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Current Oncology (Toronto, Ont.) Oct 2023Prostate cancer ranks as the second most common malignancy in males. Prostate cancer progressing on androgen deprivation therapy (ADT) is castration-resistant prostate... (Meta-Analysis)
Meta-Analysis Review
Prostate cancer ranks as the second most common malignancy in males. Prostate cancer progressing on androgen deprivation therapy (ADT) is castration-resistant prostate cancer (CRPC). Poly-ADP ribose polymerase (PARP) inhibitors (PARPis) have been at the forefront of the treatment of CRPC. We aim to better characterize the progression-free survival (PFS) and overall survival (OS) in metastatic CRPC patients treated with PARPis. A systemic review search was conducted using National Clinical Trial (NCT), PubMed, Embase, Scopus, and Central Cochrane Registry. The improvement in overall survival was statistically significant, favoring PARPis (hazard ratio (HR) 0.855; 95% confidence interval (CI) 0.752-0.974; = 0.018). The improvement in progression-free survival was also statistically significant, with results favoring PARPis (HR 0.626; 95%CI 0.566-0.692; = 0.000). In a subgroup analysis, similar results were observed where the efficacy of PARPis was evaluated in a subgroup of patients without homologous recombination repair (HRR) gene mutation, which showed improvement in PFS favoring PARPis (HR 0.747; 95%CI 0.0.637-0.877; = 0.000). Our meta-analysis of seven RCTs showed that PARPis significantly increased PFS and OS when used with or without antihormonal agents like abiraterone or enzalutamide.
Topics: Humans; Male; Androgen Antagonists; Poly(ADP-ribose) Polymerase Inhibitors; Progression-Free Survival; Prostatic Neoplasms, Castration-Resistant; Randomized Controlled Trials as Topic
PubMed: 37887569
DOI: 10.3390/curroncol30100669 -
Psycho-oncology Nov 2023To evaluate the evidence base for patient, oncological, and treatment prognostic factors associated with multiple mental wellbeing outcomes in prostate cancer patients. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To evaluate the evidence base for patient, oncological, and treatment prognostic factors associated with multiple mental wellbeing outcomes in prostate cancer patients.
METHODS
We performed a literature search of MEDLINE, EMBASE, and CINAHL databases including studies evaluating patient, oncological, or treatment factors against one of five mental wellbeing outcomes; depression, anxiety, fear of cancer recurrence, masculinity, and body image perception. Data synthesis included a random effects meta-analysis for the prognostic effect of individual factors if sufficient homogenous data was available, with a structured narrative synthesis where this was not possible.
RESULTS
A final 62 articles were included. Older age was associated with a reducing odds of depression (OR 0.97, p = 0.04), with little evidence of effect for other outcomes. Additionally, baseline mental health status was related to depression and increasing time since diagnosis was associated with reducing fear of recurrence, albeith with low certainty of evidence. However, few other patient or oncological factors demonstrated any coherent relationship with any wellbeing outcome. Androgen deprivation therapy was associated with increased depression (HR 1.65, 95% CI 1.41-1.92, p < 0.01) and anxiety, however, little difference was seen between other treatment options. Overall, whilst numerous factors were identified, most were evaluated by single studies with few evaluating masculinity and body image outcomes.
CONCLUSION
We highlight the existing evidence for prognostic factors in mental wellbeing outcomes in prostate cancer, allowing us to consider high-risk groups of patients for preventative and treatment measures. However, the current evidence is heterogenous with further work required exploring less conclusive factors and outcomes.
