***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Type 2 diabetes mellitus ( T2DM ) has consistently been associated with decreased risk of prostate cancer ; however , if this decrease is related to the use of anti‐diabetic drugs is unknown . We prospect ively studied men in the comparison cohort in the Prostate Cancer data Base Sweden 3.0 , with data on T2DM , use of metformin , sulfonylurea and insulin retrieved from national health care registers and demographic data bases . Cox proportional hazards regression models were used to compute hazard ratios ( HR ) and 95 % confidence intervals ( CI ) of prostate cancer , adjusted for confounders . The study consisted of 612,846 men , mean age 72 years ( st and ard deviation ; SD = 9 years ) , out of whom 25,882 men were diagnosed with prostate cancer during follow up , mean time of 5 years ( SD = 3 years ) . Men with more than 1 year 's duration of T2DM had a decreased risk of prostate cancer compared to men without T2DM ( HR = 0.85 , 95 % CI = 0.82–0.88 ) but among men with T2DM , those on metformin had no decrease ( HR = 0.96 , 95 % CI = 0.77–1.19 ) , whereas men on insulin ( 89 % ) or sulfonylurea ( 11 % ) had a decreased risk ( HR = 0.73 , 95 % CI = 0.55–0.98 ) , compared to men with T2DM not on anti‐diabetic drugs . Men with less than 1 year 's duration of T2DM had no decrease in prostate cancer risk ( HR = 1.11 , 95 % CI = 0.95–1.31 ) . Our results gave no support to the hypothesis that metformin protects against prostate cancer as recently proposed . However , our data gave some support to an inverse association between T2DM severity and prostate cancer risk Objective . To examine the association between metformin use and cancer stage at diagnosis among elderly men with preexisting diabetes mellitus and incident prostate cancer . Methods . This study used a population -based observational cohort of elderly men ( ≥66 years ) with preexisting diabetes and incident prostate cancer between 2008 and 2009 ( N = 2,652 ) . Cancer stage at diagnosis ( localized versus advanced ) was based on the American Joint Cancer Committee classification . Metformin use and other independent variables were measured during the one year before cancer diagnosis . Logistic regressions with inverse probability treatment weights were used to control for the observed selection bias . Results . A significantly lower percentage of metformin users were diagnosed with advanced prostate cancer as compared to nonusers ( 4.7 % versus 6.7 % , p < 0.03 ) . After adjusting for the observed selection bias and other independent variables , metformin use was associated with a 32 % reduction in the risk of advanced prostate cancer ( adjusted odds ratio , AOR : 0.68 , 95 % confidence interval , CI : 0.48 , 0.97 ) . Conclusions . This is the first epidemiological study to support the role of metformin in reducing the risk of advanced prostate cancer . R and omized clinical trials are needed to confirm the causal link between metformin use and prostate cancer diagnosis stage Background : While epidemiologic studies suggest that metformin use among diabetics may decrease prostate cancer ( PC ) incidence , the effect of metformin use on PC outcome is unclear . We investigated the association between pre-operative metformin use , dose and duration of use and biochemical recurrence ( BCR ) in PC patients with diabetes who underwent radical prostatectomy ( RP ) . Methods : We conducted a retrospective cohort analysis within the Shared Equal Access Regional Cancer Hospital ( SEARCH ) data base of 371 PC patients with diabetes who underwent RP .  Time to BCR between metformin users and non-users , and by metformin dose and duration of use was assessed using multivariable Cox proportional analysis adjusted for demographic , clinical and /or pathologic features . Time to castrate-resistant PC ( CRPC ) , metastases and PC-specific mortality were explored as secondary outcomes using unadjusted analyses . Results : Of 371 diabetic men , 156 ( 42 % ) were using metformin before RP .  