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International Braz J Urol : Official... 2022Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors,... (Review)
Review
PURPOSE
Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa.
MATERIAL AND METHODS
We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included.
RESULTS
Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade.
CONCLUSIONS
This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.
Topics: Humans; Male; Neoplasm Recurrence, Local; Prostatic Neoplasms; Salvage Therapy; Treatment Outcome; Ultrasound, High-Intensity Focused, Transrectal
PubMed: 34003610
DOI: 10.1590/S1677-5538.IBJU.2021.0091 -
European Urology Jan 2022Focal therapy is a promising, minimally invasive strategy to selectively treat localized prostate cancer. A previous systematic review indicated that there is growing... (Review)
Review
CONTEXT
Focal therapy is a promising, minimally invasive strategy to selectively treat localized prostate cancer. A previous systematic review indicated that there is growing evidence for favorable functional outcomes, but that oncological effectiveness was yet to be defined.
OBJECTIVE
To assess the effectiveness of focal therapy in patients with localized prostate cancer in terms of functional and oncological outcomes.
EVIDENCE ACQUISITION
PubMed, Embase, and The Cochrane Library were searched for studies between October 2015 and December 31, 2020. In addition, the research stages were acquired according to the Idea, Development, Exploration, Assessment, Long-term study (IDEAL) recommendations. Ongoing studies were identified through clinical trial registries.
EVIDENCE SYNTHESIS
Seventy-two studies were identified exploring eight different sources of energy to deliver focal therapy in 5827 patients. Twenty-seven studies reported on high-intensity focused ultrasound (HIFU), nine studies on irreversible electroporation, 11 on cryoablation, eight on focal laser ablation and focal brachytherapy, seven on photodynamic therapy (PDT), two on radiofrequency ablation, and one on prostatic artery embolization. The majority of studies were prospective development stage 2a studies (n = 357). PDT and HIFU, both in stage 3, showed promising results. Overall, HIFU studies reported a median of 95% pad-free patients and a median of 85% patients with no clinically significant cancer (CSC) in the treated area. For PDT, no changes in continence were reported and a median of 90% of patients were without CSC. Both treatments were well tolerated.
CONCLUSIONS
Over the past 5 yr, focal therapy has been studied for eight different energy sources, mostly in single-arm stage 2 studies. Although a first randomized controlled trial in focal therapy has been performed, more high-quality evaluations are needed, preferably via multicenter randomized controlled trials with long-term follow-up and predefined assessment of oncological and functional outcomes and health-related quality-of-life measures.
PATIENT SUMMARY
Focal treatment (FT) of prostate cancer has potential, considering that it has less impact on continence and potency than radical treatment. Our systematic review indicates that despite the method being studied extensively over the past half decade, the majority of studies remain in an early research stage. The techniques high-intensity focused ultrasound and photodynamic therapy have shown most progression toward advanced research stages and show favorable results. However, more high-quality evidence is required before FT can become available as a standard treatment.
Topics: Embolization, Therapeutic; Humans; Male; Multicenter Studies as Topic; Prospective Studies; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34489140
DOI: 10.1016/j.eururo.2021.08.005 -
Expert Review of Anticancer Therapy Jul 2023Metastatic castrate resistant prostate cancer (mCPRC) remains an aggressive form of prostate cancer that no longer responds to traditional hormonal treatment alone.... (Review)
Review
INTRODUCTION
Metastatic castrate resistant prostate cancer (mCPRC) remains an aggressive form of prostate cancer that no longer responds to traditional hormonal treatment alone. Despite the advent of novel anti-androgen medications, many patients continue to progress, and as a result, there is a growing need for additional treatment options.
AREAS COVERED
Lutetium-177 (Lu) - PSMA-617 has become one of the new frontline treatment options for refractory metastatic castrate resistant prostate cancer after the failure of novel anti-androgen therapy and chemotherapy. Lu-177 has been used in real-world prospective trials and is now becoming utilized in newer phase III clinical trials. Here, we present a comprehensive overview of the current literature, covering retrospective studies, prospective studies, and clinical trials that established Lutetium-177-PSMA-617 (Lu-PSMA-617) for the treatment of mCRPC.
EXPERT OPINION
Lu - PSMA-617 has been approved for treatment of mCRPC based on positive phase III studies. While this treatment is tolerable and effective, biomarkers are necessary to determine which patients will benefit. In the future, radioligand treatments will likely be utilized in earlier lines of therapy and potentially in combination with other prostate cancer treatments.
