Prostate Cancer The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Biomarkers of Prostatic Cancer: An Attempt to Categorize Patients into Prostatic Carcinoma, Benign Prostatic Hyperplasia, or Prostatitis Based on Serum Prostate Specific Antigen, Prostatic Acid Phosphatase, Calcium, and Phosphorus Thu, 12 Jan 2017 00:00:00 +0000 Prostatitis, BPH, and P.Ca are the most frequent pathologies of the prostate gland that are responsible for morbidity in men. Raised levels of PSA are seen in different pathological conditions involving the prostate. PAP levels are altered in inflammatory or infectious or abnormal growth of the prostate tissue. Serum calcium and phosphorus levels were also found to be altered in prostate cancer and BPH. The present study was carried out to study the levels of PSA, PAP, calcium, and phosphorus in serum of patients with Prostatitis, BPH, or P.Ca and also to evaluate the relationship between them. Males in the age group of 50–85 years with LUTS disease symptoms and with PSA levels more than 4 ng/mL were included. A total of 114 patients were analyzed including 30 controls. Prostatitis in 35.7% of cases, BPH in 35.7% of the cases, and P.Ca in 28.57% of the cases were observed. Thus, the nonmalignant cases constitute a majority. PSA, a marker specific for prostatic conditions, was significantly high in all the diseases compared to controls. A rise in serum PSA and PAP indicates prostatitis or, in combination with these two tests, decreased serum calcium shows advanced disease. Shahana Sarwar, Mohammed Abdul Majid Adil, Parveen Nyamath, and Mohammed Ishaq Copyright © 2017 Shahana Sarwar et al. All rights reserved. Analysis of Argonaute Complex Bound mRNAs in DU145 Prostate Carcinoma Cells Reveals New miRNA Target Genes Thu, 05 Jan 2017 00:00:00 +0000 Posttranscriptional gene regulation by microRNAs (miRNAs) contributes to the induction and maintenance of prostate carcinoma (PCa). To identify mRNAs enriched or removed from Ago2-containing RISC complexes, these complexes were immunoprecipitated from normal prostate fibroblasts (PNFs) and the PCa line DU145 and the bound mRNAs were quantified by microarray. The analysis of Ago complexes derived from PNFs or DU145 confirmed the enrichment or depletion of a variety of mRNAs already known from the literature to be deregulated. Novel potential targets were analyzed by luciferase assays with miRNAs known to be deregulated in PCa. We demonstrate that the mRNAs of the death effector domain-containing protein (DEDD), the tumor necrosis factor receptor superfamily, member 10b protein (TNFRSF10B), the tumor protein p53 inducible nuclear protein 1 (TP53INP1), and the secreted protein, acidic, cysteine-rich (SPARC; osteonectin) are regulated by miRNAs miR-148a, miR-20a, miR-24, and miR-29a/b, respectively. Therefore, these miRNAs represent potential targets for therapy. Surprisingly, overexpression of miR-24 induced focus formation and proliferation of DU145 cells, while miR-29b reduced proliferation. The study confirms genes deregulated in PCa by virtue of their presence/absence in the Ago2-complex. In conjunction with the already published miRNA profiles of PCa, the data can be used to identify miRNA-regulated mRNAs. Jaroslaw Szczyrba, Volker Jung, Michaela Beitzinger, Elke Nolte, Sven Wach, Martin Hart, Sandra Sapich, Marc Wiesehöfer, Helge Taubert, Gunther Wennemuth, Norbert Eichner, Thomas Stempfl, Bernd Wullich, Gunter Meister, and Friedrich A. Grässer Copyright © 2017 Jaroslaw Szczyrba et al. All rights reserved. Influence of In Utero Maternal and Neonate Factors on Cord Blood Leukocyte Telomere Length: Clues to the Racial Disparity in Prostate Cancer? Wed, 14 Dec 2016 14:08:49 +0000 Background. Modifiable factors in adulthood that explain the racial disparity in prostate cancer have not been identified. Because racial differences in utero that may account for this disparity are understudied, we investigated the association of maternal and neonate factors with cord blood telomere length, as a cumulative marker of cell proliferation and oxidative damage, by race. Further, we evaluated whether cord blood telomere length differs by race. Methods. We measured venous umbilical cord blood leukocyte relative telomere length by qPCR in 38 black and 38 white full-term male neonates. Using linear regression, we estimated geometric mean relative telomere length and tested for differences by race. Results. Black mothers were younger and had higher parity and black neonates had lower birth and placental weights. These factors were not associated with relative telomere length, even after adjusting for or stratifying by race. Relative telomere length in black (2.72) and white (2.73) neonates did not differ, even after adjusting for maternal or neonate factors (all ). Conclusions. Maternal and neonate factors were not associated with cord blood telomere length, and telomere length did not differ by race. These findings suggest that telomere length at birth does not explain the prostate cancer racial disparity. Kari A. Weber, Christopher M. Heaphy, Sabine Rohrmann, Beverly Gonzalez, Jessica L. Bienstock, Tanya Agurs-Collins, Elizabeth A. Platz, and Alan K. Meeker Copyright © 2016 Kari A. Weber et al. All rights reserved. Prostate Cancer: Epigenetic Alterations, Risk Factors, and Therapy Sun, 06 Nov 2016 