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European Urology Jul 2023The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for...
Impact of Epithelial Histological Types, Subtypes, and Growth Patterns on Oncological Outcomes for Patients with Nonmetastatic Prostate Cancer Treated with Curative Intent: A Systematic Review.
CONTEXT
The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for conventional PCa and so different approaches may be needed.
OBJECTIVE
To compare oncological outcomes for conventional and UH PCa in men with localized disease treated with curative intent.
EVIDENCE ACQUISITION
A systematic review adhering to the Referred Reporting Items for Systematic Reviews and Meta-Analyses was prospectively registered on PROSPERO (CRD42022296013) was performed in July 2021.
EVIDENCE SYNTHESIS
We screened 3651 manuscripts and identified 46 eligible studies (reporting on 1 871 814 men with conventional PCa and 6929 men with 10 different PCa UHs). Extraprostatic extension and lymph node metastases, but not positive margin rates, were more common with UH PCa than with conventional tumors. PCa cases with cribriform pattern, intraductal carcinoma, or ductal adenocarcinoma had higher rates of biochemical recurrence and metastases after radical prostatectomy than for conventional PCa cases. Lower cancer-specific survival rates were observed for mixed cribriform/intraductal and cribriform PCa. By contrast, pathological findings and oncological outcomes for mucinous and prostatic intraepithelial neoplasia (PIN)-like PCa were similar to those for conventional PCa. Limitations of this review include low-quality studies, a risk of reporting bias, and a scarcity of studies that included radiotherapy.
CONCLUSIONS
Intraductal, cribriform, and ductal UHs may have worse oncological outcomes than for conventional and mucinous or PIN-like PCa. Alternative treatment approaches need to be evaluated in men with these cancers.
PATIENT SUMMARY
We reviewed the literature to explore whether prostate cancers with unconventional growth patterns behave differently to conventional prostate cancers. We found that some unconventional growth patterns have worse outcomes, so we need to investigate if they need different treatments. Urologists should be aware of these growth patterns and their clinical impact.
Topics: Humans; Male; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms
PubMed: 37117107
DOI: 10.1016/j.eururo.2023.03.014 -
European Urology Open Science Apr 2023Prostate cancer (PCa) remains one of the leading causes of cancer-related deaths in men worldwide. Men at risk are typically offered multiparametric magnetic resonance...
A Systematic Review of the Variability in Performing and Reporting Intraprostatic Prostate-specific Membrane Antigen Positron Emission Tomography in Primary Staging Studies.
CONTEXT
Prostate cancer (PCa) remains one of the leading causes of cancer-related deaths in men worldwide. Men at risk are typically offered multiparametric magnetic resonance imaging and, if suspicious, a targeted biopsy. However, false-negative rates of magnetic resonance imaging are consistently 18%; therefore, there is growing interest in improving the diagnostic performance of imaging through novel technologies. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is being utilised for PCa staging and, more recently, for intraprostatic tumour localisation. However, significant variability has been observed in how PSMA PET is performed and reported.
OBJECTIVE
In this review, we aim to evaluate how pervasive this variability is in trials investigating the performance of PSMA PET in primary PCa workup.
EVIDENCE ACQUISITION
Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed an optimal search in five different databases. After removing duplicates, 65 studies were included in our review.
EVIDENCE SYNTHESIS
Studies dated back as early as 2016, with numerous different source countries. There was variation in the reference standard for PSMA PET, with some using biopsy specimens or surgical specimens, and in some cases, a combination of the two. Similar inconsistencies were noted when studies selected histological definitions of clinically significant PCa, while some omitted their definition altogether. The most significant variations in performing PSMA PET were the radiotracer type, dose, acquisition time after injection, and the PET camera being utilised. Substantial variation in the reporting of PSMA PET was noted, with no consistency in defining what constitutes a positive intraprostatic lesion. Across 65 studies, four different definitions were used.
CONCLUSIONS
This systematic review has highlighted considerable variation in obtaining and performing a PSMA PET study in the context of primary PCa diagnosis. Given the discrepancy in how PSMA PET was performed and reported, it questions the homogony of studies from centre to centre. Standardisation of PSMA PET is required for this to become a consistently useful and reproducible modality in the diagnosis of PCa.
