Long-Term Biochemical Control of a Prospective Cohort of Prostate Cancer Patients Treated With Interstitial Brachytherapy Versus Radical Prostatectomy.

AIMS: To report long-term oncological outcomes of men treated prospectively as part of the American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT) at our institution. MATERIALS AND METHODS: In 2003-2004, patients eligible for SPRIT attended a multidisciplinary educational session, following which they could choose radical prostatectomy, low dose rate brachytherapy (LDR-BT) or randomisation to SPIRIT. Biochemical failure was determined by the accepted definitions of a prostate-specific antigen (PSA) level ≥0.2 ng/ml after radical prostatectomy and the Phoenix definition of PSA ≥2 ng/ml above the nadir after LDR-BT. A sensitivity analysis, using a PSA >0.5 ng/ml to define biochemical failure after LDR-BT and a threshold PSA ≥0.2 ng/ml, was carried out to test the robustness of the results. To account for the competing risk of death, Gray's test was used to test the equality of the cumulative incidence function of biochemical failure between treatment groups. The Kaplan-Meier method was used to estimate overall survival and prostate cancer-specific survival. A P-value ≤0.05 was considered statistically significant. RESULTS: Of 156 patients, 100 received LDR-BT (15 after randomisation) and 56 underwent radical prostatectomy (15 after randomisation). The median follow-up was 12.6 and 14.7 years for LDR-BT and radical prostatectomy, respectively. The median age was 60 years; the median pre-treatment PSA was 5.5 (interquartile range 4.3-7.1). No significant differences in patient characteristics were found between groups. Two patients received adjuvant radiotherapy after radical prostatectomy. The cumulative incidence function of biochemical failure was 0%, 1.1% and 2.4% at 5, 10 and 15 years, respectively, in the LDR-BT arm versus 8.5%, 15.8% and 15.8% in the radical prostatectomy arm (P < 0.001). These results were consistent when varying the definition of biochemical failure defined as PSA ≥0.5 ng/ml (P = 0.01). At 15 years, overall survival was higher in patients treated with radical prostatectomy compared with those treated with LDR-BT; however, no statistical difference was found in prostate cancer-specific survival. CONCLUSION: In low-risk prostate cancer patients, LDR-BT offers excellent long-term oncological outcomes comparable with radical prostatectomy, in addition to the previously reported advantage for LDR-BT in urinary and sexual quality of life domains and patient satisfaction.

Opioid Use After Nephrectomy for Kidney Cancer in Ontario: A Population-Based Study.

OBJECTIVE: To compare the odds of early and prolonged post-operative opioid use in patients undergoing minimally invasive surgery (MIS) vs open surgery for nephrectomy. METHODS: For opioid-naïve patients in Ontario who underwent nephrectomy for kidney cancer (1994-2017, n = 7900), post-discharge opioid use was determined by prescriptions in the Ontario Drug Benefit database (age ≥65 years) and the Narcotics Monitoring System (all patients from 2012). Early opioid use was defined as ≥1 prescription 1-90 days after surgery. Two separate definitions of prolonged opioid use were examined: (1) prescription(s) for ≥60 days during post-operative days 90-365; (2) ≥1 prescriptions between both of: 1-90 days AND 91-180 days after surgery. Predictors of opioid use were assessed using multivariable generalized estimating equation logistic regression, accounting for surgeon clustering. RESULTS: Overall, 67.4% of patients received early opioid prescriptions; however, prolonged use was low, ranging from 1.6 to 4.4% of patients depending on the definition. In multivariable analysis, open nephrectomy was associated with higher odds of early opioid use compared to MIS nephrectomy (Odds Ratio [OR] 1.36, 95% Confidence Interval [CI] 1.19-1.55). Surgery type was not significantly associated with prolonged opioid use for either definition (OR 1.22, CI 0.79-1.89 and OR 1.06, CI 0.83-1.35). CONCLUSIONS: In this population-level study of patients undergoing nephrectomy for kidney cancer, patients who received open surgery were at increased odds of receiving early post-operative opioids compared to MIS. Prolonged opioid use was low overall and was not significantly with associated with type of surgery.

An online Sexual Health and Rehabilitation eClinic (TrueNTH SHAReClinic) for prostate cancer patients: a feasibility study.

PURPOSE: The primary objective was to determine the feasibility of implementing the TrueNTH SHAReClinic as a pan-Canadian sexual health and rehabilitation intervention for patients treated for localized prostate cancer. METHODS: The feasibility study was designed to evaluate the accessibility and acceptability of the intervention. Participants from five institutions across Canada were enrolled to attend one pre-treatment and five follow-up online clinic visits over 1 year following their prostate cancer (PC) treatment. RESULTS: Sixty-five patients were enrolled in the intervention. Website analytics revealed that 71% completed the intervention in its entirety, including the educational modules, with an additional 10% completing more than half of the intervention. Five thousand eighty-three views of the educational modules were made along with 654 views of the health library items. Over 1500 messages were exchanged between participants and their sexual health coaches. At 12 months, the intervention received an overall average participant rating of 4.1 out of 5 on a single item satisfaction measure. CONCLUSION: Results support the TrueNTH SHAReClinic as highly acceptable to participants as defined by intervention adherence and engagement. The TrueNTH SHAReClinic demonstrated promise for being a feasible and potentially resource-efficient approach to effectively improving the sexual well-being of patients after PC treatment.

Real-World Practice Patterns and Predictors of Continuous versus Intermittent Androgen Deprivation Therapy Use for Prostate Cancer in Older Men.

