-
European Urology May 2024Biochemical recurrence (BCR) after primary definitive treatment for prostate cancer (PCa) is a heterogeneous disease state. While BCR is associated with worse oncologic... (Review)
Review
BACKGROUND AND OBJECTIVE
Biochemical recurrence (BCR) after primary definitive treatment for prostate cancer (PCa) is a heterogeneous disease state. While BCR is associated with worse oncologic outcomes, risk factors that impact outcomes can vary significantly, necessitating avenues for risk stratification. We sought to identify prognostic risk factors at the time of recurrence after primary radical prostatectomy or radiotherapy, and prior to salvage treatment(s), associated with adverse oncologic outcomes.
METHODS
We performed a systematic review of prospective studies in EMBASE, MEDLINE, and ClinicalTrials.gov (from January 1, 2000 to October 16, 2023) according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (CRD42023466330). We reviewed the factors associated with oncologic outcomes among patients with BCR after primary definitive treatment.
KEY FINDINGS AND LIMITATIONS
A total of 37 studies were included (total n = 10 632), 25 after prostatectomy (total n = 9010) and 12 after radiotherapy (total n = 1622). Following recurrence after prostatectomy, factors associated with adverse outcomes include higher pathologic T stage and grade group, negative surgical margins, shorter prostate-specific antigen doubling time (PSADT), higher prostate-specific antigen (PSA) prior to salvage treatment, shorter time to recurrence, the 22-gene tumor RNA signature, and recurrence location on molecular imaging. After recurrence following radiotherapy, factors associated with adverse outcomes include a shorter time to recurrence, and shorter PSADT or higher PSA velocity. Grade group, T stage, and prior short-term hormone therapy (4-6 mo) were not clearly associated with adverse outcomes, although sample size and follow-up were generally limited compared with postprostatectomy data.
CONCLUSIONS AND CLINICAL IMPLICATIONS
This work highlights the recommendations and level of evidence for risk stratifying patients with PCa recurrence, and can be used as a benchmark for personalizing salvage treatment based on prognostics.
PATIENT SUMMARY
We summarize the data from previously reported clinical trials on the topic of which factors predict worse cancer outcomes for patients who recur with prostate cancer after their initial treatment.
PubMed: 38782697
DOI: 10.1016/j.eururo.2024.04.034 -
Journal of Nuclear Medicine : Official... Jul 2024Prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of multiple solid tumors, including renal cell carcinoma (RCC). Studies have demonstrated... (Meta-Analysis)
Meta-Analysis
Prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of multiple solid tumors, including renal cell carcinoma (RCC). Studies have demonstrated promising results on the utility of PSMA-targeted PET/CT imaging in RCC. This report aims to provide a systematic review and metaanalysis on the utility and detection rate of PSMA PET/CT imaging in staging or evaluation of primary RCC and restaging of metastatic or recurrent RCC. Searches were performed in PubMed, Embase, and abstract proceedings (last updated, August 2023). Studies that provided a lesion-level detection rate of PSMA radiotracers in staging or restaging of RCC were included in the metaanalysis. The overall pooled detection rate with a 95% CI was estimated, and subgroup analysis was performed when feasible. Nine studies comprising 152 patients (133 clear cell RCC [ccRCC], 19 other RCC subtypes) were included in the metaanalysis. The pooled detection rate of PSMA PET/CT in evaluation of primary or metastatic RCC was estimated to be 0.83 (95% CI, 0.67-0.92). Subgroup analysis showed a pooled PSMA detection rate of 0.74 (95% CI, 0.57-0.86) in staging or evaluation of primary RCC lesions and 0.87 (95% CI, 0.73-0.95) in restaging of metastatic or recurrent RCC. Analysis based on the type of radiotracer showed a pooled detection rate of 0.85 (95% CI, 0.62-0.95) for Ga-based PSMA tracers and 0.92 (95% CI, 0.76-0.97) for F-DCFPyL PET/CT. Furthermore, in metastatic ccRCC, the available data support a significantly higher detection rate for F-DCFPyL PET/CT than for conventional imaging modalities (2 studies). Our preliminary results show that PSMA PET/CT could be a promising alternative imaging modality for evaluating RCC, particularly metastatic ccRCC. Large prospective studies are warranted to confirm clinical utility in the staging and restaging of RCC.
