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Bladder Cancer (Amsterdam, Netherlands) May 2021The optimal management of non-invasive (mucosal and/or ductal) urothelial carcinoma of the prostate remains elusive and there is a paucity of data to guide treatment.
BACKGROUND
The optimal management of non-invasive (mucosal and/or ductal) urothelial carcinoma of the prostate remains elusive and there is a paucity of data to guide treatment.
OBJECTIVE
Our objective was to systematically review and synthesize treatment responses to conservative management of non-invasive prostatic urothelial carcinoma using intravesical therapy.
METHODS
A systematic literature search using MEDLINE, EMBASE, Cochrane Library, SCOPUS, and Web of Science databases from inception to November 2019 was performed. Risk of bias assessment was performed using the Newcastle-Ottawa scale for non-randomised studies. Pooled estimates of complete response in the bladder and prostate and prostate only were performed using a random effects model. Pre-specified subgroup analyses were generated to assess differences in complete responses for: BCG therapy vs other agents, ductal vs mucosal involvement, CIS vs papillary tumors and TURP vs no TURP.
RESULTS
Nine studies including 175 patients were identified for inclusion in the systematic review and meta-analysis. All were retrospective case series and most evaluated response to BCG therapy. The pooled global complete response rate for intravesical therapy was 60%(95%CI: 0.48, 0.72), and for prostate 88%(95%CI: 0.81, 0.96). Pre-specified analyses did not demonstrate statistically significant differences between subgroups of interest.
CONCLUSIONS
Management of non-invasive prostatic urothelial carcinoma using intravesical therapy yields satisfactory results. Caution should be taken in treating patients with papillary tumors and ductal involvement, as data for these populations is limited. TURP may not improve efficacy, but is required for staging. Current recommendations are based on low quality evidence, and further research is warranted.
PubMed: 34195319
DOI: 10.3233/BLC-200404 -
BJU International Apr 2022To perform a systematic review and network meta-analysis to compare the efficacy and safety of currently available treatments for the management of metastatic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To perform a systematic review and network meta-analysis to compare the efficacy and safety of currently available treatments for the management of metastatic hormone-sensitive prostate cancer (mHSPC), as there has been a paradigm shift with the use of next-generation androgen receptor inhibitors (ARIs) and docetaxel.
METHODS
Multiple databases were searched for articles published before May 2020 according to the Preferred Reporting Items for Systematic Review and Meta-analysis extension statement for network meta-analysis. Studies comparing overall/progression-free survival (OS/PFS) and/or adverse events (AEs) in patients with mHSPC were eligible.
RESULTS
Nine studies (N = 9960) were selected, and formal network meta-analyses were conducted. Abiraterone (hazard ratio [HR] 0.83, 95% credible interval [CrI] 0.76-0.90), docetaxel (HR 0.90, 95% CrI 0.82-0.98), and enzalutamide (HR 0.85, 95% CrI 0.73-0.99) were associated with significantly better OS than androgen-deprivation therapy (ADT), and abiraterone emerged as the best option. Abiraterone (HR 0.71, 95% CrI 0.67-0.76), apalutamide (HR 0.73, 95% CrI 0.65-0.81), docetaxel (HR 0.84, 95% CrI 0.78-0.90), and enzalutamide (HR 0.67, 95% CrI 0.63-0.71) were associated with significantly better PFS than ADT, and enzalutamide emerged as the best option. Abiraterone (HR 0.85, 95% CrI 0.78-0.93), apalutamide (HR 0.87, 95% CrI 0.77-0.98), and enzalutamide (HR 0.80, 95% CrI 0.73-0.88) were significantly more effective than docetaxel. Regarding AEs, apalutamide was the likely best option among the three ARIs. In patients with low-volume mHSPC, enzalutamide was the best option in terms of OS and PFS.
CONCLUSIONS
All three ARIs are effective therapies for mHSPC; apalutamide was the best tolerated. All three seemed more effective than docetaxel. These findings may facilitate individualised treatment strategies and inform future comparative trials.
