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BACKGROUND: Utilization of active surveillance (AS) for prostate cancer is increasing. Optimal selection criteria for this approach are undefined and questions remain on how best to expand inclusion beyond typical men with very low- or low-risk disease. We sought to review the current experience with AS for men with intermediate-risk featuresMethods:PubMed was queried for all relevant original publications describing outcomes for men with prostate cancer managed with AS. Outcomes for patients with intermediate-risk features as defined by the primary investigators were studied when available and compared with similar risk men undergoing immediate treatment. RESULTS: Cancer-specific survival for men managed initially with AS is similar to results published with immediate radical intervention. A total of five published AS series describe some outcomes for men with intermediate-risk features. Definitions of intermediate risk vary between studies. Men with Gleason 7 disease experience higher rates of clinical progression and are more likely to undergo treatment over time. Intermediate-risk men with Gleason 6 disease have similar outcomes to low-risk men. Men with Gleason 7 disease appear at higher risk for metastatic disease. Novel technologies including imaging and biomarkers may assist with patient selection and disease surveillance. CONCLUSIONS: The contemporary experiences of AS for men with intermediate-risk features suggest that although these men are at higher risk for eventual prostate-directed treatment, some are not significantly compromising chances for longer-term cure. Men with more than minimal Gleason pattern 4, however, must be carefully selected and surveyed for early signs of progression and may be at increased risk of metastases. Incorporating information from advanced imaging and biomarker technology will likely individualize future treatment decisions while improving overall surveillance strategies.

Introduction: The use of systematic biopsies in addition to targeted biopsies is based on multiple studies showing that 15-20% of "clinically significant" cancers are missed on targeted biopsies. Concern about these 'missed' cancers drives many interventions. This includes systematic biopsies in men with negative imaging and in men having targeted biopsies, and drives a preference for total gland treatment in men who may be candidates for partial gland ablation. This article summarizes recent genomic and clinical data indicating that, despite "clinically significant" histology, MRI invisible lesions are genomically and clinically favorable. These studies have demonstrated that the genetic aberrations associated with cancer visibility are the same aberrations that drive cancer invasiveness and metastasis. Thus invisible cancers, even if undiagnosed at baseline, are in most cases indolent and pose little threat to the patient. The implications are that patients should be monitored with imaging rather than systematic biopsy, and subject to repeat targeted biopsy for evidence of MR progression. Patients prefer this strategy. It has many advantages in terms of reduced burden of care, cost, psychological benefits, and less diagnosis of insignificant cancer., Conclusion: It is now appropriate to abandon systematic biopsies in most patients., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Androgen deprivation therapy (ADT) is foundational in the management of advanced prostate cancer (PCa) and has benefitted from a recent explosion in scientific advances. These include approval of new therapies that suppress testosterone (T) levels or inactivate its function, improvements in diagnostic and assay technologies, identification of lower therapeutic targets for T, discovery of the relevance of germline genetic mutations and identification of the benefits of sequential and combination therapies., Methods: This review discusses the clinical profiles of the most up-to-date options for ADT, best practices for managing patients with advanced PCa and future directions in therapy., Results and Conclusions: Modern assay technologies reveal that bilateral orchiectomy results in a serum T level of approximately 15 ng/dL as compared to the historical definition of castration of T < 50 ng/dL. Evidence shows that lowering T levels to <20 ng/dL improves patient survival and delays disease progression. Routine monitoring of T in addition to prostate-specific antigen throughout treatment is important to ensure continuing efficacy of T suppression. New drugs that inhibit androgen signaling in combination with traditional ADT suppress T activity to near zero and have significantly improved patient survival. When personalizing ADT regimens physicians should consider a number of factors including initiation and duration of ADT, monitoring of T levels and PSA, the possibility of switching monotherapies if a patient does not achieve adequate T suppression, and consideration of intermittent vs. continuous ADT according to patients' lifestyles, comorbidities, risk factors and tolerance to treatment.

Background: Based on the findings of different trials in biopsy naïve patients, target biopsy (TB) plus random biopsy (RB) during mpMRI-guided transrectal ultrasound fusion biopsy (FB) are often also adopted for the biopsy performed during active surveillance (AS) programs. At the moment, a clear consensus on the extent and modalities of the procedure is lacking., Objective: To evaluate the increase in diagnostic accuracy achieved by perilesional biopsy (PL) and different RB schemes during FB performed in AS protocol., Design, Setting, and Participants: We collected prospectively the data of 112 consecutive patients with low- or very-low-risk prostate cancer; positive mpMRI underwent biopsy at a single academic institution in the context of an AS protocol., Intervention(s): mpMRI/transrectal US FB with Hitachi RVS system with 3 TB and concurrent transrectal 24-core RB., Outcome Measurements and Statistical Analysis: The diagnostic yield of the different possible biopsy schemes (TB only; TB + 4 perilesional (PL) cores; TB + 12-core RB; TB + 24-core RB) was compared by the McNemar test. Univariable and multivariable regression analyses were adopted to identify predictors of any cancer, Gleason grade group (GGG) ≥2 cancers, and the presence of GGG≥2 cancers in the larger schemes only., Results and Limitations: The detection rate of GGG ≥2 cancers increased to 30%, 39%, and 49% by adding 4 PL cores, 14, and 24 RB cores, respectively, to TB cores (all p values <0.01). On the whole, TB alone, 14-core RB, and 24-core-RB identified 38%, 47%, and 56% of all the GGG ≥2 cancers. Such figures increased to 62% by adding to TB 4 PL cores, and to 80% by adding 14 RB cores. Most of the differences were observed in PI-RADS 4 lesions., Conclusions: We found that PL biopsy increased the detection rate of GGG ≥2 cancers as compared with TB alone. However, the combination of those cores missed a large percentage of the CS cancers identified with larger RB cores, including a 20% of CS cancers diagnosed only by the combination of TB plus 24-core RB., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Multiparametric magnetic resonance imaging (mpMRI) provides enhanced diagnostic accuracy in the detection of prostate cancer, but is not devoid of limitations. Given the recent evolution of non-MRI imaging techniques, this critical review of the literature aimed at summarizing the available evidence on ultrasound-based and nuclear medicine imaging technologies in the initial diagnosis of PCa., Methods: Three databases (PubMed®, Web of Science™, and Scopus®) were