Topics: Male; Humans; Prostatic Neoplasms; Depression; Prognosis; Androgen Antagonists; Neoplasm Recurrence, Local; Quality of Life
PubMed: 37789603
DOI: 10.1002/pon.6225 -
Scientific Reports Oct 2023The involvement of human papillomavirus (HPV) in the prostate carcinogenesis is a controversial issue. The presented meta-analysis was carried out to systematize the... (Meta-Analysis)
Meta-Analysis
The involvement of human papillomavirus (HPV) in the prostate carcinogenesis is a controversial issue. The presented meta-analysis was carried out to systematize the currently available research results regarding this question. The meta-analysis includes case-control studies from 1991 to 2022, which were collected from publicly available bibliometric databases. The meta-analysis was performed using Meta-Essentials_1.5 software. We used Begg's and Egger's methods to assess publication bias. Cochran's Q test was used to assess heterogeneity and the I index was employed for calculating the variation in the pooled estimations. The analysis was based on data from 27 case-control studies, which in total yielded 1607 tumour tissue samples of prostate and 1515 control samples (317 samples of normal tissue, 1198 samples of benign prostatic hyperplasia (BPH)). According to the data obtained, there was high risk of prostate cancer by HPV infection in both cases. HPV was found in prostate cancer in 25.8% of cases, while in normal tissue samples the virus was detected in 9.2% of cases and in 17.4% with BPH as a control. In particular, more studies on the association of HPV and prostate cancer are needed to prove the role of HPV in the development of prostate cancer. In addition to the controversial question of whether HPV infection is associated with prostate cancer risk, it is worth considering whether the samples used as a control have an impact on the results. The impact of HPV in prostate tumour tissue samples on outcome should also be investigated.
Topics: Male; Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Prostatic Hyperplasia; Papillomaviridae; Prostatic Neoplasms
PubMed: 37789036
DOI: 10.1038/s41598-023-43767-7 -
Urologia Feb 2024The major barriers to phytonutrients in prostate cancer therapy are non-specific mechanisms and bioavailability issues. Studies have pointed to a synergistic combination... (Review)
Review
The major barriers to phytonutrients in prostate cancer therapy are non-specific mechanisms and bioavailability issues. Studies have pointed to a synergistic combination of curcumin (CURC) and ursolic acid (UA). We investigate this combination using a systematic review process to assess the most likely mechanistic pathway and human testing in prostate cancer. We used the PRISMA statement to screen titles, abstracts, and the full texts of relevant articles and performed a descriptive analysis of the literature reviewed for study inclusion and consensus of the manuscript. The most common molecular and cellular pathway from articles reporting on the pathways and effects of CURC ( = 173) in prostate cancer was NF-κB ( = 25, 14.5%). The most common molecular and cellular pathway from articles reporting on the pathways and effects of UA ( = 24) in prostate cancer was caspase 3/caspase 9 ( = 10, 41.6%). The three most common molecular and cellular pathway from articles reporting on the pathways and effects of both CURC and UA ( = 193) in prostate cancer was NF-κB ( = 28, 14.2%), Akt ( = 22, 11.2%), and androgen ( = 19, 9.6%). Therefore, we have identified the potential synergistic target pathways of curcumin and ursolic acid to involve NF-κB, Akt, androgen receptors, and apoptosis pathways. Our review highlights the limited human studies and specific effects in prostate cancer.
Topics: Male; Humans; Ursolic Acid; Curcumin; NF-kappa B; Signal Transduction; Proto-Oncogene Proteins c-akt; Apoptosis; Triterpenes; Prostatic Neoplasms
PubMed: 37776274
DOI: 10.1177/03915603231202304 -
Asian Pacific Journal of Cancer... Sep 2023Prostate cancer (Pca) is one of the most prevalent health conditions affecting men, particularly older men, and cases have increased in recent years. (Meta-Analysis)
Meta-Analysis
UNLABELLED
Prostate cancer (Pca) is one of the most prevalent health conditions affecting men, particularly older men, and cases have increased in recent years.
OBJECTIVE
This review examined the survival rate and prognostic factors of patients with Pca in Southeast Asia (SEA).
METHODS
We conducted a systematic search of three databases (PubMed, Scopus, Web of Science) and a manual search until April 1, 2022. The selected papers were evaluated using the Newcastle-Ottawa Quality Assessment Form for Cohort Studies. The review protocol was registered with PROSPERO (CRD42022326521). Pooled prevalence rates were calculated using the programme R version 4.2.1. Heterogeneity was assessed using the I2 statistic and p-value. A narrative approach was used to describe prognostic factors. Studies were selected and finalised based on the review question. The quality of the included studies was assessed.
