-targeted biopsy, where all men had both an MRI and standard biopsy were included. In total 34 articles were included (14 biopsy naive, 10 prior negative biopsy, and 10 prior positive biopsy). MRI-targeted biopsy consistently resulted in greater detection of clinically significant prostate cancer, and a lower detection of clinically insignificant prostate cancer, across all three patient populations. This effect was most prominent in men with at least one previous negative biopsy, and least prominent in men on active surveillance. In the presence of a negative mpMRI detection of csPCa found at systematic biopsy ranged from 0 to 20%. MRI-targeted biopsy is more efficient than standard biopsy in detecting clinically significant disease in men with a positive MRI, and results in less detection of clinically insignificant cancer. In men with a negative MRI, a significant minority of men will have clinically significant cancer detected on systematic biopsy.

Which technology to select for primary focal treatment of prostate cancer?-European Section of Urotechnology (ESUT) position statement.

Abstract: With growing interest in focal therapy (FT) of prostate cancer (PCa) there is an increasing armamentarium of treatment modalities including high-intensity focused ultrasound (HIFU), cryotherapy, focal laser ablation (FLA), irreversible electroporation (IRE), vascular targeted photodynamic therapy (VTP), focal brachytherapy (FBT) and stereotactic ablative radiotherapy (SABR). Currently there are no clear recommendations as to which of these technologies are appropriate for individual patient characteristics. Our intention was to review the literature for special aspects of the different technologies that might be of advantage depending on individual patient and tumour characteristics. The current literature on FT was screened for the following factors: morbidity, repeatability, tumour risk category, tumour location, tumour size and prostate volume and anatomical issues. The ESUT expert panel arrived at consensus regarding a position statement on a structured pathway for available FT technologies based on a combination of the literature and expert opinion. Side effects were low across different studies and FT modalities with urinary continence rates of 90–100% and erectile dysfunction between 5 and 52%. Short to medium cancer control based on post-treatment biopsies were variable between ablative modalities. Expert consensus suggested that posterior lesions are better amenable to FT using HIFU. Cryotherapy provides best possible outcomes for anterior tumours. Apical lesions, when treated with FBT, may yield the least urethral morbidity. Further prospective trials are required to assess medium to long term disease control of different ablative modalities for FT. Amongst different available FT modalities our ESUT expert consensus suggests that some may be better for diffe`rent tumour locations. Tumour risk, tumour size, tumour location, and prostate volume are all important factors to consider and might aid in designing future FT trials.

Prostate cancer radiation and urethral strictures: a systematic review and meta-analysis.

Abstract: We performed a systematic review and meta-analysis to determine the prevalence and predictors of urethral stricture development post radiation therapy (RT) for prostate cancer (PCa). Published articles in PubMed/Medline, Cochrane, and Embase databases from January 2000 to April 2016 were queried. Inclusion criteria were any study that reported the prevalence of urethral strictures following external beam radiation therapy (EBRT), brachytherapy (BT), or both as a primary treatment for PCa. Forty-six articles met our inclusion criteria. A summary estimate of the proportion of patients who developed a urethral stricture was derived via a random effects meta-analysis. In total, 16,129 PCa patients underwent either EBRT (5681, 35.2%), BT (5849, 36.3%), or both (4599, 28.5%). Overall, 630 strictures were diagnosed at follow-up with a pooled estimate period prevalence of 2.2% (95% confidence interval, CI 1.9–2.6%) in a median follow-up time of 4 years (interquartile range, IQR 2.7–5). Of which, the pooled estimate prevalence was 1.5% (95% CI 0.9–2%) post EBRT, 1.9% (95% CI 1.3–2.4%) post BT, and 4.9% (95% CI 3.8–6%) post both EBRT and BT. Of 20 studies reporting a median time to stricture formation, the overall median time was 2.2 years (IQR 1.8–2.5, range 1.4–9). In a meta-regression analysis, receiving both EBRT and BT increased the estimated difference in proportion of stricture diagnoses by 3% (95% CI 1–6%), p = 0.018 compared to EBRT alone. An increase in median follow-up time was found to significantly increase the risk of developing urethral strictures (p = 0.04). With a short-term follow-up, urethral strictures occur in 2.2% of men with PCa receiving radiotherapy. Receiving both EBRT and BT increased the risk of stricture formation. Longer follow-up is needed to determine the long-term natural history of stricture formation after RT.

