A Phase II Prospective Blinded Trial of Magnetic Resonance Imaging and In-Bore Biopsy in Active Surveillance for Prostate Cancer.

OBJECTIVE: To demonstrate the added benefit of multiparametric (mp)MRI risk stratification during active surveillance. METHODS: This prospective, single-arm, nonrandomized study included 82 men with low-risk prostate cancer (PCa). We compared two biopsy strategies in parallel. The first biopsy strategy was an in-bore and transrectal ultrasound (TRUS) biopsy in men with suspicious mpMRI findings. The second was a TRUS biopsy in all 82 men, blinded to the results of the previously performed mpMRI. RESULTS: We identified 27/82 men with suspicious mpMRI. Of those 27 men, we detected 8/27 with csPCa on biopsy, and we identified two men with in-bore biopsy exclusively, three men with TRUS biopsy exclusively, and three men with both biopsy strategies. Of the 55/82 men with nonsuspicious mpMRI (who only received TRUS biopsies), two men had csPCa. TRUS biopsy of the entire cohort of 82 men would have led to the correct diagnosis of 80% men with csPCa, requiring all 82 men to receive biopsies (csPCa in 10% of the 82 biopsies). Conducting in-bore biopsies plus TRUS biopsies in men with suspicious mpMRI would have also led to the detection of 80% of men with csPCa, requiring only 27 men to receive biopsies (csPCa in 30% of the 27 biopsies). CONCLUSION: The combination of TRUS and in-bore biopsies, limited to men with suspicious mpMRI, resulted in a similar detection rate of csPCa compared to TRUS biopsies of all men but required only one-third of men to undergo biopsy. Our results indicate that in-bore and TRUS biopsies continue to complement each other.

Racial Differences in Germline Genetic Testing for Prostate Cancer: A Systematic Review.

PURPOSE: Testing for pathogenic variants can aid in oncologic risk stratification and identification of targeted therapies. Despite known disparities in access to prostate cancer (PCa) care, little has been written about access to germline genetic testing (GGT) for Black men and other historically marginalized populations. This systematic review sought to delineate racial/ethnic disparities in GGT for PCa. METHODS: This systematic review identified articles published from January 1996 through May 2021 in PubMed, Web of Science, and Embase. We included studies that reported rates of GGT in men with PCa in the United States by race/ethnicity as reflective of routine clinical care or research. A narrative synthesis was performed. RESULTS: Of 4,309 unique records, 91 studies examining 50 unique study populations met inclusion criteria. Of these, four populations included men who received GGT through routine clinical care, accounting for 4,415 men (72.6% White and 7.2% Black). The other 46 populations included men who received GGT as part of a research study, accounting for 30,824 men (64.3% White and 21.6% Black). Of these 46 research populations, 19 used targeted methods to increase recruitment from a specific demographic. CONCLUSION: Most studies that report GGT rates by race/ethnicity are in research settings. Many of these studies used targeted recruitment methods and subsequently have a greater proportion of Black men than clinical and US population-based studies. Other historically marginalized populations are not well represented. There remains a knowledge gap regarding the extent of racial disparities in the use of GGT, particularly in the clinical setting.

Geographic Variability, Time Trends and Association of Preoperative Magnetic Resonance Imaging with Surgical Outcomes for Elderly United States Men with Prostate Cancer: A Surveillance, Epidemiology, and End Results-Medicare Analysis.

PURPOSE: Our goal was to assess patterns of adoption and population-level outcomes of prostate magnetic resonance imaging (MRI) and association with surgical outcomes across a sample of U.S. elderly. MATERIALS AND METHODS: This population-based retrospective study used Surveillance Epidemiology, and End Results-Medicare linked data from 2003-2016 to identify men receiving prostatectomy for prostate cancer. We characterized the proportion of men receiving preoperative MRI in each year and in each hospital referral region (HRR). A 2-stage instrumental variable analysis was performed to assess the association of preoperative MRI with margin status, surgical complications and further cancer-directed therapies. RESULTS: A total of 19,369 men received prostatectomy in 72 HRRs; the mean age was 70.2 years (SD 3.2). The proportion of men receiving a preoperative MRI increased from 2.9% to 28.2% over the study period and ranged from 0.0% to 28.8% in the different HRRs. In our instrumental variable analysis, preoperative MRI was associated with lower odds of positive surgical margin (OR 0.84, 95% CI 0.72-0.97, p=0.01) lower odds of blood transfusions at 30 and 90 days (OR 0.56, 95% CI 0.38-0.83, p=0.003 and OR 0.58, 95% CI 0.41-0.84, p=0.004) but higher odds of further treatments (OR 1.49, 95% CI 1.32-1.70, p <0.001). CONCLUSIONS: Given that a minority of men receive presurgical MRIs with marked geographic variability, the association of MRI with lower odds of positive surgical margin suggests that efforts to support the dissemination of prostate MRI may improve surgical outcomes-but may come with a tendency for more resource-intensive cancer care overall.

Is perfect the enemy of good? Weighing the evidence for biparametric MRI in prostate cancer.

The role of multiparametric MRI in diagnosis, staging and treatment planning for prostate cancer is well established. However, there remain several challenges to widespread adoption. One such challenge is the duration and cost of the examination. Abbreviated exams omitting contrast-enhanced sequences may help address this challenge. In this review, we will discuss the rationale for biparametric MRI for detection and characterization of clinically significant prostate cancer prior to biopsy and synthesize the published literature. We will weigh up the advantages and disadvantages to this approach and lay out a conceptual cost/benefit analysis regarding adoption of biparametric MRI.

Changes in peripheral blood level of regulatory T cells in patients with malignant melanoma during treatment with dendritic cell vaccination and low-dose IL-2.

In this study, changes in peripheral blood regulatory T cell (Treg) levels were evaluated in 46 progressive patients with melanoma treated with a dendritic cell-based vaccine and concomitant low-dose IFN-α and IL-2. The regulatory subset of CD4 T cells, characterized by CD25(high) , was prospectively analysed in fresh blood, and treatment-associated quantitative and qualitative changes were analysed. By the 4th vaccine, patients showed a marked increase in CD4+ CD25(high) T cell subset from 6% to 22% (P<0.001). At the 6th vaccine, a general decline was observed and a significantly (P=0.01) lower level of CD4+ CD25(high) Treg cells was reached in the group of patients who attained disease stabilization (9.5%) compared to patients with continued progressive disease (14.5%). However, when FoxP3 was employed for retrospective analysis of Tregs on frozen blood, this difference did not reach significance (P=0.09). The vast majority of the Treg produced IL-10 and, to a varying extent, TGF-ß. In addition, sorted CD4+ CD25(high) CD127⁻ Tregs were able to suppress proliferation of peripheral blood mononuclear cells in a dose-dependent manner, thus suggesting a regulatory functionality. These findings emphasize the need for strategies to effectively eliminate Treg cells to optimize the clinical effectiveness of cancer immunotherapy.