08:04:31 +0000 Prostate cancer (PCa) is the most prevalent urological cancer that affects aging men in South Africa, and mechanisms underlying prostate tumorigenesis remain elusive. Research advancements in the field of PCa and epigenetics have allowed for the identification of specific alterations that occur beyond genetics but are still critically important in the pathogenesis of tumorigenesis. Anomalous epigenetic changes associated with PCa include histone modifications, DNA methylation, and noncoding miRNA. These mechanisms regulate and silence hundreds of target genes including some which are key components of cellular signalling pathways that, when perturbed, promote tumorigenesis. Elucidation of mechanisms underlying epigenetic alterations and the manner in which these mechanisms interact in regulating gene transcription in PCa are an unmet necessity that may lead to novel chemotherapeutic approaches. This will, therefore, aid in developing combination therapies that will target multiple epigenetic pathways, which can be used in conjunction with the current conventional PCa treatment. Mankgopo M. Kgatle, Asgar A. Kalla, Muhammed M. Islam, Mike Sathekge, and Razia Moorad Copyright © 2016 Mankgopo M. Kgatle et al. All rights reserved. Advances in Radiotherapy for Prostate Cancer Treatment Mon, 25 Jul 2016 13:09:45 +0000 Tarun Podder, Daniel Song, Timothy Showalter, and Luc Beaulieu Copyright © 2016 Tarun Podder et al. All rights reserved. The Single-Knot Running Vesicourethral Anastomosis after Minimally Invasive Prostatectomy: Review of the Technique and Its Modifications, Tips, and Pitfalls Tue, 31 May 2016 13:40:49 +0000 The vesicourethral anastomosis represents a step of major difficulty at the end of minimally invasive radical prostatectomy. Over 10 years ago, we have devised the single-knot running vesicourethral anastomosis, which has been widely adopted in urologic departments worldwide. Aim of the current paper is to review the technique, its adaptability in complex situations, its complications, and possible modifications, including the use of barbed sutures. Simone Albisinni, Fouad Aoun, Alexandre Peltier, and Roland van Velthoven Copyright © 2016 Simone Albisinni et al. All rights reserved. Evolving Paradigm of Radiotherapy for High-Risk Prostate Cancer: Current Consensus and Continuing Controversies Mon, 23 May 2016 14:04:20 +0000 High-risk prostate cancer is an aggressive form of the disease with an increased risk of distant metastasis and subsequent mortality. Multiple randomized trials have established that the combination of radiation therapy and long-term androgen deprivation therapy improves overall survival compared to either treatment alone. Standard of care for men with high-risk prostate cancer in the modern setting is dose-escalated radiotherapy along with 2-3 years of androgen deprivation therapy (ADT). There are research efforts directed towards assessing the efficacy of shorter ADT duration. Current research has been focused on assessing hypofractionated and stereotactic body radiation therapy (SBRT) techniques. Ongoing randomized trials will help assess the utility of pelvic lymph node irradiation. Research is also focused on multimodality therapy with addition of a brachytherapy boost to external beam radiation to help improve outcomes in men with high-risk prostate cancer. Aditya Juloori, Chirag Shah, Kevin Stephans, Andrew Vassil, and Rahul Tendulkar Copyright © 2016 Aditya Juloori et al. All rights reserved. Systematic Review of Focal Prostate Brachytherapy and the Future Implementation of Image-Guided Prostate HDR Brachytherapy Using MR-Ultrasound Fusion Mon, 16 May 2016 07:16:25 +0000 Prostate cancer is the most common malignancy found in North American and European men and the second most common cause of cancer related death. Since the practice of PSA screening has become common the disease is most often found early and can have a long indolent course. Current definitive therapy treats the whole gland but has considerable long-term side effects. Focal therapies may be able to target the cancer while decreasing dose to organs at risk. Our objective was to determine if focal prostate brachytherapy could meet target objectives while permitting a decrease in dose to organs at risk in a way that would allow future salvage treatments. Further, we wanted to determine if focal treatment results in less toxicity. Utilizing the Medline repository, dosimetric papers comparing whole gland to partial gland brachytherapy and clinical papers that reported toxicity of focal brachytherapy were selected. A total of 9 dosimetric and 6 clinical papers met these inclusion criteria. Together, these manuscripts suggest that focal brachytherapy may be employed to decrease dose to organs at risk with decreased toxicity. Of current technology, image-guided HDR brachytherapy using MRI registered to transrectal ultrasound offers the flexibility and efficiency to achieve such focal treatments. M. Sean Peach, Daniel M. Trifiletti, and Bruce Libby Copyright © 2016 M. Sean Peach et al. All rights reserved. Assessment of the Performance of Magnetic Resonance Imaging/Ultrasound Fusion Guided Prostate Biopsy against a Combined Targeted Plus Systematic Biopsy Approach Using 24-Core Transperineal Template Saturation Mapping Prostate Biopsy Mon, 16 May 2016 06:04:50 +0000 Objective. To compare the performance of multiparametric resonance imaging/ultrasound fusion targeted biopsy (MRI/US-TBx) to a combined biopsy strategy (MRI/US-TBx plus 24-core transperineal template saturation mapping biopsy (TTMB)). Methods. Between May 2012 and October 2015, all patients undergoing MRI/US-TBx at our institution were included for analysis. Patients underwent MRI/US-TBx of suspicious lesions detected on multiparametric MRI simultaneous TTMB. Subgroup analysis was performed on patients undergoing simultaneous MRI/US-TBx + TTMB. Primary outcome was PCa detection. Significant PCa was defined as ≥Gleason score (GS) PCa. McNemar’s test was used to compare detection rates between MRI/US-TBx and the combined biopsy strategy. Results. 