Cost and efficacy comparison of five prostate biopsy modalities: a platform for integrating cost into novel-platform comparative research

Abstract: The cornerstone of prostate cancer diagnosis remains the transrectal ultrasound-guided biopsy (TRUS-BX), which most frequently occurs in the office setting under local anesthesia. However, there are now other techniques of prostate biopsy aimed at improving outcomes such as patient comfort, significant cancer detection, and infectious complications. The purpose of the present study is to compare the cost and efficacy outcomes of five different approaches. We compared the comprehensive costs of a random sample size of 20−30 cases from each of the following: (1) local anesthesia TRUS-BX (reference), (2) sedation TRUS-BX, (3) general anesthesia transperineal template biopsy (TP), (4) sedation MRI-TRUS fusion biopsy (FB), and (5) sedation in-bore MRI biopsy (IB-MRI). Cost categories included pre-procedure, anesthesia pharmacy and recovery, and the technical/professional costs from urology, radiology, and pathology services. For procedure outcomes, we compared the larger cohorts of TRUS-BX, TP, and FB in terms of indication, cancer yield, and downstream decision impact. Compared with standard TRUS-BX, the total costs of sedation TRUS-BX, TP, FB, and IB-MRI increased significantly ×1.9 (90%), ×2.5 (153%), ×2.5 (150%), and ×2.2 (125%), respectively (p < 0.001). Although there was no statistical difference between the total costs of TP, FB, and IB-MRI, these costs were significantly higher than those of TRUS-BX under either local anesthesia or sedation (p < 0.05). The cost of TRUS-BX under sedation was significantly higher than that of TRUS-BX under local anesthesia (p < 0.001). Compared to TRUS-BX, more significant cancers were detected in FB (16% vs. 36%) and TP (16% vs. 34%) groups (p < 0.001). Compared with standard TRUS-BX, the additions of imaging, sedation anesthesia, and transperineal template increase costs significantly, and can be considered along with known improvements in accuracy and side effects. Ongoing efforts to combine imaging and transperineal biopsy, especially in an outpatient/local anesthesia setting may lead to a higher cost/benefit.

Which scores need a core? An evaluation of MR-targeted biopsy yield by PIRADS score across different biopsy indications

Abstract: Magnetic resonance imaging is being widely adopted in the clinical management of prostate cancer. The correlation of the Prostate Imaging Reporting and Data System (PIRADS) to the presence of cancer has been established but studies have primarily evaluated this in a single clinical setting. This study aims to characterize the correlation of PIRADS score to the diagnosis of cancer on fusion biopsy among men who are undergoing primary biopsy, those who have had a previous negative biopsy or men on active surveillance. A consecutive sample of men undergoing US-MR biopsy at a single academic institution from 2014 to 2017 were included in this retrospective study. Men were stratified into groups according to their clinical history: biopsy-naive, previous negative transrectal ultrasound (TRUS) biopsy or on active surveillance. The correlation of PIRADS score to the diagnosis of any and clinically significant cancer (Gleason score ≥ 3 + 4) was determined. A total of 255 patients with 365 discrete lesions were analyzed. PIRADS score 1–2, 3, 4 and 5 yielded any prostate cancer in 7.7, 29.7, 42.3 and 82.4% of the cases, respectively, across all indications while clinically significant cancer was found in 0, 8.9, 21.4 and 62.7%, respectively. The area under the receiver operative curves for the diagnosis of any and significant cancer was 0.69 (95%CI: 0.64–0.74) and 0.74 (95%CI: 0.69–0.79) respectively. Men who have had a previous negative biopsy had lower detection rates for any prostate cancer for PIRADS 3 and 4 lesions compared to those that were biopsy-naive or on active surveillance. Cancer detection rates are significantly associated with PIRADS score. Biopsy yields differ across biopsy indications which should be considered when selecting a PIRADS score threshold for biopsy. Biopsy of PIRADS 3 lesions could potentially be avoided in men who have previously undergone a negative TRUS biopsy.

