PURPOSE: The present systematic review and network meta-analysis (NMA) compared the current different neoadjuvant chemotherapy (NAC) regimes for bladder cancer patients to rank them. METHODS: We used the Bayesian approach in NMA of six different therapy regimens cisplatin, cisplatin/doxorubicin, (gemcitabine/cisplatin) GC, cisplatin/methotrexate, methotrexate, cisplatin, and vinblastine (MCV) and (MVAC) compared to locoregional treatment. RESULTS: Fifteen studies comprised 4276 patients who met the eligibility criteria. Six different regimes were not significantly associated with a lower likelihood of overall mortality rate compared to local treatment alone. In progression-free survival (PFS) rates, cisplatin, GC, cisplatin/methotrexate, MCV and MVAC were not significantly associated with a higher likelihood of PFS rate compared to locoregional treatment alone. In local control outcome, MCV, MVAC, GC and cisplatin/methotrexate were not significantly associated with a higher likelihood of local control rate versus locoregional treatment alone. Nevertheless, based on the analyses of the treatment ranking according to SUCRA, it was highly likely that MVAC with high certainty of results appeared as the most effective approach in terms of mortality, PFS and local control rates. GC and cisplatin/doxorubicin with low certainty of results was found to be the best second options. CONCLUSION: No significant differences were observed in mortality, progression-free survival and local control rates before and after adjusting the type of definitive treatment in any of the six study arms. However, MVAC was found to be the most effective regimen with high certainty, while cisplatin alone and cisplatin/methotrexate should not be recommended as a neoadjuvant chemotherapy regime.
- MeSH
- Bayesova věta MeSH
- cisplatina * terapeutické užití MeSH
- cystektomie MeSH
- doxorubicin terapeutické užití MeSH
- gemcitabin MeSH
- lidé MeSH
- methotrexát terapeutické užití MeSH
- nádory močového měchýře * farmakoterapie MeSH
- neoadjuvantní terapie metody MeSH
- protokoly antitumorózní kombinované chemoterapie MeSH
- síťová metaanalýza MeSH
- vinblastin terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
Introduction: It has been hypothesized that transurethral en bloc (TUEB) of bladder tumor offers benefits over conventional transurethral resection of bladder tumor (cTURBT). This study aimed to compare disease outcomes of TUEB and cTURBT with focus on the different energy sources. Methods: A systematic search was performed using PubMed and Web of Science databases in June 2021. Studies that compared the pathological (detrusor muscle presence), oncological (recurrence rates) efficacy, and safety (serious adverse events [SAEs]) of TUEB and cTURBT were included. Random- and fixed-effects meta-analytic models and Bayesian approach in the network meta-analysis was used. Results: Seven randomized clinical trials (RCTs) and seven non-RCTs (NRCT), with a total of 2092 patients. The pooled 3- and 12-month recurrence risk ratios (RR) of five and four NRCTs were 0.46 (95% CI 0.29-0.73) and 0.56 (95% CI 0.33-0.96), respectively. The pooled 3- and 12-month recurrence RRs of four and seven RCTs were 0.57 (95% CI 0.25-1.27) and 0.89 (95% CI 0.69-1.15), respectively. The pooled RR for SAEs such as prolonged hematuria and bladder perforation of seven RCTs was 0.16 (95% CI 0.06-0.41) in benefit of TUEB. Seven RCTs (n = 1077) met our eligibility criteria for network meta-analysis. There was no difference in 12-month recurrence rates between hybridknife, laser, and bipolar TUEB compared with cTURBT. Contrary, laser TUEB was significantly associated with lower SAEs compared with cTURBT. Surface under the cumulative ranking curve ranking analyses showed with high certainty that laser TUEB was the best treatment option to access all endpoints. Conclusion: While NRCTs suggested a recurrence-free benefit to TUEB compared with cTURBT, RCTs failed to confirm this. Conversely, SAEs were consistently and clinically significantly better for TUEB. Network meta-analyses suggested laser TUEB has the best performance compared with other energy sources. These early findings need to be confirmed and expanded upon.