PATIENT SUMMARY
Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is being utilised for staging and localisation of prostate cancer (PCa); however, there is significant variability in performing and reporting PSMA PET. Standardisation of PSMA PET is required for results to be consistently useful and reproducible for the diagnosis of PCa.
PubMed: 37101769
DOI: 10.1016/j.euros.2023.01.010 -
JAMA Oncology Jun 2023Recently, several large, high-quality analyses have shown opposing results regarding the association between 5α-reductase inhibitor (5-ARI) use and prostate cancer... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Recently, several large, high-quality analyses have shown opposing results regarding the association between 5α-reductase inhibitor (5-ARI) use and prostate cancer (PCa) mortality.
OBJECTIVE
To systematically evaluate the current evidence regarding 5-ARI use and PCa mortality.
DATA SOURCES
A literature search began in and was conducted through August 2022 using PubMed/Medline, Embase, and Web of Science databases.
STUDY SELECTION
Studies were deemed eligible if they included male patients of any age who were 5-ARI users and were compared with those who were nonusers if they analyzed PCa mortality in randomized clinical trials and prospective or retrospective cohort studies.
DATA EXTRACTION AND SYNTHESIS
This study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Adjusted hazard ratios (HRs) were extracted from published articles. Data analysis was performed in August 2022.
MAIN OUTCOMES AND MEASURES
The primary outcome was PCa mortality among 5-ARI users vs nonusers. The inverse variance method with adjusted HRs and random-effect models were used to determine the association between 5-ARI use and PCa mortality. Two subgroup analyses were performed to assess the effect of 2 main confounders: prostate-specific antigen level and PCa diagnosis at baseline.
RESULTS
Among 1200 unique records screened, 11 studies met the inclusion criteria. A total of 3 243 575 patients were included: 138 477 users of 5-ARI and 3 105 098 nonusers. There was no statistically significant association between 5-ARI use and PCa mortality (adjusted HR, 1.04; 95% CI, 0.80-1.35; P = .79). No significant association was found when the analysis was restricted to studies that excluded patients with a diagnosis of PCa at baseline (adjusted HR, 1.00; 95% CI, 0.60-1.67; P = .99) or the analysis was restricted to prostate-specific antigen-adjusted studies (adjusted HR, 0.76; 95% CI, 0.57-1.03; P = .08).
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis, which draws on 2 decades of epidemiologic literature and includes more than 3 million patients, found no statistically significant association between 5-ARI use and PCa mortality but provides important data to inform clinical care.
Topics: Humans; Male; Prostate-Specific Antigen; Prospective Studies; 5-alpha Reductase Inhibitors; Retrospective Studies; Prostatic Neoplasms; Oxidoreductases
PubMed: 37079318
DOI: 10.1001/jamaoncol.2023.0260 -
American Journal of Men's Health 2023Prostate cancer (PCa) is the second leading cause of cancer-causing death in the United States. As the most common malignancy in men, it is pertinent to explore whether...
Prostate cancer (PCa) is the second leading cause of cancer-causing death in the United States. As the most common malignancy in men, it is pertinent to explore whether novel immunotherapies may improve the quality of life and overall survival (OS) of patient populations. This systematic review and post hoc analysis curates a patient-by-patient pool of evidence adhering to PRISMA Statement 2020 guidelines. In total, 24 patients were analyzed for treatment history and associated variables including prostate-specific antigen (PSA) levels at diagnosis and post-treatment, Gleason score, secondary tumor locations, success/failure of therapy, and post-immunotherapy outcomes including OS. In total, 10 types of immunotherapies were identified with Pembrolizumab (among 8 patients) followed by IMM-101 (among 6 patients) being the most commonly administered. The mean OS for all patients was 27.8 months (24 patients) with the relatively highest mean OS reported with IMM-101 (56 months) followed by tumor-infiltrating lymphocytes (30 months). This research article provides critical insights into the evolving landscape of immunotherapies being tested for PCa and addresses gaps in oncological research to advance the understanding of PCa.
