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

Development of a Novel Robot for Transperineal Needle Based Interventions: Focal Therapy, Brachytherapy and Prostate Biopsies

Purpose: We report what is to our knowledge the initial experience with a new 3-dimensional ultrasound robotic system for prostate brachytherapy assistance, focal therapy and prostate biopsies. Its ability to track prostate motion intraoperatively allows it to manage motions and guide needles to predefined targets. Materials and Methods: A robotic system was created for transrectal ultrasound guided needle implantation combined with intraoperative prostate tracking. Experiments were done on 90 targets embedded in a total of 9 mobile, deformable, synthetic prostate phantoms. Experiments involved trying to insert glass beads as close as possible to targets in multimodal anthropomorphic imaging phantoms. Results were measured by segmenting the inserted beads in computerized tomography volumes of the phantoms. Results: The robot reached the chosen targets in phantoms with a median accuracy of 2.73 mm and a median prostate motion of 5.46 mm. Accuracy was better at the apex than at the base (2.28 vs 3.83 mm, p <0.001), and similar for horizontal and angled needle inclinations (2.7 vs 2.82 mm, p = 0.18). Conclusions: To our knowledge this robot for prostate focal therapy, brachytherapy and targeted prostate biopsies is the first system to use intraoperative prostate motion tracking to guide needles into the prostate. Preliminary experiments show its ability to reach targets despite prostate motion

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

Standard and saturation transrectal prostate biopsy techniques are equally accurate among prostate cancer active surveillance candidates

Q2Q2860-4Objectives To examine the ability of standard and saturation transrectal prostate biopsy techniques to predict appropriate candidates for active surveillance. Methods Between 2005 and 2007, 500 consecutive patients underwent transrectal ultrasound‐guided biopsy by a standard template (12 cores) or saturation template (≥18 cores, median 27 cores), with subsequent radical prostatectomy. Using the criteria of G leason score ≤6, clinical stage T 1 or T 2a, prostate‐specific antigen <10 and ≤33% of cores involved, 218 patients were potential candidates for active surveillance. Pathology results from the prostatectomy specimens were used to determine the accuracy of each biopsy technique. Biochemical failure after prostatectomy was evaluated using logistic and C ox proportional hazards regression. Results A standard biopsy was carried out for 124 patients and saturation biopsy for 94 patients. There was no statistically significant difference between the groups in terms of median age (P  = 0.14), preoperative prostate‐specific antigen (P  = 0.52) and clinical stage (P  = 0.23). Similar rates of G leason score ≥7 at the time of radical prostatectomy were found, with 14% for standard biopsy and 15% for saturation biopsy (P  = 0.70). Upstaging was shown in two standard biopsy patients (1.6%) and no saturation biopsy patients (P  = 0.62). A multivariate analysis adjusting for prior prostate biopsy, preoperative prostate‐specific antigen and clinical stage showed no difference in the rate of upgrading based on biopsy technique (P  = 0.26). During follow up, 5‐year biochemical failure‐free survival estimates were not significantly different (P  = 0.11). Conclusions In men with prostate cancer, standard and saturation transrectal prostate biopsies techniques are equally predictive of candidates for active surveillance

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&lt;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 .)

Low-risk Prostate Cancer: Identification, Management, and Outcomes.

ContextThe incidence of low-risk prostate cancer (PCa) has increased as a consequence of prostate-specific antigen testing.ObjectiveIn this collaborative review article, we examine recent literature regarding low-risk PCa and the available prognostic and therapeutic options.Evidence acquisitionWe performed a literature review of the Medline, Embase, and Web of Science databases. The search strategy included the terms: prostate cancer, low risk, active surveillance, focal therapy, radical prostatectomy, watchful waiting, biomarker, magnetic resonance imaging, alone or in combination.Evidence synthesisProspective randomized trials have failed to show an impact of radical treatments on cancer-specific survival in low-risk PCa patients. Several series have reported the risk of adverse pathologic outcomes at radical prostatectomy. However, it is not clear if these patients are at higher risk of death from PCa. Long-term follow-up indicates the feasibility of active surveillance in low-risk PCa patients, although approximately 30% of men starting active surveillance undergo treatment within 5 yr. Considering focal therapies, robust data investigating its impact on long-term survival outcomes are still required and therefore should be considered experimental. Magnetic resonance imaging and tissue biomarkers may help to predict clinically significant PCa in men initially diagnosed with low-risk disease.ConclusionsThe incidence of low-risk PCa has increased in recent years. Only a small proportion of men with low-risk PCa progress to clinical symptoms, metastases, or death and prospective trials have not shown a benefit for immediate radical treatments. Tissue biomarkers, magnetic resonance imaging, and ongoing surveillance may help to identify those men with low-risk PCa who harbor more clinically significant disease.Patient summaryLow-risk prostate cancer is very common. Active surveillance has excellent long-term results, while randomized trials have failed to show a beneficial impact of immediate radical treatments on survival. Biomarkers and magnetic resonance imaging may help to identify which men may benefit from early treatment