Topics: Male; Humans; Prospective Studies; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Radioisotopes; Prostate-Specific Antigen; Treatment Outcome
PubMed: 37194261
DOI: 10.1080/14737140.2023.2213892 -
European Urology Oncology Jun 2022In the past 10 yr, several agents based on prostate-specific membrane antigen (PSMA) for positron emission tomography imaging have been introduced in clinical practice... (Review)
Review
[Ga]Ga-PSMA Versus [F]PSMA Positron Emission Tomography/Computed Tomography in the Staging of Primary and Recurrent Prostate Cancer. A Systematic Review of the Literature.
CONTEXT
In the past 10 yr, several agents based on prostate-specific membrane antigen (PSMA) for positron emission tomography imaging have been introduced in clinical practice for the management of patients with prostate cancer (PCa).
OBJECTIVE
To analyse the available data in the literature to clarify the advantages and disadvantages of [Ga]Ga-PSMA and [F]PSMA in different settings of PCa.
EVIDENCE ACQUISITION
A systematic literature search was made by using two main databases. Only studies published in the past 5 yr (2016-2021) in the English language with >20 enrolled patients were selected. Two reviewers independently appraised each article using a standard protocol. All the studies were analysed using a modified version of the Critical Appraisal Skills Programme checklist for diagnostic test studies.
EVIDENCE SYNTHESIS
The systematic evaluation was made in 12 papers. Based on the quality assessment, the analysed studies demonstrated different methodologies. Three papers focused on the head-to-head comparison between F- and [Ga]Ga-PSMA (n = 123 patients). A matched-pair comparison between F- and [Ga]Ga-PSMA was reported in three papers, including 715 patients. The remaining papers used indiscriminately either Ga-PSMA or [F]PSMA (n = 1.157 patients). [F]PSMA-1007 is superior to [Ga]Ga-PSMA-11 for the identification of local recurrence (less activity close to the bladder for [F]PSMA-1007). Nonspecific/equivocal bone lesions are often recognised at [F]PSMA-1007. [F]DCFPyL is more reproducible for the identification of lymph nodes, and it shows fewer equivocal skeletal lesions and higher inter-reader agreement on skeletal lesions.
CONCLUSIONS
Despite a large body of literature on PSMA radiopharmaceutical agents labelled with Ga or F, there are limited head-to-head or matched-pair comparative data. Certain clinical indications could trigger a preference, whilst caution is needed in interpreting potential false-positive findings, especially with [F]PSMA-1007. Given the excellent performance of all accessible radiopharmaceuticals, the availability of specific tracers will likely guide choice.
PATIENT SUMMARY
In this systematic review, we analysed the currently available literature focused on [Ga] and [F]-labelled prostate-specific membrane antigen. Our purpose is to identify which tracers would be correctly employed for the management of patients with prostate cancer.
Topics: Gallium Isotopes; Gallium Radioisotopes; Humans; Male; Neoplasm Recurrence, Local; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Radiopharmaceuticals
PubMed: 35367165
DOI: 10.1016/j.euo.2022.03.004 -
International Journal of Radiation... Jul 2019Utilization of stereotactic body radiation therapy (SBRT) for treatment of localized prostate cancer is increasing. Guidelines and payers variably support the use of... (Meta-Analysis)
Meta-Analysis
PURPOSE
Utilization of stereotactic body radiation therapy (SBRT) for treatment of localized prostate cancer is increasing. Guidelines and payers variably support the use of prostate SBRT. We therefore sought to systematically analyze biochemical recurrence-free survival (bRFS), physician-reported toxicity, and patient-reported outcomes after prostate SBRT.
METHODS AND MATERIALS
A systematic search leveraging Medline via PubMed and EMBASE for original articles published between January 1990 and January 2018 was performed. This was supplemented by abstracts with sufficient extractable data from January 2013 to March 2018. All prospective series assessing curative-intent prostate SBRT for localized prostate cancer reporting bRFS, physician-reported toxicity, and patient-reported quality of life with a minimum of 1-year follow-up were included. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Meta-analyses were performed with random-effect modeling. Extent of heterogeneity between studies was determined by the I and Cochran's Q tests. Meta-regression was performed using Hartung-Knapp methods.