Topics: Androgen Antagonists; Androgen Receptor Antagonists; Docetaxel; Hormones; Humans; Male; Network Meta-Analysis; Prostatic Neoplasms
PubMed: 34171173
DOI: 10.1111/bju.15507 -
Translational Oncology Sep 2021Studies have shown that AR-V7 may be correlated with the poor prognosis of castration resistant prostate cancer (CRPC), however, clinicopathological characteristics...
Clinicopathological characteristics of androgen receptor splicing variant 7 (AR-V7) expression in patients with castration resistant prostate cancer: A systematic review and meta-analysis.
BACKGROUND
Studies have shown that AR-V7 may be correlated with the poor prognosis of castration resistant prostate cancer (CRPC), however, clinicopathological characteristics of AR-V7 have not been fully elucidated.
OBJECTIVE
This study aimed at evaluating the clinicopathological features of AR-V7 in CRPC patients.
MATERIALS AND METHODS
To evaluate the clinicopathological features of AR-V7 in CRPC patients. A search of PubMed, Embase, and Web of Science was performed using the keywords prostate cancer, prostate tumor, prostate neoplasm, prostate carcinoma, AR-V7, AR3, androgen receptor splicing variant-7, or androgen receptor-3. Twenty-four trials published by February 2020 were included in this study.
RESULTS
The proportion of Gleason score ≥ 8 was found to be significantly higher in AR-V7-positive CRPC (69.5%) than negative (54.9%) (OR 1.68, 95% CI 1.25-2.25, p < 0.001), while the rates of T3/T4 stage (OR 1.16, 95% CI 0.60-2.24, p = 0.65) and N1 stage (OR 0.99, 95% CI 0.65-1.51, p = 0.96) were not statistically correlated with AR-V7 status. The AR-V7-positive patients exhibited a significantly higher proportion of any site metastasis (61.3% versus 35.0%; OR 2.19, 95% CI 1.57-3.05, p < 0.001) and bone metastasis (81.7% versus 69.0%; OR 1.97, 95% CI 1.44-2.69, p < 0.001), and a trend close to significance was expected in visceral metastasis (28.8% versus 22.1%; OR 1.29, 95% CI 0.96-1.74, p = 0.09). Incidences of pain in AR-V7-positive CRPC (54.6%) were significantly higher than in negative CRPC (28.1%; OR 4.23, 95% CI 2.52-7.10, p < 0.001), line with worse ECOG performance status (56.7% versus 35.0%, OR 2.18, 95% CI 1.51-3.16, P < 0.001). Limitations of the study include differences in sample sizes and designs, AR-V7 detection assays, as well as disease characteristics of the included studies.
CONCLUSIONS
AR-V7 positivity is associated with a higher Gleason score, bone or any site metastasis, pain and worse ECOG performance scores in CRPC. However, it is not correlated with tumor stage or lymph node metastasis. More studies are needed to confirm these findings.
PubMed: 34130051
DOI: 10.1016/j.tranon.2021.101145 -
International Journal of Urology :... Aug 2021The objective of this study was to review publications assessing cognitive functioning in patients with prostate cancer treated with androgen deprivation therapy. We... (Review)
Review
The objective of this study was to review publications assessing cognitive functioning in patients with prostate cancer treated with androgen deprivation therapy. We conducted a systematic review of the literature published in PubMed, Embase, Web of Science, Cochrane Library, and PsycINFO up to February 2020. A total of 31 studies were included. Half of the studies (n = 16) demonstrated that androgen deprivation therapy in patients with prostate carcinoma did not result in a negative effect on cognitive functioning, however, still a substantial proportion of the studies (n = 11) reported a negative effect on cognitive functioning. In four studies the results were inconclusive. In the three studies using additional functional magnetic resonance imaging, no significant effect on neuropsychological tests was found, but grey matter volume, brain activity, and brain connectivity were affected. Given the substantial number of studies showing a significant negative effect of androgen deprivation therapy on cognitive functioning, clinicians should be aware of this side effect. Furthermore, future research should focus on the further examination of brain characteristics using functional magnetic resonance imaging, since these techniques might be more sensitive in detecting brain abnormalities as a result of androgen deprivation therapy.
