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Urologia Internationalis 2023Previous studies have revealed that Gleason score upgrading (GSU) was closely related to an increased biochemical recurrence rate and adverse oncologic outcomes in... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Previous studies have revealed that Gleason score upgrading (GSU) was closely related to an increased biochemical recurrence rate and adverse oncologic outcomes in patients with prostate cancer (PC). Therefore, we performed a meta-analysis to determine the predictive factors for GSU following radical prostatectomy (RP).
METHODS
We performed an extensive literature search using PubMed, Embase, and Cochrane in September 2022. In order to calculate the pooled odds ratio (OR), standardized mean difference (SMD), and 95% confidence intervals, a fixed effect or a DerSimonian and Laird random effect was applied.
RESULTS
Twenty-six studies included 18,745 PC patients that were available for further analysis. Our results revealed that GSU was significantly correlated with age (summary SMD = 0.13; p = 0.004), prostate volume (PV) (summary SMD = -0.19;p < 0.001), preoperative PSA (p-PSA) (summary SMD = 0.18; p < 0.001), PSA density (PSAD) (summary SMD = 0.40; p < 0.001), number of positive cores (summary SMD = 0.28; p = 0.001), percentage of positive cores (summary SMD = 0.36; p < 0.001), Prostate Imaging Reporting and Data System (PI-RADS) scores (>3/≤3) (summary OR = 2.27; p = 0.001), clinical T stage (>T2/≤T2) (summary OR = 1.73; p < 0.001), positive surgical margins (PSM) (summary OR = 2.12; p < 0.001), extraprostatic extension (EPE) (summary OR = 2.73; p < 0.001), pathological T stage (>T2/≤T2) (summary OR = 3.45; p < 0.001), perineural invasion (PNI) (summary OR = 2.40; p = 0.008), and neutrophil to lymphocyte ratio (NLR) (summary SMD = 0.50; p < 0.001). However, we found that GSU was not significantly correlated with body mass index (BMI) (summary SMD = -0.02; p = 0.602). Moreover, our sensitivity and subgroup analyses showed that the findings were reliable.
CONCLUSIONS
Age, PV, p-PSA, PSAD, number of positive cores, percentage of positive cores, PI-RADS score, clinical T stage, PSM, EPE, pathological T stage, PNI, and NLR are independent factors predicting GSU following RP. The findings may be helpful in risk stratification and personalized treatment in PC patients.
Topics: Male; Humans; Prostatic Neoplasms; Prostate; Prostate-Specific Antigen; Neoplasm Grading; Magnetic Resonance Imaging; Biopsy, Needle; Prostatectomy; Retrospective Studies
PubMed: 36990065
DOI: 10.1159/000528873 -
European Radiology Jun 2024Extraprostatic extension (EPE) of prostate cancer (PCa) is predicted using clinical nomograms. Incorporating MRI could represent a leap forward, although poor... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Extraprostatic extension (EPE) of prostate cancer (PCa) is predicted using clinical nomograms. Incorporating MRI could represent a leap forward, although poor sensitivity and standardization represent unsolved issues. MRI radiomics has been proposed for EPE prediction. The aim of the study was to systematically review the literature and perform a meta-analysis of MRI-based radiomics approaches for EPE prediction.
MATERIALS AND METHODS
Multiple databases were systematically searched for radiomics studies on EPE detection up to June 2022. Methodological quality was appraised according to Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool and radiomics quality score (RQS). The area under the receiver operating characteristic curves (AUC) was pooled to estimate predictive accuracy. A random-effects model estimated overall effect size. Statistical heterogeneity was assessed with I value. Publication bias was evaluated with a funnel plot. Subgroup analyses were performed to explore heterogeneity.
RESULTS
Thirteen studies were included, showing limitations in study design and methodological quality (median RQS 10/36), with high statistical heterogeneity. Pooled AUC for EPE identification was 0.80. In subgroup analysis, test-set and cross-validation-based studies had pooled AUC of 0.85 and 0.89 respectively. Pooled AUC was 0.72 for deep learning (DL)-based and 0.82 for handcrafted radiomics studies and 0.79 and 0.83 for studies with multiple and single scanner data, respectively. Finally, models with the best predictive performance obtained using radiomics features showed pooled AUC of 0.82, while those including clinical data of 0.76.
CONCLUSION
MRI radiomics-powered models to identify EPE in PCa showed a promising predictive performance overall. However, methodologically robust, clinically driven research evaluating their diagnostic and therapeutic impact is still needed.