PURPOSE: Androgen-regulated enzymes such as the angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are involved in the SARS-CoV-2 infection process. The expression of TMPRSS2 and its fusion gene, which are increased in the epithelium of the human prostate gland during prostate carcinogenesis, are regulated by androgens. Our goal was to assess the risk of the SARS-CoV-2 infection and the severity of the disease in PCa patients treated with androgen deprivation therapy (ADT). METHODS: We conducted a systematic review and meta-analysis according to PRISMA guidelines. We queried PubMed and Web of Science databases on 1 July 2021. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to Cochrane's Q test and I2 statistic, respectively. RESULTS: Six retrospective studies (n = 50,220 patients) were selected after considering inclusion and exclusion criteria for qualitative evidence synthesis. Four retrospective studies were included to assess the SARS-CoV-2 infection risk in PCa patients under ADT vs. no ADT and the summarized risk ratio (RR) was 0.8 (95% confidence intervals (CI) 0.44-1.47). Five retrospective studies were included to assess the severity of coronavirus disease 2019 (COVID-19) in PCa patients under ADT versus no ADT and the summarized RR was 1.23 (95% CI 0.9-1.68). CONCLUSION: We found a non-significant association between the risk of SARS-CoV-2 infection and COVID-19 severity in PCa patients treated with ADT. However, our results suggest that during the COVID-19 pandemic PCa patients can safely undergo ADT as a cancer therapy without worsening COVID-19 risk and trajectory.
- MeSH
- androgeny MeSH
- antagonisté androgenů terapeutické užití MeSH
- COVID-19 * MeSH
- lidé MeSH
- nádory prostaty * farmakoterapie epidemiologie MeSH
- pandemie MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- SARS-CoV-2 MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
CONTEXT: Degarelix is associated with high rates of injection site reaction. The US Food and Drug Administration approved relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, for the treatment of advanced prostate cancer patients. OBJECTIVE: This systematic review and network meta-analysis aimed to compare the efficacy and safety of relugolix versus degarelix. EVIDENCE ACQUISITION: A systematic search was performed using major web databases for studies published before January 30, 2021, according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) extension statement for a network meta-analysis. Studies that compared the efficacy (12-mo castration rate with testosterone ≤50 ng/dl) and safety (adverse events [AEs]) of relugolix or degarelix and of the control group (GnRH agonists) were included. We used the Bayesian approach in the network meta-analysis. EVIDENCE SYNTHESIS: Four studies (n = 2059) met our eligibility criteria. The main efficacy analysis was conducted for two different treatments (relugolix and all doses of degarelix vs GnRH agonists); relugolix (risk ratio [RR] 1.09, 95% credible interval [CrI]: 0.95-1.23) and degarelix (RR 0.98, 95% CrI: 0.91-1.06) were not associated with different 12-mo castration rates. In the subgroup analysis, degarelix 480 mg was significantly associated with a lower castration rate (RR 0.46, 95% CrI: 0.07-0.92). In all efficacy ranking analyses, relugolix achieved the best rank. The safety analyses showed that relugolix (RR 0.99, 95% CrI: 0.6-1.6 and RR 0.72, 95% CrI: 0.4-1.3, respectively) and degarelix (RR 1.1, 95% CrI: 0.75-1.35 and RR 1.05, 95% CrI: 0.42-2.6, respectively) were not associated with either all AE or serious AE rates. In the ranking analyses, degarelix achieved the worst rank of all AEs and the best rank of serious AEs. Relugolix (RR 0.44, 95% CrI: 0.16-1.2) and degarelix (RR 0.74, 95% CrI: 0.37-1.52) were not associated with different cardiovascular event (CVE) rates; both were associated with lower CVE rates than GnRH agonists in the ranking analyses. CONCLUSIONS: We found that the efficacy and safety of relugolix are comparable with those of degarelix, albeit with no injection site reaction. Such data should be interpreted with caution until large-scale direct comparison studies with a longer follow-up are available. PATIENT SUMMARY: We found that relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, has comparable efficacy and safety with degarelix, a parenteral GnRH antagonist, for the treatment of advanced prostate cancer patients.
