MRI-Targeted, Systematic, and Combined Biopsy for Prostate Cancer Diagnosis.

BACKGROUND: The use of 12-core systematic prostate biopsy is associated with diagnostic inaccuracy that contributes to both overdiagnosis and underdiagnosis of prostate cancer. Biopsies performed with magnetic resonance imaging (MRI) targeting may reduce the misclassification of prostate cancer in men with MRI-visible lesions. METHODS: Men with MRI-visible prostate lesions underwent both MRI-targeted and systematic biopsy. The primary outcome was cancer detection according to grade group (i.e., a clustering of Gleason grades). Grade group 1 refers to clinically insignificant disease; grade group 2 or higher, cancer with favorable intermediate risk or worse; and grade group 3 or higher, cancer with unfavorable intermediate risk or worse. Among the men who underwent subsequent radical prostatectomy, upgrading and downgrading of grade group from biopsy to whole-mount histopathological analysis of surgical specimens were recorded. Secondary outcomes were the detection of cancers of grade group 2 or higher and grade group 3 or higher, cancer detection stratified by previous biopsy status, and grade reclassification between biopsy and radical prostatectomy. RESULTS: A total of 2103 men underwent both biopsy methods; cancer was diagnosed in 1312 (62.4%) by a combination of the two methods (combined biopsy), and 404 (19.2%) underwent radical prostatectomy. Cancer detection rates on MRI-targeted biopsy were significantly lower than on systematic biopsy for grade group 1 cancers and significantly higher for grade groups 3 through 5 (P<0.01 for all comparisons). Combined biopsy led to cancer diagnoses in 208 more men (9.9%) than with either method alone and to upgrading to a higher grade group in 458 men (21.8%). However, if only MRI-target biopsies had been performed, 8.8% of clinically significant cancers (grade group ≥3) would have been misclassified. Among the 404 men who underwent subsequent radical prostatectomy, combined biopsy was associated with the fewest upgrades to grade group 3 or higher on histopathological analysis of surgical specimens (3.5%), as compared with MRI-targeted biopsy (8.7%) and systematic biopsy (16.8%). CONCLUSIONS: Among patients with MRI-visible lesions, combined biopsy led to more detection of all prostate cancers. However, MRI-targeted biopsy alone underestimated the histologic grade of some tumors. After radical prostatectomy, upgrades to grade group 3 or higher on histopathological analysis were substantially lower after combined biopsy. (Funded by the National Institutes of Health and others; Trio Study ClinicalTrials.gov number, NCT00102544.).

Magnetic Resonance Imaging-Targeted and Systematic Biopsy for Detection of Grade Progression in Patients on Active Surveillance for Prostate Cancer.

PURPOSE: Active surveillance for patients with low and intermediate risk prostate cancers is becoming a more utilized option in recent years. However, the use of magnetic resonance imaging and imaging-targeted biopsy for monitoring grade progression has been poorly studied in this population. We aim to define the utility of magnetic resonance imaging-targeted biopsy and systematic biopsy in an active surveillance population. MATERIALS AND METHODS: Between July 2007 and January 2020, patients with diagnosed prostate cancer who elected active surveillance were monitored with prostate magnetic resonance imaging, imaging-targeted biopsy and standard systematic biopsy. Patients were eligible for surveillance if diagnosed with any volume Gleason grade 1 disease and select Gleason grade 2 disease. Grade progression (Gleason grade 1 to ≥2 disease and Gleason grade 2 to ≥3 disease) for each biopsy modality was measured at 2 years, 4 years and 6+ years. RESULTS: In total, 369 patients had both magnetic resonance imaging-targeted and systematic biopsy and were surveilled for at least 1 year. At 2 years, systematic biopsy, magnetic resonance imaging-targeted biopsy and combined biopsy (systematic+imaging-targeted) detected grade progression in 44 patients (15.9%), 73 patients (26.4%) and 90 patients (32.5%), respectively. Magnetic resonance imaging-targeted biopsy detected more cancer grade progression compared to systematic biopsy in both the low and intermediate risk populations (p <0.001). Of all 90 grade progressions at the 2-year time point 46 (51.1%) were found by magnetic resonance imaging-targeted biopsy alone and missed by systematic biopsy. CONCLUSIONS: Magnetic resonance imaging-targeted biopsy detected significantly more grade progressions in our active surveillance cohort compared to systematic biopsy at 2 years. Our results provide compelling evidence that prostate magnetic resonance imaging and imaging-targeted biopsy should be included in contemporary active surveillance protocols.