CLINICAL RELEVANCE STATEMENT
Radiomics might improve the management of prostate cancer patients increasing the value of MRI in the assessment of extraprostatic extension. However, it is imperative that forthcoming research prioritizes confirmation studies and a stronger clinical orientation to solidify these advancements.
KEY POINTS
• MRI radiomics deserves attention as a tool to overcome the limitations of MRI in prostate cancer local staging. • Pooled AUC was 0.80 for the 13 included studies, with high heterogeneity (84.7%, p < .001), methodological issues, and poor clinical orientation. • Methodologically robust radiomics research needs to focus on increasing MRI sensitivity and bringing added value to clinical nomograms at patient level.
Topics: Humans; Prostatic Neoplasms; Male; Magnetic Resonance Imaging; Prostate; Nomograms; Radiomics
PubMed: 37955670
DOI: 10.1007/s00330-023-10427-3 -
Health Technology Assessment... Jul 2015For people with localised prostate cancer, active treatments are effective but have significant side effects. Minimally invasive treatments that destroy (or ablate)... (Review)
Review
BACKGROUND
For people with localised prostate cancer, active treatments are effective but have significant side effects. Minimally invasive treatments that destroy (or ablate) either the entire gland or the part of the prostate with cancer may be as effective and cause less side effects at an acceptable cost. Such therapies include cryotherapy, high-intensity focused ultrasound (HIFU) and brachytherapy, among others.
OBJECTIVES
This study aimed to determine the relative clinical effectiveness and cost-effectiveness of ablative therapies compared with radical prostatectomy (RP), external beam radiotherapy (EBRT) and active surveillance (AS) for primary treatment of localised prostate cancer, and compared with RP for salvage treatment of localised prostate cancer which has recurred after initial treatment with EBRT.
DATA SOURCES
MEDLINE (1946 to March week 3, 2013), MEDLINE In-Process & Other Non-Indexed Citations (29 March 2013), EMBASE (1974 to week 13, 2013), Bioscience Information Service (BIOSIS) (1956 to 1 April 2013), Science Citation Index (1970 to 1 April 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (issue 3, 2013), Cochrane Database of Systematic Reviews (CDSR) (issue 3, 2013), Database of Abstracts of Reviews of Effects (DARE) (inception to March 2013) and Health Technology Assessment (HTA) (inception to March 2013) databases were searched. Costs were obtained from NHS sources.
REVIEW METHODS
Evidence was drawn from randomised controlled trials (RCTs) and non-RCTs, and from case series for the ablative procedures only, in people with localised prostate cancer. For primary therapy, the ablative therapies were cryotherapy, HIFU, brachytherapy and other ablative therapies. The comparators were AS, RP and EBRT. For salvage therapy, the ablative therapies were cryotherapy and HIFU. The comparator was RP. Outcomes were cancer related, adverse effects (functional and procedural) and quality of life. Two reviewers extracted data and carried out quality assessment. Meta-analysis used a Bayesian indirect mixed-treatment comparison. Data were incorporated into an individual simulation Markov model to estimate cost-effectiveness.
RESULTS
The searches identified 121 studies for inclusion in the review of patients undergoing primary treatment and nine studies for the review of salvage treatment. Cryotherapy [3995 patients; 14 case series, 1 RCT and 4 non-randomised comparative studies (NRCSs)], HIFU (4000 patients; 20 case series, 1 NRCS) and brachytherapy (26,129 patients; 2 RCTs, 38 NRCSs) studies provided limited data for meta-analyses. All studies were considered at high risk of bias. There was no robust evidence that mortality (4-year survival 93% for cryotherapy, 99% for HIFU, 91% for EBRT) or other cancer-specific outcomes differed between treatments. For functional and quality-of-life outcomes, the paucity of data prevented any definitive conclusions from being made, although data on incontinence rates and erectile dysfunction for all ablative procedures were generally numerically lower than for non-ablative procedures. The safety profiles were comparable with existing treatments. Studies reporting the use of focal cryotherapy suggested that incontinence rates may be better than for whole-gland treatment. Data on AS, salvage treatment and other ablative therapies were too limited. The cost-effectiveness analysis confirmed the uncertainty from the clinical review and that there is no technology which appears superior, on the basis of current evidence, in terms of average cost-effectiveness. The probabilistic sensitivity analyses suggest that a number of ablative techniques are worthy of further research.
