Salvage Cryoablation for Recurrent Prostate Cancer Following Primary External Beam Radiotherapy or Primary Cryotherapy: A Propensity Score Matched Analysis of Mid-term Oncologic and Functional Outcomes.

INTRODUCTION: Local prostate cancer recurrence following radiotherapy (XRT) or cryoablation (CRYO) may be addressed with salvage cryotherapy (SCT), although little is known about how the primary treatment modality affects SCT results. Oncologic and functional outcomes of patients who underwent SCT after primary XRT (XRT-SCT) or cryoablation (CRYO-SCT) were studied. METHODS: Data was collected using the Duke Prostate Cancer database and the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression-free survival (BPFS).  Urinary incontinence, rectourethral fistula, and erectile dysfunction were secondary outcomes. The Kaplan-Meier log-rank test and univariable/multivariable Cox proportional hazards (CPH) models were utilized to evaluate BPFS between groups. RESULTS: 419 XRT-SCT and 63 CRYO-SCT patients met inclusion criteria, that was reduced to 63 patients in each cohort after propensity matching. There was no difference in BPFS at 2 and 5 years both before (P = .5 and P = .7) and after matching (P = .6 and P = .3). On multivariable CPH, BPFS was comparable between treatment groups (CRYO-SCT, HR=1.1, [0.2-2.2]).  On the same analysis, BPFS was lower in D'Amico high-risk (HR 3.2, P < .01) and intermediate-risk (HR 1.95, P < .05) categories compared to low-risk. There was no significant difference in functional outcomes between cohorts. CONCLUSION: Following primary cryotherapy, salvage cryoablation provides comparable intermediate oncological outcomes and functional outcomes compared to primary radiotherapy.

Safety of repeat blue light cystoscopy with hexaminolevulinate (HAL) in the management of bladder cancer: Results from a phase III, comparative, multi-center study.

PURPOSE: The therapeutic benefit of intravesical instillation of hexaminolevulinate (HAL) at the time of transurethral resection of bladder tumor (TURBT) has been demonstrated in multiple studies. The purpose of this study was to prospectively assess the safety of repeated administration of HAL from a phase III pre-trial planned analysis. MATERIALS AND METHODS: All patients evaluated in the study received at least 1 dose of HAL at the time of office cystoscopy, and a subset of these patients (n = 103, 33.2%) received a second dose a few weeks later at the time of TURBT. Adverse events (AEs) were recorded, and the safety of repeat use of HAL was determined by comparing the proportion of patients with AEs considered causally related to HAL in the surveillance examination compared to the OR examination. Association between categorical variables was tested using Fisher's Exact Test, and a P < 0.05 was considered statistically significant. RESULTS: HAL-related AEs were experienced by 6 patients (2.2%) during surveillance cystoscopy and 3 patients (3.4%) following TURBT (P = 0.76); 181 patients (59.5%) had prior exposure to HAL before enrolling in the study with no difference in the number of AEs when comparing prior exposure to HAL to no prior exposure (P = 0.76). Of the patients who previously received intravesical therapy, 8 (2.9%) had at least 1 AE during surveillance compared to 3 (9.7%) who had no prior intravesical therapy (P = 0.09). CONCLUSIONS: Repeat use of HAL is safe even when administered within a few weeks of receiving a dose of intravesical therapy.

Older Age at Diagnosis and Initial Disease Volume Predict Grade Reclassification Risk on Confirmatory Biopsy in Patients Considered for Active Surveillance.

OBJECTIVE: To identify which active surveillance candidates benefit most from confirmatory biopsies to exclude grade underclassification. MATERIALS AND METHODS: This observational study includes 556 men diagnosed between 2002 and 2015 with Gleason 3 + 3 (GG1) disease on initial diagnostic biopsy, of whom 406 received a confirmatory biopsy within 12 months for active surveillance. Multivariable logistic regression analysis was performed to determine clinicopathologic features associated with Gleason 7 or higher (GG2+) on a confirmatory biopsy. Regression tree analysis was employed to stratify patients into select risk groups. RESULTS: Eighty-five of 406 patients (20.9%) with initially GG1 disease were reclassified to GG2+ on a confirmatory biopsy. On multivariable analysis, increasing age (per year odds ratio 1.07; 95% confidence interval 1.02-1.12; P <.01) and more positive cores at diagnosis (per core, odds ratio 1.37, 95% confidence interval 1.09-1.72; P <.01) were significantly associated with reclassification, independent of prostate volume, clinical stage, initial PSA, or confirmatory biopsy type (including magnetic resonance imaging-targeted approaches or transrectal saturation random sampling). Recursive partitioning demonstrated that age over 73 and 5 or more positive cores were factors associated with the greatest reclassification risk. CONCLUSION: In our cohort, both advancing age and additional positive cores were associated with increased odds of reclassification to GG2+ on confirmatory biopsy. In men over age 73 or with 5 or more positive cores, a repeat biopsy within 12 months may be particularly beneficial to minimize tumor grade underclassification.

