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International Journal of Molecular... Aug 2023PARPi, in combination with ionizing radiation, has demonstrated the ability to enhance cellular radiosensitivity in different tumors. The rationale is that the exposure...
PARPi, in combination with ionizing radiation, has demonstrated the ability to enhance cellular radiosensitivity in different tumors. The rationale is that the exposure to radiation leads to both physical and biochemical damage to DNA, prompting cells to initiate three primary mechanisms for DNA repair. Two double-stranded DNA breaks (DSB) repair pathways: (1) non-homologous end-joining (NHEJ) and (2) homologous recombination (HR); and (3) a single-stranded DNA break (SSB) repair pathway (base excision repair, BER). In this scenario, PARPi can serve as radiosensitizers by leveraging the BER pathway. This mechanism heightens the likelihood of replication forks collapsing, consequently leading to the formation of persistent DSBs. Together, the combination of PARPi and radiotherapy is a potent oncological strategy. This combination has proven its efficacy in different tumors. However, in prostate cancer, there are only preclinical studies to support it and, recently, an ongoing clinical trial. The objective of this paper is to perform a review of the current evidence regarding the use of PARPi and radiotherapy (RT) in PCa and to give future insight on this topic.
Topics: Humans; Male; DNA Repair; Medical Oncology; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms; Radiation Oncology
PubMed: 37629155
DOI: 10.3390/ijms241612978 -
Journal of Geriatric Oncology Jun 2024Older patients are often deemed ineligible for clinical research, and many frequently-used endpoints and outcome measures are not as relevant for older patients for... (Review)
Review
INTRODUCTION
Older patients are often deemed ineligible for clinical research, and many frequently-used endpoints and outcome measures are not as relevant for older patients for younger ones. This systematic review aimed to present an overview of outcomes used in clinical research regarding patients over the age of 65 years with prostate cancer.
MATERIALS AND METHODS
PubMed and Embase were systematically searched to identify studies on prostate cancer (treatment) in patients aged ≥65 between 2016 and 2023. Data on title, study design, number of participants and age, stage of disease, treatment, and investigated outcomes were synthesized and descriptively analyzed.
RESULTS
Sixty-eight studies were included. Of these most included patients over 65 years, while others used a higher age. Overall, 39 articles (57.3%) reported on survival-related outcomes, 22 (32.4%) reported on progression of disease and 38 (55.9%) used toxicity or adverse events as an outcome measure. Health-related quality of life and functional outcomes were investigated in 29.4%, and cognition in two studies. The most frequently investigated survival-related outcomes were overall and cancer-specific survival (51.3%); however, 38.5% only studied overall survival.
DISCUSSION
The main focus of studies included in this review remains survival and disease progression. There is limited attention for health-related quality of life and functional status, although older patients often prioritize the latter. Future research should incorporate outcome measures tailored to the aged population to improve care for older patients with prostate cancer.
Topics: Humans; Male; Prostatic Neoplasms; Aged; Quality of Life; Aged, 80 and over; Disease Progression; Outcome Assessment, Health Care; Age Factors
PubMed: 38575500
DOI: 10.1016/j.jgo.2024.101763 -
European Urology Open Science Aug 2023Prostate cancer (PC) disproportionately affects men of Black race, and lower educational and socioeconomic status. Guidelines are based on randomised controlled trials...
A Systematic Review of Patient Race, Ethnicity, Socioeconomic Status, and Educational Attainment in Prostate Cancer Treatment Randomised Trials-Is the Evidence Base Applicable to the General Patient Population?
CONTEXT
Prostate cancer (PC) disproportionately affects men of Black race, and lower educational and socioeconomic status. Guidelines are based on randomised controlled trials (RCTs); however, the representation of different races, educations, and socioeconomic backgrounds in these trials is unclear.
OBJECTIVE
To assess reporting of equality, diversity, and inclusion characteristics (Equality, Diversity and Inclusion [EDI]) and differences in treatment effects between different races, and educational or socioeconomic status.
EVIDENCE ACQUISITION
We conducted a systematic review of CENTRAL, MEDLINE, and Embase in April 2020 examining RCTs investigating treatments for PC. Outcomes collected were race/ethnicity, educational attainment, and socioeconomic status. RCTs investigating PC treatment in any population or setting were included. Data extraction of characteristics was performed independently by pairs of reviewers and checked by a senior author. The Cochrane risk of bias tool assessed the quality of included papers.
