Focal Treatment of Prostate Cancer with Vascular-Targeted Photodynamic Therapy

Epidemiologic and pathologic features of prostate cancer have given rise to an interest in focal treatment for carefully selected patients. Prostate cancer remains highly prevalent, particularly in the U.S. and Europe. As screening programs have become more aggressive and widespread, a substantial proportion of men diagnosed with localized prostate cancer have disease characteristics associated with a low risk of progression. Treatments such as radical prostatectomy and radiation therapy can lead to durable recurrence-free survival in most patients, but carry variable risks of bowel, urinary, and sexual side effects. Few men and few urologists are comfortable leaving a potentially curable prostate cancer untreated. Focal therapy offers an attractive alternative for the patient faced with a choice between aggressive local intervention (radiation or surgery) and watchful waiting. Contemporary diagnostic biopsy strategies and imaging tools, and the development of predictive statistical models (nomograms), have led to improvements in tumor characterization and risk stratification, making focal therapy a viable treatment option for specific men. This article reviews the rationale and indications for focal therapy and highlights vascular-targeted photodynamic therapy (PDT) as one of many promising focal therapy techniques

Multi-institution analysis of racial disparity among African- American men eligible for prostate cancer active surveillance

There is a significant controversy on whether race should be a factor in considering active surveillance for low-risk prostate cancer. To address this question, we analyzed a multi-institution database to assess racial disparity between African-American and White-American men with low risk prostate cancer who were eligible for active surveillance but underwent radical prostatectomy. A retrospective analysis of prospectively collected clinical, pathologic and oncologic outcomes of men with low-risk prostate cancer from seven tertiary care institutions that underwent radical prostatectomy from 2003–2014 were used to assess potential racial disparity. Of the 333 (14.8%) African-American and 1923 (85.2%) White-American men meeting active surveillance criteria, African-American men were found to be slightly younger (57.5 vs 58.5 years old; p = 0.01) and have higher BMI (29.3 v 27.9; p \u3c 0.01), pre-op PSA (5.2 v 4.7; p \u3c 0.01), and maximum percentage cancer on biopsy (15.1% v 13.6%; p \u3c 0.01) compared to White-American men. Univariate and multivariate analysis demonstrated similar rates of upgrading, upstaging, positive surgical margin, and biochemical recurrence between races. These results suggest that single institution studies recommending more stringent AS enrollment criteria for AA men with a low-risk prostate cancer may not capture the complete oncologic landscape due to institutional variability in cancer outcomes. Since all seven institutions demonstrated no significant racial disparity, current active surveillance eligibility should not be modified based upon race until a prospective study has been completed. © Dinizo et al

Cathepsins B and D drive hepatic stellate cell proliferation and promote their fibrogenic potential

El pdf del artículo es el manuscrito de autor.-- PubMed: PMCID:PMC2670444Cathepsins have been best characterized in tumorigenesis and cell death and implicated in liver fibrosis; however, whether cathepsins directly regulate hepatic stellate cell (HSC) activation and proliferation, hence modulating their fibrogenic potential, is largely unknown. Here, we show that expression of cathepsin B (CtsB) and cathepsin D (CtsD) is negligible in quiescent HSCs but parallels the increase of -smooth muscle actin and transforming growth factor- during in vitro mouse HSC activation. Both cathepsins are necessary for HSC transdifferentiation into myofibroblasts, because their silencing or inhibition decreasedHSC proliferation and the expression of phenotypicmarkers ofHSC activation, with similar results observed with the human HSC cell line LX2. CtsB inhibition blunted AKT phosphorylation in activated HSCs in response to platelet-derived growth factor.Moreover, during in vivo liver fibrogenesis caused by CCl4 administration, CtsB expression increased in HSCs but not in hepatocytes, and its inactivation mitigated CCl4-induced inflammation, HSC activation, and collagen deposition. Conclusion: These findings support a critical role for cathepsins inHSC activation, suggesting that the antagonismof cathepsins inHSCsmay be of relevance for the treatment of liver fibrosis.Financial support: The work was supported by CIBEREHD and grant PI070193 (Instituto de Salud Carlos III); by grant SAF2006-06780 (Plan Nacional de I+D), Spain; and by grant P50-AA-11999 (Research Center for Liver and Pancreatic Diseases, US National Institute on Alcohol Abuse and Alcoholism).Peer reviewe

MRI-targeted or standard biopsy for prostate-cancer diagnosis

Background Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. Methods In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. Results A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P<0.001). Conclusions The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .)