Patient-reported outcomes of blue-light flexible cystoscopy with hexaminolevulinate in the surveillance of bladder cancer: results from a prospective multicentre study.

OBJECTIVE: To evaluate blue-light flexible cystoscopy (BLFC) with hexaminolevulinate in the office surveillance of patients with non-muscle-invasive bladder cancer with a high risk of recurrence by assessing its impact on pain, anxiety, subjective value of the test and patient willingness to pay. MATERIALS AND METHODS: A prospective, multicentre, phase III study was conducted during which the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, Pain and 'Was It Worth It' questionnaires were administered at baseline, after surveillance with BLFC and after resection for those referred to the operating room. Comparisons of scores were performed between groups. RESULTS: A total of 304 patients were enrolled, of whom 103 were referred for surgical examination. Of these, 63 were found to have histologically confirmed malignancy. Pain levels were low throughout the study. Anxiety levels decreased after BLFC (∆ = -2.6), with a greater decrease among those with negative pathology results (P = 0.051). No differences in anxiety were noted based on gender, BLFC results, or test performance (true-positive/false-positive). Most patients found BLFC 'worthwhile' (94%), would 'do it again' (94%) and 'would recommend it to others' (91%), with no differences based on BLFC results or test performance. Most patients undergoing BLFC (76%) were willing to pay out of pocket. CONCLUSIONS: Anxiety decreased after BLFC in patients with negative pathology, including patients with false-positive results. Most of the patients undergoing BLFC were willing to pay out of pocket, found the procedure worthwhile and would recommend it to others, irrespective of whether they had a positive BLFC result or whether this was false-positive after surgery.

Testing of a Tool for Prostate Cancer Screening Discussions in Primary Care.

BACKGROUND: As prostate cancer (PCa) screening decisions often occur in outpatient primary care, a brief tool to help the PCa screening conversation in busy clinic settings is needed. METHODS: A previously created 9-item tool to aid PCa screening discussions was tested in five diverse primary care clinics. Fifteen providers were recruited to use the tool for 4 weeks, and the tool was revised based upon feedback. The providers then used the tool with a convenience sample of patients during routine clinic visits. Pre- and post-visit surveys were administered to assess patients' knowledge of the option to be screened for PCa and of specific factors to consider in the decision. McNemar's and Stuart-Maxwell tests were used to compare pre-and post-survey responses. RESULTS: 14 of 15 providers completed feedback surveys and had positive responses to the tool. All 15 providers then tested the tool on 95 men aged 40-69 at the five clinics with 2-10 patients each. The proportion of patients who strongly agreed that they had the option to choose to screen for PCa increased from 57 to 72% (p = 0.018) from the pre- to post-survey, that there are factors in the personal or family history that may affect PCa risk from 34 to 47% (p = 0.012), and that their opinions about possible side effects of treatment for PCa should be considered in the decision from 47 to 61% (p = 0.009). CONCLUSION: A brief conversation tool for the PCa screening discussion was well received in busy primary-care settings and improved patients' knowledge about the screening decision.

Does Any Racial Disparity Exist in Oncologic Outcomes After Primary Cryotherapy for Prostate Cancer? A Matched-pair Comparative Analysis of the Cryo On-Line Data Registry.