Topics: Androgen Antagonists; Androgens; Cognition; Humans; Magnetic Resonance Imaging; Male; Prostatic Neoplasms
PubMed: 34128263
DOI: 10.1111/iju.14596 -
Physiological and pathological functions of βB2-crystallins in multiple organs: a systematic review.Aging Jun 2021Crystallins, the major constituent proteins of mammalian lenses, are significant not only for the maintenance of eye lens stability, transparency, and refraction, but...
Crystallins, the major constituent proteins of mammalian lenses, are significant not only for the maintenance of eye lens stability, transparency, and refraction, but also fulfill various physiopathological functions in extraocular tissues. βB2-crystallin, for example, is a multifunctional protein expressed in the human retina, brain, testis, ovary, and multiple tumors. Mutations in the βB2 crystallin gene or denaturation of βB2-crystallin protein are associated with cataracts, ocular pathologies, and psychiatric disorders. A prominent role for βB2-crystallins in axonal growth and regeneration, as well as in dendritic outgrowth, has been demonstrated after optic nerve injury. Studies in βB2-crystallin-null mice revealed morphological and functional abnormalities in testis and ovaries, indicating βB2-crystallin contributes to male and female fertility in mice. Interestingly, although pathogenic significance remains obscure, several studies identified a clear correlation between βB2 crystallin expression and the prognosis of patients with breast cancer, colorectal cancer, prostate cancer, renal cell carcinoma, and glioblastoma in the African American population. This review summarizes the physiological and pathological functions of βB2-crystallin in the eye and other organs and tissues and discusses findings related to the expression and potential role of βB2-crystallin in tumors.
Topics: Black or African American; Humans; Lens, Crystalline; Neoplasms; Organ Specificity; beta-Crystallin B Chain
PubMed: 34118792
DOI: 10.18632/aging.203147 -
Scientific Reports May 2021To update the current evidence on whether hepatitis C virus (HCV) infection represents a possible risk factor for renal cell cancer (RCC), prostate cancer (PCa), and... (Meta-Analysis)
Meta-Analysis
To update the current evidence on whether hepatitis C virus (HCV) infection represents a possible risk factor for renal cell cancer (RCC), prostate cancer (PCa), and bladder cancer (BC). We searched the literature on Pubmed, Web of Science, and Embases before April 2021. A systematic review and meta-analysis were performed. Finally, we extracted 12 studies based on the eligible criteria. Across 11 studies for HCV and RCC, the incorporated RR was 1.28 (95% CI 1.05-1.55), which meant that participants with HCV infection were associated with higher RCC risk. The pooled RR in hazard ratio (HR) subgroup (HR 1.59, 95% CI 1.22-2.08), cohort studies subgroup (RR 1.47, 95% CI 1.18-1.82), and North America subgroup (RR 1.71, 95% CI 1.40-2.09) detected a stronger association between HCV and RCC risk. Although an inverse association was seen for PCa (RR 0.75, 95% CI 0.54-1.03) across seven studies, it was not statistically significant (P = 0.075). There was no significant association between HCV and BC with an incorporated RR of 0.92 (95% CI, 0.82-1.03) across five studies. Our study demonstrated that HCV infection was significantly associated with increased RCC risk. There appeared to be an inverse association for HCV in PCa risk but not statistically significant. No significant association was found between HCV and BC risk. Prospective, large-scale, and well-designed cohort studies are required to validate the association between HCV and RCC, and to investigate the role of HCV on PCa.
