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1.  Pelvic Radiotherapy versus Radical Prostatectomy with Limited Lymph Node Sampling for High-Grade Prostate Adenocarcinoma 
Prostate Cancer  2016;2016:2674954.
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 (n = 71) or RP (n = 50) 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%, (p < 0.001). 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.
PMCID: PMC4804089  PMID: 27051534
2.  Hydrogen Sulfide Signaling Axis as a Target for Prostate Cancer Therapeutics 
Prostate Cancer  2016;2016:8108549.
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.
PMCID: PMC4785274  PMID: 27019751
3.  Prostate Radiotherapy in the Era of Advanced Imaging and Precision Medicine 
Prostate Cancer  2016;2016:4897515.
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.
PMCID: PMC4771898  PMID: 27022486
4.  Fortifying the Treatment of Prostate Cancer with Physical Activity 
Prostate Cancer  2016;2016:9462975.
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.
PMCID: PMC4764749  PMID: 26977321
5.  Systematic Review of the Relationship between Acute and Late Gastrointestinal Toxicity after Radiotherapy for Prostate Cancer 
Prostate Cancer  2015;2015:624736.
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.
PMCID: PMC4677238  PMID: 26697225
6.  Atypical Small Acinar Proliferation: Repeat Biopsy and Detection of High Grade Prostate Cancer 
Prostate Cancer  2015;2015:810159.
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.
PMCID: PMC4584238  PMID: 26451257
7.  Thioredoxin 1 in Prostate Tissue Is Associated with Gleason Score, Erythrocyte Antioxidant Enzyme Activity, and Dietary Antioxidants 
Prostate Cancer  2015;2015:728046.
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 (P = 0.01) and inversely associated with dietary antioxidant intake (P = 0.03). In prostate cancer tissue, Trx 1 levels were associated with erythrocyte glutathione peroxidase activity (P = 0.01). 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 (P = 0.04). Conclusion. These results suggest that the redox status of prostate tissue is associated with prostate cancer grade and both endogenous and exogenous antioxidants.
PMCID: PMC4556330  PMID: 26357575
8.  Analysis of Prostate Cancer Susceptibility Variants in South African Men: Replicating Associations on Chromosomes 8q24 and 10q11 
Prostate Cancer  2015;2015:465184.
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) (p = 2.45 × 10−5), rs6983267 (8q24) (p = 4.48 × 10−7), and rs10993994 (10q11) (p = 1.40 × 10−3) in Mixed Ancestry men and rs10993994 (p = 1.56 × 10−9) 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.
PMCID: PMC4549549  PMID: 26347821
9.  Current Patterns of Management of Advanced Prostate Cancer in Routine Clinical Practice in Spain 
Prostate Cancer  2015;2015:186740.
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.
PMCID: PMC4515532  PMID: 26246911
10.  Cellular Plasticity in Prostate Cancer Bone Metastasis 
Prostate Cancer  2015;2015:651580.
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.
PMCID: PMC4469842  PMID: 26146569
11.  Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients 
Prostate Cancer  2015;2015:285193.
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.
PMCID: PMC4352947  PMID: 25802762
12.  Triptorelin in the Relief of Lower Urinary Tract Symptoms in Advanced Prostate Cancer Patients: The RESULT Study 
Prostate Cancer  2015;2015:978194.
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 73 ± 8 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.
PMCID: PMC4324912  PMID: 25694830
14.  Robotic Prostatectomy Has a Superior Outcome in Larger Prostates and PSA Density Is a Strong Predictor of Biochemical Recurrence 
Prostate Cancer  2014;2014:763863.
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 (PSA > 0.2) was observed in 15 patients (4.3%). Prostate size ≥75 g was associated with lower Gleason score on final pathology (P = 0.004) and lower pathological stage (P = 0.02) but an increased length of hospital stay (P = 0.05). PSAD on binary logistic regression independently predicted biochemical recurrence (BCR) when defined as postoperative PSA >0.1 (P = 0.001) and PSA >0.2 (P = 0.039). 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.
PMCID: PMC4279261  PMID: 25580298
15.  Long-Term Efficacy and Tolerability of Abdominal Once-Yearly Histrelin Acetate Subcutaneous Implants in Patients with Advanced Prostate Cancer 
Prostate Cancer  2014;2014:490315.
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 (P < 0.05). 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 (n = 22), 30.7 µg/L (n = 13), and 132.9 µg/L (n = 8), respectively. The mean serum PSA was significantly greater than baseline during these years (P < 0.05). 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.
PMCID: PMC4274828  PMID: 25548680
16.  CHEK2 ∗1100delC Mutation and Risk of Prostate Cancer 
Prostate Cancer  2014;2014:294575.