Role of MRI for the detection of prostate cancer.

The use of multiparametric MRI has been hastened under expanding, novel indications for its use in the diagnostic and management pathway of men with prostate cancer. This has helped drive a large body of the literature describing its evolving role over the last decade. Despite this, prostate cancer remains the only solid organ malignancy routinely diagnosed with random sampling. Herein, we summarize the components of multiparametric MRI and interpretation, and present a critical review of the current literature supporting is use in prostate cancer detection, risk stratification, and management.

Role of multiparametric prostate MRI in the management of prostate cancer.

INTRODUCTION: Prostate cancer has traditionally been diagnosed by an elevation in PSA or abnormal exam leading to a systematic transrectal ultrasound (TRUS)-guided biopsy. This diagnostic pathway underdiagnoses clinically significant disease while over diagnosing clinically insignificant disease. In this review, we aim to provide an overview of the recent literature regarding the role of multiparametric MRI (mpMRI) in the management of prostate cancer. MATERIALS AND METHODS: A thorough literature review was performed using PubMed to identify articles discussing use of mpMRI of the prostate in management of prostate cancer. CONCLUSION: The incorporation of mpMRI of the prostate addresses the shortcomings of the prostate biopsy while providing several other advantages. mpMRI allows some men to avoid an immediate biopsy and permits visualization of areas likely to harbor clinically significant cancer prior to biopsy to facilitate use of MR-targeted prostate biopsies. This allows for reduction in diagnosis of clinically insignificant disease as well as improved detection and better characterization of higher risk cancers, as well as the improved selection of patients for active surveillance. In addition, mpMRI can be used for selection and monitoring of patients for active surveillance and treatment planning during surgery and focal therapy.

Making a case "for" focal therapy of the prostate in intermediate risk prostate cancer: current perspective and ongoing trials.

Focal therapy is growing as an alternative management options for men with clinically localized prostate cancer. Parallel to the increasing popularity of active surveillance (AS) as a treatment for low-risk disease, there has been an increased interest towards providing focal therapy for patients with intermediate-risk disease. Focal therapy can act as a logical "middle ground" in patients who seek treatment while minimizing potential side effects of definitive whole-gland treatment. The aim of the current review is to define the rationale of focal therapy in patients with intermediate-risk prostate cancer and highlight the importance of patient selection in focal therapy candidacy.

Techniques and Outcomes of MRI-TRUS Fusion Prostate Biopsy.

PURPOSE OF REVIEW: The goal of this study is to review recent findings and evaluate the utility of MRI transrectal ultrasound fusion biopsy (FBx) techniques and discuss future directions. RECENT FINDINGS: FBx detects significantly higher rates of clinically significant prostate cancer (csPCa) than ultrasound-guided systematic prostate biopsy (SBx), particularly in repeat biopsy settings. FBx has also been shown to detect significantly lower rates of clinically insignificant prostate cancer. In addition, a dedicated prostate MRI can assist in more accurately predicting the Gleason score and provide further information regarding the index cancer location, prostate volume, and clinical stage. The ability to accurately evaluate specific lesions is vital to both focal therapy and active surveillance, for treatment selection, planning, and adequate follow-up. FBx has been demonstrated in multiple high-quality studies to have improved performance in diagnosis of csPCa compared to SBx. The combination of FBx with novel technologies including radiomics, prostate-specific membrane antigen positron emission tomography (PSMA PET), and high-resolution micro-ultrasound may have the potential to further enhance this performance.

PI-RADS® Category as a Predictor of Progression to Unfavorable Risk Prostate Cancer in Men on Active Surveillance.