Topics: Carcinoma, Renal Cell; Hepatitis C; Humans; Kidney Neoplasms; Odds Ratio; Urinary Bladder Neoplasms
PubMed: 34035396
DOI: 10.1038/s41598-021-90404-2 -
Archives of Pathology & Laboratory... Jan 2022Transgender women experience health disparities in all areas of medicine. Within surgical pathology, knowledge gaps relating to the concepts of transgender care exist....
CONTEXT.—
Transgender women experience health disparities in all areas of medicine. Within surgical pathology, knowledge gaps relating to the concepts of transgender care exist. Medical transition for transgender women and transfeminine persons may involve hormone therapy and/or surgery to feminize the body. Understanding the common histologic changes in specimens from feminizing surgeries, as well as other specimens from patients on feminizing hormone therapy, will aid surgical pathologists in providing better care to this unique patient population.
OBJECTIVE.—
To summarize histologic findings in surgical pathology specimens from transgender women taking feminizing hormones.
DATA SOURCES.—
A systematic review of the OVID Medline and PubMed databases was performed to identify all studies describing histologic findings in surgical pathology specimens from transgender women from 1946 to 2019.
CONCLUSIONS.—
Much of the literature to date describing histologic findings in transgender women comes from the examination of genitourinary specimens removed during feminizing surgeries. Common benign changes associated with feminizing hormone therapy include the development of acini and lobules in the breast, testicular tubular changes, and squamous metaplasia of the prostate and urethra. Neoplastic cases include breast adenocarcinoma and fibroepithelial lesions, testicular germ cell tumors, prostatic adenocarcinoma, anal squamous cell carcinoma, pituitary adenomas, and meningiomas. Additional studies assessing the findings in other organ systems as well as population-based studies assessing rates of neoplasia are needed. However, future research relies on engagement within the surgical pathology community as well as collaboration with clinicians and patients to achieve optimal results.
Topics: Breast; Female; Hormones; Humans; Male; Pathology, Surgical; Transgender Persons; Transsexualism
PubMed: 33983412
DOI: 10.5858/arpa.2020-0704-RA -
European Journal of Cancer (Oxford,... Jul 2021Platinum-based combination chemotherapy is the standard treatment for patients with chemotherapy-eligible metastatic urothelial carcinoma (mUC). Immune-checkpoint... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Platinum-based combination chemotherapy is the standard treatment for patients with chemotherapy-eligible metastatic urothelial carcinoma (mUC). Immune-checkpoint inhibitors (ICIs) are currently assessed in this setting. This review aimed to assess the role of ICIs alone or in combination as first-line treatment in chemotherapy-eligible patients with mUC.
METHODS
Multiple databases were searched for articles published until November 2020. Studies were deemed eligible if they compared overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), complete response rates (CRRs), durations of response (DORs) and adverse events (AEs) in chemotherapy-eligible patients with mUC.
RESULTS
Three studies met our eligibility criteria. ICI combination therapy was associated with significantly better OS and PFS, higher CRR and longer DOR than chemotherapy alone (hazard ratio [HR]: 0.85, 95% confidence interval [CI]: 0.76-0.94, P = 0.002; HR: 0.80, 95% CI: 0.71-0.90, P = 0.0002; odds ratio [OR]: 1.48, 95% CI: 1.12-1.96, P = 0.006; and mean difference: 1.39, 95% CI: 0.31-2.46, P = 0.01, respectively). ICI-chemotherapy combination therapy was also associated with significantly better OS and PFS, higher ORR and CRR and longer DOR than chemotherapy alone. Although OS and PFS benefits of ICI combination therapy were larger in patients with high expression of programmed death-ligand 1 (PD-L1), PD-L1 low expression patients also had a benefit; HR for OS (high PD-L1: HR 0.79 versus low PD-L1: HR 0.89) and PFS (high PD-L1: HR 0.74 versus low PD-L1: HR 0.82). ICI monotherapy was not associated with better oncological outcomes but was associated with better safety outcomes than chemotherapy alone.