BACKGROUND: African-American (AA) men have the greatest incidence of and disease-specific mortality from prostate cancer of any racial group. Although encouraging oncologic and functional outcomes have been reported with prostate cancer cryotherapy, little is known about how ethnicity can potentially affect the oncologic outcomes of primary cryotherapy. We report the oncologic outcomes of primary cryotherapy in AA patients through a matched-pair analysis. PATIENTS AND METHODS: A 1:2 (AA to non-AA) cohort of patients was designed using the Cryo-On-Line Data Registry. The 2 arms were matched for patient age, prostate-specific antigen level, Gleason score, and prostate volume. The oncologic outcome was defined in terms of the biochemical recurrence (BCR) rates after primary cryoablation using Phoenix criteria. The results of "for-cause" post-treatment biopsies and the BCR-free survival rates were also analyzed between the 2 groups. RESULTS: The 1:2 cohort of AA and non-AA men in the present study included 109 and 218 men, respectively. Their median age (69 vs. 71 years; P = .71), median prostate-specific antigen level (6.5 vs. 6.8 ng/mL; P = .95), median prostate volume (32 vs. 30 cm3; P = .31), Gleason score distribution (P = .97), and prostate cancer risk group (P = .12) were similar statistically. The median postoperative follow-up period was also comparable between the 2 groups (AA, 32 months vs. non-AA, 27 months; P = .52). The BCR rates were similar between the AA and non-AA men (14% vs. 17%; P = .52). Likewise, the rate of positive "for-cause" prostate biopsy findings was similar between the 2 groups (AA vs. non-AA, 25% vs. 36%; P = .44). Furthermore, the 5-year biochemical relapse-free survival rates were comparable for the AA and non-AA patients (74% vs. 71%; P = .37). CONCLUSION: When matched for tumor characteristics, cryotherapy as a treatment modality for primary, clinically localized prostate cancer offers men of African-American descent similar oncologic outcomes to those of non-AA men.

Predictors of Rectourethral Fistula Formation After Primary Whole-Gland Cryoablation for Prostate Cancer: Results from the Cryo On-Line Database Registry.

PURPOSE: To define the incidence and risk factors associated with rectourethral fistula (RUF) formation following primary whole-gland cryosurgery using a multicenter centralized registry. PATIENTS AND METHODS: The Cryo On-Line Data (COLD) registry was queried for men undergoing primary whole-gland cryotherapy between 1990 and 2014 who developed a RUF. Patient factors and disease parameters were correlated with RUF using chi-square and the t-test. Variables with p < 0.25 were entered into a binary logistic regression with stepwise backward elimination to determine the factors associated with RUF formation. RESULTS: A total of 4102 men underwent primary whole-gland cryotherapy in the COLD registry at the time of analysis. Postoperative RUF was documented in 50 out of 4102 cases (1.2%). Patients with RUF had similar demographic data, prostate volume, preoperative prostate-specific antigen level, and clinical stage in comparison to those without fistula. On both univariate and multivariate analyses, postoperative urinary retention (odds ratio [OR]: 6.30; confidence interval [95% CI] 3.43-11.58, p < 0.001), preoperative Gleason score of ≥7 (OR: 1.92; 95% CI 1.08-3.43, p = 0.027), and preoperative incontinence (OR: 2.95; 95% CI 1.12-7.76, p = 0.028) were the most significant risk factors associated with RUF formation. CONCLUSION: Primary whole-gland cryotherapy for prostate cancer is associated with a historically low rate (1.2%) of postoperative RUF formation. The rate decreased further to 0.55% over the last several years, suggesting better patient selection and technical improvement. Postoperative urinary retention, Gleason score ≥7, and preoperative urinary incontinence were the key demographic, clinical, and pathologic features associated with RUF formation in this study.

Impact of 5α-Reductase Inhibitors on Disease Reclassification among Men on Active Surveillance for Localized Prostate Cancer with Favorable Features.

PURPOSE: We determined the effect of 5α-reductase inhibitors on disease reclassification in men with prostate cancer optimally selected for active surveillance. MATERIALS AND METHODS: In this retrospective review we identified 635 patients on active surveillance between 2002 and 2015. Patients with favorable cancer features on repeat biopsy, defined as absent Gleason upgrading, were included in the cohort. Patients were stratified by those who did or did not receive finasteride or dutasteride within 1 year of diagnosis. The primary end point was grade reclassification, defined as any increase in Gleason score or predominant Gleason pattern on subsequent biopsy. This was assessed by multivariable Cox proportional hazards regression analysis. RESULTS: At diagnosis 371 patients met study inclusion criteria, of whom 70 (19%) were started on 5α-reductase inhibitors within 12 months. Median time on active surveillance was 53 vs 35 months in men on vs not on 5α-reductase inhibitors (p <0.01). Men on 5α-reductase inhibitors received them for a median of 23 months (IQR 6-37). On actuarial analysis there was no significant difference in grade reclassification for 5α-reductase inhibitor use in patients overall or in the very low/low risk subset. The overall percent of patients who experienced grade reclassification was similar at 13% vs 14% (p = 0.75). After adjusting for baseline clinicopathological features 5α-reductase inhibitors were not significantly associated with grade reclassification (HR 0.80, 95% CI 0.31-1.80, p = 0.62). Furthermore, no difference in adverse features on radical prostatectomy specimens was observed in treated patients (p = 0.36). CONCLUSIONS: Among our cohort of men on active surveillance 5α-reductase inhibitor use was not associated with a significant difference in grade reclassification with time.