LIMITATIONS
The main limitations were the quantity and quality of the data available on cancer-related outcomes and dysfunction.
CONCLUSIONS
The findings indicate that there is insufficient evidence to form any clear recommendations on the use of ablative therapies in order to influence current clinical practice. Research efforts in the use of ablative therapies in the management of prostate cancer should now be concentrated on the performance of RCTs and the generation of standardised outcomes.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42012002461.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Ablation Techniques; Aged; Aged, 80 and over; Cost-Benefit Analysis; Databases, Bibliographic; Erectile Dysfunction; Humans; Incidence; Long Term Adverse Effects; Male; Middle Aged; Neoplasm Recurrence, Local; Outcome and Process Assessment, Health Care; Prevalence; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Quality-Adjusted Life Years; State Medicine; Survival Analysis; United Kingdom; Urinary Incontinence
PubMed: 26140518
DOI: 10.3310/hta19490 -
Clinical Oncology (Royal College of... Oct 2014Radiotherapy is standard treatment for localised prostate cancer and is often combined with hormone treatment to prevent androgen stimulation of prostate cancer. Hormone... (Comparative Study)
Comparative Study Meta-Analysis Review
AIMS
Radiotherapy is standard treatment for localised prostate cancer and is often combined with hormone treatment to prevent androgen stimulation of prostate cancer. Hormone therapy carries significant morbidity and can only be justified in the radical treatment of localised disease if it can be balanced against a significant gain in disease control and survival.
MATERIALS AND METHODS
We searched Medline, Premedline, Embase, Cochrane Library, Web of Science (SCI & SSCI) and Biomed Central for randomised controlled trials published in English comparing radiotherapy or hormone therapy alone with radiotherapy and hormone therapy in combination as first-line treatment in patients with non-metastatic prostate cancer reporting overall survival, disease-free survival, distant metastases-free survival, biochemical survival, adverse events (including cardiovascular) and/or health-related quality of life.
RESULTS
Fourteen trials were included and showed that combination therapy was associated with better or similar survival and disease-free outcomes compared with single-modality treatment, and that this may particularly be the case for patients with higher risk disease. The results also suggested that combination therapy is associated with more and worse adverse events and quality of life, although this was not always the case. Some of the results are at risk of reporting bias.
CONCLUSION
The published data support the use of combined treatment with androgen deprivation and radiotherapy for intermediate- and high-risk localised and locally advanced prostate cancer. Optimal timing, duration, formulation and the management of side-effects remain important questions for further research.
Topics: Androgen Antagonists; Chemoradiotherapy; Humans; Male; Prognosis; Prostatic Neoplasms; Radiotherapy
PubMed: 25059922
DOI: 10.1016/j.clon.2014.06.016 -
Scientific Reports May 2016Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim... (Meta-Analysis)
Meta-Analysis Review
Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim of this study was to investigate the clinical value of the urine PCA3 test in the diagnosis of prostate cancer by pooling the published data. Clinical trials utilizing the urine PCA3 test for diagnosing prostate cancer were retrieved from PubMed and Embase. A total of 46 clinical trials including 12,295 subjects were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.65 (95% confidence interval [CI]: 0.63-0.66), 0.73 (95% CI: 0.72-0.74), 2.23 (95% CI: 1.91-2.62), 0.48 (95% CI: 0.44-0.52), 5.31 (95% CI: 4.19-6.73) and 0.75 (95% CI: 0.74-0.77), respectively. In conclusion, the urine PCA3 test has acceptable sensitivity and specificity for the diagnosis of prostate cancer and can be used as a non-invasive method for that purpose.
Topics: Antigens, Neoplasm; Humans; Male; Odds Ratio; Prostatic Neoplasms; ROC Curve; Sensitivity and Specificity
PubMed: 27161545
DOI: 10.1038/srep25776 -
European Urology Jun 2015Many men with clinically localized prostate cancer are being monitored as part of active surveillance (AS) programs, but little is known about reasons for receiving... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Many men with clinically localized prostate cancer are being monitored as part of active surveillance (AS) programs, but little is known about reasons for receiving radical treatment.
OBJECTIVES
A systematic review of the evidence about AS was undertaken, with a meta-analysis to identify predictors of radical treatment.
EVIDENCE ACQUISITION
A comprehensive search of the Embase, MEDLINE and Web of Knowledge databases to March 2014 was performed. Studies reporting on men with localized prostate cancer followed by AS or monitoring were included. AS was defined where objective eligibility criteria, management strategies, and triggers for clinical review or radical treatment were reported.