RESULTS
A total of 11 studies were included in this review. The 1-, 3-, 5- and 10-year survival rates of SEA Pca cases were 80.8%, 51.9%, 66.1% (range 32.1-100) and 78% (range 55.9-100), respectively. Prognostic factors for Pca were discussed in terms of sociodemographic, disease-related and treatment-related aspects. The predictors of significantly lower survival were age more than 75 years, cancer detected during transurethral resection of the prostate, Gleason score more or equal to eight, high-risk group, metastases and no adjuvant radiotherapy. A meta-analysis on the pooled HR of prostate cancer could not be performed due to the heterogeneity of prognostic factors. The pooled prevalence of localised and metastatic prostate cancer in SEA countries was 39% 95% CI [20-62] and 40% 95% CI [28-53], respectively.
CONCLUSION
The survival rate in SEA countries can be determined by prognostic factors, which can be divided into sociodemographic, disease-related and treatment-related factors. Therefore, further studies are needed to improve the understanding and treatment of Pca in the region SEA.
Topics: Male; Humans; Aged; Survival Rate; Prognosis; Southeast Asian People; Transurethral Resection of Prostate; Prostatic Neoplasms
PubMed: 37774044
DOI: 10.31557/APJCP.2023.24.9.2941 -
Journal of Biomedical Informatics Nov 2023Adequate methods to promptly translate digital health innovations for improved patient care are essential. Advances in Artificial Intelligence (AI) and Machine Learning... (Review)
Review
INTRODUCTION
Adequate methods to promptly translate digital health innovations for improved patient care are essential. Advances in Artificial Intelligence (AI) and Machine Learning (ML) have been sources of digital innovation and hold the promise to revolutionize the way we treat, manage and diagnose patients. Understanding the benefits but also the potential adverse effects of digital health innovations, particularly when these are made available or applied on healthier segments of the population is essential. One of such adverse effects is overdiagnosis.
OBJECTIVE
to comprehensively analyze quantification strategies and data-driven definitions for overdiagnosis reported in the literature.
METHODS
we conducted a scoping systematic review of manuscripts describing quantitative methods to estimate the proportion of overdiagnosed patients.
RESULTS
we identified 46 studies that met our inclusion criteria. They covered a variety of clinical conditions, primarily breast and prostate cancer. Methods to quantify overdiagnosis included both prospective and retrospective methods including randomized clinical trials, and simulations.
CONCLUSION
a variety of methods to quantify overdiagnosis have been published, producing widely diverging results. A standard method to quantify overdiagnosis is needed to allow its mitigation during the rapidly increasing development of new digital diagnostic tools.
Topics: Male; Humans; Retrospective Studies; Artificial Intelligence; Overdiagnosis; Prospective Studies; Prostatic Neoplasms
PubMed: 37769829
DOI: 10.1016/j.jbi.2023.104506 -
European Urology Jan 2024In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand...
BACKGROUND
In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications.
OBJECTIVE
We aimed to critically review developments in molecular hybrid imaging and systemic radioligand therapy, to reach a multidisciplinary consensus on the current state of the art in PCa.
DESIGN, SETTING, AND PARTICIPANTS
The results of a systematic literature search informed a two-round Delphi process with a panel of 28 PCa experts in medical or radiation oncology, urology, radiology, medical physics, and nuclear medicine. The results were discussed and ratified in a consensus meeting.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Forty-eight statements were scored on a Likert agreement scale and six as ranking options. Agreement statements were analysed using the RAND appropriateness method. Ranking statements were analysed using weighted summed scores.
RESULTS AND LIMITATIONS
After two Delphi rounds, there was consensus on 42/48 (87.5%) of the statements. The expert panel recommends PSMA PET to be used for staging the majority of patients with unfavourable intermediate and high risk, and for restaging of suspected recurrent PCa. There was consensus that oligometastatic disease should be defined as up to five metastases, even using advanced imaging modalities. The group agreed that [Lu]Lu-PSMA should not be administered only after progression to cabazitaxel and that [Ra]RaCl remains a valid therapeutic option in bone-only metastatic castration-resistant PCa. Uncertainty remains on various topics, including the need for concordant findings on both []FDG and PSMA PET prior to [Lu]Lu-PSMA therapy.
CONCLUSIONS
There was a high proportion of agreement among a panel of experts on the use of molecular imaging and theranostics in PCa. Although consensus statements cannot replace high-certainty evidence, these can aid in the interpretation and dissemination of best practice from centres of excellence to the wider clinical community.