148 patients underwent MRI/US-TBx and 80 patients underwent MRI/US-TBx + TTMB. In the MRI/US-TBx versus combined biopsy strategy subgroup analysis (), there were 55 PCa and 38 significant PCa. The detection rate for the combined biopsy strategy versus MRI/US-TBx for significant PCa was 49% versus 40% () and for insignificant PCa was 20% versus 10% (), respectively. Eleven cases (14%) of significant PCa were detected exclusively on MRI/US-TBx and 7 cases (8.7%) of significant PCa were detected exclusively on TTMB. Conclusions. A combined biopsy approach (MRI/US-TBx + TTMB) detects more significant PCa than MRI/US-TBx alone; however, it will double the detection rate of insignificant PCa. Francis Ting, Pim J. Van Leeuwen, James Thompson, Ron Shnier, Daniel Moses, Warick Delprado, and Phillip D. Stricker Copyright © 2016 Francis Ting et al. All rights reserved. Predicting Low-Risk Prostate Cancer from Transperineal Saturation Biopsies Mon, 11 Apr 2016 09:44:56 +0000 Introduction. To assess the performance of five previously described clinicopathological definitions of low-risk prostate cancer (PC). Materials and Methods. Men who underwent radical prostatectomy (RP) for clinical stage ≤T2, PSA <10 ng/mL, Gleason score <8 PC, diagnosed by transperineal template-guided saturation biopsy were included. The performance of five previously described criteria (i.e., criteria 1–5, criterion 1 stringent (Gleason score 6 + ≤5 mm total max core length PC + ≤3 mm max per core length PC) up to criterion 5 less stringent (Gleason score 6-7 with ≤5% Gleason grade 4) was analysed to assess ability of each to predict insignificant disease in RP specimens (defined as Gleason score ≤6 and total tumour volume <2.5 mL, or Gleason score 7 with ≤5% grade 4 and total tumour volume <0.7 mL). Results. 994 men who underwent RP were included. Criterion 4 (Gleason score 6) performed best with area under the curve of receiver operating characteristics 0.792. At decision curve analysis, criterion 4 was deemed clinically the best performing transperineal saturation biopsy-based definition for low-risk PC. Conclusions. Gleason score 6 disease demonstrated a superior trade-off between sensitivity and specificity for clarifying low-risk PC that can guide treatment and be used as reference test in diagnostic studies. Pim J. van Leeuwen, Amila Siriwardana, Monique Roobol, Francis Ting, Daan Nieboer, James Thompson, Warick Delprado, Anne-Marie Haynes, Phillip Brenner, and Phillip Stricker Copyright © 2016 Pim J. van Leeuwen et al. All rights reserved. Salvage Brachytherapy for Biochemically Recurrent Prostate Cancer following Primary Brachytherapy Tue, 22 Mar 2016 13:52:42 +0000 Purpose. In this study, we evaluated our experience with salvage brachytherapy after discovery of biochemical recurrence after a prior brachytherapy procedure. Methods and Materials. From 2001 through 2012 twenty-one patients treated by brachytherapy within University of Kentucky or from outside centers developed biochemical failure and had no evidence of metastases. Computed tomography (CT) scans were evaluated; patients who had an underseeded portion of their prostate were considered for reimplantation. Results. The majority of the patients in this study (61.9%) were low risk and median presalvage PSA was 3.49 (range 17.41–1.68). Mean follow-up was 61 months. At last follow-up after reseeding, 11/21 (52.4%) were free of biochemical recurrence. There was a trend towards decreased freedom from biochemical recurrence in low risk patients (). International Prostate Symptom Scores (IPSS) increased at 3-month follow-up visits but decreased and were equivalent to baseline scores at 18 months. Conclusions. Salvage brachytherapy after primary brachytherapy is possible; however, in our experience the side-effect profile after the second brachytherapy procedure was higher than after the first brachytherapy procedure. In this cohort of patients we demonstrate that approximately 50% oncologic control, low risk patients appear to have better outcomes than others. John M. Lacy, William A. Wilson, Raevti Bole, Li Chen, Ali S. Meigooni, Randall G. Rowland, and William H. St. Clair Copyright © 2016 John M. Lacy et al. All rights reserved. Pelvic Radiotherapy versus Radical Prostatectomy with Limited Lymph Node Sampling for High-Grade Prostate Adenocarcinoma Wed, 09 Mar 2016 13:48:16 +0000 Purpose. To compare oncologic outcomes for patients with Gleason score (GS) ≥ 8 prostate adenocarcinoma treated with radical prostatectomy (RP) versus external beam radiotherapy