- MeSH
- Bayesova věta MeSH
- fenylmočovinové sloučeniny MeSH
- hormon uvolňující gonadotropiny terapeutické užití MeSH
- lidé MeSH
- nádory prostaty * farmakoterapie MeSH
- oligopeptidy MeSH
- pyrimidinony MeSH
- randomizované kontrolované studie jako téma MeSH
- síťová metaanalýza MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
- Geografické názvy
- Spojené státy americké MeSH
Objective: To present an update of the available literature on external beam radiation therapy (EBRT) with or without brachytherapy (BT) compared to radical prostatectomy (RP) for patients with high-risk localised prostate cancer (PCa). Methods: We conducted a systematic review and meta-analysis of the literature assessing the survival outcomes in patients with high-risk PCa who received EBRT with or without BT compared to RP as the first-line therapy with curative intent. We queried PubMed and Web of Science database in January 2021. Moreover, we used random or fixed-effects meta-analytical models in the presence or absence of heterogeneity per the I2 statistic, respectively. We performed six meta-analyses for overall survival (OS) and cancer-specific survival (CSS). Results: A total of 27 studies were selected with 23 studies being eligible for both OS and CSS. EBRT alone had a significantly worse OS and CSS compared to RP (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.16-1.65; and HR 1.55, 95% CI 1.25-1.93). However, there was no difference in OS (HR 1.1, 95% CI 0.76-1.34) and CSS (HR 0.69, 95% CI 0.45-1.06) between EBRT plus BT compared to RP. Conclusion: While cancer control affected by EBRT alone seems inferior to RP in patients with high-risk PCa, BT additive to EBRT was not different from RP. These data support the need for BT in addition to EBRT as part of multimodal RT for high-risk PCa.Abbreviations: ADT: androgen-deprivation therapy; BT: brachytherapy; CSS: cancer-specific survival; HR: hazard ratio; MFS, metastatic-free survival; MOOSE: Meta-analyses of Observational Studies in Epidemiology; OR: odds ratio; OS: overall survival; PCa: prostate cancer; RR: relative risk; RP: radical prostatectomy; RCT: randomised controlled trials; (EB)RT: (external beam) radiation therapy.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE: The accurate selection of patients who are most likely to benefit from neoadjuvant chemotherapy is an important challenge in oncology. Serum AGR has been found to be associated with oncological outcomes in various malignancies. We assessed the association of pre-therapy serum albumin-to-globulin ratio (AGR) with pathologic response and oncological outcomes in patients treated with neoadjuvant platin-based chemotherapy followed by radical nephroureterectomy (RNU) for clinically non-metastatic UTUC. METHODS: We retrospectively included all clinically non-metastatic patients from a multicentric database who had neoadjuvant platin-based chemotherapy and RNU for UTUC. After assessing the pretreatment AGR cut-off value, we found 1.42 to have the maximum Youden index value. The overall population was therefore divided into two AGR groups using this cut-off (low, < 1.42 vs high, ≥ 1.42). A logistic regression was performed to measure the association with pathologic response after NAC. Univariable and multivariable Cox regression analyses tested the association of AGR with OS and RFS. RESULTS: Of 172 patients, 58 (34%) patients had an AGR < 1.42. Median follow-up was 26 (IQR 11-56) months. In logistic regression, low AGR was not associated with pathologic response. On univariable analyses, pre-therapy serum AGR was neither associated with OS HR 1.15 (95% CI 0.77-1.74; p = 0.47) nor RFS HR 1.48 (95% CI 0.98-1.22; p = 0.06). These results remained true regardless of the response to NAC. CONCLUSION: Pre-therapy low serum AGR before NAC followed by RNU for clinically high-risk UTUC was not associated with pathological response or long-term oncological outcomes. Biomarkers that can complement clinical factors in UTUC are needed as clinical staging and risk stratification are still suboptimal leading to both over and under treatment despite the availability of effective therapies.
- MeSH
- globuliny analýza MeSH
- karcinom z přechodných buněk krev terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetné primární nádory krev terapie MeSH
- nádory ledvin krev terapie MeSH
- nádory močovodu krev terapie MeSH
- nefroureterektomie * MeSH
- neoadjuvantní terapie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- sérový albumin analýza MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH