Prostate Cancer and Prostatic Diseases最新文献

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.

Background

KEYNOTE-199 (NCT02787005) is a multicohort phase 2 study evaluating pembrolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC). Results from cohorts 4 (C4) and 5 (C5) are presented.

Methods

Eligible patients had not received chemotherapy for mCRPC and had responded to enzalutamide prior to developing resistance as defined by Prostate Cancer Clinical Trials Working Group 3 guidelines. Patients with RECIST-measurable disease were enrolled in C4, and patients with bone-only or bone-predominant disease were enrolled in C5. All patients received pembrolizumab 200 mg every 3 weeks for ≤35 cycles with ongoing enzalutamide until progression, unacceptable toxicity, or withdrawal. The primary end point was objective response rate (ORR) per RECIST v1.1 by blinded independent central review in C4. Secondary end points included disease control rate (DCR), overall survival, and safety in each cohort and both cohorts combined.

Results

A total of 126 patients were treated (C4, n = 81; C5, n = 45). Median age was 72 years (range 43–92), and 87.3% had received ≥6 months of enzalutamide prior to study entry. Confirmed ORR was 12.3% (95% CI 6.1–21.5%) for C4. Median duration of response in C4 was 8.1 months (range, 2.5+ to 15.2), and 5 of these patients experienced an objective response lasting ≥6 months. DCR was 53.1% (95% CI 41.7–64.3%) in C4 and 51.1% (95% CI 35.8–66.3%) in C5. Median overall survival was 17.6 months (95% CI 14.0–22.6) in C4 and 20.8 months (95% CI 14.1–28.9) in C5. Grade ≥3 treatment-related adverse events occurred in 35 patients (27.8%); 2 patients in C4 died from immune-related adverse events (myasthenic syndrome and Guillain-Barré syndrome).

Conclusions

The addition of pembrolizumab to ongoing enzalutamide treatment in patients with mCRPC that progressed on enzalutamide after initial response demonstrated modest antitumor activity with a manageable safety profile.

Clinical trial registry and ID

ClinicalTrials.gov, NCT02787005.

Importance and objective: Partial gland ablation (PGA) is increasingly popular as a treatment for men with intermediate-risk prostate cancer (IR-PCa) to preserve functional outcomes while controlling their cancer. We aimed to determine the impact of race and clinical characteristics on the risk of upstaging (≥pT2c) and having adverse pathological outcomes including seminal vesicle invasion (SVI), extra prostatic extension (EPE) and lymph node invasion (LNI) at radical prostatectomy (RP) among men with IR disease eligible for PGA with hemi-ablation (HA).

Design: Retrospective analysis.

Setting: Multicenter.

Participants and measures: We studied patients diagnosed with unilateral IR-PCa treated with RP between 1988 and 2020 at 9 different Veterans Affairs hospitals within the SEARCH cohort. We analyzed differences in clinicopathological characteristics and outcome variables (odds of ≥pT2c and SVI, EPE and LNI) by race using multivariable logistic regression after adjusting for covariates.

Results: Among 3127 patients, 33% were African American (AA) men with unilateral IR-PCa undergoing RP. Compared to non-AA men, AA individuals were younger (61 vs. 65 years, p < 0.001), presented with a higher prostate specific antigen (PSA) category (≥10 ng/ml; 34 vs. 26%, p < 0.001), and had a lower clinical stage (p < 0.001). Among the 2,798 (89.5%) with ≥pT2c stage, AA men exhibited higher ≥ pT2c rates (93 vs. 89%, p < 0.001), primarily due to increased pT2c staging (64 vs. 57%), where upstaging beyond pT2 was lower than non-AA men (29 vs. 32%). On multivariable analysis, AA men were found to have higher odds of ≥pT2c (odds ratio [OR]: 1.39 CI, 1.02-1.88, p = 0.04), lower odds of EPE (OR: 0.73 CI, 0.58-0.91, p < 0.01) and no statistically significant associations with LNI (OR: 0.79 CI, 0.42-1.46, p = 0.45) and SVI (OR: 1 CI, 0.74-1.35, p = 0.99) compared to non-AA men. On multivariable analysis, clinical features associated with higher odds of ≥pT2c were pre-operative PSA ≥ 15 (OR = 2.07, P = 0.01) and higher number of positive cores (HPC) on biopsy (OR = 1.36, P < 0.001). Similarly, PSA ≥ 15, Gleason grade ≥3 and HPC on biopsy were associated with higher odds of SVI, EPE and LNI, respectively.

Conclusions: In men with IR-PCa undergoing RP, AA men demonstrated an overall higher likelihood of ≥pT2c with lower upstaging beyond pT2, lower likelihood of EPE and no significant difference in likelihood of SVI and LNI compared to non-AA men. These findings support select AA men to be potential candidates for PGA, such as HA. Clinical factors are predictive of higher pathological stage and adverse pathological outcomes at RP and could be considered when selecting candidates for PGA.

Delays in the work-up and definitive management of patients with prostate cancer are common, with logistics of additional work-up after initial prostate biopsy, specialist referrals, and psychological reasons being the most common causes of delays. During the COVID-19 pandemic and the subsequent surges, timing of definitive care delivery with surgery or radiotherapy has become a topic of significant concern for patients with prostate cancer and their providers alike. In response, recommendations for the timing of definitive management of prostate cancer with radiotherapy and radical prostatectomy were published but without a detailed rationale for these recommendations. While the COVID-19 pandemic is behind us, patients are always asking the question: "When should I start radiation or undergo surgery?" In the absence of level I evidence specifically addressing this question, we will hereby present a narrative review to summarize the available data on the effect of treatment delays on oncologic outcomes for patients with localized prostate cancer from prospective and retrospective studies.