The Impact of Metformin Use with Survival Outcomes in Urologic Cancers: A Systematic Review and Meta-Analysis

Background. Conflicting results exist between the potential protective effects of metformin and the prognosis of urologic cancers. This meta-analysis summarized the effects of metformin exposure on the recurrence, progression, cancer-specific survival (CSS), and overall survival (OS) of the three main urologic cancers (kidney cancer, bladder cancer, and prostate cancer). Methods. We systematically searched PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure databases (January 2010 to December 2019), which identified studies regarding metformin users and nonusers with urologic cancers and extracted patient data. A random effect model or fixed effect model was used to analyze hazard ratios (HRs) and 95% confidence intervals (CIs). Results. Among the 1883 confirmed studies, 27 eligible studies were identified, including 123,212 participants. In prostate cancer, patients using metformin have significant benefits for recurrence ( HR = 0.74 ; 95% CI: 0.61-0.90; P = 0.007 ; I 2 = 56 % ), CSS ( HR = 0.74 ; 95% CI: 0.61-0.91; P = 0.002 ; I 2 = 79 % ), and OS ( HR = 0.76 ; 95% CI: 0.65-0.90; P < 0.001 ; I 2 = 86 % ). Moreover, further subgroup analysis showed that the beneficial effects of metformin may be more significant for patients receiving radical radiotherapy. For kidney cancer, metformin was beneficial for progression ( HR = 0.80 ; 95% CI: 0.65-0.98; P = 0.14 ; I 2 = 46 % ). Analysis revealed that the effect of metformin on the overall survival of kidney cancer patients may be related to nationality (American: HR = 0.76 ; 95% CI: 0.59-0.98; P = 0.88 ; I 2 = 0 % ). For bladder cancer, no obvious benefits of metformin use were identified. However, subgroup analysis indicated that metformin may improve the recurrence of bladder cancer, but this improvement was only found in patients with a median follow-up time of more than 4 years ( HR = 0.43 ; 95% CI: 0.28-0.67; P = 0.61 ; I 2 = 0 % ).

Download Full-text

211P The impact of low muscle mass to overall survival in bladder cancer patients undergoing chemotherapy: A systematic review and meta-analysis

Annals of Oncology ◽

10.1016/j.annonc.2020.10.222 ◽

2020 ◽

Vol 31 ◽

pp. S1322

Author(s):

K.V. Japar ◽

F. Kwenandar ◽

V. Damay ◽

T.I. Hariyanto ◽

A. Kurniawan

Keyword(s):

Systematic Review ◽

Overall Survival ◽

Bladder Cancer ◽

Cancer Patients ◽

Muscle Mass ◽

Meta Analysis ◽

The Impact

Download Full-text

The impact of metformin use on survival in kidney cancer patients with diabetes: a meta-analysis

International Urology and Nephrology ◽

10.1007/s11255-017-1548-4 ◽

2017 ◽

Vol 49 (6) ◽

pp. 975-981 ◽

Cited By ~ 17

Author(s):

Yang Li ◽

Liyi Hu ◽

Qinghong Xia ◽

Yongqiang Yuan ◽

Yonghua Mi

Keyword(s):

Cancer Patients ◽

Kidney Cancer ◽

Meta Analysis ◽

Patients With Diabetes ◽

The Impact

Download Full-text

The impact of androgen deprivation and pelvic radiation on the development of bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.439 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 439-439 ◽

Cited By ~ 1

Author(s):

Navid Hafez ◽

Rong Wang ◽

Michael E. Hurwitz ◽

Xiaomei Ma ◽

Daniel Peter Petrylak

Keyword(s):