Topics: Male; Humans; Quality of Life; Prostatic Neoplasms; Immunotherapy; Prostate-Specific Antigen
PubMed: 37002863
DOI: 10.1177/15579883231165140 -
Cureus Feb 2023The prognosis in the setting of metastatic castration-resistant prostate cancer patients (mCRPC) remains limited. Therefore, novel treatment strategies remain an unmet... (Review)
Review
The prognosis in the setting of metastatic castration-resistant prostate cancer patients (mCRPC) remains limited. Therefore, novel treatment strategies remain an unmet need. Antibody-drug conjugates (ADC) emerged as a new drug concept with the potential to deliver a cytotoxic payload with limited off-target toxicity and potentially bystander effect. Following the success of ADCs in breast cancer and urothelial tumours, their activity in prostate cancer is now under investigation. Thus, the aim of this systematic review was to identify published and ongoing prospective clinical trials regarding ADC treatment in prostate cancer. A systematic search of PubMed, MEDLINE, and Web of Science was conducted as per PRISMA guidelines to identify prospective clinical trials of ADCin prostate cancer. Trials are currently ongoing on ClinicalTrials.gov and in the EU. The Clinical Trials Register was also identified. Abstracts, publications in languages other than English, review articles, retrospective analyses, and phase I trials were excluded. A total of six phase I/II prospective clinical trials already published were included. Seven ongoing trials were also identified. All studies were in the refractory/advanced tumour setting, and two included only mCRPC patients. The ADC targets were prostate-specific membrane antigen (PSMA), trophoblast cell surface antigen-2 (TROP-2), six-transmembrane epithelial antigen of prostate-1 (STEAP-1), tissue factor (TF), delta-like protein 3 (DLL-3), B7-H3 family of proteins (B7-H3), and human epidermal growth factor receptor 2 (HER2). Regarding the efficacy of PSMA ADC treatment in the second-line or beyond mCRPC setting, a PSA ≥ 50% decline rate in 14% of all treated patients was reported. One patient achieved a complete response with TROP-2 ADC. Overall, a wide range of safety issues were raised, particularly in connection with neuropathy and hematologic toxicity. Novel therapies have been changing the scope of treatment in mCRPC. ADCs seem to provide efficacy benefits, even with potential toxicity. The results of most prospective ongoing studies are still awaited, and a longer follow-up time is warranted to evaluate the real impact of ADCs in PCa.
PubMed: 36874351
DOI: 10.7759/cureus.34490 -
Frontiers in Oncology 2023Androgen-deprivation therapy (ADT) is used for the treatment of prostate cancer. However, the specific risk factors for the development of castration-resistant disease...
BACKGROUND
Androgen-deprivation therapy (ADT) is used for the treatment of prostate cancer. However, the specific risk factors for the development of castration-resistant disease are still unclear. The present study sought to identify predictors of patient prognostic outcomes through analyses of clinical findings in large numbers of prostate cancer patients following ADT treatment.
METHODS
Data pertaining to 163 prostate cancer patients treated at the Second Affiliated Hospital of Bengbu Medical University and Maoming People's Hospital from January 1, 2015, to December 30, 2020, were retrospectively analyzed. Dynamic changes in prostate-specific antigen (PSA) levels were regularly assessed, including both time to nadir (TTN) and nadir PSA (nPSA). Univariate and multivariate analyses were performed with Cox risk proportional regression models, while differences in biochemical progression-free survival (bPFS) were compared among groups with Kaplan-Meier curves and log-rank tests.
RESULTS
The bPFS values over the median 43.5-month follow-up period differed significantly between patients with nPSA levels < 0.2 ng/mL and ≥ 0.2 ng/mL, being 27.6 months and 13.5 months, respectively (log-rank P < 0.001). A significant difference in median bPFS was also observed when comparing patients with a TTN ≥ 9 months (27.8 months) to those with a TTN < 9 months (13.5 months) (log-rank P < 0.001).
CONCLUSIONS
TTN and nPSA are valuable predictors of prognosis in prostate cancer patients after ADT treatment, with better outcomes evident in patients with nPSA < 0.2 ng/mL and TTN > 9 months.