Metformin use was associated with more recent year of surgery ( P<0.0001 ) but no clinical or pathologic characteristics . After adjustment for year of surgery , clinical and pathologic features , there were no associations between metformin use ( hazard ratio ( HR ) 0.93 ; 95 % confidence interval ( CI ) 0.61–1.41 ) , high metformin dose ( HR 0.96 ; 95 % CI 0.57–1.61 ) or duration of use ( HR 1.00 ; 95 % CI 0.99–1.02 ) and time to BCR . A total of 14 patients ( 3.8 % ) developed CRPC , 10 ( 2.7 % ) distant metastases and 8 ( 2.2 % ) died from PC . Unadjusted analysis suggested that high metformin dose vs non-use was associated with increased risk of CRPC ( HR 5.1 ; 95 % CI 1.6–16.5 ) , metastases ( HR 4.8 ; 95 % CI 1.2–18.5 ) and PC-specific mortality ( HR 5.0 ; 95 % CI 1.1–22.5 ) . Conclusions : Metformin use , dose or duration of use was not associated with BCR in this cohort of diabetic PC patients treated with RP . The suggestion that higher metformin dose was associated with increased risk of CRPC , metastases and PC-specific mortality merits testing in large prospect i ve studies with longer follow-up Objective A history of diabetes has been fairly consistently related to a reduced prostate cancer risk , but previous investigations have not always addressed whether the relation with diabetes varies by prostate cancer aggressiveness or the association between diabetes and prostate cancer is modified by physical activity level and body mass , variables closely related to glucose metabolism . Methods We prospect ively examined the diabetes – prostate cancer risk relationship among 33,088 men in the screening arm of the Prostate , Lung , Colorectal and Ovarian ( PLCO ) Cancer Screening Trial . Results During 8.9 years follow-up , we ascertained 2,058 incident prostate cancer cases . Diabetes history was related to decreased risk of total prostate cancer ( RR = 0.80 , 95 % CI = 0.68–0.95 ) . The apparent protection afforded by diabetes was primarily due to the inverse relation with non-aggressive disease ( i.e. , the combination of low grade ( Gleason sum < 8) and low stage ( clinical stages I or II ) ; RR = 0.75 ; 95 % CI = 0.62–0.91 ) . In contrast , no association was noted between diabetes and aggressive disease ( i.e. , high grade or high stage ( Gleason sum ≥8 or clinical stages III or IV ) ; RR = 1.04 , 95 % CI = 0.74–1.45 ) . In further analyses , the association between diabetes and aggressive prostate cancer was suggestively positive for men who were lean ( RR = 1.64 , 95 % CI = 0.87–3.07 ; BMI < 25 kg/m2 ) and it was positive for men who were the most physically active ( RR = 1.63 ; 95 % CI = 1.07–2.62 ; 3 + hours vigorous activity/week ) . By comparison , no relations of diabetes to aggressive prostate cancer were noted for their heavier or physically less active counterparts ( p-value for tests of interaction = 0.10 and 0.03 BMI and physical activity , respectively ) . Conclusion In this study , diabetes showed divergent relations with prostate cancer by tumor aggressiveness . Specifically , diabetes was inversely associated with early stage prostate cancer but it showed no relation with aggressive prostate cancer . Exploratory analyses suggested a positive association  between diabetes and aggressive prostate cancer in the subgroup of men with a low BMI Abstract Objective : Diabetic men have lowered overall prostate cancer ( PCa ) risk , while their risk of high- grade disease may be elevated . The antidiabetic drug metformin may reduce the risk . This study evaluated PCa incidence among users of metformin and other antidiabetic drugs in the Finnish R and omized Study of Screening for Prostate Cancer ( FinRSPC ) . Methods : The study population ( 78,615 men ) was linked to the national prescription data base . Hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for PCa were estimated using Cox regression , with medication use as a time-dependent variable . The effect of diabetes was estimated by comparing antidiabetic drug users to non-users , while drug-specific effects were evaluated within antidiabetic drug users . Analyses were performed in both study arms of FinRSPC . Results : Compared to non-users , men using antidiabetic drugs had lowered overall PCa risk ( HR 0.85 , 95 % CI 0.79–0.92 ) , and this association was not affected by PCa screening . However , the risk of metastatic PCa was increased ( HR 1.44 , 95 % CI 1.09–1.91 ) . Among antidiabetic drug users , metformin decreased