Overexpression of α (1,6) fucosyltransferase in the development of castration-resistant prostate cancer cells.

Abstract: Glycosylation is recognized as one of the most common modifications on proteins. Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer. While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer. In this study, using a proteomics approach, we analyzed androgen-dependent and androgen-resistant LAPC4 cells and identified FUT8 to be significantly overexpressed in the androgen-resistant LAPC4 cells. These findings were independently confirmed in LAPC4 cells that were treated with non-steroidal anti-androgen (bicalutamide) and in the in vivo castrated tumor xenograft models. Similarly, we also demonstrated that overexpression of FUT8 might be responsible for the decreased PSA expression in prostate cancer specimens. To our knowledge, this is the first study reporting the functional role of fucosylated enzyme in the development of castration-resistant prostate cancer.

Prognostic association of plasma cell-free DNA-based androgen receptor amplification and circulating tumor cells in pre-chemotherapy metastatic castration-resistant prostate cancer patients.

Abstract: The prognostic significance of plasma cell-free DNA (cfDNA) androgen receptor amplification (ARamp) in metastatic castration-resistant prostate cancer (mCRPC) compared with circulating tumor cell (CTC) counts is not known. As part of correlative aims of a prospective study in mCRPC, concurrent and serial collections of plasma and CTCs were performed. Specimen collections were performed at baseline after progression on androgen deprivation therapy and then 12 weeks later. QuantStudio3D digital PCR system was used to determine plasma cfDNA AR copy number variations and Cell search assay for enumerating CTC counts. Association of baseline cfDNA ARamp status/CTC counts with overall survival (OS) (primary goal) was evaluated using Kaplan–Meier method and log-rank test (p ≤ 0.05 for significance) and receiver operator curves (ROCs) for ARamp status and CTC counts ≥5. A multivariate analysis was performed using Cox regression models that included ARamp, CTC counts, and other clinical factors. ARamp was detected in 19/70 patients at baseline. At the time of analysis, 28/70 patients had died (median follow-up 806 days; interquartile range: 535–966). ARamp was associated with poor OS (2-year OS of 35% in ARamp vs. 71% in non-ARamp; log-rank p value ≤0.0001). Baseline CTC counts ≥5 (vs. <5) was also associated with poor survival (2-year OS of 44 vs. 74%; log-rank p = 0.001). ROC analysis demonstrated area under the curve of 0.66 for ARamp-based prognosis and 0.68 for CTC count-based prognosis (p = 0.84 for difference). The best two variables included for multivariable analysis were ARamp and CTC counts ≥5; however, the two-factor model was not significantly better than using ARamp alone for predicting survival (hazard ratio = 5.25; p = 0.0002). CTCs and plasma cfDNA ARamp were observed to have equal prognostic value in mCRPC. Larger cohorts that incorporate molecular and clinical factors are needed to further refine prognosis in CRPC.

Combining immune check-point blockade and cryoablation in an immunocompetent hormone sensitive murine model of prostate cancer.