RESULTS
Thirty-eight unique prospective series were identified comprising 6116 patients. Median follow-up was 39 months across all patients (range, 12-115 months). Ninety-two percent, 78%, and 38% of studies included low, intermediate, and high-risk patients. Overall, 5- and 7-year bRFS rates were 95.3% (95% confidence interval [CI], 91.3%-97.5%) and 93.7% (95% CI, 91.4%-95.5%), respectively. Estimated late grade ≥3 genitourinary and gastrointestinal toxicity rates were 2.0% (95% CI, 1.4%-2.8%) and 1.1% (95% CI, 0.6%-2.0%), respectively. By 2 years post-SBRT, Expanded Prostate Cancer Index Composite urinary and bowel domain scores returned to baseline. Increasing dose of SBRT was associated with improved biochemical control (P = .018) but worse late grade ≥3 GU toxicity (P = .014).
CONCLUSIONS
Prostate SBRT has substantial prospective evidence supporting its use, with favorable tumor control, patient-reported quality of life, and levels of toxicity demonstrated. SBRT has sufficient evidence to be supported as a standard treatment option for localized prostate cancer while ongoing trials assess its potential superiority.
Topics: Clinical Trials as Topic; Confidence Intervals; Dose Fractionation, Radiation; Humans; Male; Prospective Studies; Prostatic Neoplasms; Publication Bias; Quality of Life; Radiosurgery; Treatment Outcome
PubMed: 30959121
DOI: 10.1016/j.ijrobp.2019.03.051 -
Disability and Rehabilitation Sep 2022Urinary incontinence is one of the most clinically relevant side effects in the treatment of prostate cancer patients. The aim of this systematic review and... (Meta-Analysis)
Meta-Analysis
Supervised pelvic floor muscle exercise is more effective than unsupervised pelvic floor muscle exercise at improving urinary incontinence in prostate cancer patients following radical prostatectomy - a systematic review and meta-analysis.
BACKGROUND
Urinary incontinence is one of the most clinically relevant side effects in the treatment of prostate cancer patients. The aim of this systematic review and meta-analysis was to analyze the specific exercise effects of supervised versus unsupervised pelvic floor muscle exercise (PFME) and exercise volume on urinary incontinence status after radical prostatectomy.
METHODS
A systematic data search was performed for studies published from January 2000 to December 2020 using the following databases: PubMed, Embase, SciSearch, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews and Effects. The review was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A random-effects meta-analysis of urinary incontinence remission was performed. The relation between time since surgery and urinary incontinence remission was analyzed using a non-linear dose-response meta-analysis.
RESULTS
The meta-analysis included 20 randomized controlled trials involving 2188 men ( = 1105 in intervention groups; = 1083 in control groups). PFME versus no PFME had a beneficial effect on urinary incontinence remission at 3 months, 3-6 months, and more than 6 months post-surgery, with risk differences ranging from 12 to 25%. These effects were particularly evident for higher volume, supervised PFME in the first 6 months post-surgery. Additional biofeedback therapy appeared to be beneficial but only during the first 3 months post-surgery.
CONCLUSIONS
There is good evidence that the supervised PFME causes a decrease in short-term urinary incontinence rates. Unsupervised PFME has similar effects as no PFME in postoperative urinary incontinence. PFME programs should be implemented as an early rehabilitative measure to improve postoperative short-term urinary incontinence in patients with prostate cancer.IMPLICATIONS FOR REHABILITATIONProstate cancer, surgery, and urinary incontinenceThe surgical treatment of prostate cancer often leads to urinary incontinence.Pelvic floor training leads to a significant improvement of this situation.Exercise therapy support is very important in this context and is even more effective than unsupported training.
Topics: Exercise Therapy; Humans; Male; Pelvic Floor; Prostatectomy; Prostatic Neoplasms; Treatment Outcome; Urinary Incontinence
PubMed: 34550846
DOI: 10.1080/09638288.2021.1937717 -
European Urology Apr 2020Accurate staging of high-risk localised, advanced, and metastatic prostate cancer is becoming increasingly more important in guiding local and systemic treatment.... (Meta-Analysis)
Meta-Analysis
Gallium-68 Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer-Updated Diagnostic Utility, Sensitivity, Specificity, and Distribution of Prostate-specific Membrane Antigen-avid Lesions: A Systematic Review and Meta-analysis.
CONTEXT
Accurate staging of high-risk localised, advanced, and metastatic prostate cancer is becoming increasingly more important in guiding local and systemic treatment. Gallium-68 prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has increasingly been utilised globally to assess the local and metastatic burden of prostate cancer, typically in biochemically recurrent or advanced disease. Following our previous meta-analysis, a high-volume series has been reported highlighting the utility of Ga-PSMA PET in this setting.