EVIDENCE SYNTHESIS
A total of 265 trials were included, and 138 of these were available as full-text articles. Fifty-four trials including 19 039 participants reported any EDI data. All 54 trials reported race, 11 reported ethnicity, three reported educational attainment, and one reported socioeconomic status. Patients of White race were the majority of the recruited population (82.6%), while the minority prevalence was as follows: Black 9.8% and Asian 5.7%. Three studies reported mortality outcomes depending on the participant's race. All three studies investigated different treatments, so a meta-analysis was not performed. No studies reported outcomes stratified by the educational or socioeconomic status of participants.
CONCLUSIONS
There is poor reporting of patient race, ethnicity, socioeconomic background, and educational attainment in RCTs for PC treatments between 2010 and 2020. Addressing this for future studies will help explain differences in the incidence of and mortality from PC and improve the generalisability of results.
PATIENT SUMMARY
In this study, we reviewed prostate cancer treatment trials to see whether these reported race, education, and socioeconomic backgrounds of their patient populations. We conclude that reporting of these characteristics is poor. This needs to be improved in future to improve outcomes for patients with prostate cancer of all ethnical, racial, and socioeconomic groups.
PubMed: 37545851
DOI: 10.1016/j.euros.2023.05.015 -
International Journal of Surgery... Mar 2024Pelvic lymph node dissection (PLND) is commonly performed during radical prostatectomy (RP) for prostate cancer staging. This study aimed to comprehensively analyze... (Meta-Analysis)
Meta-Analysis
A comparative analysis of perioperative complications and biochemical recurrence between standard and extended pelvic lymph node dissection in prostate cancer patients undergoing radical prostatectomy: a systematic review and meta-analysis.
INTRODUCTION
Pelvic lymph node dissection (PLND) is commonly performed during radical prostatectomy (RP) for prostate cancer staging. This study aimed to comprehensively analyze existing evidence compare perioperative complications associated with standard (sPLND) versus extended PLND templates (ePLND) in RP patients.
METHODS
A meta-analysis of prospective studies on PLND complications was conducted. Systematic searches were performed on Web of Science, Pubmed, Embase, and the Cochrane Library until May 2023. Risk ratios (RRs) were estimated using random-effects models in the meta-analysis. The statistical analysis of the data was carried out using Review Manager software.
RESULTS
Nine studies, including three randomized clinical trial and six prospective studies, with a total of 4962 patients were analyzed. The meta-analysis revealed that patients undergoing ePLND had a higher risk of partial perioperative complications, such as lymphedema ( I2 =28%; RR 0.05; 95% CI: 0.01-0.27; P <0.001) and urinary retention ( I2 =0%; RR 0.30; 95% CI: 0.09-0.94; P =0.04) compared to those undergoing sPLND. However, there were no significant difference was observed in pelvic hematoma ( I2 =0%; RR 1.65; 95% CI: 0.44-6.17; P =0.46), thromboembolic ( I2 =57%; RR 0.91; 95% CI: 0.35-2.38; P =0.85), ureteral injury ( I2 =33%; RR 0.28; 95% CI: 0.05-1.52; P =0.14), intraoperative bowel injury ( I2 =0%; RR 0.87; 95% CI: 0.14-5.27; P =0.88), and lymphocele ( I2 =0%; RR 1.58; 95% CI: 0.54-4.60; P =0.40) between sPLND and ePLND. Additionally, no significant difference was observed in overall perioperative complications ( I2 =85%; RR 0.68; 95% CI: 0.40-1.16; P =0.16). Furthermore, ePLND did not significantly reduce biochemical recurrence ( I2 =68%; RR 0.59; 95% CI: 0.28-1.24; P =0.16) of prostate cancer.
CONCLUSION
This analysis found no significant differences in overall perioperative complications or biochemical recurrence between sPLND and ePLND, but ePLND may offer enhanced diagnostic advantages by increasing the detection rate of lymph node metastasis.