overall PCa risk ( HR 0.81 , 95 % CI 0.69–0.95 ) in a dose-dependent manner . When stratified by FinRSPC study arm , the risk reduction was observed only in the screening arm . Sulphonylureas increased the risk of metastatic PCa ( HR 2.04 , 95 % CI 1.11–3.77 ) . Use of thiazoledenediones or insulin was not associated with PCa risk . Conclusion : Among antidiabetic drug  users , metformin lowered the overall PCa risk , while the risk of metastatic disease was elevated in sulphonylurea users . As sulphonylureas stimulate insulin secretion , the results suggest that hyperinsulinemia may be a risk factor for PCa PURPOSE In the initial report of the Lupron Depot Neoadjuvant Prostate Cancer Study Group patients who received 3 months of and rogen deprivation had a significant decrease in the positive margin rate . We monitored these patients for 5 years and to our knowledge present the longest followup of any neoadjuvant trial . MATERIAL S AND METHODS A multi-institutional prospect i ve r and omized trial was performed between February 1992 and April 1994 involving patients with stage cT2b prostate cancer , including 138 who received 3 months of leuprolide plus flutamide before radical prostatectomy and 144 who underwent radical prostatectomy only .  Patients were followed every 6 months with serum prostate specific antigen ( PSA ) testing for 5 years . Biochemical recurrence was defined as PSA greater than 0.4 ng./ml . RESULTS At 5 years there was no difference in the biochemical recurrence rate . PSA was less than 0.4 ng./ml . in 64.8 % of the patients in the neoadjuvant and rogen ablation plus prostatectomy and 67.6 % in the prostatectomy only group ( p = 0.663 ) . CONCLUSIONS Although 3 months of and rogen deprivation before radical prostatectomy result ed in an apparently significant decrease in positive surgical margins , a 5-year followup does not indicate any difference in the recurrence rate . Until studies document improvement in biochemical or clinical recurrence with longer periods of treatment , induction and rogen deprivation before radical prostatectomy is not indicated Objective : Prostate cancer and type 2 diabetes mellitus ( DM2 ) are both common diseases found in the elderly male population . The diabetic drug , metformin , has been shown to have antineoplastic properties and demonstrated better treatment outcomes when used as adjuvant therapy in patients with breast cancer . The hormonally‐sensitive cancer analogous to breast cancer in men is prostate cancer . We investigated improved survival , lower risks of recurrences , and lower , more stable levels of prostate‐specific antigen ( PSA ) in patients with DM2 along with prostate cancer on metformin . Methods : Patients with prostate cancer along with DM2 who remained on metformin were compared  with controls who were not on metformin matched by age , weight , race and Gleason score cancer staging . The endpoints of our study included final PSA values , number of recurrences , metastases and number living for each group . Results : There were significantly fewer deaths ( 23 % versus 10 % ) , fewer recurrences ( 15 % versus 8 % ) , fewer metastases ( 5 % versus 0 % ) and fewer secondary cancers ( 17 % versus 6 % ) in the metformin group ( P < 0.004 ) . The final PSA value was lower in the metformin‐treated group with a result approaching significance ( P = 0.067 ) . The primary treatments for prostate cancer ( ie , surgery , radiation and and rogen depletion ) were found to be comparable in both the groups . Conclusions : Our retrospective study shows that adjuvant metformin therapy leads to a better prognosis in prostate cancer . Not only are PSA levels controlled for several years but also there are significantly fewer cancer recurrences  in metformin‐treated patients . Overall , these results are promising and should be followed up with a prospect i ve study to assess long‐term survival Objective To describe the outcome , assessed as the level of prostate specific antigen ( PSA ) , of a mature ( more than half 
    Output:
    
In conclusion , compared with non-metformin treatment , metformin therapy can significantly improve OS , CSS and RFS in PCa patients .
No association was noted between metformin therapy and PCa incidence .