combined with androgen deprivation (RT + ADT). Methods. Between 2001 and 2014, 121 patients with GS ≥ 8 were treated at our institution via RT + ADT () or RP () with ≥ 1 year of biochemical follow-up. Endpoints included biochemical failure (BF), distant metastasis, and initiation of salvage ADT. Results. The RT + ADT group was older, had higher biopsy GS, and had greater risk of lymph node involvement. All other pretreatment characteristics were similar between groups. Mean number of lymph nodes (LNs) sampled for patients undergoing RP was 8.2 (±6.18). Mean biochemical follow-up for all patients was 61 months. Five-year estimates of BF for the RT + ADT and RP groups were 7.2% versus 42.3%, (). The RT + ADT group also had lower rates of distant metastasis (2% versus 7.8%) and salvage ADT (8% versus 33.8%). Conclusion. In this analysis, RT + ADT was associated with improved biochemical and metastatic control when compared to RP with limited LN sampling. How RT + ADT compares with more aggressive lymphadenectomy, as is currently our institutional standard, remains an important unanswered question. Christopher B. Baker, Andrew M. McDonald, Eddy S. Yang, Rojymon Jacob, Soroush Rais-Bahrami, Jeffrey W. Nix, and John B. Fiveash Copyright © 2016 Christopher B. Baker et al. All rights reserved. Hydrogen Sulfide Signaling Axis as a Target for Prostate Cancer Therapeutics Thu, 25 Feb 2016 13:16:49 +0000 Hydrogen sulfide (H2S) was originally considered toxic at elevated levels; however just in the past decade H2S has been proposed to be an important gasotransmitter with various physiological and pathophysiological roles in the body. H2S can be generated endogenously from L-cysteine by multiple enzymes, including cystathionine gamma-lyase, cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase in combination with cysteine aminotransferase. Prostate cancer is a major health concern and no effective treatment for prostate cancers is available. H2S has been shown to inhibit cell survival of androgen-independent, androgen-dependent, and antiandrogen-resistant prostate cancer cells through different mechanisms. Various H2S-releasing compounds, including sulfide salts, diallyl disulfide, diallyl trisulfide, sulforaphane, and other polysulfides, also have been shown to inhibit prostate cancer growth and metastasis. The expression of H2S-producing enzyme was reduced in both human prostate cancer tissues and prostate cancer cells. Androgen receptor (AR) signaling is indispensable for the development of castration resistant prostate cancer, and H2S was shown to inhibit AR transactivation and contributes to antiandrogen-resistant status. In this review, we summarized the current knowledge of H2S signaling in prostate cancer and described the molecular alterations, which may bring this gasotransmitter into the clinic in the near future for developing novel pharmacological and therapeutic interventions for prostate cancer. Mingzhe Liu, Lingyun Wu, Sabine Montaut, and Guangdong Yang Copyright © 2016 Mingzhe Liu et al. All rights reserved. Prostate Radiotherapy in the Era of Advanced Imaging and Precision Medicine Tue, 16 Feb 2016 13:49:07 +0000 Tremendous technological advancements in prostate radiotherapy have decreased treatment toxicity and improved clinical outcomes for men with prostate cancer. While these advances have allowed for significant treatment volume reduction and whole-organ dose escalation, further improvement in prostate radiotherapy has been limited by classic techniques for diagnosis and risk stratification. Developments in prostate imaging, image-guided targeted biopsy, next-generation gene expression profiling, and targeted molecular therapies now provide information to stratify patients and select treatments based on tumor biology. Image-guided targeted biopsy improves detection of clinically significant cases of prostate cancer and provides important information about the biological behavior of intraprostatic lesions which can further guide treatment decisions. We review the evolution of prostate magnetic resonance imaging (MRI) and MRI-ultrasound fusion-guided prostate biopsy. Recent advancements in radiation therapy including dose escalation, moderate and extreme hypofractionation, partial prostate radiation therapy, and finally dose escalation by simultaneous integrated boost are discussed. We also review next-generation sequencing and discuss developments in targeted molecular therapies. Last, we review ongoing clinical trials and future treatment paradigms that integrate targeted biopsy, molecular profiling and therapy, and prostate radiotherapy. Caleb R. Dulaney, Daniel O. Osula, Eddy S. Yang, and Soroush Rais-Bahrami Copyright © 2016 Caleb R. Dulaney et al. All rights reserved. Fortifying the Treatment of Prostate Cancer with Physical Activity Wed, 10 Feb 2016 14:00:45 +0000 Over the past decade, significant data have shown that obese men experience a survival detriment after treatment for prostate cancer. While methods to combat obesity are of utmost importance for the prostate cancer patient, newer data reveal the overall metabolic improvements that accompany increased activity levels and intense exercise beyond weight loss. Along these lines, a plethora of data have shown improvement in prostate cancer-specific outcomes after treatment accompanied with these activity levels. This review discusses the metabolic mechanisms in which increased activity levels and exercise can help improve both outcomes for men treated for prostate cancer while lowering the side effects of treatment. Colin E. Champ, Lanie Francis, Rainer J. Klement, Roger Dickerman, and Ryan P. Smith Copyright © 2016 Colin E. Champ et al. All rights reserved. Systematic Review of the Relationship between Acute and Late Gastrointestinal Toxicity after Radiotherapy for Prostate Cancer Mon, 30 Nov 2015 13:53:52 +0000 A small but meaningful percentage of men who are treated with external beam radiation therapy for prostate cancer will develop late gastrointestinal toxicity. While numerous strategies to prevent gastrointestinal injury have been studied, clinical trials concentrating on late toxicity have been difficult to carry out. Identification of subjects at high risk for late gastrointestinal injury could allow toxicity prevention trials to be performed using reasonable sample sizes. Acute radiation therapy toxicity has been shown to predict late toxicity in several organ systems. Late toxicities may occur as a consequential effect of acute injury. In this systematic review of published reports, we found that late gastrointestinal toxicity following prostate radiotherapy seems to be statistically and potentially causally related to acute gastrointestinal morbidity as a consequential effect. We submit that acute gastrointestinal toxicity may be used to identify at-risk patients who may benefit from additional attention for medical interventions and close follow-up to prevent late toxicity. Acute gastrointestinal toxicity could also be explored as a surrogate endpoint for late effects in prospective trials. Matthew Sean Peach, Timothy N. Showalter, and Nitin Ohri Copyright © 2015 Matthew Sean Peach et al. All rights reserved. Atypical Small Acinar Proliferation: Repeat Biopsy and Detection of High Grade Prostate Cancer Mon, 14 Sep 2015 07:18:37 +0000 Purpose. Atypical small acinar proliferation (ASAP) is diagnosed in 1-2% of prostate biopsies. 30–40% of patients with ASAP may be diagnosed with prostate cancer (PCa) on repeat biopsy. Our objective was to examine the association between ASAP and subsequent diagnosis of intermediate/high risk PCa. Materials and Methods. Ninety-six patients who underwent prostate biopsy from 2000 to 2013 and were diagnosed with ASAP were identified. Clinicopathologic features were analyzed. Comparison was made between those with subsequent PCa on repeat biopsy and those with benign repeat pathology. Results. 56/96 (58%) patients had a repeat biopsy. 22/56 (39%) were subsequently diagnosed with PCa. There was no significant difference in patients’ characteristics. Presence of HGPIN on initial biopsy was associated with a benign repeat biopsy (68% versus 23%). 17/22 (77%) had Gleason grade (GG) 3+3 disease and only 5/22 (23%) had GG 3+4 disease. Conclusions. 22/56 patients (39%) of patients who underwent a subsequent prostate biopsy following a diagnosis of ASAP were found to have PCa. 77% of these men were diagnosed with GG 3+3 PCa. Only 23% were found to have intermediate risk PCa and no high risk PCa was identified. Immediate repeat prostate biopsy in patients diagnosed with ASAP may be safely delayed. A multi-institutional cohort is being analyzed. Andrew Leone, Katherine Rotker, Christi Butler, Anthony Mega, Jianhong Li, Ali Amin, Stephen F. Schiff, Gyan Pareek, Dragan Golijanin, and Joseph F. Renzulli II Copyright © 2015 Andrew Leone et al. All rights reserved. Thioredoxin 1 in Prostate Tissue Is Associated with Gleason Score, Erythrocyte Antioxidant Enzyme Activity, and Dietary Antioxidants Tue, 18 Aug 2015 10:11:13 +0000 Background. Prostate cancer is the most common noncutaneous cancer and second leading cause of cancer-related mortality in men in the US. Growing evidence suggests that oxidative stress is involved in prostate cancer. Methods. In this study, thioredoxin 1 (Trx 1), an enzyme and subcellular indicator of redox status, was measured in prostate biopsy tissue from 55 men from the North Carolina-Louisiana Prostate Cancer Project. A pathologist blindly scored levels of Trx 1. The association between Trx 1 and the Gleason score, erythrocyte antioxidant enzyme activity, and dietary antioxidant intake was determined using Fisher’s exact test. Results. Trx 1 levels in benign prostate tissue in men with incident prostate cancer were positively associated with the Gleason score () and inversely associated with dietary antioxidant intake (). In prostate cancer tissue, Trx 1 levels were associated with erythrocyte glutathione peroxidase activity (). No association was found for other erythrocyte enzymes. Greater Gleason score of malignant tissue corresponds to a greater difference in Trx 1 levels between malignant and benign tissue (). Conclusion. These results suggest that the redox status of prostate tissue is associated with prostate cancer grade and both endogenous and exogenous antioxidants. Terrence M. Vance, Gissou Azabdaftari, Elena A. Pop, Sang Gil Lee, L. Joseph Su, Elizabeth T. H. Fontham, Jeannette T. Bensen, Susan E. Steck, Lenore Arab, James L. Mohler, Ming-Hui Chen, Sung I. Koo, and Ock K. Chun Copyright © 2015 Terrence M. Vance et al. All rights reserved. Analysis of Prostate