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.
PMCID: PMC4241328  PMID: 25431674
17.  Robotic Radical Prostatectomy in Patients with Previous Prostate Surgery and Radiotherapy 
Prostate Cancer  2014;2014:367675.
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.
PMCID: PMC4120925  PMID: 25120933
18.  Role of p73 Dinucleotide Polymorphism in Prostate Cancer and p73 Protein Isoform Balance 
Prostate Cancer  2014;2014:129582.
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, P = 0.053) as well as PCa specific death (HR = 0.69, 95%Cl = 0.45–1.06, P = 0.09). Western blot analyses for p73 protein isoforms indicate that cells heterozygous for the p73 DNP have lower levels of ∆Np73 relative to TAp73 (P < 0.001). 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.
PMCID: PMC4109114  PMID: 25097786
19.  Single High Intensity Focused Ultrasound Session as a Whole Gland Primary Treatment for Clinically Localized Prostate Cancer: 10-Year Outcomes 
Prostate Cancer  2014;2014:186782.
Objectives. To assess the treatment outcomes of a single session of whole gland high intensity focused ultrasound (HIFU) for patients with localized prostate cancer (PCa). Methods. Response rates were defined using the Stuttgart and Phoenix criteria. Complications were graded according to the Clavien score. Results. At a median follow-up of 94months, 48 (44.4%) and 50 (46.3%) patients experienced biochemical recurrence for Phoenix and Stuttgart definition, respectively. The 5- and 10-year actuarial biochemical recurrence free survival rates were 57% and 40%, respectively. The 10-year overall survival rate, cancer specific survival rate, and metastasis free survival rate were 72%, 90%, and 70%, respectively. Preoperative high risk category, Gleason score, preoperative PSA, and postoperative nadir PSA were independent predictors of oncological failure. 24.5% of patients had self-resolving LUTS, 18.2% had urinary tract infection, and 18.2% had acute urinary retention. A grade 3b complication occurred in 27 patients. Pad-free continence rate was 87.9% and the erectile dysfunction rate was 30.8%. Conclusion. Single session HIFU can be alternative therapy for patients with low risk PCa. Patients with intermediate risk should be informed about the need of multiple sessions of HIFU and/or adjuvant treatments and HIFU performed very poorly in high risk patients.
PMCID: PMC4089848  PMID: 25045541
20.  Urodynamic Evaluation after High-Intensity Focused Ultrasound for Patients with Prostate Cancer 
Prostate Cancer  2014;2014:462153.
This prospective study assesses the impact of high-intensity focused ultrasound (HIFU) on lower urinary tract by comparing pre- and postoperative symptoms and urodynamic changes. Thirty consecutive patients with clinically organ-confined prostate cancer underwent urodynamic study before HIFU and then at 3–6 months after surgery. Continence status and symptoms were analyzed by means of International Prostate Symptoms Score IPSS and International Index Erectile Function IIEF5. As a result, there were a significant improvement in bladder outlet, maximum flow at uroflowmetry, and reduction in postvoid residual PVR at 6-month follow-up and a concomitant significant reduction of detrusor pressure at opening and at maximum flow. De novo overactive bladder and impaired bladder compliance were detected in 10% of patients at 3 months, with progressive improvement at longer follow-up. Baseline prostate volume and length of the procedure were predictors of 6-month IPSS score and continence status. In conclusion, following HIFU detrusor overactivity, decreased bladder compliance and urge incontinence represent de novo dysfunction due to prostate and bladder neck injury during surgery. However, urodynamic study shows a progressive improvement in all storage and voiding patterns at 6-month follow-up. Patients with high prostate volume and long procedure length suffered from irritative symptoms even at long term.
PMCID: PMC4052071  PMID: 24955253
21.  Prostate Cancer in South Africa: Pathology Based National Cancer Registry Data (1986–2006) and Mortality Rates (1997–2009) 
Prostate Cancer  2014;2014:419801.
Prostate cancer is one of the most common male cancers globally; however little is known about prostate cancer in Africa. Incidence data for prostate cancer in South Africa (SA) from the pathology based National Cancer Registry (1986–2006) and data on mortality (1997–2009) from Statistics SA were analysed. World standard population denominators were used to calculate age specific incidence and mortality rates (ASIR and ASMR) using the direct method. Prostate cancer was the most common male cancer in all SA population groups (excluding basal cell carcinoma). There are large disparities in the ASIR between black, white, coloured, and Asian/Indian populations: 19, 65, 46, and 19 per 100 000, respectively, and ASMR was 11, 7, 52, and 6 per 100 000, respectively. Prostate cancer was the second leading cause of cancer death, accounting for around 13% of male deaths from a cancer. The average age at diagnosis was 68 years and 74 years at death. For SA the ASIR increased from 16.8 in 1986 to 30.8 in 2006, while the ASMR increased from 12.3 in 1997 to 16.7 in 2009. There has been a steady increase of incidence and mortality from prostate cancer in SA.