Prostate Cancer ◽

Bladder Cancer ◽

Cancer Patients ◽

Animal Studies ◽

Androgen Deprivation ◽

Elderly Age ◽

Bladder Tissue ◽

Kaplan Meier ◽

Similar Patient ◽

The Impact

439 Background: The male predilection of urothelial bladder cancer (UBC) as well as the expression of the androgen receptor in bladder tissue point to the role for androgens in UBC tumorigenesis. Animal studies demonstrate a potential role for androgen deprivation in diminishing UBC. More recently, two separate groups demonstrated decreased rates of both primary and recurrent UBC in prostate cancer patients previously receiving androgen deprivation therapy (ADT). Given the common use of radiation therapy (RT) in the treatment of localized prostate cancer, and previous data supporting the increased frequency of UBC in prostate cancer patients treated with RT, the interaction between ADT and RT in UBC remains an important consideration. Methods: Using the linked SEER-Medicare database, we investigated the interactions among ADT, RT and UBC by performing a retrospective cohort study of elderly (age 66-99) prostate cancer patients diagnosed between 1999-2011. Kaplan-Meier analysis and Cox proportional modeling were used to determine the risk of developing secondary bladder cancer after prostate cancer treatment (based on exposure to ADT, RT, both, or neither). All analyses were two-sided. Results: Of 121,927 patients with primary prostate cancer, 1,466 (1.20%) developed subsequent UBC with a median follow up of 5.08 years (range 0.003-12.00). Compared with patients never receiving ADT or RT (n = 43,809), the hazard ratios for the development of secondary bladder cancer in patients ever receiving ADT but no RT (n = 14,009), RT but no ADT (n = 16,672), or both ADT and RT (n = 17,465) were 0.76 (95% confidence interval [CI]: 0.63-0.91 ), 0.73 (95% CI: 0.64-0.83), and 0.69 (95% CI: 0.61-0.79), respectively. Conclusions: Both ADT and RT are independently associated with a reduced risk of secondary bladder cancers in prostate cancer patients. The finding of decreased UBC incidence in patients receiving RT was surprising, and in direct contradiction to previous studies of similar patient populations. Possible explanations include differences in cohort selection, changes in RT delivery, and differences in control groups.

Download Full-text

Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment

Frontiers in Oncology ◽

10.3389/fonc.2021.633462 ◽

2021 ◽

Vol 11 ◽

Author(s):

Bo Fan ◽

Alradhi Mohammed ◽

Yuanbin Huang ◽

Hong Luo ◽

Hongxian Zhang ◽

...

Keyword(s):

Overall Survival ◽

Bladder Cancer ◽

Case Control Study ◽

Meta Analysis ◽

Case Control ◽

Female Patients ◽

Kaplan Meier ◽

History Of ◽

The Impact ◽

Control Study

Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa (P=0.175). Stratified analyses of sex showed that aspirin intake did not lead to a lower risk of BCa in female patients (P=0.063). However, the male population who regularly took aspirin had a lower incidence of BCa (OR=0.748, 95% CI= 0.584-0.958, P=0.021). Subgroup analyses stratified by smoking found a significant reduction in the risk of BCa in current smokers with aspirin intake (OR=0.522, 95% CI=0.342-0.797, P=0.002). In terms of prognosis of BCa, patients with a history of aspirin intake did not had a markedly longer OS or RFS than those with no history of aspirin intake by Kaplan-Meier curves. Stratified analysis by sex showed no correlation between aspirin intake and the recurrence or survival of BCa for either male or female patients. However, in people younger than 68, aspirin intake seemed to have prolonged effects for overall survival (HR=3.876; 95% CI=1.326-11.325, P=0.019). Then, we performed a meta-analysis and the combined results from 19 articles and our study involving more than 39524 BCa cases indicated that aspirin intake was not associated with the occurrence of BCa (P=0.671). Subgroup analysis by whether regular use of aspirin, by the mean duration of use of aspirin, by sex, by smoking exposure, by research region and by study type also supported the above results. In terms of the impact of aspirin intake on the prognosis of patients with BCa, 11 articles and our study involving 8825 BCa cases were eligible. The combined results showed that patients with aspirin intake did not have significantly influence on survival, recurrence, progression and metastasis than those without aspirin intake. On the whole, both our retrospective study and literature meta-analysis suggested a lack of a strong relevant association between the use of aspirin and the incidence or prognosis of BCa. Thus, additional long-term follow-up prospective research is warranted to clarify the association of aspirin with BCa incidence and prognosis.