queried for studies examining their diagnostic performance in the primary diagnosis of PCa, weighted against a histological confirmation of PCa diagnosis, using a free-text protocol. Retrospective and prospective studies, both comparative and non-comparative, systematic reviews (SR) and meta-analysis (MA) were included. Based on authors' expert opinion, studies were selected, data extracted, and results qualitatively described., Results: Micro-ultrasound (micro-US) appears as an appealing diagnostic strategy given its high accuracy in detection of PCa, apparently non-inferior to mpMRI. The use of multiparametric US (mpUS) likely gives an advantage in terms of effectiveness coming from the combination of different modalities, especially when certain modalities are combined. Prostate-specific membrane antigen (PSMA) PET/CT may represent a whole-body, one-step approach for appropriate diagnosis and staging of PCa. The direct relationship between lesions avidity of radiotracers and histopathologic and prognostic features, and its valid diagnostic performance represents appealing characteristics. However, intrinsic limits of each of these techniques exist and further research is needed before definitively considering them reliable tools for accurate PCa diagnosis. Other novel technologies, such as elastography and multiparametric US, currently relies on a limited number of studies, and therefore evidence about them remains preliminary., Conclusion: Evidence on the role of non-MRI imaging options in the primary diagnosis of PCa is steadily building up. This testifies a growing interest towards novel technologies that might allow overcoming some of the limitations of current gold standard MRI imaging., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: An informed decision regarding a treatment option requires data on its long-term efficacy and side-effect profile. While the side-effects of robotic radical prostatectomy have been well-quantified, the data on its long-term efficacy are lacking. We here provide 15-year oncological outcomes of clinically-localized prostate cancer (CLPCa) patients treated with robot-assisted laparoscopic prostatectomy (RALP)., Methods: We treated 1,807 men with CLPCa with RALP between 2001 and 2005 and prospectively collected follow-up data through 2020. We examined the rates of biochemical failure (BCF), metastatic progression, secondary therapy use, PCa-specific mortality (PCSM), and overall survival (OS) using Kaplan-Meier and competing-risk cumulative incidence methods as appropriate., Results: The median follow-up was 14.1 years. Six hundred eight and 312 men had D'Amico intermediate- and high-risk disease, respectively. Overall, the 15-year rates of BCF, metastasis, secondary therapy use, PCSM, and OS were 28.1%, 4.0%, 16.3%, 2.5%, and 82.1%, respectively. The rates of oncologic failure increased with increasing D'Amico (preoperative) and Diaz (postoperative) risk scores - BCF, metastasis, and PCSM rates in D'Amico low-, intermediate-, and high-risk groups at 15-years were 15.2%, 38.3%, and 44.1% [BCF], 1.1%, 4.1%, and 13.0% [metastasis], and 0.5%, 3.4%, and 6.6% [PCSM], respectively, and in Diaz risk groups 1, 2, 3, 4, and 5 were 5.5%, 20.6%, 41.8%, 66.9%, and 89.2% [BCF], 0%, 0.5%, 3.2%, 20.5%, and 60.0% [metastasis], and 0%, 0.8%, 0.6%, 13.5%, and 37.5% [PCSM], respectively. The OS rates in D'Amico low-to-high and Diaz 1-to-5 risk groups at 15-years were 85.9%, 78.6%, and 75.2%, and 89.4%, 83.2%, 80.6%, 67.2%, and 23.4%, respectively., Conclusions: Men diagnosed with clinically-localized prostate cancer in the contemporaneous PSA-screening era and treated with RALP achieve durable long-term oncological control. The data reported here (in a risk-stratified manner) represent the longest follow-up after robotic radical prostatectomy, and as such, should be of value when counseling patients regarding expected oncologic outcomes from RALP., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Nowadays a tool able to predict the risk of lymph-node invasion (LNI) in patients underwent target biopsy (TB) only before radical prostatectomy (RP) is still lacking. Our aim is to develop a model based on mp-MRI and target biopsy (TB) alone able to predict the risk of LNI., Methods: We retrospectively extracted data of patients with preoperative positive mp-MRI and TB only who underwent RARP with ePLND from April 2014 to March 2020. A logistic regression model was performed to evaluate the impact of pre- and intra-operative factors on the risk of LNI. Model discrimination was assessed using an area under (AUC) the ROC curve. A nomogram, and its calibration plot, to predict the risk of LNI were generated based on the logistic model. A validation of the model was done using a similar cohort., Results: 461 patients were included, of which 52 (11.27) had LNI. After logistic regression analysis and multivariable model DRE, PI-RADS, seminal vesicle invasion, PSA and worst GS at I and II target lesions were significant predictors of LNI. The AUC was 0.74 [0.67-0.81] 95% CI. The calibration plot shows that our model is very close to the ideal one which is in the 95% CI. After the creation of a visual nomogram, the cut-off to discriminate between the risk or not of LNI was set with Youden index at 60 points that correspond to a risk of LNI of 7%. The model applied on a similar cohort shown a LH+ of 2.58 [2.17-2.98] 95% CI., Conclusions: Our nomogram for patients undergoing MRI-TB only takes into account clinical stage, SVI at MRI, biopsy Gleason pattern and PSA and it is able to identify patients with risk of LNI when a score higher than 7% is achieved., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Prostate cancer remains the most frequently diagnosed cancer among men. High-Intensity Focused Ultrasound (HIFU) has emerged as a thermal ablative technique for partial-gland-ablation (PGA), aiming to minimize collateral damage while maximizing tumor control. Monitoring after HIFU PGA relies on serial PSA testing, multiparametric-MRI, and biopsies. The diagnostic accuracy of MRI for clinically-significant cancer(csPCa) recurrence is challenging., Objective: This systematic review and meta-analysis aim to evaluate the accuracy of MRI in detecting early recurrence of localized prostate cancer following HIFU PGA., Methods: Adhering to PRISMA guidelines, a comprehensive literature search was conducted until May 8 th 2024 using MEDLINE and Scopus. The inclusion criteria encompassed randomized controlled trials and cohort studies involving men diagnosed with localized prostate cancer who had as primary treatment HIFU PGA. The primary outcome measures included the sensitivity, specificity, positive-predictive value (PPV), and negative-predictive value (NPV) of MRI for csPCa(ISUP ≥ 2) based on biopsy results. We pooled data from studies with sufficient csPCa and csPCa-free patients (≥5) post HIFU for statistical analysis., Results: Fifteen studies meet the inclusion criteria, encompassing 1093 patients and 12 studies were eligible for meta-analysis. MRI sensitivity in detecting clinically-significant prostate cancer (csPCa) recurrence post HIFU PGA varied widely (0-89%), with a pooled sensitivity of 0.52 (95% CI:0.36-0.68). Specificity ranged from 44% to 100%, with a pooled specificity of 0.81 (95% CI:0.68-0.91). The pooled NPV was 0.82 (95% CI:0.72-0.90), and the pooled PPV was 0.50 (95% CI:0.35-0.65). Three studies reported in-field diagnostic performance with sensitivities ranging from 0.42 to 0.80 and specificities from 0.45 to 0.97., Conclusion: MRI accuracy for clinically-significant recurrence after partial gland ablation with HIFU for localized prostate cancer shows low diagnostic performance in the treated lobe with pooled sensitivity of 0.52 (95% CI:0.36-0.68) and specificity of 0.81 (95% CI:0.68-0.91). Limits of this review include the low number of studies reporting about site of recurrence in or out of the treated lobe., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Androgen-receptor pathway inhibitors (ARPIs) have dramatically changed the management of advanced/metastatic prostate cancer (PCa). However, their cardiovascular toxicity remains to be clarified., Objective: To analyze and compare the risks of cardiovascular events secondary to treatment of PCa patients with different ARPIs., Methods: In August 2023, we queried PubMed, Scopus, and Web of Science databases to identify randomized controlled studies (RCTs) that analyze PCa patients treated with abiraterone, apalutamide, darolutamide, and enzalutamide. The primary outcomes of interest were the incidence of cardiac disorder, heart failure, ischemic heart disease (IHD), atrial fibrillation (AF), and hypertension. Network meta-analyses (NMAs) were conducted to compare the differential outcomes of each ARPI plus androgen deprivation therapy (ADT) compared to standard of care (SOC)., Results: Overall, 26 RCTs were included. ARPIs were associated with an increased risk of cardiac disorders (RR: 1.74, 95% CI: 1.13-2.68, p = 0.01), heart failure (RR: 2.49, 95% CI: 1.05-5.91, p = 0.04), AF (RR: 2.15, 95% CI: 1.14-4.07, p = 0.02), and hypertension (RR: 2.06, 95% CI: 1.67-2.54, p < 0.01) at grade ≥3. Based on NMAs, abiraterone increased the risk of grade ≥3 cardiac disorder (RR:2.40, 95% CI: 1.42-4.06) and hypertension (RR:2.19, 95% CI: 1.77-2.70). Enzalutamide was associated with the increase of grade ≥3 AF(RR: 3.17, 95% CI: 1.05-9.58) and hypertension (RR:2.30, 95% CI: 1.82-2.92)., Conclusions: The addition of ARPIs to ADT increases the risk of cardiac disorders, including IHD and AF, as well as hypertension. Each ARPI exhibits a distinct cardiovascular event profile. Selecting patients carefully and vigilant monitoring for cardiovascular issues is imperative for those undergoing ARPI + ADT treatment., (© 2024. The Author(s).)

Background: Since its initial description the prostate biopsy technique for detection of prostate cancer (PCA) has constantly evolved. Multiparametric magnetic resonance imaging (mpMRI) has been proven to have a sensitivity exceeding 90% to detect the index lesion. This narrative review discusses the evidence around several biopsy strategies, especially in the context of patients that might be eligible for focal therapy., Method: A non-systematic literature research was performed on February 15th 2024 using the Medical Literature Analysis and Retrieval System Online (Medline), Web of Science and Google Scholar., Results: The transrectal (TR) route is associated with an increased postoperative sepsis rate, even with adequate antibiotic prophylaxis. The transperineal (TP) route is now recommended by international guidelines, firstly for its decreased rate of urosepsis. Recent evidence shows a non-inferiority of TP compared to TR route, and even a higher detection rate of clinically significant PCA (csPCA) in the anterior and apical region, that are usually difficult to target using the TR route. Several targeting techniques (cognitive, software-fusion or in-bore) enhance our ability to provide an accurate risk assessment of prostate cancer aggressiveness and burden, while reducing the number of cores and reducing the number of clinically insignificant prostate cancer (ciPCA). While MRI-TB have proven their role, the role of systematic biopsies (SB) is still important because it detects 5-16% of csPCA that would have been missed by MRI-TB alone. The strategies of SB depend mainly on the route used (TR vs. TP) and the number of cores to be collected (10-12 cores vs. saturation biopsies vs. trans-perineal template mapping-biopsies or Ginsburg Protocol vs. regional biopsies)., Conclusion: Several biopsy strategies have been described and should be known when assessing patients for focal therapy. Because MRI systematically under evaluates the lesion size, systematic biopsies, and especially perilesional biopsies, can help to increase sensitivity at the cost of an increased number of cores., (© 2024. The Author(s).)

Introduction: To date, radio-recurrent prostate cancer (PCa) ranks as the fourth most common urological malignancy when considering the number of men with localized PCa who undergo radiation treatment and subsequently experience a biochemical recurrence. This systematic review aimed to summarize available evidence about the outcomes of local salvage strategies in patients with local PCa recurrence following primary external-beam radiation therapy (EBRT)., Methods: We conducted a comprehensive bibliographic search on MEDLINE, Scopus, and Web of Science Core Collection databases in October 2023 to identify studies published in the last 20 years evaluating outcomes of local salvage procedures in patients with locally radio-recurrent PCa following EBRT. The meta-analysis was performed using ProMeta 3 software when two or more studies reported the same outcome. The effect size (ES) was estimated using rates reported with its 95% confidence interval (CI)., Results: Overall, 28 studies (6 prospective and 22 retrospective) including 1544 patients were included in the review. Two-year recurrence-free survival (RFS) was 84.0% (95% CI: 67.0-93.0%), 69.0% (95% CI: 42.0-87.0%), 58.0% (95% CI: 43.0-71.0%), and 45% (95% CI: 38.0-52.0%), for patients undergoing brachytherapy (BT), EBRT, Cryotherapy and High-Intensity Focused Ultrasound (HIFU), respectively. After salvage prostatectomy, RFS ranged from 75% to 78.5% at a median follow-up ranging from 18 to 35 months. Estimates for severe gastrointestinal toxicity were 2%, 3%, 3%, 4%, and 11% following cryotherapy, BT, HIFU, EBRT, and salvage radical prostatectomy, respectively., Conclusions: In patients who underwent EBRT as primary treatment, prostate salvage re-irradiation through BT or EBRT represents the modality providing the best balance between efficacy and safety. Unfortunately, due to the low level of evidence, strong recommendations regarding the choice of any of these techniques cannot be made., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: There are many FDA-approved drugs for advanced prostate cancer (PC), yet public interest in these drugs is not well understood. We compared public interest and state-level predictors of interest in five common oral adjunctive hormonal therapies., Methods: Google Trends™ was queried for: "Enzalutamide", "Abiraterone Acetate", "Bicalutamide", "Apalutamide", and "Darolutamide" in the United States from January 2004 to November 2022. Data are presented as relative search index (RSI) by month. RSI ranges from 0 to 100 with 100 being peak popularity, 50 being half of the peak popularity, and 0 representing insufficient data to be determined., Results: Several drugs abruptly increased in popularity following FDA approval including abiraterone, enzalutamide, and apalutamide. All drugs decreased in popularity from January 2020 to July 2020, corresponding with the COVID-19 pandemic. In the most recent 5 years, enzalutamide and abiraterone were the most common searched drugs, with bicalutamide a close 3 rd place. States that did not expand Medicaid were significantly more likely to have bicalutamide as the top search drug vs. states that expanded Medicaid (p = 0.012). Across all states with data (n = 39), higher bicalutamide RSIs were significantly associated with lower household income (r = 0.385, p = 0.02) and greater percent of uninsured adults (r = 0.426, p = 0.007). This is the first study using Google Trends to compare advanced PC drugs by search popularity., Conclusions: Despite the emergence of more effective medications, bicalutamide remains relatively popular, particularly in states with lower household income, more uninsured adults, or those that did not expand Medicaid, possibly due to its lower cost., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To review the literature on salvage treatments after focal therapy (FT) for prostate cancer (PCa)., Materials and Methods: A non-systematic literature review was conducted on PubMed, Scopus, and Web of Science up to March 15, 2024, for studies that assessed salvage treatment outcomes in patients with recurrent PCa after primary FT. Original prospective and retrospective studies with more than 10 patients were included. Reviews, editorial comments, conference abstracts, and studies focusing solely on whole-gland treatments were excluded., Results: Twenty-one studies with a total of 1012 patients were included. The most reported salvage treatments were salvage radical prostatectomy followed by re-do ablation therapy. Only one study evaluated salvage radiation therapy. Except for one prospective study, all studies were retrospective. Oncological outcomes showed acceptable biochemical recurrence rates. Functional outcomes varied, with significant impacts observed on erectile function across modalities, though continence rates were less impacted. Complications were generally low across all treatment options., Conclusion: Salvage treatment post-primary FT is feasible, safe, and has reasonable oncologic outcomes. However, significant declines in sexual function are common, while continence is comparatively less affected. The literature primarily consists of retrospective studies; hence, future research should focus on large-scale prospective evaluations to better define treatment protocols and improve patient outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Androgen signaling is central to prostate cancer and men's health. Prior data indicates that increasing body fat is unfavorable in the localized setting yet associated with favorable outcomes in men with metastatic disease. Understanding the biological links between adiposity and prostate cancer may optimize the therapeutic index with ASI. We hypothesized that host adiposity and androgen synthesis are linked to the efficacy and toxicity of ASI for men with metastatic castration-resistant prostate cancer (mCRPC)., Methods: A post-hoc analysis was done of NCT02703623 where men with mCRPC (n = 186) were treated for 8 weeks with abiraterone acetate, prednisone, and apalutamide (AAPA), and a satisfactory response was defined as a PSA decline >50%. Body composition was measured on baseline CT scans. Germline DNA WES was performed with a focus on variants in steroidogenic genes. Adipokine levels were measured in pre-treatment plasma., Results: Germline polymorphisms in 3 genes involved in androgen synthesis (AKR1C3 rs12529, CYP17A1 rs6162, SRD5A2 rs523349) were associated with differences in body composition at baseline on ADT alone (prior to receipt of AAPA). Elevated subcutaneous adipose tissue index (SATi, p = 0.02), visceral adipose tissue index (VATi, p = 0.03), and BMI (p = 0.04) were associated with satisfactory response to AAPA. Leptin had positive correlation with VATi (r = 0.47) and SATi (r = 0.48)., Conclusion: Inherited polymorphisms in androgen synthesis correlated with differences in body composition after exposure to ADT and warrant further investigation as candidate markers for body composition toxicity. Elevated subcutaneous and visceral adiposity were associated with improved response to ASI., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: To report the effects of a 12-week high-intensity interval training (HIIT) program on cardiometabolic biomarkers in patients with prostate cancer on active surveillance (AS) from the Exercise During Active Surveillance for Prostate Cancer (ERASE) Trial., Methods: Fifty-two men with prostate cancer on AS were randomized to either an exercise (HIIT; n = 26) or usual care (UC; n = 26) group. The HIIT intervention consisted of progressive, supervised, aerobic HIIT at an intensity of 85 to 95% VO 2peak for 28 to 40 min per session performed three times/week for 12 weeks. Blood samples were collected at baseline and postintervention to analyze cardiometabolic biomarkers. Analysis of covariance was used to examine between-group mean differences., Results: Blood data were obtained from 49/52 (94%) participants at postintervention. Participants were aged 63.4 ± 7.1 years and 40% were obese. The HIIT group attended 96% of the planned exercise sessions. No significant between-group changes in weight were observed after the intervention. Compared to UC, HIIT significantly improved total cholesterol (-0.40 mmol/L; 95% confidence interval[CI], -0.70 to -0.10; p = 0.011), non-high-density lipoprotein-c (-0.35 mmol/L; 95% CI, -0.60 to -0.11; p = 0.006), insulin (-13.6 pmol/L; 95% CI, -25.3 to -1.8; p = 0.025), insulin-like growth factor (IGF)-1 (-15.0 ng/mL; 95% CI, -29.9 to -0.1; p = 0.048), and IGF binding protein (IGFBP)-3 (152.3 ng/mL; 95% CI, 12.6 to 292.1; p = 0.033). No significant differences were observed for fasting glucose, HbA1c, other lipid markers, IGFBP-1, adiponectin, and leptin., Conclusions: The ERASE Trial showed that a 12-week aerobic HIIT program improved several cardiometabolic biomarkers in patients with prostate cancer on AS that may contribute to cardiovascular health benefits and potentially influence signaling pathways in the progression of prostate cancer. Further research is needed to confirm the effects of exercise on cardiometabolic markers in men with prostate cancer on AS and determine if these effects are associated with improved long-term clinical outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Although multiparametric magnetic resonance imaging (mpMRI) is recommended for primary risk stratification and follow-up in Active Surveillance (AS), it is not part of common AS inclusion criteria. The objective was to compare AS eligibility by systematic biopsy (SB) and combined MRI-targeted (MRI-TB) and SB within real-world data using current AS guidelines., Methods: A retrospective multicenter study was conducted by a German prostate cancer (PCa) working group representing six tertiary referral centers and one outpatient practice. Men with PCa and at least one MRI-visible lesion according to Prostate Imaging Reporting and Data System (PI-RADS) v2 were included. Twenty different AS inclusion criteria of international guidelines were applied to calculate AS eligibility using either a SB or a combined MRI-TB and SB. Reasons for AS exclusion were assessed., Results: Of 1941 patients with PCa, per guideline, 583-1112 patients with PCa in both MRI-TB and SB were available for analysis. Using SB, a median of 22.1% (range 6.4-72.4%) were eligible for AS. Using the combined approach, a median of 15% (range 1.7-68.3%) were eligible for AS. Addition of MRI-TB led to a 32.1% reduction of suitable patients. Besides Gleason Score upgrading, the maximum number of positive cores were the most frequent exclusion criterion. Variability in MRI and biopsy protocols potentially limit the results., Conclusions: Only a moderate number of patients with PCa can be monitored by AS to defer active treatment using current guidelines for inclusion in a real-world setting. By an additional MRI-TB, this number is markedly reduced. These results underline the need for a contemporary adjustment of AS inclusion criteria., (© 2021. The Author(s).)

Background: Enzalutamide and abiraterone acetate plus prednisone (AAP) have similar efficacy in metastatic castration-resistant prostate cancer (mCRPC), but different mechanisms of action. The aim was to compare patient-reported health-related quality of life (HRQoL) in men treated with enzalutamide vs AAP for mCRPC., Methods: We systematically reviewed the literature in June 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Patient-reported outcomes (PROs) until the last follow-up were summarised in a narrative synthesis. Short-term changes (12 weeks) in HRQoL, measured by the Functional Assessment of Cancer Therapy-Prostate total score (FACT-P), were compared between treatment groups and were analysed for enzalutamide and AAP in separate meta-analyses. Higher FACT-P scores indicate better HRQoL., Results: Eight studies were included in the systematic review, four of which were randomised clinical trials (RCTs) eligible for the meta-analyses. The meta-analyses showed mean within-subject FACT-P changes from baseline to week 12 of -1.3 points (95% confidence interval [CI] -2.7; 0.1) for enzalutamide and 4.7 points (95% CI -0.1; 9.6) for AAP. One RCT and three non-randomised studies directly compared enzalutamide with AAP. The RCT showed better short-term HRQoL for AAP (6.8 FACT-P-points, 95% CI 1.7; 11.8) and better long-term HRQoL for AAP in men ≥75 years (7.35 FACT-P-points, 95% CI 2.59; 12.11). The non-randomised studies showed no difference in long-term HRQoL but had all a serious risk of bias. Limitations of the included studies include that the PRO in the included trials were inconsistently reported and that only one study defined the HRQoL measures in their published protocol., Conclusions: AAP seems to be associated with better short-term HRQoL than enzalutamide. This difference was not apparent at longer follow-up, but the long-term studies had serious risks of bias., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The reduction of overtreatment by active surveillance (AS) is limited in patients with low-risk prostate cancer (PCa) due to high rates of patients switching to radical treatment. MRI improves biopsy accuracy and could therewith affect inclusion in or continuation of AS. We aim to assess the effect of MRI with target biopsies on the total rate of patients discontinuing AS, and in particular discontinuation due to Grade Group (GG) reclassification., Methods: Three subpopulations included in the prospective PRIAS study with GG 1 were studied. Group A consists of patients diagnosed before 2009 without MRI before or during AS. Group B consists of patients diagnosed without MRI, but all patients underwent MRI within 6 months after diagnosis. Group C consists of patients who underwent MRI before diagnosis and during follow-up. We used cumulative incidence curves to estimate the rates of discontinuation., Results: In Group A (n = 500), the cumulative probability of discontinuing AS at 2 years is 27.5%; GG reclassification solely accounted for 6.9% of the discontinuation. In Group B (n = 351) these numbers are 30.9 and 22.8%, and for Group C (n = 435) 24.2 and 13.4%. The three groups were not randomized, however, baseline characteristics are highly comparable., Conclusions: Performing an MRI before starting AS reduces the cumulative probability of discontinuing AS at 2 years. Performing an MRI after already being on AS increases the cumulative probability of discontinuing AS in comparison to not performing an MRI, especially because of an increase in GG reclassification. These results suggest that the use of MRI could lead to more patients being considered unsuitable for AS. Considering the excellent long-term cancer-specific survival of AS before the MRI era, the increased diagnostic accuracy of MRI could potentially lead to more overtreatment if definitions and treatment options of significant PCa are not adapted., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Luteinizing hormone-releasing hormone (LHRH)-agonists in prostate cancer (PCa) patients induce sarcopenic obesity. The effect of LHRH-antagonist on body composition has never been explored. We evaluated changes in fat (FBM) and lean body mass (LBM) in PCa patients undergoing Degarelix., Methods: This is a single-center prospective study, enrolling 29 non-metastatic PCa patients eligible to LHRH-antagonist from 2017 to 2019. All patients received monthly subcutaneous injection of Degarelix for 12 months. Changes in FBM and LBM between baseline and 12-month Degarelix, as measured by dual-energy x-ray absorptiometry, were the co-primary endpoints. Secondary endpoints were changes in serum lipids, glucose profile and follicle-stimulating hormone (FSH). Appendicular lean mass index (ALMI) and ALMI/FBM ratio were assessed as post-hoc analyses. Linear mixed models with random intercept tested for estimated least squared means differences (EMD)., Results: FBM significantly increased after 12 months (EMD +2920.7, +13.8%, p < 0.001), whereas LBM remained stable (EMD -187.1, -0.3%, p = 0.8). No differences occurred in lipid profile. Glycated hemoglobin significantly increased and serum FSH significantly decreased. A significant inverse relationship was found between serum FSH and ALMI/FBM ratio after 12 month (r = -0.44, p = 0.02)., Conclusions: The BLADE study prospectively evaluated changes in body composition after LHRH-antagonist. LHRH-antagonist therapy is associated to an increased risk of obesity and diabetes, but lean body mass and serum lipids are not affected. This may represent an additional evidence supporting the reduced cardiovascular risk associated with LHRH-antagonist. The role of FSH in influencing sarcopenic obesity in PCa after androgen deprivation deserves to be further explored., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: There is uncertainty on how multiparametric MRI (mpMRI) and MRI-targeted biopsy (MRI-TB) can be best used to manage low-risk prostate cancer patients on Active Surveillance (AS). We performed a scoping review to evaluate the benefits and harm associated with four different biopsy scenarios in which mpMRI can be implemented in AS., Methods: Medline, Embase and Cochrane Library databases (1 January 2013-18 September 2020) were searched. Included studies were on men with low-risk prostate cancer enrolled in AS, who had mpMRI ± MRI-TB and standard prostate biopsy (systematic transrectal ultrasound or transperineal saturation biopsy), at confirmatory or follow-up biopsy. Primary outcomes were the number of Gleason score upgrades and biopsies avoided., Results: Eight confirmatory biopsy studies and three follow-up biopsy studies were included. Compared to the benchmark of using standard biopsy (SB) for all men, the addition of MRI-TB increased the detection of Gleason score upgrades at both confirmatory (6/8 studies) and follow-up biopsy (3/3 studies), with increments of 1.7-11.8 upgrades per 100 men. 6/7 studies suggested that the use of a positive mpMRI to triage men for MRI-TB or SB alone would detect fewer Gleason score upgrades than benchmark at confirmatory biopsy, but the combination of MRI-TB and SB would detect more upgrades than the benchmark. For follow-up biopsy, the evidence on mpMRI triage biopsy scenarios was inconclusive due to the small number of included studies., Conclusions: The addition of MRI-TB to benchmark (SB for all men) maximises the detection of Gleason score upgrades at confirmatory and follow-up biopsy. When the use of mpMRI to triage men for a biopsy is desired, the combination of MRI-TB and SB should be considered for men with positive mpMRI at confirmatory biopsy. The evidence on mpMRI triage scenarios was inconclusive in the follow-up biopsy setting., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