Cancer Susceptibility Variants in South African Men: Replicating Associations on Chromosomes 8q24 and 10q11 Wed, 12 Aug 2015 11:41:14 +0000 Genome-wide association studies (GWAS) have implicated single nucleotide polymorphisms (SNPs) on chromosomes 2p15, 6q25, 7p15.2, 7q21, 8q24, 10q11, 10q26, 11q13, 17q12, 17q24, 19q13, and Xp11, with prostate cancer (PCa) susceptibility and/or tumour aggressiveness, in populations of African, European, and Asian ancestry. The objective of this study was to confirm these associations in South African Mixed Ancestry and White men. We evaluated 17 prioritised GWAS SNPs in South African cases (331 Mixed Ancestry and 155 White) and controls (178 Mixed Ancestry and 145 White). The replicated SNP associations for the different South African ethnic groups were rs7008482 (8q24) (), rs6983267 (8q24) (), and rs10993994 (10q11) () in Mixed Ancestry men and rs10993994 () in White men. No significant associations were observed for the analyses stratified by disease aggressiveness in the individual and the combined population group analysis. The present study demonstrates that a number of known PCa susceptibility variants may contribute to disease susceptibility in South African men. Larger genetic investigations extended to other South African population groups are warranted to confirm the role of these and other SNPs in disease susceptibility. Pedro Fernandez, Muneeb Salie, Danielle du Toit, and Andre van der Merwe Copyright © 2015 Pedro Fernandez et al. All rights reserved. Current Patterns of Management of Advanced Prostate Cancer in Routine Clinical Practice in Spain Mon, 13 Jul 2015 11:19:32 +0000 Objective. To describe urologists’ practice patterns when managing patients with advanced prostate cancer (PCa) in Spain. Methods. This was an observational study conducted by 120 urologists using retrospective data of advanced PCa patients attending hospitals and outpatient centers. Results. Urologists evaluated a total of 375 patients (mean age: 75 years; ECOG 0-1: 77%; mean serum PSA levels at study entry: 50.5 ng/Ml). Approximately 50% of patients had bone metastases, and 60.6% experienced pain as the main symptom of progressive disease. Primary androgen deprivation therapy (ADT) use was 99.7%, with continuous ADT as the dominant strategy (91.9%). After failure of initial ADT, antiandrogen withdrawal was the next method most commonly used in 57% of patients. Choice of secondary hormonal treatment was made mostly by urologists (96%), who continued to monitor patients. Patient follow-up after chemotherapy and supportive care were mainly done in urology units, although responsibility was shared with medical oncologists and radiologists. Conclusion. The urologists’ attitudes towards management of PCa in the routine practice in Spain show the urologist as an integral component even when patients progress to advanced stages of the disease. Maria José Ribal, Juan Ignacio Martínez-Salamanca, and Camilo García Freire Copyright © 2015 Maria José Ribal et al. All rights reserved. Cellular Plasticity in Prostate Cancer Bone Metastasis Wed, 03 Jun 2015 07:12:31 +0000 Purpose. Experimental data suggest that tumour cells can reversibly transition between epithelial and mesenchymal states (EMT and MET), a phenomenon known as cellular plasticity. The aim of this review was to appraise the clinical evidence for the role of cellular plasticity in prostate cancer (PC) bone metastasis. Methods. An electronic search was performed using PubMed for studies that have examined the differential expression of epithelial, mesenchymal, and stem cell markers in human PC bone metastasis tissues. Results. The review included nineteen studies. More than 60% of the studies used ≤20 bone metastasis samples, and there were several sources of heterogeneity between studies. Overall, most stem cell markers analysed, except for CXCR4, were positively expressed in bone metastasis tissues, while the expression of EMT and MET markers was heterogeneous between and within samples. Several EMT and stemness markers that are involved in osteomimicry, such as Notch, Met receptor, and Wnt/β pathway, were highly expressed in bone metastases. Conclusions. Clinical findings support the role of cellular plasticity in PC bone metastasis and suggest that epithelial and mesenchymal states cannot be taken in isolation when targeting PC bone metastasis. The paper also highlights several challenges in the clinical detection of cellular plasticity. Dima Y. Jadaan, Mutaz M. Jadaan, and John P. McCabe Copyright © 2015 Dima Y. Jadaan et al. All rights reserved. Prostate Cancer Patients’ Refusal of Cancer-Directed Surgery: A Statewide Analysis Mon, 20 Apr 2015 13:32:35 +0000 Introduction. Prostate cancer is the most common cancer among men in USA. The surgical outcomes of prostate cancer remain inconsistent. Barriers such as socioeconomic factors may play a role in patients’ decision of refusing recommended cancer-directed surgery. Methods. The Nebraska Cancer Registry data was used to calculate the proportion of prostate cancer patients recommended the cancer-directed surgery and the surgery refusal rate. Multivariate logistic regression was applied to analyze the socioeconomic indicators that were related to the refusal of surgery. Results. From 1995 to 2012, 14,876 prostate cancer patients were recommended to undergo the cancer-directed surgery in Nebraska, and 576 of them refused the surgery. The overall refusal rate of surgery was 3.9% over the 18 years. Patients with early-stage prostate cancer were more likely to refuse the surgery. Patients who were Black, single, or covered by Medicaid/Medicare had increased odds of refusing the surgery. Conclusion. Socioeconomic factors were related to the refusal of recommended surgical treatment for prostate cancer. Such barriers should be addressed to improve the utilization of surgical treatment and patients’ well-being. K. M. Islam and Jiajun Wen Copyright © 2015 K. M. Islam and Jiajun Wen. All rights reserved. Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients Mon, 23 Feb 2015 13:10:02 +0000 Background. New nontoxic targeted approaches are needed for patients with castrate resistant prostate cancer (CRPC). Our preclinical studies show that activated T cells (ATC) armed with anti-CD3 x anti-Her2 bispecific antibody (Her2Bi) kill prostate cancer cells lines, induce a Th1 cytokine pattern upon engagement of tumor cells, prevent the development of prostate tumors, and retard tumor growth in immunodeficient mice. These studies provided strong rationale for our phase I dose-escalation pilot study to test ATC armed with Her2Bi (aATC) for safety in men with CRPC. Methods. Seven of 8 men with CRPC were evaluable after receiving two infusions per week for 4 weeks. The men received 2.5, 5 or 10 × 109 aATC per infusion with low dose interleukin-2 and granulocyte-macrophage colony stimulating factor. Results. There were no dose limiting toxicities, and there was 1 partial responder and 3 of 7 patients had significant decreases in their PSA levels and pain scores. Immune evaluations of peripheral blood mononuclear cells in 2 patients before and after immunotherapy showed increases in IFN-γ EliSpot responses and Th1 serum cytokines. Conclusions. These results provide a strong rationale for developing phase II trials to determine whether aATC are effective for treating CRPC. Ulka Vaishampayan, Archana Thakur, Ritesh Rathore, Nicola Kouttab, and Lawrence G. Lum Copyright © 2015 Ulka Vaishampayan et al. All rights reserved. Triptorelin in the Relief of Lower Urinary Tract Symptoms in Advanced Prostate Cancer Patients: The RESULT Study Wed, 28 Jan 2015 08:43:33 +0000 This prospective, noninterventional, open-label, multicentre, Belgian study assessed the prevalence of moderate to severe lower urinary tract symptoms (LUTS) in patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin therapy and its effects on LUTS were evaluated focusing on symptom relief and changes in quality of life (QOL) related to urinary symptoms (November 2006 to May 2010). Inclusion criteria were age >18 years, histologically confirmed advanced or metastatic prostate cancer, and life expectancy ≥12 months. Exclusion criteria were treatment with any LHRH analogue within the last 6 months or any other investigational agent within the last 3 months before study entry. Patients who received one or more triptorelin doses and had one or more efficacy assessments were evaluated. In total, 325 patients were included with a median age of 74 years (50 to 95 years). Mean age at first diagnosis was years. Moderate (IPSS 8–19) to severe (IPSS ≥ 20) LUTS were observed in 62% of patients. Triptorelin reduced LUTS severity. This improvement was perceived within the first 24 weeks of treatment and was maintained after 48 weeks. A decrease in PSA level was also observed. Alexandre Peltier, Fouad Aoun, Vincent De Ruyter, Patrick Cabri, and Roland Van Velthoven Copyright © 2015 Alexandre Peltier et al. All rights reserved. Erratum to “Prostate Cancer in South Africa: Pathology Based National Cancer Registry Data (1986–2006) and Mortality Rates (1997–2009)” Mon, 22 Dec 2014 11:50:36 +0000 Chantal Babb, Margaret Urban, Danuta Kielkowski, and Patricia Kellett Copyright © 2014 Chantal Babb et al. All rights reserved. Robotic Prostatectomy Has a Superior Outcome in Larger Prostates and PSA Density Is a Strong Predictor of Biochemical Recurrence Mon, 15 Dec 2014 07:53:57 +0000 Objectives. The aims of this study were to compare the outcomes of robotic assisted laparoscopic prostatectomy (RALP) between patients who had larger (≥75 g) and smaller (<75 g) prostates and to evaluate the performance of PSA density (PSAD) in determining the oncological outcome of surgery. Methods and Materials. 344 patients who underwent RALP at a single institution were included in the study. Preoperative risk factors and postoperative, oncological outcomes, erectile function, and continence status were recorded prospectively. Results. During a mean follow-up of 20 months, biochemical recurrence was observed in 15 patients (4.3%). Prostate size ≥75 g was associated with lower Gleason score on final pathology and lower pathological stage but an increased length of hospital stay . PSAD on binary logistic regression independently predicted biochemical recurrence (BCR) when defined as postoperative PSA >0.1 and PSA >0.2 . In both instances PSA was no longer a significant independent predictor. Conclusions. RALP in large prostates (≥75 g, <150 g) is as safe as RALP in smaller prostates and is associated with a lower pathological grade and stage. Higher PSAD is independently