Topics: Male; Humans; Prospective Studies; Pelvis; Lymph Node Excision; Prostatic Neoplasms; Prostatectomy; Randomized Controlled Trials as Topic
PubMed: 38052016
DOI: 10.1097/JS9.0000000000000997 -
Lipids in Health and Disease May 2024Cancer prognosis remains a critical clinical challenge. Lipidomic analysis via mass spectrometry (MS) offers the potential for objective prognostic prediction,... (Review)
Review
Cancer prognosis remains a critical clinical challenge. Lipidomic analysis via mass spectrometry (MS) offers the potential for objective prognostic prediction, leveraging the distinct lipid profiles of cancer patient-derived specimens. This review aims to systematically summarize the application of MS-based lipidomic analysis in prognostic prediction for cancer patients. Our systematic review summarized 38 studies from the past decade that attempted prognostic prediction of cancer patients through lipidomics. Commonly analyzed cancers included colorectal, prostate, and breast cancers. Liquid (serum and urine) and tissue samples were equally used, with liquid chromatography-tandem MS being the most common analytical platform. The most frequently evaluated prognostic outcomes were overall survival, stage, and recurrence. Thirty-eight lipid markers (including phosphatidylcholine, ceramide, triglyceride, lysophosphatidylcholine, sphingomyelin, phosphatidylethanolamine, diacylglycerol, phosphatidic acid, phosphatidylserine, lysophosphatidylethanolamine, lysophosphatidic acid, dihydroceramide, prostaglandin, sphingosine-1-phosphate, phosphatidylinosito, fatty acid, glucosylceramide and lactosylceramide) were identified as prognostic factors, demonstrating potential for clinical application. In conclusion, the potential for developing lipidomics in cancer prognostic prediction was demonstrated. However, the field is still nascent, necessitating future studies for validating and establishing lipid markers as reliable prognostic tools in clinical practice.
Topics: Humans; Prognosis; Neoplasms; Lipidomics; Biomarkers, Tumor; Mass Spectrometry; Female; Lipids; Male; Breast Neoplasms; Prostatic Neoplasms; Lysophospholipids; Colorectal Neoplasms
PubMed: 38796445
DOI: 10.1186/s12944-024-02121-0 -
World Journal of Urology Mar 2024To characterize patient outcomes following visually directed high-intensity focused ultrasound (HIFU) for focal treatment of localized prostate cancer. (Meta-Analysis)
Meta-Analysis
PURPOSE
To characterize patient outcomes following visually directed high-intensity focused ultrasound (HIFU) for focal treatment of localized prostate cancer.
METHODS
We performed a systematic review of cancer-control outcomes and complication rates among men with localized prostate cancer treated with visually directed focal HIFU. Study outcomes were calculated using a random-effects meta-analysis model.
RESULTS
A total of 8 observational studies with 1,819 patients (median age 67 years; prostate-specific antigen 7.1 mg/ml; prostate volume 36 ml) followed over a median of 24 months were included. The mean prostate-specific antigen nadir following visually directed focal HIFU was 2.2 ng/ml (95% CI 0.9-3.5 ng/ml), achieved after a median of 6 months post-treatment. A clinically significant positive biopsy was identified in 19.8% (95% CI 12.4-28.3%) of cases. Salvage treatment rates were 16.2% (95% CI 9.7-23.8%) for focal- or whole-gland treatment, and 8.6% (95% CI 6.1-11.5%) for whole-gland treatment. Complication rates were 16.7% (95% CI 9.9-24.6%) for de novo erectile dysfunction, 6.2% (95% CI 0.0-19.0%) for urinary retention, 3.0% (95% CI 2.1-3.9%) for urinary tract infection, 1.9% (95% CI 0.1-5.3%) for urinary incontinence, and 0.1% (95% CI 0.0-1.4%) for bowel injury.
CONCLUSION
Limited evidence from eight observational studies demonstrated that visually directed HIFU for focal treatment of localized prostate cancer was associated with a relatively low risk of complications and acceptable cancer control over medium-term follow-up. Comparative, long-term safety and effectiveness results with visually directed focal HIFU are lacking.
Topics: Male; Humans; Aged; Prostate-Specific Antigen; Treatment Outcome; Ultrasound, High-Intensity Focused, Transrectal; Prostatic Neoplasms; Erectile Dysfunction
PubMed: 38507093
DOI: 10.1007/s00345-024-04840-6 -
Frontiers in Endocrinology 2023Studies using novel antiandrogens (NAA) in patients with metastatic castration-resistant prostate cancer (mCRPC) have shown overall survival benefit. As patients develop... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies using novel antiandrogens (NAA) in patients with metastatic castration-resistant prostate cancer (mCRPC) have shown overall survival benefit. As patients develop resistance to NAA therapy, the poly(ADP-ribose) polymerase inhibitor (PARPi) olaparib in combination with NAA may become a promising therapy. However the overall benefit of olaparib monotherapy or combination therapy still needs to be evaluated. Therefore, we performed a network meta-analysis to assess the efficacy and toxicity between olaparib, olaparib combined with abiraterone and NAA.
