title: 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. Mortality after radical prostatectomy or external beam radiotherapy for localized prostate cancer. Intermediate and Longer-Term Outcomes From a Prospective Active-Surveillance Program for Favorable-Risk Prostate Cancer. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial Radical prostatectomy versus watchful waiting in early prostate cancer. A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer Prospective study of determinants and outcomes of deferred treatment or watchful waiting among men with prostate cancer in a nationwide cohort. Reclassification rates are higher among African American men than Caucasians on active surveillance. Prospective trial of cryosurgical ablation of the prostate: five-year results. Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial Comparative risk‐adjusted mortality outcomes after primary surgery, radiotherapy, or androgen‐deprivation therapy for localized prostate cancer Duration of androgen suppression in the treatment of prostate cancer.
abstract: 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 . ) BACKGROUND No r and omized trials have compared survival outcomes for men with localized prostate cancer ( PC ) being treated with radical prostatectomy ( RP ) or external beam radiotherapy ( EBRT ) . The goal of the study , therefore , was to estimate the association of RP ( compared with EBRT ) with overall and PC mortality . METHODS We analyzed an observational cohort from the population -based Prostate Cancer Outcomes Study , which included men aged 55 to 74 years diagnosed with localized PC between October 1994 and October 1995 who underwent either RP ( n = 1164 ) or EBRT ( n = 491 ) within 1 year of diagnosis . Patients were followed until death or study end ( December 31 , 2010 ) . Overall and disease-specific mortality were assessed with multivariable survival analysis , with propensity scores to adjust for potential treatment selection confounders ( demographics , comorbidities , and tumor characteristics ) . All statistical tests were two-sided . RESULTS After 15 years of follow-up , there were 568 deaths , including 104 from PC . RP was associated with statistically significant advantages for overall ( hazard ratio [ HR ] = 0.60 , 95 % confidence interval [ CI ] = 0.53 to 0.70 , P < .0001 . ) and disease-specific mortality ( HR = 0.35 , 95 % CI = 0.26 to 0.49 , P < .0001 . ) . Mortality benefits for RP were also observed within treatment propensity quintiles , when subjects were pair-matched on propensity scores , and in subgroup analyses based on age , tumor characteristics , and comorbidity . CONCLUSIONS Population -based observational data on men diagnosed with localized PC in the mid-1990s suggest a mortality benefit associated with RP vs EBRT . Possible explanations include residual selection bias or a true survival advantage . Results might be less applicable for men facing treatment decisions today PURPOSE To assess long-term outcomes of men with favorable-risk prostate cancer in a prospect i ve , active-surveillance program . METHODS Curative intervention was recommended for disease reclassification to higher cancer grade or volume on prostate biopsy . Primary outcomes were overall , cancer-specific , and metastasis-free survival . Secondary outcomes were the cumulative incidence of reclassification and curative intervention . Factors associated with grade reclassification and curative intervention were evaluated in a Cox proportional hazards model . RESULTS A total of 1,298 men ( median age , 66 years ) with a median follow-up of 5 years ( range , 0.01 to 18.00 years ) contributed 6,766 person-years of follow-up since 1995 .  Overall , cancer-specific , and metastasis-free survival rates were 93 % , 99.9 % , and 99.4 % , respectively , at 10 years and 69 % , 99.9 % , and 99.4 % , respectively , at 15 years . The cumulative incidence of grade reclassification was 26 % at 10 years and was 31 % at 15 years ; cumulative incidence of curative  intervention was 50 % at 10 years and was 57 % at 15 years . The median treatment-free survival was 8.5 years ( range , 0.01 to 18 years ) . Factors associated with grade reclassification were older age ( hazard ratio [ HR ] , 1.03 for each additional year ; 95 % CI , 1.01 to 1.06 ) , prostate-specific antigen density ( HR , 1.21 per 0.1 unit increase ; 95 % CI , 1.12 to 1.46 ) , and greater number of positive biopsy cores ( HR , 1.47 for each additional positive core ; 95 % CI , 1.26 to 1.69 ) . Factors associated with intervention were prostate-specific antigen density ( HR , 1.38 per 0.1 unit increase ; 95 % CI , 1.22 to 1.56 ) and a greater number of positive biopsy cores ( HR , 1.35 for one additional positive core ; 95 % CI , 1.19 to 1.53 ) . CONCLUSION Men with favorable-risk prostate cancer should be informed of the low likelihood of harm from their diagnosis and should be encouraged to consider surveillance rather than curative intervention Summary Background Whether the addition of radiation therapy ( RT ) improves overall survival in men with locally advanced prostate cancer managed with and rogen deprivation therapy ( ADT )  is unclear . Our aim