PURPOSE: We identified baseline imaging and clinical characteristics of patients that may improve risk stratification among patients being evaluated for active surveillance. MATERIALS AND METHODS: From July 2007 to January 2020 patients referred to our institution for prostate cancer were evaluated and those who remained on active surveillance were identified. Men underwent multiparametric magnetic resonance imaging upon entry into our active surveillance protocol during which baseline demographic and imaging data were documented. Patients were then followed and outcomes, specifically progression to Gleason Grade Group (GG)3 or greater disease, were recorded. RESULTS: Of the men placed on active surveillance 344 had at least 1 PI-RADS score documented. For those with an index lesion PI-RADS category of 5, 33% (17/51) had progression to GG3 or greater on active surveillance with a median time to progression of 31 months. When comparing the progression-free survival times and progression rates in each category, PI-RADS category was found to be associated with progression to GG3 or greater on active surveillance (p <0.01). On univariable analysis factors associated with progression included an index lesion PI-RADS category of 5, prostate specific antigen density and the size of the largest lesion. On multivariable analysis only PI-RADS category of 5 and prostate specific antigen density were associated with progression on active surveillance. CONCLUSIONS: PI-RADS lesion categories at baseline multiparametric magnetic resonance imaging during active surveillance enrollment can be used to predict cancer progression to GG3 or greater on active surveillance. This information, along with other clinical data, can better assist urologists in identifying and managing patients appropriate for active surveillance.

Focal therapy for prostate cancer: recent advances and future directions.

Prostate cancer is the most frequently diagnosed cancer in men after skin cancer. Owing to the rising popularity of prostate-specific antigen screening, large numbers of patients are receiving a diagnosis of prostate cancer and undergoing whole-gland treatment. Some patients with a diagnosis of low-risk, localized disease may not benefit from whole-gland treatment, however, given its known morbidity. In response to advances in prostate imaging and evidence suggesting that the prognosis in prostate cancer is related to the index lesion, many patients have begun to opt for focal therapy, which targets a lesion rather than the entire prostate. This "middle ground" of therapy, between active surveillance and whole-gland treatment, is appealing to patients because the risk for side effects is believed to be lower with focal therapy than with whole-gland treatment. This review discusses the oncologic rationale for focal therapy in localized prostate cancer, examines the major therapy modalities, and addresses future directions.

Contemporary treatments in prostate cancer focal therapy.

PURPOSE OF REVIEW: Radical treatments for prostate cancer are associated with significant morbidity, including incontinence and erectile dysfunction. Advances in the field of prostate MRI and desire to reduce treatment morbidities have led to a rapid growth in focal treatments for prostate cancer. Here, we review novel focal prostate cancer treatments and their associated recent clinical data, with a particular focus on data reported within the last 24 months. RECENT FINDINGS: High-intensity focal ultrasound, focal laser ablation, irreversible electroporation, focal cryotherapy, and photodynamic therapy have been used as treatment modalities for localized prostate cancer treatment. Despite the great variety of treatment techniques, each of these modalities is characterized by a significant rate of prostate cancer persistence within treatment zones (6-50%) and the presence of residual cancer within the prostate on rebiopsy (24-49%). These treatments, however, are associated with very low rates of high-grade complications, rare incontinence, and only mild or transient reductions in erectile function. The most common adverse events are urinary tract infections, hematuria, and urinary retention. SUMMARY: Prostate cancer focal therapy is an attractive option for well-selected patients because of its low complication profile; however, long-term oncologic outcome is still lacking and early recurrence rates are high, limiting the ability of most urologic associations from endorsing its routine use.

Use of multiparametric magnetic resonance imaging and fusion-guided biopsies to properly select and follow African-American men on active surveillance.