Abstract: Prostate cancer remains the second leading cause of cancer related death in men. Immune check point blocking antibodies have revolutionized treatment of multiple solid tumors, but results in prostate cancer remain marginal. Previous reports have suggested that local therapies, in particular cryoablation might increase tumor immunogenicity. In this work, we examine potential synergism between tumor cryoabalation and check point blocking antibodies. FVB/NJ mice were injected subcutaneously into each flank with either 1 × 106 or 0.2 × 106 isogenic hormone sensitive Myc-Cap cells to establish synchronous grafts. Mice were treated with four intraperitoneal injections of anti-PD-1 (10 mg/kg), anti-CTLA-4 (1 mg/kg), or isotype control antibody with or without adjuvant cryoablation of the larger tumor graft and with or without neo-adjuvant androgen deprivation with degarelix (ADT). Mouse survival and growth rates of tumor grafts were measured. The immune dependency of observed oncological effects was evaluated by T cell depletion experiments. Treatment with anti-CTLA-4 antibody and cryoablation delayed the growth of the distant tumor by 14.8 days (p = 0.0006) and decreased the mortality rate by factor of 4 (p = 0.0003) when compared to cryoablation alone. This synergy was found to be dependent on CD3+ and CD8+ cells. Combining PD-1 blockade with cryoablation did not show a benefit over use of either treatment alone. Addition of ADT to anti-PD1 therapy and cryoablation doubled the time to accelerated growth in the untreated tumors (p = 0.0021) and extended survival when compared to cryoablation combined with ADT in 25% of the mice. Effects of combining anti-PD1 with ADT and cryoablation on mouse survival were obviated by T cell depletion. Trimodal therapy consisting of androgen deprivation, cryoablation and PD-1 blockade, as well as the combination of cryoablation and low dose anti-CTLA-4 blockade showed that local therapies with cryoablation could be considered to augment the effects of checkpoint blockade in prostate cancer.

Does the association of prostate cancer with night-shift work differ according to rotating vs. fixed schedule? A systematic review and meta-analysis.

Abstract: Recent studies suggested that the relation between night-shift work and prostate cancer may differ between rotating and fixed schedules. We aimed to quantify the independent association between night-shift work and prostate cancer, for rotating and fixed schedules. We searched MEDLINE for studies assessing the association of night-shift work, by rotating or fixed schedules, with prostate cancer. We computed summary relative risk (RR) estimates with 95% confidence intervals (95% CI) using the inverse variance method and quantified heterogeneity using the I2 statistic. Meta-regression analysis was used to compare the summary RR estimates for rotating and fixed schedules, while reducing heterogeneity. A total of nine studies assessed the effect of rotating and, in addition, four of them provided the effect of fixed night-shift work, in relation to daytime workers. Rotating night-shift work was associated with a significantly increased risk of prostate cancer (RR = 1.06, 95% CI of 1.01 to 1.12; I2 = 50%), but not fixed night-shift work (RR of 1.01, 95% CI of 0.81 to 1.26; I2 = 33%). In meta-regression model including study design, type of population, and control of confounding, the summary RR was 20% higher for rotating vs. fixed schedule, with heterogeneity fully explained by these variables. This is the first meta-analysis suggesting that an increased risk of prostate cancer may be restricted to workers with rotating night shifts. However, the association was weak and additional studies are needed to further clarify this relation before it can be translated into measures for risk reduction in occupational settings.

Positive margin length and highest Gleason grade of tumor at the margin predict for biochemical recurrence after radical prostatectomy in patients with organ-confined prostate cancer.

Abstract: To evaluate the pathologic features after radical prostatectomy to determine if the length of positive surgical margin (PSM) and the highest Gleason grade within the tumor at the PSM could risk stratify patients for biochemical recurrence (BCR). We performed a retrospective, matched, cohort study to identify patients with pathologically organ-confined (pT2) tumors and negative nodes (pN0/Nx), receiving no adjuvant therapy. Specimens underwent single pathologist review. BCR-free survival was estimated using the Kaplan–Meier method and compared between subgroups using two-sided log-rank test. Using Classification and Regression Tree analysis (CART), we identified an optimal cutoff for the PSM length which differentiated risk for BCR. Cox proportional hazards regression models were fit to assess the association between variables and BCR-free survival. Two-hundred PSM patients were matched to 200 patients with negative surgical margins (NSM). Median follow-up was 64 months. 5 year BCR-free survival was 90% (95% CI 84–97%) in the NSM group and 70% (95% CI 63–79%) in the PSM group. There was an increased risk of BCR with any PSM. Multivariable analysis demonstrated an association with length of PSM ( > 1 mm vs. ≤ 1 mm, HR 2.29; 95% CI 1.2–4.5) and having a highest Gleason grade of the cancer focus at the margin ≥ 4 (HR 6.8; 95% CI 1.6–29). We demonstrated that patients with pathologic T2 tumors with PSM > 1 mm or a Gleason grade of tumor focus at the margin ≥ 4 are at elevated risk for BCR. However, this study suggests that patients with pT2 tumors with positive surgical margins have a relatively low risk of biochemical recurrence and adjuvant radiation may be over treating this sub population. The subsets at greatest risk for BCR may benefit from more frequent PSA monitoring to direct salvage therapies.