PMCID: PMC4052517  PMID: 24955252
22.  Comparison of Transperineal Mapping Biopsy Results with Whole-Mount Radical Prostatectomy Pathology in Patients with Localized Prostate Cancer 
Prostate Cancer  2014;2014:781438.
Objective. We sought to evaluate the accuracy of transperineal mapping biopsy (TMB) by comparing it to the pathology specimen of patients who underwent radical prostatectomy (RP) for localized prostate cancer. Methods. From March 2007 to September 2009, 78 men at a single center underwent TMB; 17 of 78 subsequently underwent RP. TMB cores were grouped into four quadrants and matched to data from RP whole-mount slides. Gleason score, tumor location and volume, cross-sectional area, and maximal diameter were measured; sensitivity and specificity were assessed. Results. For the 17 patients who underwent RP, TMB revealed 12 (71%) had biopsy Gleason grades ≥ 3 + 4 and 13 (76%) had bilateral disease. RP specimens showed 14 (82%) had Gleason scores ≥ 3 + 4 and 13 (76%) had bilateral disease. Sensitivity and specificity of TMB for prostate cancer detection were 86% (95% confidence interval [CI] 72%–94%) and 83% (95% CI 62%–95%), respectively. Four quadrants negative for cancer on TMB were positive on prostatectomy, and six positive on TMB were negative on prostatectomy. Conclusion. TMB is a highly invasive procedure that can accurately detect and localize prostate cancer. These findings help establish baseline performance characteristics for TMB and its utility for organ-sparing strategies.
PMCID: PMC4037573  PMID: 24900923
24.  Increased aPKC Expression Correlates with Prostatic Adenocarcinoma Gleason Score and Tumor Stage in the Japanese Population 
Prostate Cancer  2014;2014:481697.
Background. Levels of the protein kinase aPKC have been previously correlated with prostate cancer prognosis in a British cohort. However, prostate cancer incidence and progression rates, as well as genetic changes in this disease, show strong ethnic variance, particularly in Asian populations. Objective. The aim of this study was to validate association of aPKC expression with prostatic adenocarcinoma stages in a Japanese cohort. Methods. Tissue microarrays consisting of 142 malignant prostate cancer cases and 21 benign prostate tissues were subject to immunohistological staining for aPKC. aPKC staining intensity was scored by three independent pathologists and categorized as absent (0), dim (1+), intermediate (2+), and bright (3+). aPKC staining intensities were correlated with Gleason score and tumor stage. Results. Increased aPKC staining was observed in malignant prostate cancer, in comparison to benign tissue. Additionally, aPKC staining levels correlated with Gleason score and tumor stage. Our results extend the association of aPKC with prostate cancer to a Japanese population and establish the suitability of aPKC as a universal prostate cancer biomarker that performs consistently across ethnicities.
PMCID: PMC4020167  PMID: 24868468
25.  Obesity and the Odds of Weight Gain following Androgen Deprivation Therapy for Prostate Cancer 
Prostate Cancer  2014;2014:230812.
Background. Increasing body mass index (BMI) is associated with increased risk of mortality; however, quantifying weight gain in men undergoing androgen deprivation therapy (ADT) for prostate cancer (PC) remains unexplored. Methods. Between 1995 and 2001, 206 men were enrolled in a randomized trial evaluating the survival difference of adding 6 months of ADT to radiation therapy (RT). BMI measurements were available in 171 men comprising the study cohort. The primary endpoint was weight gain of ≥10 lbs by 6-month followup. Logistic regression analysis was performed to assess whether baseline BMI or treatment received was associated with this endpoint adjusting for known prognostic factors. Results. By the 6-month followup, 12 men gained ≥10 lbs, of which 10 (83%) received RT + ADT and, of these, 7 (70%) were obese at randomization. Men treated with RT as compared to RT + ADT were less likely to gain ≥10 lbs (adjusted odds ratio (AOR): 0.18 [95% CI: 0.04–0.89]; P = 0.04), whereas this risk increased with increasing BMI (AOR: 1.15 [95% CI: 1.01–1.31]; P = 0.04). Conclusions. Consideration should be given to avoid ADT in obese men with low- or favorable-intermediate risk PC where improved cancer control has not been observed, but shortened life expectancy from weight gain is expected.
PMCID: PMC4016923  PMID: 24864213

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