OBJECTIVES: To determine the rate of Gleason Grade Group (GGG) upgrading in African-American (AA) men with a prior diagnosis of low-grade prostate cancer (GGG 1 or GGG 2) on 12-core systematic biopsy (SB) after multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy (FB); and whether AA men who continued active surveillance (AS) after mpMRI and FB fared differently than a predominantly Caucasian (non-AA) population. PATIENTS AND METHODS: A database of men who had undergone mpMRI and FB was queried to determine rates of upgrading by FB amongst men deemed to be AS candidates based on SB prior to referral. After FB, Kaplan-Meier curves were generated for AA men and non-AA men who then elected AS. The time to GGG upgrading and time continuing AS were compared using the log-rank test. RESULTS: AA men referred with GGG 1 disease on previous SB were upgraded to GGG ≥3 by FB more often than non-AA men, 22.2% vs 12.7% (P = 0.01). A total of 32 AA men and 258 non-AA men then continued AS, with a median (interquartile range) follow-up of 39.19 (24.24-56.41) months. The median time to progression was 59.7 and 60.5 months, respectively (P = 0.26). The median time continuing AS was 61.9 months and not reached, respectively (P = 0.80). CONCLUSIONS: AA men were more likely to be upgraded from GGG 1 on SB to GGG ≥3 on initial FB; however, AA and non-AA men on AS subsequently progressed at similar rates following mpMRI and FB. A greater tendency for SB to underestimate tumour grade in AA men may explain prior studies that have shown AA men to be at higher risk of progression during AS.

Combining disparate surgical residencies into one: lessons learned.

BACKGROUND: Attitudes, career goals, and educational experiences of general surgery residents are profiled during the acquisition of a community residency program by an academic residency program. MATERIALS AND METHODS: The study population included all general surgery residents postgraduate years 2-5 in a tertiary academic medical center divided into community program matriculants (CPM) or academic program matriculants (APM). A survey compared perceptions before and after residency amalgamation in seven training categories as follows: relationships among residents, relationships with faculty, systems interactions, clinical training, surgical training, scholarship, and career plans. Responses were recorded on a Likert scale. Fisher exact test and one-sided t-test were applied. RESULTS: Thirty-five trainees (83%) participated, 23 APM (66%) and 12 CPM (34%). Neither cohort reported significant negative perceptions regarding surgical training, career planning, or scholarship (P > 0.05). There was a greater likelihood of significant negative perceptions regarding inter-resident relationships among CPM (P < 0.05). CPM perceived significantly improved opportunities for scholarship (P < 0.01) and nationwide networking through faculty (P < 0.05) after acquisition. There was a nearly significant trend toward CPM perceiving greater access to competitive specialties after acquisition. Overall, CPM perceptions were affected more often after acquisition; however, when affected, APM were less likely to be positively affected (odds ratio, 2.9). CONCLUSIONS: Acquisition of a community surgery residency by an academic program does not seem to negatively affect trainees' perceptions regarding training. The effect of such acquisition on CPMs' decision to pursue competitive fellowships remains ill defined, but CPM perceived improved research opportunities, faculty networking, and programmatic support to pursue a career in academic surgery.

TNF, acting through inducibly expressed TNFR2, drives activation and cell cycle entry of c-Kit+ cardiac stem cells in ischemic heart disease.

TNF, signaling through TNFR2, has been implicated in tissue repair, a process that in the heart may be mediated by activated resident cardiac stem cells (CSCs). The objective of our study is to determine whether ligation of TNFR2 can induce activation of resident CSCs in the setting of ischemic cardiac injury. We show that in human cardiac tissue affected by ischemia heart disease (IHD), TNFR2 is expressed on intrinsic CSCs, identified as c-kit(+)/CD45(-)/VEGFR2(-) interstitial round cells, which are activated as determined by entry to cell cycle and expression of Lin-28. Wild-type mouse heart organ cultures subjected to hypoxic conditions both increase cardiac TNF expression and show induced TNFR2 and Lin-28 expression in c-kit(+) CSCs that have entered cell cycle. These CSC responses are enhanced by exogenous TNF. TNFR2(-/-) mouse heart organ cultures subjected to hypoxia increase cardiac TNF but fail to induce CSC activation. Similarly, c-kit(+) CSCs isolated from mouse hearts exposed to hypoxia or TNF show induction of Lin-28, TNFR2, cell cycle entry, and cardiogenic marker, α-sarcomeric actin (α-SA), responses more pronounced by hypoxia in combination with TNF. Knockdown of Lin-28 by siRNA results in reduced levels of TNFR2 expression, cell cycle entry, and diminished expression of α-SA. We conclude that hypoxia-induced c-kit(+) CSC activation is mediated by TNF/TNFR2/Lin-28 signaling. These observations suggest that TNFR2 signaling in resident c-kit(+) CSCs induces cardiac repair, findings which provide further understanding of the unanticipated harmful effects of TNF blockade in human IHD.