OBJECTIVE
To perform a systematic review and meta-analysis to update reported predictors of positive Ga-PSMA PET according to prior therapy and proportion of positivity in various anatomical locations with sensitivity and specificity profiles.
EVIDENCE ACQUISITION
We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science databases in July 2018 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality assessment was performed using Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analyses of proportions were performed using a random-effect model. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models.
EVIDENCE SYNTHESIS
A total of 37 articles including 4790 patients were analysed. For patients with biochemical recurrence, positive Ga-PSMA PET scans increased with higher pre-PET prostate-specific antigen (PSA) levels. For PSA categories 0-0.19, 0.2-0.49, 0.5-0.99, 1-1.99, and ≥2ng/ml, the percentages of positive scans were 33%, 45%, 59%, 75%, and 95%, respectively. No significant differences in positivity were noted between Gleason sums ≤7 and ≥8. Significant differences in positivity after biochemical recurrence in the prostate bed were noted between radical prostatectomy (22%) and radiotherapy (52%) patients. On per-node analysis, high sensitivity (75%) and specificity (99%) were observed.
CONCLUSIONS
Ga-68-PSMA PET improves detection of metastases with biochemical recurrence, particularly at low pre-PET PSA levels of >0.2ng/ml (33%) and 0.2-0.5ng/ml (45%). Ga-68-PSMA-PET produces favourable sensitivity and specificity profiles on meta-analysis of pooled data. This analysis highlights different anatomic patterns of metastatic spread according to PSMA PET in the primary and biochemically recurrent settings.
PATIENT SUMMARY
Gallium-68 prostate-specific membrane antigen positron emission tomography is now an established imaging technique that has been developed in response to inadequacies in standard of care imaging modalities to improve the detection of metastatic disease in prostate cancer, particularly in the setting of disease recurrence. To date, this imaging modality in the setting of primary staging is controversial, given the paucity of data. In light of the growing body of evidence, we summarised the data to date to provide clinicians with an overview of this imaging modality.
Topics: Antigens, Surface; Edetic Acid; Gallium Isotopes; Gallium Radioisotopes; Glutamate Carboxypeptidase II; Humans; Male; Neoplasm Staging; Oligopeptides; Positron-Emission Tomography; Prostatic Neoplasms; Radiopharmaceuticals; Sensitivity and Specificity
PubMed: 30773328
DOI: 10.1016/j.eururo.2019.01.049 -
Urologic Oncology Nov 2023Extracellular vesicle (EV) biomarkers have promising diagnostic and screening capabilities for several cancers, and growing evidence indicates that EV biomarkers can be... (Meta-Analysis)
Meta-Analysis Review
Extracellular vesicle (EV) biomarkers have promising diagnostic and screening capabilities for several cancers, and growing evidence indicates that EV biomarkers can be used as diagnostic markers for prostate cancer (CaP). However, data on the diagnostic accuracy of EV biomarkers for CaP diagnosis are conflicting. We performed a systematic review and meta-analysis, aimed to summarize the diagnostic performance of EV biomarkers for CaP. We systematically searched PubMed, Medline, and Web of Science from inception to 12 September 2022 for studies that assessed the diagnostic accuracy of EV biomarkers for CaP. We summarized the pooled sensitivity and specificity calculated using a random-effects model. We identified 19 studies involving 976 CaP patients and 676 noncancerous controls; one study conducted independent validation tests. Ten studies emphasized EV RNAs, 6 on EV proteins, and 9 on biomarker panels. MiR-141, miR-221, and PSMA were the most frequently reported RNAs and proteins for CaP diagnosis. For individual RNAs and proteins, the pooled sensitivity and specificity were 70% (95% CI: 68%-71%), 79% (95% CI: 77%-80%), 85% (95% CI: 81%-87%), and 83% (95% CI: 80%-86%), respectively. The pooled sensitivity and specificity of the EV panels were 84% (95% CI: 82%-86%) and 86% (95% CI: 84%-88%), respectively. The studies may have been somewhat limited by the EV isolation and detection techniques. EV biomarkers showed promising diagnostic capability for CaP. Addressing deficiencies in EV isolation and detection techniques has important implications for the application of these novel noninvasive biomarkers in clinical practice.