PubMed: 36845723
DOI: 10.3389/fonc.2023.1047388 -
Frontiers in Endocrinology 2023Second-generation androgen receptor inhibitors (ARIs) have been developed and approved for treating castration-resistant prostate cancer (CRPC). There is a lack of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Second-generation androgen receptor inhibitors (ARIs) have been developed and approved for treating castration-resistant prostate cancer (CRPC). There is a lack of direct comparison of the therapeutic effects and adverse events between the conventional ARI (bicalutamide) and three second-generation ARIs (enzalutamide, apalutamide and darolutamide).
METHODS
Our network meta-analysis evaluated therapeutic effects and adverse events of the conventional ARI (bicalutamide) and the second-generation ARIs in treating CRPC. We systematically searched the Pubmed, Cochrane library and Embase databases for studies published until October 2022 and only randomized clinical trials (RCTs) were included. The progression-free survival, prostate-specific antigen (PSA) progression-free survival, overall survival (PFS/PSA-PFS/OS), PSA response rate and relative adverse events (AEs) of CRPC patients were collected and synthesized. We then performed subgroup analysis. The non-metastatic and metastatic CRPC (nm/mCRPC) observations were analyzed separately. Data analyses were performed using R software (4.2.1) based on Bayesian framework.
RESULTS
6,993 subjects from seven eligible RCTs were analyzed. Enzalutamide, apalutamide and darolutamide were more effective than bicalutamide in treating CRPC, and the performance of darolutamide was slightly worse than the other two second-generation ARIs. Similar adverse events rate were observed among the second-generation ARIs and bicalutamide. Apalutamide showed a slightly higher rate of Grade 3+ AEs, percentages of AE-related drug withdrawals and AE-related mortality. Patients receiving enzalutamide had significantly higher rate of hypertension and fatigue. In subgroup analysis, enzalutamide showed better therapeutic effects compared with bicalutamide in both nmCRPC and mCRPC groups. In nmCRPC group, enzalutamide and apalutamide had more benefits on PFS and PSA-PFS compared with darolutamide. We displayed the probability ranking map of PFS, PSA-PFS, OS, time to cytotoxic chemotherapy, PSA response rate and relative AE outcomes.
CONCLUSION
The current network meta-analysis indicated that the second-generation ARIs were superior to the conventional ARI, bicalutamide. The three second-generation ARIs showed incomplete equivalence on CRPC treatment. The darolutamide was slightly less effective compared with enzalutamide and apalutamide. The adverse events of apalutamide were worse than the others, but no statistical significance was observed among these vital AEs. All ARIs were generally well-tolerated. These results may provide reference to clinical decision and further direct comparison trials.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022370842.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen; Prostate-Specific Antigen; Network Meta-Analysis; Treatment Outcome; Androgen Receptor Antagonists
PubMed: 36843606
DOI: 10.3389/fendo.2023.1131033 -
Current Oncology (Toronto, Ont.) Feb 2023(1) Background: Local therapy is highly promising in a multimodal approach strategy for patients with low-volume metastatic prostate cancer (mPCa). We aimed to... (Review)
Review
(1) Background: Local therapy is highly promising in a multimodal approach strategy for patients with low-volume metastatic prostate cancer (mPCa). We aimed to systematically assess and summarize the safety, oncologic, and functional outcomes of cytoreductive prostatectomy (cRP) in mPCa. (2) Methods: Three databases were queried in September 2022 for publications that analyzed mPCa patients treated with cytoreductive prostatectomy without restrictions. The outcomes of interest were progression-free survival (PFS), cancer-specific survival (CSS), overall survival (OS), perioperative complication rates, and functional outcomes following cRP. (3) Results: Overall, 26 studies were included in this systematic review. Among eight population-based studies, cRP was associated with a reduced risk of CSS and OS compared with no local therapy (NLT) after adjusting for the effects of possible confounders. Furthermore, one population-based study showed that cRP reduced the risk of CSS even when compared with radiotherapy (RT) of the prostate after adjusting for the effects of possible confounders. In addition, one randomized controlled trial (RCT) demonstrated that local therapy (comprising 85% of cRP) significantly improved the prostate-specific antigen (PSA)-PFS and OS. Overall, cRP had acceptable perioperative complication rates and functional outcomes. (4) Conclusions: Mounting evidence suggests that cRP offers promising oncological and functional outcomes and technical feasibility and that it is associated with limited complications. Well-designed RCTs that limit selection bias in patients treated with cRP are warranted.