Download Full-text

Safety of image-guided radiotherapy in definitive radiotherapy for localized prostate cancer: a population-based analysis

British Journal of Radiology ◽

10.1259/bjr.20200456 ◽

2021 ◽

Vol 94 (1121) ◽

pp. 20200456

Author(s):

Yao-Hung Kuo ◽

Ji-An Liang ◽

Guan-Heng Chen ◽

Chia-Chin Li ◽

Chun-Ru Chien

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Cancer Mortality ◽

Phase Iii ◽

Localized Prostate Cancer ◽

Image Guided Radiotherapy ◽

Definitive Radiotherapy ◽

Image Guided ◽

The Impact

Objectives: Image-guided radiotherapy (IGRT) is a recommended advanced radiation technique that is associated with fewer acute and chronic toxicities. However, one Phase III trial showed worse overall survival in the IGRT arm. The purpose of this observational study is to evaluate the impact of IGRT on overall survival. Methods: We used the Taiwan Cancer Registry Database to enroll cT1-4N0M0 prostate cancer patients who received definitive radiotherapy between 2011 and 2015. We used inverse probability treatment weighting (IPW) to construct balanced IGRT and non-IGRT groups. We compared the overall survival of those in the IGRT and non-IGRT groups. Supplementary analyses (SA) were performed with alternative covariates in propensity score (PS) models and PS approaches. The incidence rates of prostate cancer mortality (IPCM), other cancer mortality (IOCM), and cardiovascular mortality (ICVM) were also evaluated. Results: There were 360 patients in the IGRT arm and 476 patients in the non-IGRT arm. The median follow-up time was 50 months. The 5-year overall survival was 88% in the IGRT arm and 86% in the non-IGRT arm (adjusted hazard ratio [HR] of death = 0.93; 95% CI, 0.61–1.45; p = 0.77). The SA also showed no significant differences in the overall survival between those in the IGRT and non-IGRT arms. Both groups did not significantly differ in terms of IPCM, IOCM, and ICVM. Conclusions: The overall survival of localized prostate cancer patients who underwent IGRT was not inferior to those who did not. Advances in knowledge: We demonstrated that the overall survival for prostate cancer patients with IGRT was not worse than those who did not undergo IGRT; this important outcome comparison has not been previously examined in the general population.

Download Full-text

C-reactive protein with the survival outcomes of bladder cancer patients: a meta-analysis

10.21203/rs.3.rs-131105/v1 ◽

2020 ◽

Author(s):

Ahouanse Roland Donald ◽

Hailiang Ran ◽

Die Fang ◽

Yusan Che ◽

Yuanyuan Xiao

Keyword(s):

Bladder Cancer ◽

Cancer Patients ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Disease Free Survival ◽

C Reactive Protein ◽

Cancer Specific Survival ◽

Reactive Protein ◽

Effect Model

Abstract Objectives Accumulating evidences suggested that serum C-reactive protein (CRP) was associated with the survival of bladder cancer patients. However, incongruent findings have been reported. Methods We comprehensively searched PubMed, Embase, and Web of science through August 2020 in order to find all eligible studies on the association between CRP and the overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS) of bladder cancer patients. The pooled hazard ratios (HRs) together with their 95% confidence intervals (CIs) were estimated by fixed-effect model if the heterogeneity was low, and random-effect model if the heterogeneity was high. A series of subgroup meta-analysis were performed with regard to the specific characteristics of study design. Results Thirteen eligible studies were included in this meta-analysis. The pooled results of 8 included studies revealed that an elevated CRP was associated with poor OS (HR = 2.24, 95% CI: 1.16–4.34) and CSS (HR = 1.53 95% CI: 1.36–1.72) of bladder cancer. Besides, the combined results of 3 included studies also indicated an inferior DFS for bladder cancer patients of elevated CRP level (HR = 2.07, 95% CI: 1.24–3.35). Subgroup analyses supported the robust association between elevated CRP and CSS. Conclusions These findings suggested that bladder cancer patients reported increase serum CRP had inferior prognostic outcomes.

