***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 
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    ***EXAMPLES*** 
    Input: BACKGROUND The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen ( PSA ) testing remains uncertain . METHODS We compared active monitoring , radical prostatectomy , and external-beam radiotherapy for the treatment of clinical ly localized prostate cancer . Between 1999 and 2009 , a total of 82,429 men 50 to 69 years of age received a PSA test ; 2664 received a diagnosis of localized prostate cancer , and 1643 agreed to undergo r and omization to active monitoring ( 545 men ) , surgery ( 553 ) , or radiotherapy ( 545 ) . The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up . Secondary outcomes included the rates of disease progression , metastases , and all-cause deaths . RESULTS There were 17 prostate-cancer-specific deaths overall : 8 in the active-monitoring group ( 1.5 deaths per 1000 person-years ; 95 % confidence interval [ CI ] , 0.7 to 3.0 ) , 5 in the surgery group ( 0.9 per 1000 person-years ; 95 % CI , 0.4 to 2.2 ) , and 4 in the radiotherapy group ( 0.7 per 1000 person-years ; 95 % CI , 0.3 to 2.0 ) ; the difference among the groups was not significant ( P=0.48 for the overall comparison ) . In addition , no significant difference was seen among the groups in the number of deaths from any cause ( 169 deaths overall ; P=0.87 for the comparison among the three groups ) . Metastases developed in more men in the active-monitoring group ( 33 men ; 6.3 events per 1000 person-years ; 95 % CI , 4.5 to 8.8 ) than in the surgery group ( 13 men ; 2.4 per 1000 person-years ; 95 % CI , 1.4 to 4.2 ) or the radiotherapy group ( 16 men ; 3.0 per 1000 person-years ; 95 % CI , 1.9 to 4.9 ) ( P=0.004 for the overall comparison ) . Higher rates of disease progression were seen in the active-monitoring group ( 112 men ; 22.9 events per 1000 person-years ; 95 % CI , 19.0 to 27.5 ) than in the surgery group ( 46 men ; 8.9 events per 1000 person-years ; 95 % CI , 6.7 to 11.9 ) or the radiotherapy group ( 46 men ; 9.0 events per 1000 person-years ; 95 % CI , 6.7 to 12.0 ) ( P<0.001 for the overall comparison ) . CONCLUSIONS At a median of 10 years , prostate-cancer-specific mortality was low irrespective of the treatment assigned , with no significant difference among treatments . Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring . ( Funded by the National Institute for Health Research ; ProtecT Current Controlled Trials number , IS RCT N20141297 ; Clinical Trials.gov number , NCT02044172 . ) Purpose : We evaluated focal therapy with high intensity focused ultrasound hemiablation in a prospect i ve trial . Material s and Methods : We performed a prospect i ve , multicenter , single arm study in patients with unilateral low/intermediate risk prostate cancer who were treated from April 2013 through March 2016 in Germany in AUO ( Arbeitsgemeinschaft Urologische Onkologie ) Study Protocol AP 68/11 . Unilateral prostate cancer was assessed by transrectal ultrasound guided biopsy and multiparametric magnetic resonance imaging . Hemiablation was done using the Ablatherm ® or the Focal One ® device . The oncologic outcome was assessed by the salvage treatment rate , multiparametric magnetic resonance imaging and rebiopsy at 12 months . Functional outcome , quality of life , anxiety and depression were measured by vali date d question naires at baseline and every 3 months . Results : Of the 54 recruited patients 51 completed 12‐month or greater visits . Mean ± SD followup was 17.4 ± 4.5 months . Mean prostate specific antigen decreased from 6.2 ± 2.0 to 2.9 ± 1.9 ng/ml at 12 months ( p < 0.001 ) . Biopsy at 12 months was positive for any prostate cancer and for clinical ly significant prostate cancer in 13 ( 26.5 % ) and 4 ( 8.2 % ) of the 49 patients , respectively . Posttreatment multiparametric magnetic resonance imaging had limited 25 % sensitivity for clinical ly significant prostate cancer . Ten patients ( 19.6 % ) underwent salvage treatment . Potency was maintained in 21 of the 30 men who were potent preoperatively . There was no increase in incontinence . Quality of life , anxiety and depression did not change postoperatively . The study was limited by a short followup and the lack of a control arm . Conclusions : Focal therapy hemiablation is safe with little alteration of functional outcome . The oncologic