METHODS
We searched PubMed, EMBASE, the Cochrane Library and American Society of Clinical Oncology (ASCO) University Meeting abstracts for randomized controlled trials reporting olaparib and NAA from 2010 up to March, 2023. Network meta-analysis using Stata 16.0 and R 4.4.2, hazard ratios (HR) with 95% confidence intervals (CI) were used to assess the results.
RESULTS
Four trials reported olaparib, olaparib plus abiraterone and apalutamide plus abiraterone. radiographic progression-free survival (rPFS) was significantly lower in patients on apalutamide plus abiraterone compared to olaparib (HR, 1.43; 95% CI, 1.06-1.93). rPFS was similar for olaparib plus abiraterone and olaparib (HR, 1.35; 95% CI, 0.99-1.84); likewise, olaparib plus abiraterone and apalutamide plus abiraterone were similar (HR, 1.06; 95% CI, 0.83-1.35). In addition, there was no significant difference between the three interventions for OS. But olaparib has the highest probability of being a preferred treatment for improving rPFS and OS.
CONCLUSION
rPFS was in favor of olaparib compared with apalutamide plus abiraterone. But there were no difference between olaparib plus abiraterone and either olaparib or apalutamide plus abiraterone. Apalutamide plus abiraterone might be the most preferred intervention in cases where AEs are involved.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com, identifier INPLASY2023100072.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Antineoplastic Agents
PubMed: 38027160
DOI: 10.3389/fendo.2023.1225033 -
International Journal of Clinical... Jun 2024Triplet therapy, androgen receptor signaling inhibitors (ARSIs) plus docetaxel plus androgen-deprivation therapy (ADT), is a novel guideline-recommended treatment for... (Meta-Analysis)
Meta-Analysis
Impact of disease volume on survival efficacy of triplet therapy for metastatic hormone-sensitive prostate cancer: a systematic review, meta-analysis, and network meta-analysis.
BACKGROUND
Triplet therapy, androgen receptor signaling inhibitors (ARSIs) plus docetaxel plus androgen-deprivation therapy (ADT), is a novel guideline-recommended treatment for metastatic hormone-sensitive prostate cancer (mHSPC). However, the optimal selection of the patient most likely to benefit from triplet therapy remains unclear.
METHODS
We performed a systematic review, meta-analysis, and network meta-analysis to assess the oncologic benefit of triplet therapy in mHSPC patients stratified by disease volume and compare them with doublet treatment regimens. Three databases and meeting abstracts were queried in March 2023 for randomized controlled trials (RCTs) evaluating patients treated with systemic therapy for mHSPC stratified by disease volume. Primary interests of measure were overall survival (OS). We followed the PRISMA guideline and AMSTAR2 checklist.
RESULTS
Overall, eight RCTs were included for meta-analyses and network meta-analyses (NMAs). Triplet therapy outperformed docetaxel plus ADT in terms of OS in both patients with high-(pooled HR: 0.73, 95%CI 0.64-0.84) and low-volume mHSPC (pooled HR: 0.71, 95%CI 0.52-0.97). There was no statistically significant difference between patients with low- vs. high-volume in terms of OS benefit from adding ARSI to docetaxel plus ADT (p = 0.9). Analysis of treatment rankings showed that darolutamide plus docetaxel plus ADT (90%) had the highest likelihood of improved OS in patients with high-volume disease, while enzalutamide plus ADT (84%) had the highest in with low-volume disease.
CONCLUSIONS
Triplet therapy improves OS in mHSPC patients compared to docetaxel-based doublet therapy, irrespective of disease volume. However, based on treatment ranking, triplet therapy should preferably be considered for patients with high-volume mHSPC while those with low-volume are likely to be adequately treated with ARSI + ADT.