Topics: Carcinoma, Renal Cell; Positron Emission Tomography Computed Tomography; Humans; Kidney Neoplasms; Neoplasm Staging; Glutamate Carboxypeptidase II; Antigens, Surface
PubMed: 38782453
DOI: 10.2967/jnumed.124.267417 -
BMJ Open May 2024Androgen deprivation therapy (ADT), a common treatment for prostate cancer, has debilitating impacts on physical and psychological quality of life. While some...
Effectiveness of educational and psychological survivorship interventions to improve health-related quality of life outcomes for men with prostate cancer on androgen deprivation therapy: a systematic review.
OBJECTIVES
Androgen deprivation therapy (ADT), a common treatment for prostate cancer, has debilitating impacts on physical and psychological quality of life. While some interventions focus on managing the physical side effects of ADT, there is a paucity of interventions that also address psychosocial and educational needs. The objective of this systematic review was to identify psychological and educational survivorship interventions targeting health-related quality of life (HRQoL) outcomes in men on ADT.
DESIGN
A systematic review of randomised controlled trials.
DATA SOURCES
Web of Science, Cochrane, EBSCO Host, PubMed, SCOPUS from inception (1984) to 28 January 2023.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Psychological and/or educational survivorship interventions targeting HRQoL outcomes for men on ADT; minimum 80% of participants on ADT; used a validated HRQoL outcome measure; published in English in a peer-reviewed journal.
DATA EXTRACTION AND SYNTHESIS
Data extraction using pre-specified study criteria was conducted. Heterogeneity of eligible studies precluded a meta-analysis.
RESULTS
A total of 3381 publications were identified with eight meeting the criteria. Interventions were either psychological with a cognitive behavioural approach (n=4), or educational with (n=2) or without (n=2) psychoeducational components.Two studies reported a statistically significant improvement using a specific HRQoL measure. Most studies were not adequately powered and/or included small sample sizes limiting the conclusions that can be drawn on effectiveness. The most effective interventions were (i) individually based, (ii) educational with a psychoeducational component, (iii) supplemented with information packages and/or homework and (iv) included personalised needs assessments.
CONCLUSION
There is a paucity of literature reporting psychological and educational survivorship interventions targeting HRQoL outcomes for men on ADT. What is urgently needed are person-centred survivorship interventions that are flexible enough to identify and address individual needs, taking into account the impact ADT has on both physical and psychological quality of life.
PROSPERO REGISTRATION NUMBER
CRD4202230809.
Topics: Humans; Male; Quality of Life; Prostatic Neoplasms; Androgen Antagonists; Patient Education as Topic; Cancer Survivors; Survivorship; Randomized Controlled Trials as Topic
PubMed: 38777593
DOI: 10.1136/bmjopen-2023-080310 -
Clinical Nuclear Medicine May 2024The aim of this study was to perform a head-to-head comparison of multiparametric MRI (mpMRI) and the combination of prostate-specific membrane antigen (PSMA) PET plus...
PURPOSE
The aim of this study was to perform a head-to-head comparison of multiparametric MRI (mpMRI) and the combination of prostate-specific membrane antigen (PSMA) PET plus MRI (PSMA + MRI) for detecting intraprostatic clinically significant prostate cancer (csPCa).
PATIENTS AND METHODS
Relevant databases were searched through November 2023. Only studies directly comparing mpMRI and PSMA + MRI (PET/MRI or PET/CT + mpMRI) were included. A meta-analysis with a random-effects model was used to estimate pooled sensitivity, specificity, and area under the curve for each approach.
RESULTS
A total of 19 studies were included. On a patient-level analysis, PSMA + MRI had higher sensitivity (9 studies) than mpMRI for csPCa detection (96% [95% confidence interval (CI): 92%, 98%] vs 89% [95% CI: 81%, 94%]; P = 0.04). The patient-level specificity (4 studies) of PSMA + MRI was 55% (95% CI: 31%-76%) compared with 50% (95% CI: 44%-57%) of mpMRI (P = 0.67). Region-level sensitivity (10 studies) was 85% (95% CI: 74%-92%) for PSMA + MRI and 71% (95% CI: 58%-82%) for mpMRI (P = 0.09), whereas specificity (4 studies) was 87% (95% CI: 76%-94%) and 90% (95% CI: 82%-95%), respectively (P = 0.59). Lesion-level sensitivity and specificity were similar between modalities with pooled data from less than 4 studies.