CONCLUSIONS
Our analysis indicates a superior oncologic benefit to first-line ICI combination therapies in patients with chemotherapy-eligible mUC over standard chemotherapy. In contrast, ICI monotherapy was associated with favorable safety outcomes compared with chemotherapy but failed to show its superiority over chemotherapy in oncological benefits. PD-L1 status alone cannot help guide treatment decision-making. However, caution should be exercised in interpreting the conclusions drawn from this study, given that there is the heterogeneity of the population of interest, risk of bias and the nature of the studies evaluated whose data remain immature or unpublished.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Carcinoma; Clinical Decision-Making; Female; Humans; Immune Checkpoint Inhibitors; Male; Middle Aged; Patient Selection; Progression-Free Survival; Time Factors; Urinary Bladder Neoplasms; Urothelium
PubMed: 33962359
DOI: 10.1016/j.ejca.2021.03.049 -
Antioxidants (Basel, Switzerland) Apr 2021γ-Glutamyltransferase (GGT), a membrane-bound enzyme, contributes to the metabolism of glutathione (GSH), which plays a critical physiological role in protecting cells... (Review)
Review
γ-Glutamyltransferase (GGT), a membrane-bound enzyme, contributes to the metabolism of glutathione (GSH), which plays a critical physiological role in protecting cells against oxidative stress. GGT has been proposed as a biomarker of carcinogenesis and tumor progression given that GGT activity is important during both the promotion and invasion phases in cancer cells. Moreover, GGT expression is reportedly related to drug-resistance possibly because a wide range of drugs are conjugated with GSH, the availability of which is influenced by GGT activity. While serum GGT activity is commonly used as a quick, inexpensive, yet reliable means of assessing liver function, recent epidemiological studies have shown that it may also be an indicator of an increased risk of prostate cancer development. Moreover, elevated serum GGT is reportedly an adverse prognostic predictor in patients with urologic neoplasms, including renal cell carcinoma, prostate cancer, and urothelial carcinoma, although the background mechanisms have still not been well-characterized. The present review article summarizes the possible role of GGT in cancer cells and focuses on evidence evaluation through a systematic review of the latest literature on the prognostic role of serum GGT in patients with genitourinary cancer.
PubMed: 33916150
DOI: 10.3390/antiox10040549 -
Journal of Cancer 2021Several epidemiological studies have assessed the association of sugary drinks consumption with cancer, but the results remain controversial. We performed this...
Several epidemiological studies have assessed the association of sugary drinks consumption with cancer, but the results remain controversial. We performed this analysis to evaluate possible causal relationship between sugary drinks consumption and cancer risk and mortality. We searched PubMed, Embase, and Web of Science databases in English. Observational studies evaluating the association of sugary drinks intake with cancer were included. Random-effects meta-analysis was used to calculate the risk estimates. A total of 71 observational articles with 32 case-control and 39 cohort studies were included in the meta-analysis. 60 addressed cancer risk, and 11 reported cancer mortality. Compared with the lowest level, the highest level of sugar-sweetened beverages (SSB) consumption showed an increased overall cancer risk (RR=1.12 95% CI: 1.06-1.19, P=0.000) and mortality (RR=1.07 95% CI: 1.01-1.14, P=0.029), and fruit juice intake showed a positive association with cancer risk in cohort studies (RR=1.06 95% CI: 1.01-1.11, P=0.013). Subgroup analyses based on cancer type indicated that risk of breast cancer, hepatocellular carcinoma, colorectal cancer, and prostatic cancer mortality had a positive association with SSB consumption. For dose-response analysis, evidence of a linear association was found between overall cancer risk and SSB or fruit juice consumption, and the risk increase by 4% for one servings/d increment in SSB intake and 14% in fruit juice. Our findings suggest the consumption of sugary beverages may increase the risk and mortality of cancer, especially risk of breast cancer, hepatocellular carcinoma, colorectal cancer, and prostatic cancer, and mortality of breast cancer, though the evidence was limited.
PubMed: 33854607
DOI: 10.7150/jca.51322