EVIDENCE SYNTHESIS
The 26 AS cohorts included 7627 men, with a median follow-up of 3.5 yr (range of medians 1.5-7.5 yr). The cohorts had a wide range of inclusion criteria, monitoring protocols, and triggers for radical treatment. There were eight prostate cancer deaths and five cases of metastases in 24,981 person-years of follow-up. Each year, 8.8% of men (95% confidence interval 6.7-11.0%) received radical treatment, most commonly because of biopsy findings, prostate-specific antigen triggers, or patient choice driven by anxiety. Studies in which most men changed treatment were those including only low-risk Gleason score 6 disease and scheduled rebiopsies.
CONCLUSIONS
The wide variety of AS protocols and lack of robust evidence make firm conclusions difficult. Currently, patients and clinicians have to make judgments about the balance of risks and benefits in AS protocols. The publication of robust evidence from randomized trials and longer-term follow-up of cohorts is urgently required.
PATIENT SUMMARY
We reviewed 26 studies of men on active surveillance for prostate cancer. There was evidence that studies including men with the lowest risk disease and scheduled rebiopsy had higher rates of radical treatment.
Topics: Biopsy; Disease Progression; Humans; Male; Neoplasm Grading; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Factors; Watchful Waiting
PubMed: 25616709
DOI: 10.1016/j.eururo.2015.01.004 -
European Urology Jul 2003Brachytherapy is emerging as a new treatment option for prostate cancer, and is increasingly being used in Europe and North America. (Comparative Study)
Comparative Study Review
OBJECTIVES
Brachytherapy is emerging as a new treatment option for prostate cancer, and is increasingly being used in Europe and North America.
METHODS
A systematic review of studies that compared clinical or cost effectiveness of prostate brachytherapy with radical prostatectomy or external beam radiation for patients with localised prostate cancer.
RESULTS
No randomised controlled trials were identified, but five observational studies with comparable patient groups were included in the review. There were no valid data on overall or disease-free survival. There was no difference in disease-free survival based on PSA as a surrogate measure, or in rates of complications. No cost effectiveness studies were found. Based on Norwegian data, the one-year cost of the three treatment options seem fairly similar, while long term cost data are lacking due to lack of data on long term clinical outcome.
CONCLUSION
The evidence on the clinical effectiveness of therapies for localised prostate cancer is scarce, but the outcome appears to be comparable for radical prostatectomy, external beam radiotherapy and brachytherapy.
Topics: Aged; Aged, 80 and over; Brachytherapy; Cost-Benefit Analysis; Health Care Costs; Humans; Male; Middle Aged; Neoplasm Staging; Norway; Prostatectomy; Prostatic Neoplasms; Radiation Dosage; Radiotherapy, Conformal; Randomized Controlled Trials as Topic; Risk Assessment; Survival Analysis; Treatment Outcome
PubMed: 12814673
DOI: 10.1016/s0302-2838(03)00187-8 -
The Oncologist Jul 2021Prostate cancer remains the leading diagnosed cancer and the second leading cause of death among American men. Despite improvements in screening modalities, diagnostics,...
Prostate cancer remains the leading diagnosed cancer and the second leading cause of death among American men. Despite improvements in screening modalities, diagnostics, and treatment, disparities exist among Black men in this country. The primary objective of this systematic review is to describe the reported disparities in screening, diagnostics, and treatments as well as efforts to alleviate these disparities through community and educational outreach efforts. Critical review took place of retrospective, prospective, and socially descriptive data of English language publications in the PubMed database. Despite more advanced presentation, lower rates of screening and diagnostic procedures, and low rates of trial inclusion, subanalyses have shown that various modalities of therapy are quite effective in Black populations. Moreover, patients treated on prospective clinical trials and within equal-access care environments have shown similar outcomes regardless of race. Additional prospective studies and enhanced participation in screening, diagnostic and genetic testing, clinical trials, and community-based educational endeavors are important to ensure equitable progress in prostate cancer for all patients. IMPLICATIONS FOR PRACTICE: Notable progress has been made with therapeutic advances for prostate cancer, but racial disparities continue to exist. Differing rates in screening and utility in diagnostic procedures play a role in these disparities. Black patients often present with more advanced disease, higher prostate-specific antigen, and other adverse factors, but outcomes can be attenuated in trials or in equal-access care environments. Recent data have shown that multiple modalities of therapy are quite effective in Black populations. Novel and bold hypotheses to increase inclusion in clinical trial, enhance decentralized trial efforts, and enact successful models of patient navigation and community partnership are vital to ensure continued progress in prostate cancer disparities.