CONCLUSIONS
PSMA + MRI had superior pooled sensitivity and similar specificity for the detection of csPCa compared with mpMRI in this meta-analysis of head-to-head studies.
PubMed: 38776063
DOI: 10.1097/RLU.0000000000005265 -
Chinese Clinical Oncology May 2024Histopathological examination, a cornerstone in diagnosing cancer, faces challenges due to its time-consuming nature. This review explores the potential of ex-vivo...
BACKGROUND
Histopathological examination, a cornerstone in diagnosing cancer, faces challenges due to its time-consuming nature. This review explores the potential of ex-vivo fluorescent confocal microscopy (FCM) in urology, addressing the need for real-time pathological assessment, particularly in prostate cancer. This systematic review aims to assess the applications of FCM in urology, including its role in prostate cancer diagnosis, surgical margin assessment, and other urological fields.
METHODS
Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a systematic search of PubMed and SCOPUS was conducted, focusing on English written original articles published after January 1, 2018, discussing the use of FCM in urological practice. The search included keywords related to FCM and urological terms. The risk of bias assessment was performed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.
RESULTS
A total of 17 relevant studies were included in the review that focuses on three main urological issues: prostate cancer (15 articles), bladder cancer (1 article), and renal biopsy (1 article). FCM exhibited significant promise in diagnosing prostate cancer. These studies reported an accuracy range of 85.33% to 95.1% in distinguishing between cancerous and non-cancerous prostate tissues. Moreover, FCM proved valuable for assessing surgical margins in real-time during radical prostatectomy, reducing the need for frozen section analysis. In some investigations, researchers explored the integration of artificial intelligence (AI) with FCM to automate diagnostic processes. Concerning bladder cancer, FCM played a beneficial role in evaluating urethral and ureteral margins during radical cystectomy. Notably, it showed substantial agreement with conventional histopathology and frozen section examination. In the context of renal biopsy, FCM demonstrated the potential to differentiate normal renal parenchyma from cancerous tissue, although the available evidence is limited in this area. The main limitation of the current study is the scarcity of data regarding the topic of interest.
CONCLUSIONS
Ex-vivo FCM holds promise in urology, particularly in prostate cancer diagnosis and surgical margin assessment. Its real-time capabilities may reduce diagnostic delays and patient stress. However, most studies remain experimental, requiring further research to validate clinical utility.
PubMed: 38769791
DOI: 10.21037/cco-23-150 -
Journal of Community Genetics Jun 2024Polygenic scores (PGS) have been developed for cancer risk-estimation and show potential as tools to prompt earlier referral for high-risk individuals and aid... (Review)
Review
BACKGROUND
Polygenic scores (PGS) have been developed for cancer risk-estimation and show potential as tools to prompt earlier referral for high-risk individuals and aid risk-stratification within cancer screening programmes. This review explores the potential for using PGS to identify individuals at risk of the most common cancers seen in primary care.
METHODS
Two electronic databases were searched up until November 2023 to identify quantitative, qualitative, and mixed methods studies that reported on the acceptability and clinical impact of using PGS to identify individuals at highest risk of breast, prostate, colorectal and lung cancer in primary care. The Mixed Methods Appraisal Tool (MMAT) was used to assess the quality of included studies and a narrative synthesis was used to analyse data.
RESULTS
A total of 190 papers were identified, 18 of which were eligible for inclusion. A cancer risk-assessment tool incorporating PGS was acceptable to the general practice population and their healthcare providers but major challenges to implementation were identified, including lack of evidence for PGS in non-European ancestry and a need for healthcare provider education in genomic medicine. A PGS cancer risk-assessment had relatively limited impact on psychosocial outcomes and health behaviours. However, for prostate cancer, potential applications for its use in primary care were shown.
CONCLUSIONS
Cancer risk assessment incorporating PGS in primary care is acceptable to patients and healthcare providers but there is a paucity of research exploring clinical impact. Few studies were identified, and more research is required before clinical implementation of PGS can be recommended.