associated with BCR and is superior to PSA as a predictor of BCR after RALP. S. Bishara, N. Vasdev, T. Lane, G. Boustead, and J. Adshead Copyright © 2014 S. Bishara et al. All rights reserved. Long-Term Efficacy and Tolerability of Abdominal Once-Yearly Histrelin Acetate Subcutaneous Implants in Patients with Advanced Prostate Cancer Thu, 04 Dec 2014 08:54:43 +0000 Objectives. Long-term assessment of the efficacy and tolerability of subcutaneous abdominal histrelin acetate implants that have been inserted for more than two years. Materials and Methods. Retrospective data collected over a six-year period at a single center from charts of 113 patients who received the subcutaneous abdominal histrelin acetate implant. Results. Following insertion of the first implant, 92.1% and 91.8% of patients had a serum testosterone level of ≤30 ng/dL at 24 and 48 weeks, respectively. Serum testosterone levels remained at <30 ng/dL for 96% of patients at two years and for 100% of patients at 3, 4, and 5 years. The testosterone levels remained significantly less than baseline . Six patients (5.3%) had androgen-independent progression when followed up on the long term, increasing the mean serum PSA at 3, 4, and 5 years to 35.0 µg/L , 30.7 µg/L , and 132.9 µg/L , respectively. The mean serum PSA was significantly greater than baseline during these years . Eight patients (7.1%) experienced minor, but not serious, adverse events from the histrelin acetate. Conclusion. Subcutaneous abdominal histrelin acetate implants are an effective long-term and well-tolerated administration method for treating patients with advanced prostate cancer. Sean Woolen, Cameron Holzmeyer, Emily Nesbitt, and Paul F. Siami Copyright © 2014 Sean Woolen et al. All rights reserved. CHEK2∗1100delC Mutation and Risk of Prostate Cancer Thu, 06 Nov 2014 08:10:45 +0000 Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer. CHEK2 plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, of CHEK2 on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussed CHEK2∗1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23–3.18) for unselected cases and 3.39 (1.78–6.47) for familial cases, indicating that CHEK2∗1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2∗1100delC should be considered in men with a familial history of prostate cancer. Victoria Hale, Maren Weischer, and Jong Y. Park Copyright © 2014 Victoria Hale et al. All rights reserved. Robotic Radical Prostatectomy in Patients with Previous Prostate Surgery and Radiotherapy Wed, 09 Jul 2014 12:01:22 +0000 Herein, we will review the available literature about robot-assisted radical prostatectomy in patients who have undergone prostate surgery or radiotherapy. Current data about this topic consists of small case series with limited follow-up. Despite being technically demanding, robot-assisted radical prostatectomy (RARP) can be considered feasible in either setting. Prostate surgery or prostatic irradiation should not be considered as a contraindication for robot-assisted radical prostatectomy. Nevertheless, patient counseling about the possible complications and the need for reintervention is of extreme importance in this patient population. Early oncologic and functional results of RARP performed in case of radiorecurrent prostate cancer look promising. Regarding postprostate surgery RARP, some series have reported comparable results, while some have demonstrated more inferior outcomes than those of naive cases. In order to assess the exact functional and oncologic outcome of RARP in patients with previous prostate surgery and radiotherapy, studies enrolling higher number of patients and providing longer follow-up data are needed. Ömer Acar and Tarık Esen Copyright © 2014 Ömer Acar and Tarık Esen. All rights reserved. Role of p73 Dinucleotide Polymorphism in Prostate Cancer and p73 Protein Isoform Balance Sun, 06 Jul 2014 07:14:01 +0000 Background. Molecular markers for prostate cancer (PCa) risks are currently lacking. Here we address the potential association of a dinucleotide polymorphism (DNP) in exon 2 of the p73 gene with PCa risk/progression and discern any disruption of p73 protein isoforms levels in cells harboring a p73 DNP allele. Methods. We investigated the association between p73 DNP genotype and PCa risk/aggressiveness and survival by fitting logistic regression models in 1,292 incident cases and 682 controls. Results. Although we detected no association between p73 DNP and PCa risk, a significant inverse relationship between p73 DNP and PCa aggressiveness (AT/AT + GC/AT versus GC/GC, OR = 0.55, 95%Cl = 0.31–0.99) was detected. Also, p73 DNP is marginally associated with overall death (dominant model, HR = 0.76, 95%Cl = 0.57–1.00, ) as well as PCa specific death (HR = 0.69, 95%Cl = 0.45–1.06, ). Western blot analyses for p73 protein isoforms indicate that cells heterozygous for the p73 DNP have lower levels of ∆Np73 relative to TAp73 (). Conclusions. Our findings are consistent with an association between p73 DNP and low risk for PCa aggressiveness by increasing the expressed TAp73/∆Np73 protein isoform ratio. L. Michael Carastro, Hui-Yi Lin, Hyun Y. Park, Donghwa Kim, Selina Radlein, Kaia K. Hampton, Ardeshir Hakam, Babu Zachariah, Julio Pow-Sang, and Jong Y. Park Copyright © 2014 L. Michael Carastro et al. All rights reserved.