Development of comorbidities in men with prostate cancer treated with androgen deprivation therapy: an Australian population-based cohort study.

Abstract: The increasing use of androgen deprivation therapy has prompted further evaluation of its potential adverse effects as the treatment may exacerbate or increase the risk of developing new comorbid diseases. This study aims to assess the patterns of comorbidities among Australian men with prostate cancer treated with androgen deprivation therapy. Pharmaceutical Benefits Scheme (PBS) 10% data between 1 January 2003 and 31 December 2014 was utilised in this retrospective cohort study. Men who had received their first androgen deprivation therapy between 2004 and 2010 were selected as the prostate cancer cohort. Comorbidities were identified using the dispensing claims data and classified with the Rx-Risk-V model. Comparisons were made between the prostate cancer cohort and specific control groups (age-matched and sex-matched without any dispensing of anti-neoplastic agents during the study period and without the individual comorbidity of interest evaluated at baseline at 1:10 ratio) for the development of nine individual comorbidities over time using Cox regression models. The prostate cancer cohort had a significant higher risk of developing cardiovascular conditions (hazard ratio 1.37, 95% CI: 1.26–1.48), depression (1.86, 95% CI: 1.73–2.01), diabetes (1.30, 95% CI: 1.15–1.47), gastric acid disorders (1.48, 95% CI: 1.39–1.57), hyperlipidaemia (1.18, 95% CI: 1.09–1.29), osteoporosis (1.65, 95% CI: 1.48–1.85) and pain/pain-inflammation (1.47, 95% CI: 1.39–1.55) compared to the control groups. The hazard ratios for cardiovascular conditions and depression were highest in the first year and declined over time. There were no significant differences between the two groups for reactive airway diseases and Alzheimer’s disease. Men with prostate cancer treated with androgen deprivation therapy had a higher likelihood of developing new comorbidities than men who did not receive androgen deprivation therapy. Our results support the need for developing coordinated care models that effectively address multiple chronic diseases experienced by prostate cancer survivors.

Association of androgen deprivation therapy with thromboembolic events in patients with prostate cancer: a systematic review and meta-analysis.

Abstract: Whether androgen deprivation therapy (ADT) causes excess thromboembolic events (TEs) in men with prostate cancer (PCa) remains controversial and is the subject of the US Food and Drug Administration safety warning This study aims to perform a systematic review and meta-analysis on previous studies to determine whether ADT is associated with TEs in men with PCa Medline, Embase, and Cochrane Library databases were searched for relevant studies These studies comprised those that compared ADT versus control to treat PCa, reported TEs as outcome, and were published before January 2018 Multivariate adjusted hazard ratios (HRs) and associated 95% confidence intervals (CIs) were calculated using random- or fixed-effects models Five retrospective population-based cohort studies involving 170,851 ADT users and 256,704 non-ADT users were identified Deep venous thrombosis (DVT) was found significantly associated with gonadotropin-releasing hormone (GnRH) agonists alone (HR = 147, 95% CI: 107–203; P = 0017; I2 = 963%), GnRH agonists plus oral antiandrogen (AA) (HR = 255, 95% CI: 221–294; P < 0001; I2 = 00%), and AA alone (HR = 149, 95% CI: 113–196; P = 0004; I2 = 00%), but not with orchiectomy (HR = 180, 95% CI: 093–347; P = 0079; I2 = 948%) In addition, pulmonary embolism (PE) was significantly associated with GnRH agonists alone (HR = 226, 95% CI: 178–286; P < 0001; I2 was unavailable) and orchiectomy (HR = 212, 95% CI: 144–311; P < 0001; I2 = 572%) This relationship was also supported with subgroup analyses based on different continents and races GnRH agonists alone, GnRH plus AA, and AA alone cause excess DVT in men with PCa after controlling the demographic and disease characteristics and other confounding factors, although statistically significant difference was not observed in orchiectomy group Additionally, GnRH agonists alone and orchiectomy can increase the incidence of PE