Efficacy and Safety of Blue Light Flexible Cystoscopy with Hexaminolevulinate in the Surveillance of Bladder Cancer: A Phase III, Comparative, Multicenter Study.

PURPOSE: We compared blue light flexible cystoscopy with white light flexible cystoscopy for the detection of bladder cancer during surveillance. MATERIALS AND METHODS: Patients at high risk for recurrence received hexaminolevulinate intravesically before white light flexible cystoscopy and randomization to blue light flexible cystoscopy. All suspicious lesions were documented. Patients with suspicious lesions were referred to the operating room for repeat white and blue light cystoscopy. All suspected lesions were biopsied or resected and specimens were examined by an independent pathology consensus panel. The primary study end point was the proportion of patients with histologically confirmed malignancy detected only with blue light flexible cystoscopy. Additional end points were the false-positive rate, carcinoma in situ detection and additional tumors detected only with blue light cystoscopy. RESULTS: Following surveillance 103 of the 304 patients were referred, including 63 with confirmed malignancy, of whom 26 had carcinoma in situ. In 13 of the 63 patients (20.6%, 95% CI 11.5-32.7) recurrence was seen only with blue light flexible cystoscopy (p <0.0001). Five of these cases were confirmed as carcinoma in situ. Operating room examination confirmed carcinoma in situ in 26 of 63 patients (41%), which was detected only with blue light cystoscopy in 9 of the 26 (34.6%, 95% CI 17.2-55.7, p <0.0001). Blue light cystoscopy identified additional malignant lesions in 29 of the 63 patients (46%). The false-positive rate was 9.1% for white and blue light cystoscopy. None of the 12 adverse events during surveillance were serious. CONCLUSIONS: Office based blue light flexible cystoscopy significantly improves the detection of patients with recurrent bladder cancer and it is safe when used for surveillance. Blue light cystoscopy in the operating room significantly improves the detection of carcinoma in situ and detects lesions that are missed with white light cystoscopy.

Associations Between Prostate Volume and Oncologic Outcomes in Men Undergoing Focal Cryoablation of the Prostate.

INTRODUCTION: The purpose of this study was to assess the relationship of total prostate volume (TPV) and oncologic outcomes following focal prostate cryoablation. MATERIALS AND METHODS: A query of the Cryo On-Line Database (COLD) registry for men who underwent primary focal prostate cryoablation revealed 829 patients with complete data. The impact of TPV on oncologic outcomes including progression-free survival (PFS) and post-cryoablation biopsy outcome was assessed using Kaplan-Meier curves and Cox and logistic regression models. RESULTS: The median follow-up time was 25.2 months (interquartile range [IQR], 12.7-48.2 months). The median age at time of treatment was 68 years (IQR, 63-74 years) with median prostate-specific antigen (PSA) 5.6 ng/mL (IQR, 4.4-7.5 ng/mL), and median TPV 35 mL (IQR, 26.5-46 mL). PFS was achieved in 83.2%, with positive post-cryoablation biopsy detected in 81 (35.7%) of 228 patients. Higher TPV was associated with higher biochemical progression (BP) using the Phoenix definition (39 vs. 34.5 mL; P = .003) and was an independent predictor of BP (hazard ratio, 1.01; P = .02). Conversely, men who had a positive post-cryoablation biopsy had significantly smaller median TPV on univariate and multivariate analyses (31 vs. 39 mL; P < .001), (odds ratio, 0.97; P = .001), respectively. Higher median pretreatment PSA density was associated with higher BP (0.18 vs. 0.16; P = .005) and positive post-cryoablation biopsy rates (0.2 vs. 0.16; P = .003). CONCLUSION: Prostate volume has contradictory effects on BP and post-cryoablation biopsy outcome in men who underwent primary focal prostate cryoablation. Remnant viable tissue in larger prostates continues to produce more PSA over time, which may impact BP. This may raise the need to develop a new definition for oncologic success following focal gland therapy rather than the American Society for Radiation Oncology (ASTRO) and Phoenix definitions.

Avoidance of androgen deprivation therapy in radiorecurrent prostate cancer as a clinically meaningful endpoint for salvage cryoablation.