PATIENT SUMMARY
There are situations when dealing with prostate cancer (PCa) where both the doctors who diagnose and track the disease development and response to treatment, and those who give treatments are unsure about what the best course of action is. Examples include what methods they should use to obtain images of the cancer and what to do when the cancer has returned or spread. We reviewed published research studies and provided a summary to a panel of experts in imaging and treating PCa. We also used the research summary to develop a questionnaire whereby we asked the experts to state whether or not they agreed with a list of statements. We used these results to provide guidance to other health care professionals on how best to image men with PCa and what treatments to give, when, and in what order, based on the information the images provide.
Topics: Humans; Male; Molecular Imaging; Nuclear Medicine; Positron-Emission Tomography; Precision Medicine; Prostatic Neoplasms
PubMed: 37743194
DOI: 10.1016/j.eururo.2023.09.003 -
Urology Journal Feb 2024To compare the effects of RALP and LRP on health-related QoL following radical prostatectomy, focusing on studies performed via validated QoL questionnaires measuring...
Comparison of Health-Related Quality of Life Changes in Prostate Cancer Patients Undergoing Laparoscopic versus Robotic-Assisted Laparoscopic Radical Prostatectomy: A Systematic review.
PURPOSE
To compare the effects of RALP and LRP on health-related QoL following radical prostatectomy, focusing on studies performed via validated QoL questionnaires measuring particularly general health-related QoL.
MATERIAL AND METHODS
A systematic search was conducted using Web of Science, PubMed (MEDLINE) on 15 January 2023 with the following search terms solely or in combination: "robotic radical prostatectomy", "laparoscopic radical prostatectomy," and "quality of life". After retrieving the titles and abstracts of selected articles, the full texts of related articles were screened.
RESULTS
After full-text evaluation, among 185 articles, 23 articles were found eligible for inclusion. Hoze et al. reported that the global health status at the 12th month of the surgery was almost the same in both groups according to EORTC- QLQ-C30 scores (76.3 in the RALRP group vs. 76.1 in the LRP group). Wang et al. reported a 75 point of EORTC-QOL-C30 global health status ten years after LRP. Wyler et al. found that the 1-3 month EORTC-QLQ-C30 global health score was significantly worser than the baseline score, 65.3±18.3 vs. 77.2±18.2; however, it returned to baseline in 13-24 months (77.7±16.8) even proceed baseline score in experienced hands at 49-58 months follow up, 78.2±17.8 vs. 85.3±15.5. The frequently used patient-reported quality of life questionnaire following RALRP was EORTC-QLQ.
CONCLUSION
Both robotic-assisted and laparoscopic radical prostatectomy are valid treatment options to achieve a good quality of life following surgery. The intermediate and long-term results in regard to QoL are comparable between the two procedures. RALRP might be superior to LRP in terms of immediate health-related quality of life, which might contribute to early recovery of urinary function.
Topics: Male; Humans; Robotic Surgical Procedures; Quality of Life; Prostatic Neoplasms; Prostatectomy; Laparoscopy; Treatment Outcome
PubMed: 37727913
DOI: 10.22037/uj.v20i.7707 -
European Urology Oncology Jun 2024Testing for mutations in Breast Cancer Gene 1/2 (BRCA) has emerged as a novel decision-making tool for clinicians. Patients with metastatic castration-resistant prostate... (Meta-Analysis)
Meta-Analysis Comparative Study Review
Poly (ADP-ribose) Polymerase Inhibitors Have Comparable Efficacy with Platinum Chemotherapy in Patients with BRCA-positive Metastatic Castration-resistant Prostate Cancer. A Systematic Review and Meta-analysis.
CONTEXT
Testing for mutations in Breast Cancer Gene 1/2 (BRCA) has emerged as a novel decision-making tool for clinicians. Patients with metastatic castration-resistant prostate cancer (mCRPC) harboring pathogenic BRCA mutations can benefit from poly (ADP-ribose) polymerase inhibitor (PARPi) and platinum treatments, whereas the impact of the mutation on sensitivity to cabazitaxel and prostate-specific membrane antigen (PSMA)-ligand therapy is currently unknown.