was to compare outcomes in such patients with locally advanced prostate cancer . Methods Patients with : locally advanced ( T3 or T4 ) prostate cancer ( n=1057 ) ; or organ-confined disease ( T2 ) with either a prostate-specific antigen ( PSA ) concentration more than 40 ng/mL ( n=119 ) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher ( n=25 ) , were r and omly assigned ( done central ly with stratification and dynamic minimisation , not masked ) to receive lifelong ADT and RT ( 65–69 Gy to the prostate and seminal vesicles , 45 Gy to the pelvic nodes ) . The primary endpoint was overall survival . The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded . All efficacy analyses were done by intention to treat and were based on data from all patients . This trial is registered at controlledtrials.com as IS RCT N24991896 and Clinical trials.gov as NCT00002633 . Results Between 1995 and 2005 , 1205 patients were r and omly assigned ( 602 in the ADT only group and 603 in the ADT and RT group ) ; median follow-up was 6·0 years ( IQR 4·4–8·0 ) . At the time of analysis , a total of 320 patients had died , 175 in the ADT only group and 145 in the ADT and RT group . The addition of RT to ADT  improved overall survival at 7 years ( 74 % , 95 % CI 70–78 vs 66 % , 60–70 ; hazard ratio [ HR ] 0·77 , 95 % CI 0·61–0·98 , p=0·033 ) . Both toxicity and health-related quality -of-life results showed a small effect of RT on late gastrointestinal toxicity ( rectal bleeding grade > 3 , three patients ( 0·5 % ) in the ADT only group , two ( 0·3 % ) in the ADT and RT group ; diarrhoea grade > 3 , four patients ( 0·7 % ) vs eight ( 1·3 % ) ; urinary toxicity grade > 3 , 14 patients ( 2·3 % ) in both groups ) . Interpretation The benefits of combined modality treatment — ADT and RT — should be discussed with all patients with locally advanced prostate cancer . Funding Canadian Cancer Society Research Institute , US National Cancer Institute , and UK Medical Research Council BACKGROUND In 2008 , we reported that radical prostatectomy , as compared with watchful waiting , reduces the rate of death from prostate cancer . After an additional 3 years of follow-up , we now report estimated 15-year results . METHODS From October 1989 through February 1999 , we r and omly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy .  Follow-up was complete through December 2009 , with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death . Relative risks , with 95 % confidence intervals , were estimated with the use of a Cox proportional-hazards model . RESULTS During a median of 12.8 years , 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died ( P=0.007 ) . In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting , death was due to prostate cancer . This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6 % and 20.7 % , respectively ( a difference of 6.1 percentage points ; 95 % confidence interval [ CI ] , 0.2 to 12.0 ) , and a relative risk with surgery of 0.62 ( 95 % CI , 0.44 to 0.87 ; P=0.01 ) . The survival benefit was similar before and after 9 years of follow-up , was observed also among men with low-risk prostate cancer , and was confined to men younger than 65 years of age . The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age . Among men who underwent radical prostatectomy  , those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth ( relative risk , 6.9 ; 95 % CI , 2.6 to 18.4 ) . CONCLUSIONS Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer . Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment . ( Funded by the Swedish Cancer Society and the National Institutes of Health . ) 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 To examine consequences of deferred treatment ( DT ) as initial management of prostate cancer ( PCa ) in a contemporary , prospect i ve cohort of American men diagnosed with PCa . PARTICIPANTS AND METHODS We evaluated deferred treatment for PCa in the Health Professionals Follow-up Study , a prospect i ve study of 51,529 men . Cox proportional hazards models were used to calculate hazard ratios ( HRs ) for time to eventual treatment among men who deferred treatment for more than 1 year after diagnosis . HRs for time to metastasis or death as a result of PCa were compared between patients who deferred treatment and those who underwent immediate treatment within 1 year of diagnosis . RESULTS From among 3,331 cohort participants diagnosed with PCa from 1986 to 2007 , 342 ( 10.3 % ) initially deferred treatment . Of these , 174 ( 51 % ) remained untreated throughout follow-up ( mean 7.7 years ) ; the remainder were treated an average of 3.9 years after diagnosis . Factors associated with progression to treatment among DT patients included younger age , higher clinical stage , higher Gleason score , and higher prostate-specific antigen at diagnosis . We observed similar rates for development of metastases ( n = 20 and n = 199 ; 7.2 v 8.1 per 1,000 person-years ; P = .68 ) and death as a result of PCa ( n = 8 and n = 80 ; 2.4 v 2.6 per 1,000 person-years ; P = .99 ) for DT and immediate treatment , respectively . CONCLUSION In this nationwide cohort , more than half the men who opted