BACKGROUND: To investigate the ability of salvage cryoablation of the prostate (SCAP) to delay the need for androgen deprivation therapy (ADT) in local recurrence after radiation therapy to the prostate using the Cryo-On-Line Database (COLD) registry. METHODS: The COLD registry is comprised of a combination of retrospectively and prospectively collected data on patients undergoing primary and SCAP. Patients with local recurrence after radiation therapy were identified. Kaplan-Meier analysis was used to calculate ADT-free survival. RESULTS: We identified 898 patients that have undergone SCAP in the COLD registry. Overall, the calculated 5-year ADT-free survival probability was 0.713. When stratified by D'Amico risk group, 264 high-risk patients (71.9%), 234 intermediate-risk (86.7%),and 228 low-risk (87.7%) were free of ADT post-SCAP. This correlates with a 5-year ADT-free survival of 60.7, 73.9, and 82.4%, respectively. Patients with post-SCAP PSA nadir of <0.2 ng/mL had a 5 year ADT-free survival of 87.1% compared to 48.7% with a PSA nadir ≥0.2 ng/mL. Pre-operative ADT use or full versus partial gland SCAP did not have an effect on ADT use post-operatively. In 118 (55.4%) of patients with post-operative biochemical recurrence, ADT was not used. CONCLUSION: For patients with local recurrence after radiation, SCAP is an option that provides a high chance of avoiding or delaying ADT. The potential to delay ADT and its associated side effects should be a part of counseling sessions with the patient when discussing treatment options for locally recurrent prostate cancer after radiation. Avoidance of ADT is more clinically relevant than PSA elevation.

Prognostic Significance of a Negative Confirmatory Biopsy on Reclassification Among Men on Active Surveillance.

OBJECTIVE: To examine the association between absence of disease on confirmatory biopsy and risk of pathologic reclassification in men on active surveillance (AS). MATERIALS AND METHODS: Men with grade groups 1 and 2 disease on AS between 2002 and 2015 were identified who received a confirmatory biopsy within 1 year of diagnosis and ≥3 biopsies overall. The primary outcomes were pathologic reclassification by grade (any increase in primary Gleason pattern or Gleason score) or volume (>33% of sampled cores involved or increase in the number of cores with >50% involvement). The effect of a negative confirmatory biopsy survival was evaluated using Kaplan-Meier analysis and a Cox proportional hazards modeling. RESULTS: Out of 635 men, 224 met inclusion criteria (median follow-up: 55.8 months). A total of 111 men (49.6%) had a negative confirmatory biopsy. Decreased grade reclassification (69.7% vs 83.9%; P = .01) and volume reclassification (66.3% vs 87.4%; P = .004) was seen at 5 years for men with a negative confirmatory biopsy compared with those with a positive biopsy. On adjusted analysis, a negative confirmatory biopsy was associated with a decreased risk of grade reclassification (hazard ratio, 0.51; 95% confidence interval, 0.28-0.94; P = .03) and volume reclassification (hazard ratio, 0.32; 95% confidence interval, 0.17-0.61; P = .0006) at a median of 4.7 years. CONCLUSION: Absence of cancer on the confirmatory biopsy is associated with a significant decrease in rate of grade and volume reclassification among men on AS. This information may be used to better counsel men on AS.

Prostate Specific Antigen Nadir of 0.1 or Less Is a Predictor of Treatment Success in Men Undergoing Salvage Whole Prostate Gland Cryoablation.

PURPOSE: To assess factors that affect prostate biopsy results following salvage whole gland cryoablation. PATIENTS AND METHODS: One hundred seventy-four patients underwent prostate biopsy following salvage whole gland cryoablation of the prostate in the Cryo-OnLine Database registry. Wilcoxon rank-sum and χ2 tests and logistic regression analysis were used to assess predictors of positive biopsy. Prostate specific antigen (PSA) nadir was divided into a statistical tertile for comparisons between different nadir PSA cut points. RESULTS: Fifty-two of 174 (29.9%) of this highly select group of men who underwent biopsy had a posttreatment biopsy demonstrating malignant cancer. Men who had positive biopsy following salvage therapy had significantly higher median nadir PSA, shorter median time to prostate biopsy, and shorter median time to biochemical failure. Compared to the lowest tertile (PSA nadir defined as ≤0.1 ng/mL), PSA in the second tertile (0.11-0.8 ng/mL) and third tertile (>0.8 ng/mL) demonstrated increased odds ratio (OR) for positive biopsy, 4.34 (95% confidence interval [CI] 1.66, 11.4, p = 0.003) and 2.81 (95% CI 1.14, 7.00, p = 0.02), respectively, in adjusted models. In addition, men with a presalvage PSA >20 (OR 7.65; 95% CI 2.03, 28.9; p = 0.003) and Gleason score ≥8 (OR 2.26; 95% CI 0.93, 5.47; p = 0.07) had a higher OR of positive biopsy. CONCLUSIONS: Nadir PSA of 0.1 ng/mL or less following salvage cryotherapy is predictive of treatment success. Routine biopsy should be reserved for men with nadir PSA >0.1 ng/mL and patients with high risk features of prostate cancer before salvage cryoablation.