outcome is acceptable on short‐term followup . Followup multiparametric magnetic resonance imaging performed poorly and should not replace repeat biopsy . Focal therapy has no impact on posttreatment anxiety and depression PURPOSE Cryosurgical ablation of the prostate is a novel therapeutic modality that induces cell lysis in the prostate by direct application of low temperatures . We have been conducting an ongoing prospect i ve pilot study of the use of cryosurgical prostate ablation in treating patients with nonmetastatic prostate adenocarcinoma since January 1993 . Results in 145 consecutive patients with mean 36 months and minimum 12 months of followup are presented . MATERIAL S AND METHODS Accrual was open to patients with clinical stages T1a to T3c prostate adenocarcinoma . Pelvic lymph node dissections were recommended but not required for patients with prostate specific antigen ( PSA ) greater than 15 ng./ml . before study entry . PSA changes , r and om prostate biopsy findings and morbidities after cryosurgical prostate ablation were recorded for each patient . RESULTS Overall actuarial rates at 42 months for maintaining PSA less than 0.3 and less than 1.0 were 59 % and 66 % , respectively . The overall actuarial progression-free rate at 60 months was 56 % . Among 160 biopsies performed 16 % showed some evidence of residual carcinoma . Overall crude rates of maintaining either a negative biopsy or PSA less than 0.3 at 6 and 24 months after cryosurgical prostate ablation were 87 % and 73 % , respectively . Significantly higher morbidities were seen in previously radiated patients undergoing cryosurgical prostate ablation compared to those with no prior radiation . Among nonradiated patients 85 % experienced no significant morbidity after cryosurgical prostate ablation . CONCLUSIONS Although preliminary , short-term outcomes after cryosurgical prostate ablation appear to be comparable to identical outcomes reported for external beam radiotherapy . Based on these results cryosurgical prostate ablation appears to be an effective therapeutic alternative for treating patients with localized prostate adenocarcinoma Introduction Focal therapy offers the possibility of cancer control , without the side effect profile of radical therapies . Early single centre prospect i ve development studies using high intensity focused ultrasound ( HIFU ) have demonstrated encouraging genitourinary functional preservation and short-term cancer control . Large multi-centre trials are required to evaluate medium-term cancer control and reproduce functional recovery . We describe the study design of an investigator-led UK multi-centre , single arm trial using HIFU to deliver focal therapy for men with localised prostate cancer . Methods One-hundred and forty men with histologically proven localised low or intermediate risk prostate cancer ( PSA < 15 , Gleason ≤ 7 , ≤ T2cN0M0 ) will undergo precise characterisation of the prostate using a combination of multi-parametric (mp)MRI and transperineal template prostate mapping ( TPM ) biopsies . Unilateral dominant tumours , the so-called index lesion , will be eligible for treatment provided the contra-lateral side is free of ‘ clinical ly significant ’ disease ( as defined by Gleason ≥ 7 or maximum cancer core length ≥ 4 mm ) . Patients will receive focal therapy using HIFU ( Sonablate 500 ® ) . Treatment effect will be assessed by targeted biopsies of the treated area and TPM biopsies at 36-months . Results Primary outcome is the absence of clinical ly significant disease based on 36-month post-treatment TPM biopsies . Secondary outcomes address a ) genitourinary function using vali date d patient question naires ( IPSS , IPSS-QoL , IIEF-15 , EPIC-Urinary , EPIC-Bowel , FACT-P , EQ-5D ) , b ) the predictive validity of imaging , and c ) risk factors for treatment failure . Conclusions INDEX will be the first multi-centre , medium term follow-up trial to evaluate the outcomes of a tissue preserving strategy for men with localised prostate cancer  using the TPM-ablate-TPM strategy Surgery and other invasive therapies are complex interventions , the assessment of which is challenged by factors that depend on operator , team , and setting , such as learning curves , quality variations , and perception of equipoise . We propose recommendations for the assessment of surgery based on a five-stage description of the surgical