PubMed: 38769249
DOI: 10.1007/s12687-024-00709-8 -
Medicine May 2024Incretin-based drugs, a class of Antidiabetic medications (ADMs) used in the treatment of type 2 diabetes, may affect the incidence of prostate cancer (PCa). But... (Meta-Analysis)
Meta-Analysis
Incretin-based drugs, a class of Antidiabetic medications (ADMs) used in the treatment of type 2 diabetes, may affect the incidence of prostate cancer (PCa). But real-world evidence for this possible effect is lacking. Therefore, the aim of this study is to assess the effect of incretin-based drugs on the incidence of PCa, including glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. We searched PubMed, Embase, and Cochrane Library databases for eligible studies through September 2023. Two independent reviewers performed screening and data extraction. We used the Cochrane Handbook for Systematic Reviews and the Newcastle-Ottawa Scale (NOS) to assess the quality of included randomized controlled trials (RCTs) and cohort studies. We did a meta-analysis of available trial data to calculate overall risk ratios (RRs) for PCa. A total of 1238 articles were identified in our search. After screening for eligibility, 7 high-quality studies met the criteria for meta-analysis, including 2 RCTs and 5 cohort studies, with a total of 1165,738 patients. Compared with the control group, we found that incretin-based drugs reduced the relative risk of PCa by 35% (95% confidence interval (CI), 0.17-0.49; P = .0006). In subgroup analysis, the RR values for GLP-1 receptor agonists and DPP-4 inhibitors were 62% (95% CI, 0.45-0.85; P = .003) and 72% (95% CI, 0.46-1.12; P = .14), respectively. Incretin-based drugs are associated with lower incidence of prostate cancer and may have a preventive effect on prostate cancer in patients with type 2 diabetes.
Topics: Humans; Male; Prostatic Neoplasms; Diabetes Mellitus, Type 2; Incidence; Incretins; Hypoglycemic Agents; Dipeptidyl-Peptidase IV Inhibitors
PubMed: 38758855
DOI: 10.1097/MD.0000000000038018 -
World Journal of Urology May 2024Transperineal Prostate Biopsy (TPB) is a commonly used technique for the diagnosis of prostate cancer due to growing concerns related to infectious complications...
BACKGROUND
Transperineal Prostate Biopsy (TPB) is a commonly used technique for the diagnosis of prostate cancer due to growing concerns related to infectious complications associated with transrectal ultrasound-guided prostate biopsy (TRUSB). TPB is associated with an infective complication rate of near zero, however, acute urinary retention (AUR) remains the leading complication causing morbidity. Previously in TRUSB, there was weak evidence that alpha-blockers reduce AUR rates, and their usage has been extrapolated to clinical practice with TPB. This review aims to explore if there is an evidence base for using alpha-blockers to prevent AUR following TPB.
METHODS
A systematic approach was used to search Ovid Medline and Embase using keywords related to "Transperineal" and "Retention". Articles were then screened by applying inclusion and exclusion criteria to find studies that compared alpha-blocker recipients to no alpha-blocker use in the perioperative period and the subsequent effect on AUR in TPB.
RESULTS
361 records were identified in the initial search to produce 5 studies included in the final review. No randomised controlled trials (RCTs) were identified. One observational study showed a reduction in AUR rate from 12.5% to 5.3% with a single dose of tamsulosin. A previous systematic review of complications associated with prostate biopsy concluded there may be a potential benefit to alpha-blockers given in the TPB perioperative period. Three observational studies demonstrated a harmful effect related to alpha-blocker use; however, this was well explained by their clear limitations.
CONCLUSION
Based on this review and the extrapolation from TRUSB data, perioperative alpha-blockers may offer some weak benefits in preventing AUR following TPB. However, there is significant scope and need for an RCT to further develop the evidence base further given the significant gap in the literature and lack of a standard alpha blocker protocol in TPB.
Topics: Humans; Male; Urinary Retention; Prostate; Perineum; Prostatic Neoplasms; Adrenergic alpha-Antagonists; Postoperative Complications; Image-Guided Biopsy
PubMed: 38758413
DOI: 10.1007/s00345-024-05001-5 -
Clinical & Translational Oncology :... May 2024No head-to-head trials had been performed to estimate the relative effectiveness of poly ADP-ribose polymerase inhibitor (PARPi) and androgen receptor signaling...