Timing, incidence and management of delayed bleeding after partial nephrectomy in patients at risk for recurrent, bilateral, multifocal renal tumors.

INTRODUCTION: Delayed bleeding is a potentially serious complication after partial nephrectomy (PN), with reported rates of 1%-2%. Patients with multiple renal tumors, including those with hereditary forms of kidney cancer, are often managed with resection of multiple tumors in a single kidney which may increase the risk of delayed bleeding, though outcomes have not previously been reported specifically in this population. The objective of this study was to evaluate the incidence and timing of delayed bleeding as well as the impact of intervention on renal functional outcomes in a cohort primarily made up of patients at risk for bilateral, multifocal renal tumors. METHODS: A retrospective review of a prospectively maintained database of patients with known or suspected predisposition to bilateral, multifocal renal tumors who underwent PN from 2003 to 2023 was conducted. Patients who presented with delayed bleeding were identified. Patients with delayed bleeding were compared to those without. Comparative statistics and univariate logistic regression were used to determine potential risk factors for delayed bleeding. RESULTS: A total of 1256 PN were performed during the study period. Angiographic evidence of pseudoaneurysm, AV fistula and/or extravasation occurred in 24 cases (1.9%). Of these, 21 were symptomatic presenting with gross hematuria in 13 (54.2%), decreasing hemoglobin in 4(16.7%), flank pain in 2(8.3%), and mental status change in 2 (8.3%), while 3 patients were asymptomatic. Median number of resected tumors was 5 (IQR 2-8). All patients underwent angiogram with super-selective embolization. Median time to bleed event was 13.5 days (IQR 7-22). Factors associated with delayed bleeding included open approach (OR 2.2, IQR(1.06-5.46), P = 0.04 and left-sided surgery (OR 4.93, IQR(1.67-14.5), P = 0.004. Selective embolization had little impact on ultimate renal functional outcomes, with a median change of 11% from the baseline eGFR after partial nephrectomy and embolization. One patient required total nephrectomy for refractory bleeding after embolization. CONCLUSIONS: Delayed bleeding after PN in a cohort of patients with multifocal tumors is an infrequent event, with similar rates to single tumor series. Patients should be counseled regarding timing and symptoms of delayed bleeding and multidisciplinary management with interventional radiology is critical for timely diagnosis and treatment.

Patient-reported Satisfaction and Regret Following Focal Therapy for Prostate Cancer: A Prospective Multicenter Evaluation.

Background: Several reports are available regarding the treatment decision regret of patients receiving conventional treatments for localized prostate cancer (PCa); yet data on patients undergoing focal therapy (FT) are sparse. Objective: To evaluate the treatment decision satisfaction and regret among patients who underwent FT for PCa with high-intensity focused ultrasound (HIFU) or cryoablation (CRYO). Design setting and participants: We identified consecutive patients who underwent HIFU or CRYO FT as the primary treatment for localized PCa at three US institutions. A survey with validated questionnaires, including the five-question Decision Regret Scale (DRS), International Prostate Symptom Score (IPSS), and International Index of Erectile Function (IIEF-5), was mailed to the patients. The regret score was calculated based on the five items of the DRS, and regret was defined as a DRS score of >25. Outcome measurements and statistical analysis: Multivariable logistic regression models were applied to assess the predictors of treatment decision regret. Results and limitations: Of 236 patients, 143 (61%) responded to the survey. Baseline characteristics were similar between responders and nonresponders. During a median (interquartile range) follow-up of 43 (26-68) mo, the treatment decision regret rate was 19.6%. On a multivariable analysis, higher prostate-specific antigen (PSA) at nadir after FT (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.1-2, p = 0.009), presence of PCa on follow-up biopsy (OR 3.98, 95% CI 1.5-10.6, p = 0.006), higher post-FT IPSS (OR 1.18, 95% CI 1.01-1.37, p = 0.03), and newly diagnosed impotence (OR 6.67, 95% CI 1.57-27, p = 0.03) were independent predictors of treatment regret. The type of energy treatment (HIFU/CRYO) was not a predictor of regret/satisfaction. Limitations include retrospective abstraction. Conclusions: FT for localized PCa is well accepted by the patients, with a low regret rate. Higher PSA at nadir, presence of cancer on follow-up biopsy, bothersome postoperative urinary symptoms, and impotence after FT were independent predictors of treatment decision regret. Patient summary: In this report, we looked at the factors affecting satisfaction and regret in patients with prostate cancer undergoing focal therapy. We found that focal therapy is well accepted by the patients, while presence of cancer on follow-up biopsy as well as bothersome urinary symptoms and sexual dysfunction can predict treatment decision regret.