Topics: Male; Humans; Biomarkers; MicroRNAs; Prostatic Neoplasms; Sensitivity and Specificity; Extracellular Vesicles; Biomarkers, Tumor
PubMed: 37914569
DOI: 10.1016/j.urolonc.2023.08.019 -
Heart Failure Reviews Jan 2022Therapeutic intervention for prostate cancer mostly relies on eliminating circulating androgen or antagonizing its effect at the cellular level. As the use of endocrine... (Review)
Review
Therapeutic intervention for prostate cancer mostly relies on eliminating circulating androgen or antagonizing its effect at the cellular level. As the use of endocrine therapies grows, an under-reported incidence of cardiovascular toxicities occurs in prostate cancer patients. In this review, we summarize data of clinical studies, investigating the cardiovascular and metabolic alterations associated with the use of old and new endocrine drugs (gonadotropin-releasing hormone [GnRH] agonists and antagonists, androgen receptor inhibitors, 17α-hydroxylase/c-17,20-lyase [CYP17] inhibitor) in prostate cancer. To date, studies looking for links between cardiovascular complications and hormone-mediated therapies in prostate cancer have reached conflicting results. Several confounding factors, such as age of patients and related cardiovascular liability, other comorbidities, and use of concomitant drugs, have to be carefully evaluated in future clinical trials. Further research is needed given the continuous advancements being made in prostate cancer treatment.
Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Cardiovascular Diseases; Gonadotropin-Releasing Hormone; Humans; Male; Prostatic Neoplasms
PubMed: 32500365
DOI: 10.1007/s10741-020-09984-2 -
JAMA Oncology Jun 2024Prostate magnetic resonance imaging (MRI) is increasingly integrated within the prostate cancer (PCa) early detection pathway. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Prostate magnetic resonance imaging (MRI) is increasingly integrated within the prostate cancer (PCa) early detection pathway.
OBJECTIVE
To systematically evaluate the existing evidence regarding screening pathways incorporating MRI with targeted biopsy and assess their diagnostic value compared with prostate-specific antigen (PSA)-based screening with systematic biopsy strategies.
DATA SOURCES
PubMed/MEDLINE, Embase, Cochrane/Central, Scopus, and Web of Science (through May 2023).
STUDY SELECTION
Randomized clinical trials and prospective cohort studies were eligible if they reported data on the diagnostic utility of prostate MRI in the setting of PCa screening.
DATA EXTRACTION
Number of screened individuals, biopsy indications, biopsies performed, clinically significant PCa (csPCa) defined as International Society of Urological Pathology (ISUP) grade 2 or higher, and insignificant (ISUP1) PCas detected were extracted.
MAIN OUTCOMES AND MEASURES
The primary outcome was csPCa detection rate. Secondary outcomes included clinical insignificant PCa detection rate, biopsy indication rates, and the positive predictive value for the detection of csPCa.
DATA SYNTHESIS
The generalized mixed-effect approach with pooled odds ratios (ORs) and random-effect models was used to compare the MRI-based and PSA-only screening strategies. Separate analyses were performed based on the timing of MRI (primary/sequential after a PSA test) and cutoff (Prostate Imaging Reporting and Data System [PI-RADS] score ≥3 or ≥4) for biopsy indication.
RESULTS
Data were synthesized from 80 114 men from 12 studies. Compared with standard PSA-based screening, the MRI pathway (sequential screening, PI-RADS score ≥3 cutoff for biopsy) was associated with higher odds of csPCa when tests results were positive (OR, 4.15; 95% CI, 2.93-5.88; P ≤ .001), decreased odds of biopsies (OR, 0.28; 95% CI, 0.22-0.36; P ≤ .001), and insignificant cancers detected (OR, 0.34; 95% CI, 0.23-0.49; P = .002) without significant differences in the detection of csPCa (OR, 1.02; 95% CI, 0.75-1.37; P = .86). Implementing a PI-RADS score of 4 or greater threshold for biopsy selection was associated with a further reduction in the odds of detecting insignificant PCa (OR, 0.23; 95% CI, 0.05-0.97; P = .048) and biopsies performed (OR, 0.19; 95% CI, 0.09-0.38; P = .01) without differences in csPCa detection (OR, 0.85; 95% CI, 0.49-1.45; P = .22).
CONCLUSION AND RELEVANCE
The results of this systematic review and meta-analysis suggest that integrating MRI in PCa screening pathways is associated with a reduced number of unnecessary biopsies and overdiagnosis of insignificant PCa while maintaining csPCa detection as compared with PSA-only screening.
Topics: Humans; Male; Prostatic Neoplasms; Magnetic Resonance Imaging; Early Detection of Cancer; Prostate-Specific Antigen
PubMed: 38576242
DOI: 10.1001/jamaoncol.2024.0734