Download Full-text

The Effect of Prostate Cancer Radiotherapy on Testosterone Level: A Systematic Review and Meta-analysis

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200128112558 ◽

2020 ◽

Vol 20 (6) ◽

pp. 636-642

Author(s):

Keywan Mortezaee ◽

Elham Motallebzadeh ◽

Alireza Milajerdi ◽

Bagher Farhood ◽

Masoud Najafi ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Testosterone Level ◽

Subgroup Analysis ◽

Meta Analysis ◽

Systematic Search ◽

Treatment Technique ◽

Cancer Radiotherapy ◽

Patient Number ◽

Prostate Cancer Radiotherapy

Introduction: In the current study, a systematic search and meta-analysis were performed to evaluate the effect of prostate cancer radiotherapy on testosterone levels of patients. Methods: To illuminate the effect of radiotherapy on the testosterone level of prostate cancer patients, a systematic search was conducted in accordance with the PRISMA guideline in electronic databases of Scopus, Embase, PubMed, Web of Science, and clinical trials up to December 2018 using relevant keywords. Based on a certain set of inclusion and exclusion criteria, 12 eligible studies that had data on the testosterone level following prostate cancer radiotherapy were included in the meta-analysis. Results: According to the various techniques of prostate cancer radiotherapy, the dose values scattered to the testicular tissues ranged from 0.31 to 10 Gy. Combining the findings from 12 studies, it was found that prostate cancer radiotherapy leads to a significant reduction in the testosterone level (Weighted Mean Difference [WMD]: -51.38 ng/dL, 95% CI: -75.86, -26.90, I2=0.0%, P<0.05). Furthermore, subgroup analysis by the patient number showed a significant reduction in the testosterone level at patient number < 50 (WMD: -80.32 ng/dL, 95% CI: -125.10, -35.55, I2= 0.0%) and 50 < patient number < 100 (WMD: -46.99 ng/dL, 95% CI: - 87.15, -6.82, I2= 0.0%). Subgroup analysis based on treatment technique type revealed a significant reduction in testosterone level after conventional radiotherapy (WMD: -56.67, 95% CI: -100.45,-12.88, I2= 34.3%) and IMRT/SBRT technique (WMD: -57.42, 95% CI: -99.39, -15.46, I2= 0.0%) in comparison with the proton therapy (WMD: 0.00, 95% CI: -80.24, 80.24). Conclusion: The findings showed a significant decrease in the testosterone level of prostate cancer patients after radiotherapy compared with pre-treatment levels.

Download Full-text

The prognostic role of androgen receptor in early-stage breast cancer patients: A meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.528 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 528-528 ◽

Cited By ~ 1

Author(s):

Ivana Bozovic-Spasojevic ◽

Dimitrios Zardavas ◽

Evandro De Azambuja ◽

Lieveke Ameye ◽

Christos Sotiriou ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Androgen Receptor ◽

Cancer Patients ◽

Early Stage ◽

Meta Analysis ◽

Prognostic Impact ◽

Breast Cancer Patients ◽

Prognostic Role ◽

The Impact

528 Background: Androgen receptor (AR) expression has been observed in ~70% of breast cancer (BC) patients, but its prognostic role is not established yet. To assess this we performed a meta-analysis of studies that evaluated the impact of AR on disease free survival (DFS) and/or on overall survival (OS) in early stage BC. Methods: Published studies were identified by an electronic search on PubMed using the MeSH terms "breast neoplasm" and "androgen receptor" (up to June 2012). Identified studies were assessed against the following criteria for inclusion in the analysis: early stage BC and reported results of AR status in correlation with clinical outcome. We report combined HRs with 95% confidence intervals (CI) using AR negative patients as reference. Results: Twenty studies were eligible for the meta-analysis out of 493 initially identified and 12 among them, including 6,525 patients, were considered as evaluable (i.e., reporting enough information to allow aggregation of results). AR positivity was associated with lower risk of relapse in all breast cancer patients, and better overall survival in both univariate (U) and multivariate (M) analysis. AR prognostic impact in different subtypes was also assessed (see Table). Conclusions: Our analysis demonstrated that AR delivers prognostic information overall, serving as a positive prognostic factor in early stage BC. Further studies are needed to delineate its prognostic impact within the different subtypes of the disease. [Table: see text]

Download Full-text