Introduction: To determine associations between prostate cancer (PCa) tumor burden measured on biopsy or multiparametric magnetic resonance imaging (mpMRI) and outcomes in intermediate-risk (IR) International Society of Urological Pathology (ISUP) grade 2 men managed with primary radical prostatectomy (RP)., Methods: This retrospective, multicenter study was conducted in eight referral centers. The cohort included IR PCa patients who had ISUP 2 at biopsy. We defined biopsy tumor burden as low/high based on the absence/presence of more than 25% positive cores. Tumor burden on imaging was defined as low/high based on maximum lesion diameter, <15 mm and ≥15 mm at mpMRI, respectively. The histological endpoint of the study was adverse features at RP, defined as ≥pT3a stage and/or lymph node invasion and/or ISUP ≥3 at final pathology. The clinical endpoint was biochemical recurrence (BCR) after RP., Results: A total of 698 IR patients was included, of whom 335 (48%) had adverse features. In multivariate logistic regression analysis, there was no statistical association between tumor burden at biopsy and adverse features (p = 0.7). Tumor size ≥15 mm at mpMRI was significantly associated with adverse pathology (OR 1.65, 95%CI 1.14-2.39; p = 0.01). No significant association was observed between tumor burden at biopsy and BCR (p = 0.4). Tumor size ≥15 mm at mpMRI was significantly associated with BCR (HR 1.96, 95% CI 1.01-3.80; p = 0.04)., Conclusions: Our data support extending the inclusion criteria to ISUP 2 men with >25% positive cores, provided they have a low tumor size at mpMRI (<15 mm). Prospective studies should be performed to validate these findings., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Bipolar androgen therapy (BAT) is effective in a subset of metastatic castration-resistant prostate cancer (mCRPC) patients. Treatment selection biomarkers are needed due to other therapies that can be equally efficacious. We performed post-hoc analysis to determine whether baseline serum testosterone (T) is a treatment selection marker in the TRANSFORMER study, a randomized trial of abiraterone-pretreated mCRPC patients assigned to BAT (n = 94) or enzalutamide (n = 101). The findings suggest that patients with poor outcomes to abiraterone and serum T ≥ 20 ng/dL may benefit preferentially from BAT over enzalutamide. Baseline testosterone could be considered in the treatment selection process when BAT is an option., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Unlike in other mouse models of atherogenesis, it has recently been suggested that orchiectomy plays a role in accelerating atherosclerosis and inhibiting the progression of cardiovascular disease in the ApoE -/- :Ins2 +/Akita mouse model of hyperglycemia. Androgen-deprivation therapy (ADT) is a common treatment for prostate cancer, a population with high prevalence of cardiovascular disease and its risk factors. Our objectives were to test and further characterize the effects of pharmacological castration which is currently the acceptable modality to deliver ADT in the clinic., Methods: Male ApoE -/- :Ins2 +/Akita mice received one of three modes of ADT (gonadotropin-releasing hormone (GnRH)-antagonist (degarelix), GnRH-agonist (leuprolide), or bilateral orchiectomy) and were compared to corresponding untreated control mice (n = 9-13/group). Mice were followed for 5 months. Body weight, fasting blood glucose, glucose tolerance, serum C-peptide, leptin, and testosterone levels along with atherosclerotic aortic plaque size and characteristics were determined. In a separate experiment, the survival of mice, untreated and on ADT, was determined., Results: Castration was achieved for all three modes of ADT. However, degarelix-treated mice gained significantly less weight, had lower serum leptin levels and systolic blood pressure compared to orchiectomy and leuprolide-treated mice. ADT improved dysglycemia and atherosclerotic burden. GnRH-antagonist significantly improved survival compared to GnRH-agonist but not compared to orchiectomy., Conclusions: Further characterization of the ApoE -/- :Ins2 +/Akita mouse model confirms that pharmacological ADT ameliorated metabolic syndrome and cardiovascular complications. Improved dysglycemia and atherosclerosis associated with increased survival which was longest after degarelix followed by orchiectomy.

Background: Gonadotrophin releasing hormone (GnRH) agonists and antagonists reduce testosterone levels for the treatment of advanced and metastatic prostate cancer. Androgen deprivation therapy (ADT) is associated with increased risk of cardiovascular (CV) events and CV disease (CVD), especially in patients with preexisting CVD treated with GnRH agonists. Here, we investigated the potential relationship between serum levels of the cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NTproBNP), D-dimer, C-reactive protein (CRP), and high-sensitivity troponin (hsTn) and the risk of new CV events in prostate cancer patients with a history of CVD receiving a GnRH agonist or antagonist., Methods: Post-hoc analyses were performed of a phase II randomized study that prospectively assessed CV events in patients with prostate cancer and preexisting CVD, receiving GnRH agonist or antagonist. Cox proportional hazards models were used to determine whether the selected biomarkers had any predictive effect on CV events at baseline and across a 12-month treatment period., Results: Baseline and disease characteristics of the 80 patients who took part in the study were well balanced between treatment arms. Ischemic heart disease (66%) and myocardial infarction (37%) were the most common prior CVD and the majority (92%) of patients received CV medication. We found that high levels of NTproBNP (p = 0.008), and hsTn (p = 0.004) at baseline were associated with the development of new CV events in the GnRH agonist group but not in the antagonist. In addition, a nonsignificant trend was observed between higher levels of NTproBNP over time and the development of new CV events in the GnRH agonist group., Conclusions: The use of cardiac biomarkers may be worthy of further study as tools in the prediction of CV risk in prostate cancer patients receiving ADT. Analysis was limited by the small sample size; larger studies are required to validate biomarker use to predict CV events among patients receiving ADT.