development process . We also encourage the widespread use of prospect i ve data bases and registries . Reports of new techniques should be registered as a professional duty , anonymously if necessary when outcomes are adverse . Case series studies should be replaced by prospect i ve development studies for early technical modifications and by prospect i ve research data bases for later pre-trial evaluation . Protocol s for these studies should be registered publicly . Statistical process control techniques can be useful in both early and late assessment . R and omised trials should be used whenever possible to investigate efficacy , but adequate pre-trial data are essential to allow power calculations , clarify the definition and indications of the intervention , and develop quality measures . Difficulties in doing r and omised clinical trials should be addressed by measures to evaluate learning curves and alleviate equipoise problems . Alternative prospect i ve design s , such as interrupted time series studies , should be used when r and omised trials are not feasible . Established procedures should be monitored with prospect i ve data bases to analyse outcome variations and to identify late and rare events . Achievement of improved design , conduct , and reporting of surgical research will need concerted action by editors , funders of health care and research , regulatory bodies , and professional societies OBJECTIVE To determine the minimal important difference ( MID ) in generic and prostate-specific health-related quality of life ( HRQoL ) using distribution- and anchor-based methods . STUDY DESIGN AND SETTING Prospect i ve cohort study of 602 newly diagnosed prostate cancer patients recruited from an urban academic hospital and a Veterans Administration hospital . Participants completed generic ( SF-36 ) and prostate-specific HRQoL surveys at baseline and at 3 , 6 , 12 , and 24 months posttreatment . Anchor-based and distribution-based methods were used to develop MID estimates . We compared the proportion of participants returning to baseline based on MID estimates from the two methods . RESULTS MID estimates derived from combining distribution- and anchor-based methods for the SF-36 subscales are physical function = 7 , role physical = 14 , role emotional = 12 , vitality = 9 , mental health = 6 , social function = 9 , bodily pain = 9 , and general health = 8 ; and for the prostate-specific scales are urinary function = 8 , bowel function = 7 , sexual function = 8 , urinary bother = 9 , bowel bother = 8 , and sexual bother = 11 . Proportions of participants returning to baseline values corresponding to MID estimates from the two methods were comparable . CONCLUSIONS This is the first study to assess the MID for generic and prostate-specific HRQoL using anchor-based and distribution-based methods . Although variation exists in the MID estimates derived from these two methods , the recovery patterns corresponding to these estimates were comparable A recent r and omized trial to compare external beam radiation therapy ( EBRT ) to cryoablation for localized disease showed cryoablation to be noninferior to external beam EBRT in disease progression and overall and disease‐specific survival . We report on the quality of life ( QOL ) outcomes for this trial PURPOSE Patients currently diagnosed with low risk prostate cancer are often overtreated and experience complications , result ing in detriment to quality of life . Targeted focal therapy is a minimally invasive procedure design ed to ablate tumor foci while minimizing collateral damage to maintain quality of life . MATERIAL S AND METHODS This institutional review board approved , prospect i ve study was done to assess the safety and efficacy of targeted focal therapy using cryotherapy in men 40 to 85 years old diagnosed with low risk , organ confined prostate cancer at our institution between 2006 and 2009 . Low risk , organ confined prostate cancer was defined as Gleason score 7 or less ( 3 + 4 ) on transrectal ultrasound biopsy , tumor burden 50 % or less and prostate specific antigen less than 10 ng/dl . Patients were evaluated for eligibility after undergoing 3-dimensional mapping biopsy . Median 
    Output:
    
Based on very low quality evidence , primary whole gl and cryotherapy has uncertain effects on oncologic outcomes , QoL , and major adverse events compared to external beam radiotherapy .