for DT remained without treatment for 7.7 years after diagnosis . Older men and men with lesser cancer severity at diagnosis were more likely to remain untreated . PCa mortality did not differ between DT and active treatment patients OBJECTIVE To evaluate the risk of reclassification on serial biopsy for Caucasian and African American ( AA ) men with very low-risk ( VLR ) prostate cancer enrolled in a large prospect i ve active surveillance ( AS ) registry . METHODS The Johns Hopkins AS registry is a prospect i ve observational study that has enrolled 982 men since 1994 . Including only men who met all National Comprehensive Cancer Network VLR criteria ( clinical stage ≤T1 , Gleason score ≤6 , prostate-specific antigen [ PSA ] level < 10 ng/mL , PSA density < 0.15 ng/mL/cm(3 ) , positive cores <3 , percent cancer per core ≤50 ) , we analyzed a cohort of 654 men ( 615 Caucasians and 39 AAs ) . The association of race with reclassification on serial biopsy was assessed with competing-risks regressions . RESULTS AA men on AS were more likely than Caucasians to experience upgrading on serial biopsy ( 36 % vs 16 % ; adjusted P < .001 ) . Adjusting for PSA level , prostate size , volume of cancer on biopsy , treatment year , and body mass index , AA race was an independent predictor of biopsy reclassification ( subdistribution hazard ratio , 1.8 ; P = .003 ) . Examining specific modes of reclassification , AA race was independently associated with reclassification by grade ( subdistribution hazard ratio , 3.0 ; P = .002 ) but not by volume . CONCLUSION AA men with VLR prostate cancer followed on AS are at significantly higher risk of grade reclassification compared with Caucasians . Therefore , if the goal of AS is to selectively monitor men with low- grade disease , AA men may require alternate selection criteria OBJECTIVES To determine in a prospect i ve pilot study the safety and efficacy of cryosurgical ablation for localized prostate carcinoma . METHODS A total of 87 cryosurgical procedures were performed on 76 consecutive patients between December 1994 and February 1998 . All patients had histologically proved adenocarcinoma of the prostate , with prostate-specific antigen ( PSA ) readings of less than 30 ng/mL.  Clinical evaluations , PSA determinations , and patient self-reported quality -of-life question naires ( functional assessment of cancer treatment-prostate ; FACT-P ) were used to determine biochemical and clinical disease-free status and complications . Patients had a mean follow-up of 50 months ( minimum 36 ) . RESULTS Follow-up biopsies were performed in 73 patients , and 72 were negative for malignancy after one or more treatments . Ten patients required two treatments and 1 patient required three treatments . The 5-year overall and cancer-specific survival rate was 89 % ( 95 % confidence interval , 83 % to 97 % ) and 98.6 % ( 95 % confidence interval , 96 % to 100 % ) , respectively . The undetectable PSA rate ( less than 0.3 ng/mL ) for low-risk patients ( n = 13 ) was 60 % at 5 years ; for moderate-risk patients ( n = 23 ) , it was 77 % , and for high-risk patients ( n = 40 ) , 48 % . The corresponding percentage of patients with a PSA level less than 1.0 ng/mL at 5 years was 75 % , 89 % , and 76 % . Sloughing occurred in 3 patients ( 3.9 % ) , incontinence in 1 ( 1.3 % ) , and testicular abscess in 1 ( 1.3 % ) . At 3 years , 18 ( 47 % ) of 38 patients capable of unassisted intercourse at the time of cryosurgery had resumed sexual intercourse , 5 spontaneously and 13 with sildenafil or prostagl and in . CONCLUSIONS The results of this prospect i ve evaluation show cryosurgery to be both a safe and an effective option in the treatment of localized prostate cancer PURPOSE Active surveillance is increasingly accepted as a treatment option for favorable-risk prostate cancer . Long-term follow-up has been lacking . In this study , we report the long-term outcome of a large active surveillance protocol in men with favorable-risk prostate cancer . PATIENTS AND METHODS In a prospect i ve single-arm cohort study carried out at a single academic health sciences center , 993 men with favorable- or intermediate-risk prostate cancer were managed with an initial expectant approach . Intervention was offered for a prostate-specific antigen ( PSA ) doubling time of less than 3 years , Gleason score progression , or unequivocal clinical progression . Main outcome measures were overall and disease-specific survival , rate of treatment , and PSA failure rate in the treated patients . RESULTS Among the 819 survivors , the median follow-up time from the first biopsy is 6.4 years ( range , 0.2 to 19.8 years ) . One hundred forty-nine ( 15 % ) of 993 patients died , and 844 patients are alive ( censored rate , 85.0 % ) . There were 15 deaths ( 1.5 % ) from prostate cancer . The 10- and 15-year actuarial cause-specific survival rates were 98.1 % and 94.3 % , respectively . An additional 13 patients ( 1.3 % ) developed metastatic disease and are alive with confirmed metastases ( n = 9 ) or have died of other causes ( n = 4 ) . At 5 , 10 , and 15 years , 75.7 % , 63.5 % , and 55.0 % of patients remained untreated and on