OBJECTIVES
No head-to-head trials had been performed to estimate the relative effectiveness of poly ADP-ribose polymerase inhibitor (PARPi) and androgen receptor signaling inhibitor (ARSi) in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC). We aimed to perform a systematic review and network meta-analysis to evaluate the comparative effectiveness of various systemic treatment agents for patients with mCRPC.
METHODS
A comprehensive literature search was conducted for abstracts and full-text articles from the database's inception through April 27, 2023. The study concentrated on assessing radiographic progression-free survival (rPFS) for both overall and homologous recombination repair mutation (HRRm) population, with overall survival (OS) as the secondary measure. Under the Bayesian framework, the overall effect was pooled using the fixed-effects model in base case analysis. Scenario analysis using restricted mean survival time (RMST) methods was performed to test the robustness of the results.
RESULTS
Nine studies with 6,830 patients and 8 unique treatment options were included. Network meta-analysis demonstrated that talazoparib in combination with enzalutamide (TALA + ENZA; overall population, hazard ratio [HR], 0.20; 95% credible interval [CrI]: 0.16-0.26; RMST, 3.51; 95% confidence interval [CI] 2.46-4.60; HRRm population, HR, 0.15; 95% CrI: 0.09-0.23; RMST, 4.14; 95% CI 2.84-5.39) was superior to other treatments in the first-line setting in terms of rPFS. The results of Bayesian framework and RMST models showed consistent efficacy ranks. When extrapolated to overall survival benefit, within the Bayesian framework, olaparib plus abiraterone acetate and prednisone (OLAP + AAP) achieved the highest OS benefit for the overall population, which was not statistically significant when compared to TALA + ENZA. However, TALA + ENZA achieved the highest OS benefit at 3 years by applying RMST.
CONCLUSIONS
We suggest that talazoparib in combination with enzalutamide is probably a preferred treatment agent for the overall population and HRRm patients with mCRPC. Given the limitations of network framework and the modeling assumptions undertaken to finalize the analyses, results should be cautiously interpreted.
PubMed: 38750344
DOI: 10.1007/s12094-024-03506-4 -
Scientific Reports May 2024Despite the availability of various drugs for benign prostatic hyperplasia (BPH), alpha(α)-blockers are the preferred first-line treatment. However, there remains a... (Meta-Analysis)
Meta-Analysis Comparative Study
Despite the availability of various drugs for benign prostatic hyperplasia (BPH), alpha(α)-blockers are the preferred first-line treatment. However, there remains a scarcity of direct comparisons among various α-blockers. Therefore, this network meta-analysis (NMA) of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of α-blockers in the management of BPH. A comprehensive electronic search covered PubMed, Embase, Ovid MEDLINE, and Cochrane Library until August 2023. The primary endpoints comprised international prostate symptom score (IPSS), maximum flow rate (Qmax), quality of life (QoL), and post-void residual volume (PVR), while treatment-emergent adverse events (TEAEs) were considered as secondary endpoints. This NMA synthesized evidence from 22 studies covering 3371 patients with six kinds of α-blockers with 12 dose categories. IPSS has been considerably improved by tamsulosin 0.4 mg, naftopidil 50 mg and silodosin 8 mg as compared to the placebo. Based on the p-score, tamsulosin 0.4 mg had the highest probability of ranking for IPSS, PVR, and Qmax, whereas doxazosin 8 mg had the highest probability of improving QoL. A total of 297 adverse events were reported among all the α-blockers, silodosin has reported a notable number of TEAEs. Current evidence supports α-blockers are effective in IPSS reduction and are considered safer. Larger sample size with long-term studies are needed to refine estimates of IPSS, QoL, PVR, and Qmax outcomes in α-blocker users.
Topics: Humans; Prostatic Hyperplasia; Male; Network Meta-Analysis; Adrenergic alpha-Antagonists; Treatment Outcome; Quality of Life; Randomized Controlled Trials as Topic; Tamsulosin
PubMed: 38750153
DOI: 10.1038/s41598-024-61977-5