Prostate Cancer and Prostatic Diseases最新文献

Background

Prednisolone/prednisone coadministration with abiraterone may explain abiraterone-related increase in cardiovascular risk. We explored this postulation and glucocorticoid’s association with cardiovascular risk.

Methods

Patients with prostate cancer on androgen deprivation therapy and enzalutamide, or abiraterone with 5 mg (ABI + P5) or 10 mg (ABI + P10) daily total prednisolone/prednisone were followed up for major adverse cardiovascular events (MACE).

Results

We analyzed 933 patients. ABI + P10, but not enzalutamide, had higher risk of MACE than ABI + P5. Cumulative glucocorticoid dose before enzalutamide/abiraterone initiation was associated with MACE.

Conclusions

Prednisolone/prednisone coadministration with abiraterone likely contributed to abiraterone-related increased cardiovascular risk. Prevalent cumulative glucocorticoid dose was associated with cardiovascular risk.

Background/Objectives

Endorsing the principles of minimal invasiveness in benign-prostatic hyperplasia (BPH) surgery, we conducted the first evaluation of transurethral intraprostatic anesthesia (TUIA) using Schelin catheter® (SC) prior to iTIND positioning.

Subjects/Methods

Of 23 patients enrolled, 11 (48%) received TUIA via SC whereas the remaining underwent standard anesthesia protocol. Pain was assessed using visual analogue scale (VAS).

Results

No differences between cohorts were observed for pain during the device implantation and removal. Conversely, significantly lower median VAS scores were reported at 24- (1.0 vs. 3.0) and 48- (1.0 vs. 2.5) hour follow-up favoring TUIA.

Conclusions

SC TUIA offers effective pain control during iTIND procedures, supporting its use in outpatient settings.

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.

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.

Background: Genomic testing can add risk stratification information to clinicopathological features in prostate cancer, aiding in shared medical decision-making between the clinician and patient regarding whether active surveillance (AS) or definitive treatment (DT) is most appropriate. Here we examined initial AS selection and 3-year AS durability in patients diagnosed with localized intermediate-risk prostate cancer who underwent Prolaris testing before treatment decision-making.

Methods: This retrospective observational cohort study included 3208 patients from 10 study sites who underwent Prolaris testing at diagnosis from September 2015 to December 2018. Prolaris utilizes a combined clinical cell cycle risk score calculated at diagnostic biopsy to stratify patients by the Prolaris AS threshold (below threshold, patient recommended to AS or above threshold, patient recommended to DT). AS selection rates and 3-year AS durability were compared in patients recommended to AS or DT by Prolaris testing. Univariable and multivariable logistic regression models and Cox proportional hazard models were used with molecular and clinical variables as predictors of initial treatment decision and AS durability, respectively.

Results: AS selection was ~2 times higher in patients recommended to AS by Prolaris testing than in those recommended to DT (p < 0.0001). Three-year AS durability was ~1.5 times higher in patients recommended to AS by Prolaris testing than in those recommended to DT (p < 0.0001). Prolaris treatment recommendation remained a statistically significant predictor of initial AS selection and AS durability after accounting for CAPRA or Gleason scores.

Conclusions: Prolaris added significant information to clinical risk stratification to aid in treatment decision making. Intermediate-risk prostate cancer patients who were recommended to AS by Prolaris were more likely to initially pursue AS and were more likely to remain on AS at 3 years post-diagnosis than patients recommended to DT.

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.

Background: To compare surgical, pathological, and functional outcomes of patients undergoing NeuroSAFE-guided RARP vs. RARP alone.

Methods: In February 2024, a literature search and assessment was conducted through PubMed^®, Scopus^®, and Web of Science^™, to retrieve data of men with PCa (P) undergoing RARP with NeuroSAFE (I) versus RARP without NeuroSAFE (C) to evaluate surgical, pathological, oncological, and functional outcomes (O), across retrospective and/or prospective comparative studies (Studies). Surgical (operative time [OT], number of nerve-sparing [NS] RARP, number of secondary resections after NeuroSAFE), pathological (PSM), oncological (biochemical recurrence [BCR]), and functional (postoperative continence and sexual function recovery) outcomes were analyzed, using weighted mean difference (WMD) for continuous variables and odd ratio (OR) for dichotomous variables.

Results: Overall, seven studies met the inclusion criteria (one randomized clinical trial, one prospective non-randomized trial and five retrospective studies) and were eligible for SR and MA. A total of 4,207 patients were included in the MA, with 2247 patients (53%) undergoing RARP with the addition of NeuroSAFE, and 1 960 (47%) receiving RARP alone. The addition of NeuroSAFE enhanced the likelihood of receiving a nerve-sparing (NS) RARP (OR 5.49, 95% CI 2.48-12.12, I² = 72%). In the NeuroSAFE cohort, a statistically significant reduction in the likelihood of PSM at final pathology (OR 0.55, 95% CI 0.39-0.79, I² = 73%) was observed. Similarly, a reduced likelihood of BCR favoring the NeuroSAFE was obtained (OR 0.47, 95% CI 0.35-0.62, I² = 0%). At 12-month postoperatively, NeuroSAFE led to a significantly higher likelihood of being pad-free (OR 2.01, 95% CI 1.25-3.25, I² = 0%), and of erectile function recovery (OR 3.50, 95% CI 2.34-5.23, I² = 0%).

Conclusion: Available evidence suggests that NeuroSAFE might represent a histologically based approach to NVB preservation, broadening the indications of NS RARP, reducing the likelihood of PSM and subsequent BCR. In addition, it might translate into better functional postoperative outcomes. However, the current body of evidence is mostly derived from non-randomized studies with a high risk of bias.

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.

Background: Recent advances in the detection and treatment of prostate cancer (PCa) have reduced morbidity and mortality from this common cancer. Despite these improvements, PCa remains the second leading cause of cancer death in men in the United States. Further understanding of the genetic underpinnings of lethal PCa is required to drive risk detection and prevention and ultimately reduce mortality. We therefore set out to identify germline variants associated with cases of lethal prostate cancer (LPCa).

Methods: Using a two-stage study design, we compared whole-exome sequencing data of 550 LPCa patients to 488 healthy male controls. Men were classified as having LPCa based on medical record review. Candidate genes were identified using gene- and gene-set-based rare truncating variant association tests. Case-control burden testing through Firth's penalized logistic regression and case-gnomAD allelic burden testing through a one-sided mid-p Fisher's exact test were conducted. Each gene's p-values from these tests were combined into an omnibus p-value for candidate gene selection. In the subsequent validation stage, genes were assessed using the UK Biobank and Firth's penalized logistic regression for each ancestry, combined through meta-analysis.

Results: Gene-based rare variant association tests identified 12 genes nominally associated with LPCa. Rare-variant association tests identified a gene set with a significantly higher burden of truncating germline mutations in LPCa patients than controls. Combining gene- and gene-set test results, four nominally significant genes (PPP1R3A, TG, PPFIBP2, and BTN3A3) were selected as candidates. Subsequent validation using the UK Biobank found that PPP1R3A was significantly associated with LPCa risk (odds ratio 2.34, CI 1.20-4.59). Specifically, pGln662ArgfsTer7 was identified as the predominant variant in PPP1R3A among LPCa patients in our dataset.

Conclusions: Both individual gene and gene-set analyses identified candidates associated with LPCa. The novel association of PPP1R3A and LPCa risk merits further investigation.