Background: To understand the value of multiparametric magnetic resonance imaging (mpMRI) and targeted biopsies at recruitment on active surveillance (AS) outcomes., Materials and Methods: This retrospective single-center study enrolled two cohorts of 206 and 310 patients in AS. The latter group was submitted to mpMRI and targeted biopsies at recruitment. Kaplan-meier curves quantified progression-free survival (PFS) and Bioptic-PFS (B-PFS: no upgrading or >3 positive cores) in the two cohorts. Cox-regression analyses tested independent predictors of PFS and B-PFS. In patients submitted to radical prostatectomy (RP) after AS, significant cancer (csPCa) was defined as: GS ≥ 4 + 3 and/or pT ≥ 3a and/or pN+ . Logistic-regression analyses predicted csPCa at RP., Results and Limitations: Median time follow-up and median time of persistence in AS were 46 (24-70) and 36 (23-58) months, respectively. Patients submitted to mpMRI at AS begin, showed greater PFS at 1- (98% vs. 91%), 3- (80% vs. 57%), and 5-years (70% vs. 35%) follow-up, respectively (all p < 0.01). At Cox-regression analysis only confirmatory mpMRI± targeted biopsy (HR: 0.3; 95% CI 0.2-0.5; p < 0.01) at AS begin was an independent predictor of PFS. Globally, 50 (16%) vs. 128 (62%) and 26 (8.5%) vs. 64 (31%) [all p < 0.01] men in the two groups experienced any-cause and bioptic AS discontinuation, respectively. Patients submitted to confirmatory mpMRI experienced greater 1-(98% vs. 93%), 3-(90% vs. 75%), and 5-years (83% vs. 56%) B-PFS, respectively (all p < 0.01). At Cox-regression analysis, mpMRI±-targeted biopsy at AS begin was associated with B-PFS (HR: 0.3; 95% CI 0.2-0.6; p < 0.01). No differences were recorded in csPCa rates between the two groups (22% vs. 28%; p = 0.47). Limitations of the study are the single-center retrospective nature and the absence of long-term follow-up., Conclusions: Confirmatory mpMRI±-targeted biopsies are associated with higher PFS and B-PFS during AS. However, a non-negligible percentage of patients experience csPCa after switching to active treatment.

Background: Protocol-based active surveillance (AS) biopsies have led to poor compliance. To move to risk-based protocols, more accurate imaging biomarkers are needed to predict upgrading on AS prostate biopsy. We compared restriction spectrum imaging (RSI-MRI) generated signal maps as a biomarker to other available non-invasive biomarkers to predict upgrading or reclassification on an AS biopsy., Methods: We prospectively enrolled men on prostate cancer AS undergoing repeat biopsy from January 2016 to June 2019 to obtain an MRI and biomarkers to predict upgrading. Subjects underwent a prostate multiparametric MRI and a short duration, diffusion-weighted enhanced MRI called RSI to generate a restricted signal map along with evaluation of 30 biomarkers (14 clinico-epidemiologic features, 9 molecular biomarkers, and 7 radiologic-associated features). Our primary outcome was upgrading or reclassification on subsequent AS prostate biopsy. Statistical analysis included operating characteristic improvement using AUROC and AUPRC., Results: The individual biomarker with the highest area under the receiver operator characteristic curve (AUC) was RSI-MRI (AUC = 0.84; 95% CI: 0.71-0.96). The best non-imaging biomarker was prostate volume-corrected Prostate Health Index density (PHI, AUC = 0.68; 95% CI: 0.53-0.82). Non-imaging biomarkers had a negligible effect on predicting upgrading at the next biopsy but did improve predictions of overall time to progression in AS., Conclusions: RSI-MRI, PIRADS, and PHI could improve the predictive ability to detect upgrading in AS. The strongest predictor of clinically significant prostate cancer on AS biopsy was RSI-MRI signal output., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Pre-biopsy multiparametric magnetic resonance imaging (mpMRI) of the prostate is used to conduct targeted prostate biopsy (TB), guided by ultrasound and registered (fused) to the MRI. Systematic biopsy (SB) continues to be used together with TB or in mpMRI-negative patients. There is insufficient evidence on how to use SB to inform clinical decision-making in the mpMRI era. The purpose of this study was to estimate the effect of prostate volume and number of SB cores on sampling clinically significant prostate cancer (csPCa) using a simulation method based on clinical data., Methods: SBs were simulated using data from 42 patients enrolled in a transrectal ultrasound robot-assisted biopsy trial. Linear mixed models were used to examine the relationship between the number of SB cores and prostate volume on 1) clinically significant cancer detection probability (csCDP) and 2) percent of mpMRI depicted regions of interest (ROIs) sampled with the SB., Results: Median values and interquartile range (IQR) were 47.16 cm 3 (35.61-65.57) for prostate volume, 0.57 cm 3 (0.39-0.83) for ROI volume, and 4.0 (2-4) for PI-RADS v2.1 scores on MRI. csCDP increased with the increasing number of simulated SB cores and decreased substantially with larger prostate volume. Similarly, the percent of ROIs sampled increased with the increasing number of simulated SB cores and was lower for prostate volumes ≥60 cm 3 compared to glands <60 cm 3 ., Conclusions: The effect of the number of SBs performed on detecting csPCa varies largely with gland volume. The common 12-core SB can achieve adequate cancer detection and sampling of ROIs in smaller glands, but not in larger glands. In addition to TB or in mpMRI-negative patients, the number of SB cores can be adjusted to prostate volume. Performing 12-core SB alone in ≥60 cm 3 glands results in inadequate sampling and potential PCa underdiagnosis., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Focal therapy (FT) is a promising alternative to whole-gland treatments for Localized Prostate Cancer. Ten different FT modalities have been described in literature. However, FT is not yet recommended by the International Guidelines, due to the lack of robust data on Oncological Outcomes. The objective of our Narrative Review is to evaluate the oncological profile of the available FT modalities and to offer a comprehensive overview of the definitions of Cancer Control for FT., Material and Methods: Literature search was performed on 21 st  February 2023 using PubMed, EMBASE, and Scopus, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). Articles reporting whole gland-treatments were excluded. All articles reporting oncological outcomes were included., Results: One-hundred-twenty-four studies, reporting data on more than 8000 patients treated with FT, were included. Overall, 40 papers were on High Intensity Focal Ultrasound (HIFU), 24 on Focal Cryotherapy, 13 on Irreversible Electroporation (IRE), 11 on Focal brachytherapy, 10 on Focal Laser Ablation (FLA), 8 on Photo-Dynamic Therapy (PDT), 3 on Microwave ablation, 3 on Robotic Partial Prostatectomy, 2 on bipolar Radio Frequency Ablation (bRFA), 1 on Prostatic Artery Embolization (PAE) and 9 comparative papers. Overall, the Biochemical Recurrence (BCR) rate ranged from 0% (Focal Brachytherapy) to 67.5% (HIFU); the Salvage treatment rate ranged from 1% (IRE) to 54% (HIFU) considering re-treatment with FT and from 0% (Focal Brachytherapy) to 66.7% considering standard Radical Treatments. There is no univocal definition of Cancer Control, however the "Phoenix criteria" for BCR were the most commonly used., Conclusions: FT is a promising alternative treatment for localized prostate cancer in terms of Oncological Outcomes, however there is a wide heterogeneity in the definition of cancer control, the reporting of oncological outcomes and a lack of high-quality clinical trials. Solid comparative studies with standard treatments and an unambiguous consensus on how to describe Cancer Control in the field of Focal