Topics: Black or African American; Early Detection of Cancer; Humans; Male; Prospective Studies; Prostatic Neoplasms; Retrospective Studies; United States
PubMed: 33683758
DOI: 10.1002/onco.13749 -
Prostate Cancer and Prostatic Diseases Dec 2023The goal of precision medicine in prostate cancer (PCa) is to individualize the treatment according to the patient's germline mutation status. PCa has a very high rate... (Review)
Review
BACKGROUND
The goal of precision medicine in prostate cancer (PCa) is to individualize the treatment according to the patient's germline mutation status. PCa has a very high rate of genetic predisposition compared with other cancers in men, with an estimated rate of cancers ascribable to hereditary factors of 5-15%.
METHODS
A systematic search (PubMed, Web of Science, and ClinicalTrials.gov) of English literature from 2000 to 2022, using the keywords "prostate cancer", "germline mutations", "family history", and "inheritance" was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.
RESULTS
The search identified 980 publications. Of these, 200 papers were removed before screening (duplicates, non-English literature, and publication year before 2000) and 245 records were excluded after title/abstract screening. Finally, 50 articles were included in the final analysis. We analyze the latest evidence on the genetic basis of PCa predisposition and clinical implications for more personalized screening protocols and therapeutic management of this high-prevalent cancer.
DISCUSSION
Emerging data show that germline mutations in homologous recombination genes (BRCA1/2, ATM, CHECK2), in mismatch repair genes (MLH1, MLH2, MSH6), and other additional genes are associated with the development and aggressiveness of PCa. Germline testing and genetic counseling have increasingly important implications in cancer screening and therapeutic decisions making for patients affected by PCa. Patients with localized PCa and some gene mutations are more likely to develop aggressive cancer, so active treatment may be preferable to active surveillance for these patients. Moreover, in patients with metastatic PCa, these gene alterations may be useful biomarkers for predicting response to specific therapy such as PARP inhibitors, recently approved for the treatment of metastatic castration-resistant PCa. The evidence supports recent guidelines and recommendations considering germline genetic testing for patients with a positive family history of PCa or men with high risk or metastatic disease.
Topics: Male; Humans; Prostatic Neoplasms; Germ-Line Mutation; BRCA1 Protein; Precision Medicine; BRCA2 Protein
PubMed: 36434163
DOI: 10.1038/s41391-022-00609-3 -
World Journal of Urology Nov 2023Doses delivered to the urethra have been associated with an increased risk to develop long-term urinary toxicity in patients undergoing stereotactic body radiotherapy...
PURPOSE
Doses delivered to the urethra have been associated with an increased risk to develop long-term urinary toxicity in patients undergoing stereotactic body radiotherapy (SBRT) for prostate cancer (PCa). Aim of the present systematic review is to report on the role of urethra-sparing SBRT (US-SBRT) techniques for prostate cancer, with a focus on outcome and urinary toxicity.
METHOD
A systematic review of the literature was performed on the PubMed database on May 2023. Based on the urethra-sparing technique, 13 studies were selected for the analysis and classified in the two following categories: "urethra-steering" SBRT (restriction of hotspots to the urethra) and "urethra dose-reduction" SBRT (dose reduction to urethra below the prescribed dose).
RESULTS
By limiting the urethra D to 90GyEQD2 (α/β = 3 Gy) with urethra-steering SBRT techniques, late genitourinary (GU) grade 2 toxicity remains mild, ranging between 12.1% and 14%. With dose-reduction strategies decreasing the urethral dose below 70 GyEQD2, the risk of late GU toxicity was further reduced (< 8% at 5 years), while maintaining biochemical relapse-free survival rates up to 93% at 5 years.
CONCLUSION
US-SBRT techniques limiting maximum doses to urethra below a 90Gy (α/β = 3 Gy) threshold result in a low rate of acute and late grade ≥ 2 GU toxicity. A better understanding of clinical factors and anatomical substructures involved in the development of GU toxicity, as well as the development and use of adapted dose constraints, is expected to further reduce the long-term GU toxicity of prostate cancer patients treated with SBRT.
Topics: Male; Humans; Urethra; Radiosurgery; Neoplasm Recurrence, Local; Prostatic Neoplasms; Urogenital System
PubMed: 37668718
DOI: 10.1007/s00345-023-04579-6