Topics: Humans; Male; Androgen Antagonists; Androgen Receptor Antagonists; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Network Meta-Analysis; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Tumor Burden
PubMed: 38582807
DOI: 10.1007/s10147-024-02485-4 -
The World Journal of Men's Health Apr 2024A high incidence of psychosocial problems in prostate cancer patients has been reported including anxiety, depression and distress. These can add to the patients'...
A Systematic Review of the Association between Psychological Resilience and Improved Psychosocial Outcomes in Prostate Cancer Patients. Could Resilience Training Have a Potential Role?
PURPOSE
A high incidence of psychosocial problems in prostate cancer patients has been reported including anxiety, depression and distress. These can add to the patients' disease burden and have been associated with unfavorable cancer treatment outcomes. Interventions designed to address them have found limited success, but psychological resilience (PR) training has never been formally tested. The measurement of PR in prostate cancer patients has been described and has been associated with more favorable psychosocial outcomes in these patients but it has never been systematically reviewed. The aim of this study was to conduct the first systematic review of those studies that have measured it using standardized scales and to determine the potential for resilience training to help overcome the significant psychosocial problems faced by prostate cancer patients.
MATERIALS AND METHODS
We searched the literature to identify articles that measured PR among prostate cancer patients.
RESULTS
Of 384 articles identified by the search criteria, there were 19 studies suitable for inclusion regarding 5,417 patients. The most commonly-used scale was the original Connor-Davidson Resilience Scale, or an abbreviated version of it. Possible scores range from 0 to 100, mean scores from these studies ranged from 72.9 to 87.1 (standard deviations varied between 13.2 and 16.3). PR was consistently associated with improved psychological outcomes including depression, anxiety and distress, although these were measured with a wide variety of methods making it difficult to quantify the effects. There was also evidence of PR mediating the physical effects of prostate cancer and treatment including urinary symptoms, fatigue and insomnia.
CONCLUSIONS
As resilience training has been successful in other cancer settings, it seems likely that it could improve the significant adverse psychosocial outcomes that have been reported in prostate cancer patients and trials designed to objectively test it should be encouraged.
PubMed: 38606864
DOI: 10.5534/wjmh.230319 -
Maturitas Jun 2024Prostate cancer survivors treated with androgen deprivation therapy may be at increased risk of cardiovascular disease. Dietary recommendations for the prevention and/or... (Review)
Review
The effect of dietary interventions or patterns on the cardiometabolic health of individuals treated with androgen deprivation therapy for prostate cancer: A systematic review.
Prostate cancer survivors treated with androgen deprivation therapy may be at increased risk of cardiovascular disease. Dietary recommendations for the prevention and/or management of cardiovascular disease for these individuals are lacking. This review synthesizes the evidence on the effect of dietary interventions on cardiometabolic biomarkers and cardiovascular disease risk in prostate cancer survivors receiving androgen deprivation therapy. A systematic review was conducted across PubMed, CINAHL, Embase, and Cochrane CENTRAL. Intervention or observational cohort studies evaluating diets, nutrients, or nutraceuticals with or without concurrent exercise interventions on cardiovascular disease, cardiovascular events, or cardiovascular disease biomarkers in those treated with androgen deprivation therapy were included. Confidence in the body of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluations. Twelve studies reported across fifteen papers were included. Interventions were heterogenous, with most studies including an exercise co-intervention (n = 8). Few significant findings for the effects of diet on cardiometabolic markers were likely due to weak methodology and sample sizes. Strongest evidence was for the effect of a healthy Western dietary pattern with exercise on improved blood pressure (Confidence: moderate). The healthy Western dietary pattern with exercise may improve high-density lipoprotein cholesterol (Confidence: Low) and flow-mediated dilation. Soy may improve total cholesterol (Confidence: Very low). A low-carbohydrate diet with physical activity may improve high-density lipoprotein cholesterol, incidence of metabolic syndrome, and Framingham cardiovascular disease risk score. Evidence of the effect of dietary interventions on cardiometabolic biomarkers and cardiovascular disease risk of prostate cancer survivors receiving androgen deprivation therapy is insufficient to inform practice. Well-designed dietary interventions aimed at improving cardiometabolic outcomes of this population are warranted to inform future dietary recommendations.
Topics: Humans; Male; Prostatic Neoplasms; Androgen Antagonists; Cardiovascular Diseases; Exercise; Diet; Dietary Supplements
PubMed: 38430616
DOI: 10.1016/j.maturitas.2024.107940