Therapy are needed., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Racial differences in Health-Related Quality of Life (HRQoL) after treatment of prostate cancer (PCa) are not well studied. We compared treatment patterns and HRQoL in African American (AA) and non-AA men undergoing active surveillance (AS), radical prostatectomy (RP), or radiation (XRT)., Methods: Men diagnosed with PCa from 2007-2017 in the Center for Prostate Disease Research Database were identified. HRQoL was evaluated using Expanded PCa Index Composite and SF-36 Health Survey., Results: In 1006 men with localized PCa, 223 (22.2%) were AA (mean follow up 5.2 yrs). AA men with low-risk disease were less likely to undergo AS (28.5 vs. 38.8%) and more likely to undergo XRT (22.3 vs. 10.6%) than non-AA men, p < 0.001. In intermediate-risk disease, AA received more XRT (43.0 vs. 26.9%) and less RP (50.5 vs 66.8%), p = 0.016. In all men, RP resulted in worse urinary function and sexual HRQoL compared to AS and XRT. Bowel HRQoL did not vary by treatment in AA men, however, in non-AA men, XRT resulted in worse bowel scores than AS and RP. HRQoL was then compared for each treatment modality. AA men had worse sexual bother (p = 0.024) after RP than non-AA men, No racial differences were found in urinary, bowel, hormonal, or SF-36 scores for men undergoing AS, RP or XRT., Conclusion: AA men are less often treated with AS for low-risk disease and are more likely to undergo XRT. AA men experience worse sexual bother after RP, however, the effect of XRT on bowel symptoms is worse in non-AA men., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The utilization of MRI to risk stratify elevated PSA prior to prostate biopsy has been inconsistently adopted and varies considerably by practice setting. This study aims to evaluate the usage and performance of MRI as an advanced risk stratification tool of elevated PSA prior to biopsy and identify factors associated with differential utilization of MRI at a large academic setting with ready access to 3T multiparametric MRI of the prostate., Methods: A retrospective single-center study of 2900 men presenting with elevated PSA 2-20 ng/mL from 2018 through 2021 was conducted. We analyzed trends in MRI utilization and outcomes of prostate biopsy by MRI usage. Univariate and multivariate logistic regressions were performed to calculate odds ratios to identify patient- and provider-level predictors of MRI usage., Results: Rates of prebiopsy MRI utilization increased from 56% in 2018 to 89% in 2021 (p < 0.001). Prebiopsy MRI led to biopsy avoidance in 31% of men. MRI usage enhanced detection of clinically significant prostate cancer by 13% and reduced identification of Gleason Grade Group 1 disease by 3% and negative biopsies by 10% (p < 0.001). Men who received MRI were more likely to be younger than 75 years in age and have private or Medicare insurance, PSA >4 ng/mL, and PHI >27. In both univariate and multivariate analysis, black race and Medicaid insurance were associated with reduced MRI utilization (all p < 0.001). Urologic provider was an independent predictor of MRI usage (p < 0.001)., Conclusions: Use of MRI as a risk stratification tool for elevated PSA rose during this 4-year study period. Men who self-identify as black or men with Medicaid coverage have diminished rates of MRI usage. Considerable provider-level variability in MRI use was observed. Future research aimed at identifying factors affecting implementation of MRI as a routine risk assessment tool is warranted., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Population-based studies assessing various active surveillance (AS) protocols for prostate cancer, to date, have inferred AS participation by the lack of definitive treatment and use of post-diagnostic testing. This is problematic as evidence suggests that most men do not adhere to AS protocols. We sought to develop a novel method of identifying men on AS or watchful waiting (WW) independent of post-diagnostic testing and aimed to identify possible predictors of follow-up intensity in men on AS/WW., Methods: A predictive model was developed using SEER watchful waiting data to identify men ≥66 years on AS between 2010-2015, irrespective of post-diagnostic testing, and applied to SEER-Medicare database. AS intensity among different variables including age, prostate-specific antigen (PSA) level, number of total and positive biopsy cores, Charlson comorbidity index, race (Black vs. non-Black), US census region, and county poverty, income, and education levels were compared using multivariable regression analyses for PSA testing, surveillance biopsy, and magnetic resonance imaging (MRI)., Results: A total of 2238 men were identified as being on AS. Of which, 81%, 33%, and 10% had a PSA test, surveillance biopsy, and MRI scan within 1-2 years, respectively. On multivariable analyses, Black men were less likely to have a PSA test (adjusted rate ratio [ARR] 0.60, 95% CI: 0.53-0.69), MRI scan (ARR 0.40, 95% CI: 0.24-0.68), and surveillance biopsy (ARR 0.71, 95% CI: 0.55-0.92) than non-Black men. Men within the highest income quintile were more likely to undergo PSA test (ARR 1.16, 95% CI: 1.05-1.27) and MRI scan (ARR 1.60, 95% CI 1.15-2.27) compared to men with the lowest income., Conclusions: Black men and men with lower incomes on AS underwent less rigorous monitoring. Further study is needed to understand and ameliorate differences in AS rigor stemming from sociodemographic differences., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The goal of prostate cancer focal therapy is to achieve oncologic control while reducing the rate of adverse events associated with whole-gland treatments. Numerous focal therapy modalities are currently available with early data demonstrating highly variable rates of cancer control and preservation of sexual/urinary function., Methods: All English language clinical trial publications evaluating various focal therapies for localized prostate cancer were reviewed. The literature search was limited to studies from the modern era of MRI-guided treatment, as MRI is hypothesized to improve tumor localization and targeting. Primary outcomes were post-treatment cancer-free rates, in-field/out-of-field recurrence rates, and rates of conversion to radical therapy. Secondary outcomes were related to functional status and adverse events., Results: Numerous focal therapies were identified with clinical data including high-intensity focused ultrasound, transurethral ultrasound ablation, focal laser ablation, focal cryotherapy, irreversible electroporation, and photodynamic therapy. Recurrence rates among all technologies were low to moderate (0-51%) and rates of freedom from radical treatment were highly variable (46-98%). Rates of erectile dysfunction and incontinence generally ranged from 0 to 44% and 0 to 12%, respectively, with variability between focal therapy modalities. Caution should be exercised when comparing studies as outcomes are strongly associated with patient selection. No individual focal therapy is currently recommended by society guidelines. Randomized controlled trials are ongoing in search of a standard of care., Conclusion: For localized MRI-visible prostate cancer, early clinical trial data demonstrate that focal therapy can provide good to moderate cancer control while having preferable side effect profiles compared to whole-gland treatments. While current studies do not make head-to-head comparisons between technologies, early data suggest a potential for these technologies to provide adequate cancer control in a well-selected patient population. The oncologic outcomes of some focal therapies appear promising; however, longer-term follow-up data are needed to assess the durability of early outcomes., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)