Propensity Score-Matched Comparison of Partial to Whole-Gland Cryotherapy for Intermediate-Risk Prostate Cancer: An Analysis of the Cryo On-Line Data Registry Data.

OBJECTIVE: To compare the oncologic and functional outcomes of partial vs whole-gland cryotherapy for men with intermediate-risk prostate cancer. SUBJECTS/PATIENTS: Men with intermediate-risk prostate cancer treated with primary prostate cryotherapy from 1993 to 2013 were selected from the Cryo On-Line Data Registry for a 1:1 matched comparison between those undergoing whole-gland and partial prostate cryotherapy (targeted ablation, unilateral/bilateral nerve-sparing ablations). A propensity score was developed based on age, prebiopsy serum prostate-specific antigen, biopsy Gleason score, clinical stage, prostate volume, neoadjuvant androgen deprivation status, year of surgery, and pretreatment potency. Outcomes were biochemical progression-free survival (BPFS) using the American Society for Therapeutic Radiation Oncology (ASTRO) and Phoenix criteria, 12-month continence (strictly pad free), and sexual function (potency sufficient for sexual intercourse). After propensity score matching, BPFS was compared using Kaplan-Meier analysis and functional outcomes using chi-square tests. RESULTS: In all, 897 men were identified (731 whole gland and 166 partial). Postmatching, 166 pairs of men were analyzed (mean follow-up 31 months). The 2/5-year BPFS rate was 87.2%/76.4% for whole-gland vs 80.7%/70.0% for partial ablation using Phoenix (p = 0.26) and 72.3%/69.6% for whole-gland vs 82.1%/75.0% for partial ablation using ASTRO criteria (p = 0.10). Of 164 pairs, the 12-month continence rate was similar, 94.1% vs 95.1% (p = 0.803). Of 139 pairs, the 12-month rate of effective intercourse was 29.5% for whole-gland and 46.8% for partial ablation (odds ratio 2.1, p = 0.003). The incidence of post-treatment urinary retention was 6.0% and 6.6% (p = 0.88) following whole-gland and partial ablation, respectively, and that of rectourethral fistula was 1.2% and 0% (p = 0.50). CONCLUSION: Partial ablation results in better post-treatment sexual function compared with whole-gland ablation in men with intermediate-risk prostate cancer. We did not observe a difference in early BPFS between the two groups.

Intermediate-Term Outcomes for Men with Very Low/Low and Intermediate/High Risk Prostate Cancer Managed by Active Surveillance.

PURPOSE: We compare intermediate term clinical outcomes among men with favorable risk and intermediate/high risk prostate cancer managed by active surveillance. MATERIALS AND METHODS: A total of 635 men with localized prostate cancer have been on active surveillance since 2002 at a high volume academic hospital in the United States. Median followup is 50.5 months (IQR 31.1-80.3). Time to event analysis was performed for our clinical end points. RESULTS: Of the cohort 117 men (18.4%) had intermediate/high risk disease. Overall 5 and 10-year all cause survival was 98% and 94%, respectively. Cumulative metastasis-free survival at 5 and 10 years was 99% and 98%, respectively. To date no cancer specific deaths had been observed. Overall freedom from intervention was 61% and 49% at 5 and 10 years, respectively. Overall cumulative freedom from failure of active surveillance, defined as metastasis or biochemical failure after local therapy with curative intent, was 97% and 91% at 5 and 10 years, respectively. Of the men 21 (9.9%) experienced biochemical failure after deferred treatment and the 5-year progression-free probability was 92%. Compared to men with favorable risk disease those with intermediate/high risk cancer experienced no difference in metastases, surveillance failure or curative intervention. However, patients at higher risk were at significantly increased risk for all cause mortality, likely reflecting patient selection factors. These conclusions may be limited by the small number of events and the duration of our study. CONCLUSIONS: Patients with localized prostate cancer who are on active surveillance demonstrated a low rate of active surveillance failure, prostate cancer specific mortality and metastases regardless of baseline risk.