Topics: Male; Humans; Cytoreduction Surgical Procedures; Prostatic Neoplasms; Prostatectomy; Prostate-Specific Antigen
PubMed: 36826131
DOI: 10.3390/curroncol30020170 -
Frontiers in Endocrinology 2023Orchiectomy has been replaced by medication represented by luteinizing hormone-releasing hormone (LHRH) agonist as the first-line therapy for androgen deprivation...
BACKGROUND
Orchiectomy has been replaced by medication represented by luteinizing hormone-releasing hormone (LHRH) agonist as the first-line therapy for androgen deprivation therapy (ADT). After the wide application of LHRH agonist, the side-effects of long-term ADT were noticed. It is time to reconsider the role of medication and surgeries in the treatment of prostate cancer.
METHODS
Embase, Pubmed, Web of science and Cochrane library were searched for relevant trials. Quality of the studies and risk of bias were assessed by using the Newcastle-Ottawa Scale (NOS). Therapeutic and adverse effects, as well as long-term metabolic adverse effects were extracted from the selected studies. The data synthesized in meta-analyses were performed with R software (4.2.1). Risk ratio (RR) with its 95% confidence interval (CI) was calculated by combining outcome data including complete and partial response rate, progression rate, death rate and adverse effects such as hot flash and increase in pain. Descriptive analysis was performed among the prostate specific antigen (PSA), testosterone and metabolic adverse effects due to a lack of homogeneity of frailty measures.
RESULTS
1,711 participants from 11 studies were included in our systematic review. 1,258 patients from six studies were included in the meta-analysis. Based on the meta-analysis, the therapeutic and adverse outcomes included overall response rate, complete response rate, partial response rate, stable rate, progression rate, death rate and hot flashes. No statistical significance was observed between LHRH agonists and orchiectomy. Compared with surgery, LHRH agonist elevated the risk of the increase in pain. In descriptive analysis, it was shown that the therapeutic effects between PSA and testosterone also showed no significant difference. Both groups had lipid and glucose metabolic disorders, and a few studies reported worse lipid metabolic performance in orchiectomy group and worse insulin resistance in LHRH agonist group.
CONCLUSION
We found that the therapeutic outcomes were similar between the two options. The results of lipid and glucose metabolic abnormality were controversial in existing studies. The direct comparison studies on metabolic adverse effects should be performed in the future. The therapeutic, metabolic, psychological and economical effects should be considered before applying ADT methods.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022365891.
Topics: Humans; Male; Androgen Antagonists; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Lipids; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone
PubMed: 36814583
DOI: 10.3389/fendo.2023.1131715 -
Diagnostics (Basel, Switzerland) Feb 2023Recently, several studies introduced the potential use of positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen... (Review)
Review
BACKGROUND
Recently, several studies introduced the potential use of positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals in radioiodine-refractory thyroid cancer (TC).
METHODS
The authors accomplished a comprehensive literature search of original articles concerning the performance of PSMA-targeted PET/CT in TC patients. Original papers exploring this molecular imaging examination in radioiodine-refractory TC patients undergoing restaging of their disease were included.
RESULTS
A total of 6 documents concerning the diagnostic performance of PSMA-targeted PET/CT in TC (49 patients) were included in this systematic review. The included articles reported heterogeneous values of PSMA-targeted PET/CT detection rates in TC, ranging from 25% to 100% and overall inferior to [F]-fluorodeoxyglucose PET/CT when the two molecular imaging examinations were compared. Two studies reported the administration of [Lu]PSMA-radioligands with theragnostic purpose in three patients.
CONCLUSIONS
The available literature data in this setting are limited and heterogeneous. The employment of PET with PSMA-targeting radiopharmaceuticals in this setting did not affect patient management. Nevertheless, prospective multicentric studies are needed to properly assess its potential role in TC patients.
PubMed: 36766670
DOI: 10.3390/diagnostics13030564