surveillance . The cumulative hazard ratio for nonprostate-to-prostate cancer mortality was 9.2:1 . CONCLUSION Active surveillance for favorable-risk prostate cancer is feasible and seems safe in the 15-year time frame . In our cohort , 2.8 % of patients have developed metastatic disease , and 1.5 % have died of prostate cancer . This mortality rate is consistent with expected mortality in favorable-risk patients managed with initial definitive intervention BACKGROUND We did a r and omised phase III trial comparing external irradiation alone and external irradiation combined with an analogue of luteinising-hormone releasing hormone ( LHRH ) to investigate the added value of long-term and rogen suppression in locally advanced prostate cancer . METHODS Between 1987 and 1995 , 415 patients were r and omly assigned radiotherapy alone or radiotherapy plus immediate and rogen suppression . Eligible patients had T1 - 2 tumours of WHO grade 3 or T3 - 4 N0 - 1 M0 tumours ; the median age of participants was 71 years ( range 51 - 80 ) . In both treatment groups , 50 Gy radiation was delivered to the pelvis over 5 weeks , and 20 Gy over 2 weeks as a prostatic boost . Goserelin ( 3.6 mg subcutaneously every 4 weeks ) was started on the first day of irradiation and continued for 3 years ; cyproterone acetate ( 150 mg orally ) was given for 1 month starting 1 week before the first goserelin injection . The primary endpoint was clinical disease-free survival . Analyses were by intention to treat . FINDINGS 412 patients had evaluable data , with median follow-up of 66 months ( range 1 - 126 ) . 5-year clinical disease-free survival was 40 % ( 95 % CI 32 - 48 ) in the radiotherapy-alone group and 74 % ( 67 - 81 ) in the combined-treatment group ( p=0.0001 ) . 5-year overall survival was 62 % ( 52 - 72 ) and 78 % ( 72 - 84 ) , respectively ( p=0.0002 ) and 5-year specific survival 79 % ( 72 - 86 ) and 94 % ( 90 - 98 ) . INTERPRETATION Immediate and rogen suppression with an LHRH analogue given during and for 3 years after external irradiation improves disease-free and overall survival of patients with locally advanced prostate cancer Because no adequate r and omized trials have compared active treatment modalities for localized prostate cancer , the authors analyzed risk‐adjusted , cancer‐specific mortality outcomes among men who underwent radical prostatectomy , men who received external‐beam radiation therapy , and men who received primary and rogen‐deprivation therapy BACKGROUND The combination of radiotherapy plus long-term medical suppression of and rogens ( > or = 2 years ) improves overall survival in patients with locally advanced prostate cancer . We compared the use of radiotherapy plus short-term and rogen suppression with the use of radiotherapy plus long-term and rogen suppression in the treatment of locally advanced prostate cancer . METHODS We r and omly assigned patients with locally advanced prostate cancer who had received external-beam radiotherapy plus 6 months of and rogen suppression  to two groups , one to receive no further treatment ( short-term suppression ) and the other to receive 2.5 years of further treatment with a luteinizing hormone-releasing hormone agonist ( long-term suppression ) . An outcome of noninferiority of short-term and rogen suppression as compared with long-term suppression required a hazard ratio of more than 1.35 for overall survival , with a one-sided alpha level of 0.05 . An interim analysis showed futility , and the results are presented with an adjusted one-sided alpha level of 0.0429 . RESULTS A total of 1113 men were registered , of whom 970 were r and omly assigned , 483 to short-term suppression and 487 to long-term suppression . After a median follow-up of 6.4 years , 132 patients in the short-term group and 98 in the long-term group had died ; the number of deaths due to prostate cancer was 47 in the short-term group and 29 in the long-term group . The 5-year overall mortality for short-term and long-term suppression was 19.0 % and 15.2 % , respectively ; the observed hazard ratio was 1.42 ( upper 95.71 % confidence limit , 1.79 ; P=0.65 for noninferiority ) . Adverse events in both groups included fatigue , diminished sexual function , and hot flushes . CONCLUSIONS The combination of radiotherapy plus 6 months of and rogen suppression provides inferior survival as compared with radiotherapy plus 3 years of and rogen suppression in the treatment of locally advanced prostate cancer . ( Clinical Trials.gov number , NCT00003026 .
target: Results The AUA ( American Urological Association ) , ASTRO , and SUO ( Society of Urologic Oncology ) formulated an evidence ‐based guideline based on a risk stratified clinical framework for the management of localized prostate cancer .
background: Purpose This guideline is structured to provide a clinical framework stratified by cancer severity to facilitate care decisions and guide the specifics of implementing the selected management options .
  The summary presented represents Part I of the two‐part series dedicated to Clinical ly Localized Prostate Cancer : AUA/ASTRO/SUO Guideline discussing risk stratification and care options by cancer severity .