Fosfomycin vs. quinolone-based antibiotic prophylaxis for transrectal ultrasound-guided biopsy of the prostate: a systematic review and meta-analysis

Abstract: Infection-related complications secondary to quinolone resistance have been on the rise following transrectal ultrasound-guided biopsy of the prostate (TRUSBP). The aim of this review was to compare the efficacy of fosfomycin with quinolone-based antibiotic prophylaxis for TRUSBP. A systematic review in line with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) and Cochrane guidelines was conducted. All studies comparing fosfomycin vs. non-fosfomycin antimicrobial prophylaxis for TRUSBP were considered. The main outcomes were number of urinary tract infections (UTIs) (overall, afebrile, febrile, and urosepsis) and fluoroqinolone resistance. Secondary outcomes were positive urine and blood cultures, and adverse effects of drugs. Five studies comparing fosfomycin and non-fosfomycin antimicrobials were included in the review. In all, 1447 and 1665 patients were included in the fosfomycin and non-fosfomycin cohorts, respectively. The systematic review report significantly lower UTIs in the fosfomycin cohort (M-H, Fixed, 95% CI), 0.20 (0.13, 0.30), p < 0.00001. Urine cultures from patients given fosfomycin showed significantly lower resistance rates (M-H, Fixed, 95% CI) 0.27 (0.15, 0.50), p < 0.0001. The adverse effect profile between the two cohorts were similar (M-H, Fixed, 95% CI) 1.13 (0.51, 2.50), p = 0.33. On Grade Pro evaluation, overall UTI, afebrile UTI, febrile UTI, and urosepsis were rates as moderate, low, very low, and moderate quality evidence, respectively. Positive blood and urine culture were rated as moderate and very low-quality evidence, respectively. Fluoroquinolone resistance was rated as low-quality evidence. Adverse effects was rated as very low-quality evidence. This review suggests that fosfomycin has significantly lower septic complications with an equivalent side effect profile in comparison with quinolone-based prophylaxis regimen for TRUSBP. There is an urgent need for appropriate antibiotic stewardship and it is paramount that studies with robust methodology are developed to establish the role of fosfomycin over existing antibiotic regimens for TRUSBP.

The evolving landscape of metastatic hormone-sensitive prostate cancer: a critical review of the evidence for adding docetaxel or abiraterone to androgen deprivation.

Abstract: Until 2015, androgen deprivation therapy (ADT) alone was the standard-of-care for metastatic hormone-sensitive prostate cancer (mHSPC). In 2015, the CHAARTED and STAMPEDE-Docetaxel studies demonstrated marked survival benefit with the addition of docetaxel to ADT in the mHSPC setting, leading to a change in the standard-of-care for mHSPC. The recent LATITUDE and STAMPEDE-Abiraterone trials showed similar substantial improvement in survival with the addition of abiraterone plus prednisone to ADT in this space. We conducted a review of the randomized phase III studies that have investigated either the addition of docetaxel or abiraterone to ADT in patients with mHSPC. We describe the study designs, key eligibility criteria, and key results for the CHAARTED, STAMPEDE-Docetaxel, GETUG-AFU 15, LATITUDE, and STAMPEDE-Abiraterone clinical trials. We compare the data for abiraterone/prednisone plus ADT in mHSPC with the evidence for docetaxel plus ADT in these patients. Finally, we discuss several factors that should be considered when choosing between docetaxel/ADT or abiraterone/prednisone/ADT in mHSPC. The management of mHSPC is evolving. Abiraterone plus prednisone in addition to ADT has emerged as an alternative standard-of-care to docetaxel plus ADT, and ongoing trials should clarify whether combination vs. sequential approaches with AR-targeting agents and taxane chemotherapy are preferred for initial management in the hormone-sensitive setting.