OBJECTIVE
To assess the efficacy of PARPi, platinum, cabazitaxel, and PSMA-ligand therapies in BRCA-positive mCRPC.
EVIDENCE ACQUISITION
Databases were queried in February 2022. We performed data synthesis by using both proportional and individual patient data. For prostate-specific antigen (PSA) response rate (≥50% decrease from baseline [PSA50]) evaluation, we pooled event rates with 95% confidence intervals (CIs). Progression-free (PFS) and overall (OS) survival analyses with individual patient data were performed with the mixed-effect Cox proportional hazard model and single-arm random-effect analysis, providing pooled medians.
EVIDENCE SYNTHESIS
We included 23 eligible studies with 901 BRCA-positive mCRPC patients. PSA50 response rates for PARPi and platinum were 69% (CI: 53-82%), and 74% (CI: 49-90%), respectively. Analyses of OS data showed no difference between PARPi and platinum treatments (hazard ratio: 0.86; CI: 0.49-1.52; p = 0.6). The single-arm OS and PFS analyses revealed similarities among different PARPis; pooled PFS and OS medians were 9.7 mo (CI: 8.1-12.5) and 17.4 mo (CI: 12.7-20.1), respectively.
CONCLUSIONS
Our data revealed that different PARPis were similarly effective in terms of PFS and OS. Moreover, we found that PARPi and platinum therapy were comparable in terms of PSA50 response rate and OS, highlighting that platinum is a valid treatment option for BRCA-positive mCRPC patients. However, prospective interventional studies comparing these agents are essential to provide a higher level of evidence.
PATIENT SUMMARY
In this report, we found that different poly (ADP-ribose) polymerase inhibitors had similar efficacy, and platinum was a valid treatment option in BRCA-positive metastatic castration-resistant prostate cancer patients.
Topics: Humans; Prostatic Neoplasms, Castration-Resistant; Poly(ADP-ribose) Polymerase Inhibitors; Male; Treatment Outcome; BRCA2 Protein; Antineoplastic Agents; Neoplasm Metastasis; BRCA1 Protein
PubMed: 37722977
DOI: 10.1016/j.euo.2023.09.001 -
Cancer Treatment Reviews Nov 2023PARP inhibitors (PARPi) are a standard-of-care (SoC) treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Several clinical trials... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
PARP inhibitors (PARPi) are a standard-of-care (SoC) treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Several clinical trials have shown the potential of combining PARPi with other anticancer agents. Therefore, we conducted a systematic review and meta-analysis to comprehensively evaluate the efficacy and safety of PARPi in patients with metastatic prostate cancer.
METHODS
MEDLINE, Cochrane CENTRAL, EMBASE, CINAHL, and Web of Science were searched on March 22nd, 2023, for phase 2 or 3 clinical trials. Efficacy (progression-free survival [PFS], overall survival [OS], PSA decline >50% [PSA50], and objective response rate [ORR]) and safety outcomes were assessed in the included studies.
RESULTS
Seventeen clinical trials (PARPi monotherapy [n = 7], PARPi + androgen-receptor signaling inhibitors [ARSI] [n = 6], and PARPi + immune checkpoint inhibitors [ICI] [n = 4]) were included in the quantitative analyses. PARPi monotherapy improved radiographic PFS and OS over SoC in mCRPC patients with alterations in BRCA1 or BRCA2 genes but not in those with alterations in the ATM gene. Higher rates of PSA50 and ORR were reported in participants treated with PARPi + ARSI than in single-agent PARPi or PARPi + ICI. Although the rate of high-grade adverse events was similar across all groups, treatment discontinuation was higher in patients treated with PARPi-based combinations than PARPi monotherapy.
CONCLUSION
The efficacy of PARPi is not uniform across mCRPC patients with alterations in DNA damage repair genes, and optimal patient selection remains a clinical challenge. No unexpected safety signals for this class of agents emerged from this analysis.
Topics: Male; Humans; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms, Castration-Resistant; Immune Checkpoint Inhibitors; Patient Selection; Progression-Free Survival
PubMed: 37716332
DOI: 10.1016/j.ctrv.2023.102623