Prostate Volumes Derived From MRI and Volume-Adjusted Serum Prostate-Specific Antigen: Correlation With Gleason Score of Prostate Cancer

The purpose of this article is to study relationships between MRI-based prostate volume and volume-adjusted serum prostate-specific antigen (PSA) concentration estimates and prostate cancer Gleason score

Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Cancer

Purpose: Magnetic resonance imaging-guided transurethral ultrasound ablation uses directional thermal ultrasound under magnetic resonance imaging thermometry feedback control for prostatic ablation. We report 12-month outcomes from a prospective multicenter trial (TACT). Materials and methods: A total of 115 men with favorable to intermediate risk prostate cancer across 13 centers were treated with whole gland ablation sparing the urethra and apical sphincter. The co-primary 12-month endpoints were safety and efficacy. Results: In all, 72 (63%) had grade group 2 and 77 (67%) had NCCN® intermediate risk disease. Median treatment delivery time was 51 minutes with 98% (IQR 95-99) thermal coverage of target volume and spatial ablation precision of ±1.4 mm on magnetic resonance imaging thermometry. Grade 3 adverse events occurred in 9 (8%) men. The primary endpoint (U.S. Food and Drug Administration mandated) of prostate specific antigen reduction ≥75% was achieved in 110 of 115 (96%) with median prostate specific antigen reduction of 95% and nadir of 0.34 ng/ml. Median prostate volume decreased from 37 to 3 cc. Among 68 men with pretreatment grade group 2 disease, 52 (79%) were free of grade group 2 disease on 12-month biopsy. Of 111 men with 12-month biopsy data, 72 (65%) had no evidence of cancer. Erections (International Index of Erectile Function question 2 score 2 or greater) were maintained/regained in 69 of 92 (75%). Multivariate predictors of persistent grade group 2 at 12 months included intraprostatic calcifications at screening, suboptimal magnetic resonance imaging thermal coverage of target volume and a PI-RADS™ 3 or greater lesion at 12-month magnetic resonance imaging (p <0.05). Conclusions: The TACT study of magnetic resonance imaging-guided transurethral ultrasound whole gland ablation in men with localized prostate cancer demonstrated effective tissue ablation and prostate specific antigen reduction with low rates of toxicity and residual disease

Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017

Purpose: Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-dri

Genomic Predictors of Outcome in Prostate Cancer

CONTEXT: Given the highly variable behavior and clinical course of prostate cancer (PCa) and the multiple available treatment options, a personalized approach to oncologic risk stratification is important. Novel genetic approaches offer additional information to improve clinical decision making. OBJECTIVE: To review the use of genomic biomarkers in the prognostication of PCa outcome and prediction of therapeutic response. EVIDENCE ACQUISITION: Systematic literature review focused on human clinical studies reporting outcome measures with external validation. The literature search included all Medline, Embase, and Scopus articles from inception through July 2014. EVIDENCE SYNTHESIS: An improved understanding of the genetic basis of prostate carcinogenesis has produced an increasing number of potential prognostic and predictive tools, such as transmembrane protease, serine2:v-ets avian erythroblastosis virus E26 oncogene homolog (TMPRSS2:ERG) gene fusion status, loss of the phosphatase and tensin homolog (PTEN) gene, and gene expression signatures utilizing messenger RNA from tumor tissue. Several commercially available gene panels with external validation are now available, although most have yet to be widely used. The most studied commercially available gene panels, Prolaris, Oncotype DX Genomic Prostate Score, and Decipher, may be used to estimate disease outcome in addition to clinical parameters or clinical nomograms. ConfirmMDx is an epigenetic test used to predict the results of repeat prostate biopsy after an initial negative biopsy. Additional future strategies include using genetic information from circulating tumor cells in the peripheral blood to guide treatment decisions at the initial diagnosis and at subsequent decision points. CONCLUSIONS: Major advances have been made in our understanding of PCa biology in recent years. Our field is currently exploring the early stages of a personalized approach to augment traditional clinical decision making using commercially available genomic tools. A more comprehensive appreciation of value, limitations, and cost is important. PATIENT SUMMARY: We summarized current advances in genomic testing in prostate cancer with a special focus on the estimation of disease outcome. Several commercial tests are currently available, but further understanding is needed to appreciate the potential benefits and limitations of these novel tests