Prostate cancer diagnosis and characterization with mass spectrometry imaging.

Abstract: Prostate cancer (PCa), the most common cancer and second leading cause of cancer death in American men, presents the clinical challenge of distinguishing between indolent and aggressive tumors for proper treatment. PCa presents significant alterations in metabolic pathways that can potentially be measured using techniques like mass spectrometry (MS) or MS imaging (MSI) and used to characterize PCa aggressiveness. MS quantifies metabolomic, proteomic, and lipidomic profiles of biological systems that can be further visualized for their spatial distributions through MSI. PubMed was queried for all publications relating to MS and MSI in human PCa from April 2007 to April 2017. With the goal of reviewing the utility of MSI in diagnosis and prognostication of human PCa, MSI articles that reported investigations of PCa-specific metabolites or metabolites indicating PCa aggressiveness were selected for inclusion. Articles were included that covered MS and MSI principles, limitations, and applications in PCa. We identified nine key studies on MSI in intact human prostate tissue specimens that determined metabolites which could either differentiate between benign and malignant prostate tissue or indicate PCa aggressiveness. These MSI-detected biomarkers show promise in reliably identifying PCa and determining disease aggressiveness. MSI represents an innovative technique with the ability to interrogate cancer biomarkers in relation to tissue pathologies and investigate tumor aggressiveness. We propose MSI as a powerful adjuvant histopathology imaging tool for prostate tissue evaluations, where clinical translation of this ex vivo technique could make possible the use of MSI for personalized medicine in diagnosis and prognosis of PCa. Moreover, the knowledge provided from this technique can majorly contribute to the understanding of molecular pathogenesis of PCa and other malignant diseases.

Addition of abiraterone, docetaxel, bisphosphonate, celecoxib or combinations to androgen-deprivation therapy (ADT) for metastatic hormone-sensitive prostate cancer (mHSPC): a network meta-analysis.

Abstract: Patients with metastatic prostate cancer have poor prognosis. In this study, we compared the addition of abiraterone, docetaxel, bisphosphonate, celecoxib or combinations to standard ADT vs. ADT alone for patients with mHSPC in terms of overall survival (OS), failure-free survival (FFS), and adverse events. We searched PubMed and performed a network meta-analysis to generate probabilistic inferences and provide efficacy rankings in terms of posterior hazard ratios with 95% credible intervals (CrI), surface under the cumulative ranking curve (SUCRA), probability better than competing treatments, and probability best. Seven trials were included (LATITUTE, STAMPEDE, CHAARTED, GETUG-AFU15, ZAPCA, CALGB 90202, and MRC PR05). Compared to ADT alone, evidence suggests abiraterone + ADT (OS HR: 0.60; 95% CrI: 0.50–0.71, FFS HR: 0.31; 95% CrI: 0.25–0.38) could be superior in terms of OS and FFS compared to docetaxel + ADT (OS 0.74; 95% CrI: 0.63–0.86, FFS 0.62; 95% CrI: 0.53–0.74), bisphosphonate + ADT (OS: 0.87; 95% CrI: 0.75–1.00, FFS 0.87; 95% CrI: 0.75–1.00), celecoxib + ADT (OS: 0.91; 95% CrI: 0.71–1.17, FFS: 0.86; 95% CrI: 0.68–1.08), or triple combinations. Abiraterone + ADT suggests improved survival with 97% certainty for a 19% reduction in risk of death compared to docetaxel + ADT (HR: 0.81; 95% CrI: 0.66–1.00). Addition of abiraterone to standard ADT may possibly outperform the addition of docetaxel, bisphosphonates, celecoxib, or combinations to standard ADT in terms of OS and FFS.