Transperineal vs transrectal magnetic resonance and ultrasound image fusion prostate biopsy: a pair-matched comparison.

The objective of this study was to compare transperineal (TP) versus transrectal (TR) magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) fusion prostate biopsy (PBx). Consecutive men who underwent prostate MRI followed by a systematic biopsy. Additional target biopsies were performed from Prostate Imaging Reporting & Data System (PIRADS) 3-5 lesions. Men who underwent TP PBx were matched 1:2 with a synchronous cohort undergoing TR PBx by PSA, Prostate volume (PV) and PIRADS score. Endpoint of the study was the detection of clinically significant prostate cancer (CSPCa; Grade Group ≥ 2). Univariate and multivariable analyses were performed. Results were considered statistically significant if p < 0.05. Overall, 504 patients met the inclusion criteria. A total of 168 TP PBx were pair-matched to 336 TR PBx patients. Baseline demographics and imaging characteristics were similar between the groups. Per patient, the CSPCa detection was 2.1% vs 6.3% (p = 0.4) for PIRADS 1-2, and 59% vs 60% (p = 0.9) for PIRADS 3-5, on TP vs TR PBx, respectively. Per lesion, the CSPCa detection for PIRADS 3 (21% vs 16%; p = 0.4), PIRADS 4 (51% vs 44%; p = 0.8) and PIRADS 5 (76% vs 84%; p = 0.3) was similar for TP vs TR PBx, respectively. However, the TP PBx showed a longer maximum cancer core length (11 vs 9 mm; p = 0.02) and higher cancer core involvement (83% vs 65%; p < 0.001) than TR PBx. Independent predictors for CSPCa detection were age, PSA, PV, abnormal digital rectal examination findings, and PIRADS 3-5. Our study demonstrated transperineal MRI/TRUS fusion PBx provides similar CSPCa detection, with larger prostate cancer core length and percent of core involvement, than transrectal PBx.

The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease.

Adequate vitamin D levels may promote cardiovascular health by improving endothelial function and down-regulating inflammation. The objective of this pilot trial was to investigate the effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease (CAD). Using a double-blind placebo wait-list control design, 90 subjects with CAD and vitamin D deficiency (< 20 ng/ml) were randomized 1:1 to 50,000 IU of oral ergocalciferol or placebo weekly for 12 weeks. Endothelial function (reactive hyperemia peripheral arterial tonometry, RH-PAT), circulating adhesion molecules, and pro-inflammatory cytokines were measured at baseline and 12 weeks. The median increase in serum 25-vitamin D from baseline was 26 ± 17 ng/ml in the active group and 4 ± 8 ng/ml in the placebo group (between-group difference = 22 ng/ml, p < 0.001). The median within-subject change in RH-PAT score was 0.13 ± 0.73 with active treatment and -0.04 ± 0.63 with placebo (between-group difference = 0.17, p = 0.44). Within-group and between-group differences in intercellular adhesion molecule levels were greater with placebo (between-group difference = 6 ng/ml, p = 0.048). Vascular cell adhesion molecule levels decreased in both groups by a similar magnitude (median difference between groups = 8.5 ng/ml, p = 0.79). There was no difference between groups in magnitude of reduction in interleukin (IL)-12 (-8.6 ng/ml, p = 0.72) and interferon-gamma (0.52 ng/ml, p = 0.88). No significant differences in blood pressure, e-selectin, high-sensitivity c-reactive protein, IL-6 or the chemokine CXCL-10 were found with treatment. In conclusion, repleting vitamin D levels in subjects with CAD failed to demonstrate any benefits on surrogate markers of cardiovascular health. These results question the role of vitamin D supplementation in modifying cardiovascular disease.