PURPOSE: Phase-III randomized control trial evidence suggests intermittent androgen deprivation therapy (IADT) is not significantly inferior to continuous androgen deprivation therapy (ADT) for patients with prostate cancer (PC). However, clinical practice and guidelines differ in their recommendations. We evaluate real-world utilization and practice patterns of IADT. MATERIALS AND METHODS: Ontario men ≥65 years of age with PC who initiated ADT for ≥3 months were identified (1997-2017). Lapses in ADT ≥6 months (initial gap) and ≥3 months (subsequent gaps) were used to classify IADT. Neoadjuvant/adjuvant therapy was excluded. Disease stage adjustment was completed for patients with likely metastatic disease based on de novo presentation with ADT. Patient and physician predictors of IADT were analyzed using multivariable logistic regression. RESULTS: We identified 8,544 patients with 1,715 having previously received local therapy. Among all patients, 16.4% received IADT. This ranged from 11.4%-24.8% across health-planning regions and increased to 26.6% in those with previous local therapy. Mean followup was 8.3 years. Patients with prior local therapy (OR 1.85, 95% CI 1.59-2.17, p <0.001) and those in the highest income quintile (OR 1.32, 95% CI 1.08-1.60, p=0.005) had increased odds of receiving IADT. Radiation oncologists were more likely to use IADT than urologists (OR 1.99, 95% CI 1.59-2.50, p <0.001), as were physicians with more experience (≥10 years in practice: OR 1.44, 95% CI 1.11-1.88, p=0.007). In specialty-stratified analyses, case volume was significantly associated with IADT for radiation oncologists (highest quartile: OR 1.73, 95% CI 1.14-2.62, p=0.009). CONCLUSIONS: IADT remains underutilized for patients with PC who ≥65 years of age with only 1 in 4 to 1 in 6 eligible patients receiving this form of care. Clinical, sociodemographic and physician characteristics play an important role in treatment selection.

Long-term use of 5-alpha-reductase inhibitors is safe and effective in men on active surveillance for prostate cancer.

BACKGROUND: Although 5-alpha-reductase inhibitors (5ARIs) have been shown to benefit men with prostate cancer (PCa) on active surveillance (AS), their long-term safety remains controversial. Our objective is to describe the long-term association of 5ARI use with PCa progression in men on AS. MATERIALS/SUBJECTS AND METHODS: The cohort of men with low-risk PCa was derived from a prospectively maintained AS database at the Princess Margaret (1995-2016). Pathologic, grade, and volume progression were the primary end points. Kaplan-Meier time-to-event analysis was performed and Cox proportional hazards regression was used to determine predictors of progression where 5ARI exposure was analyzed as a time-dependent variable. Patients who came off AS prior to any progression events were censored at that time. RESULTS: The cohort included 288 men with median follow-up of 82 months (interquartile range: 37-120 months). Among non-5ARI users (n = 203); 114 men (56.2%) experienced pathologic progression compared with 24 men (28.2%) in the 5ARI group (n = 85), (p < 0.001). Grade and volume progression were higher in the non-5ARI group compared with the 5ARI group (n = 82; 40.4% vs. n = 19; 22.4% respectively, p = 0.003 for grade progression; n = 87; 43.1% and n = 15; 17.7%, respectively for volume progression p < 0.001). Lack of 5ARI use was independently positively associated with pathologic progression (HR: 2.65; CI: 1.65-4.24), grade progression (HR: 2.75; CI: 1.49-5.06), and volume progression (HR: 3.15; CI: 1.78-5.56). The frequency of progression to high-grade (Grade Group 4-5) tumors was not significantly different between the groups. CONCLUSIONS: Use of 5ARIs diminished both grade and volume progression without an increased risk of developing Grade Groups 4-5 disease.

The Prostate Cancer Rehabilitation Clinic: a biopsychosocial clinic for sexual dysfunction after radical prostatectomy.

Purpose: The most prevalent intervention for localized prostate cancer (pca) is radical prostatectomy (rp), which has a 10-year relative survival rate of more than 90%. The improved survival rate has led to a focus on reducing the burden of treatment-related morbidity and improving the patient and partner survivorship experience. Post-rp sexual dysfunction (sdf) has received significant attention, given its substantial effect on patient and partner health-related quality of life. Accordingly, there is a need for sdf treatment to be a fundamental component of pca survivorship programming. Methods: Most research about the treatment of post-rp sdf involves biomedical interventions for erectile dysfunction (ed). Although findings support the effectiveness of pro-erectile agents and devices, most patients discontinue use of such aids within 1 year after their rp. Because side effects of pro-erectile treatment have proved to be inadequate in explaining the gap between efficacy and ongoing use, current research focuses on a biopsychosocial perspective of ed. Unfortunately, there is a dearth of literature describing the components of a biopsychosocial program designed for the post-rp population and their partners. Results: In this paper, we detail the development of the Prostate Cancer Rehabilitation Clinic (pcrc), which emphasizes multidisciplinary intervention teams, active participation by the partner, and a broad-spectrum medical, psychological, and interpersonal approach. Conclusions: The goal of the pcrc is to help patients and their partners achieve optimal sexual health and couple intimacy after rp, and to help design cost-effective and beneficial rehabilitation programs.

The role of lifestyle characteristics on prostate cancer progression in two active surveillance cohorts.

BACKGROUND: Although much research has examined the relationship between lifestyle and prostate cancer (PCa) risk, few studies focus on the relationship between lifestyle and PCa progression. The present study examines this relationship among men initially diagnosed with low- to intermediate-risk PCa and managed with active surveillance (AS). METHODS: Men enrolled in two separate AS programs were recruited for this study. Data regarding clinical, demographic and lifestyle characteristics were collected. Results were then compared between men whose disease remained low- to intermediate-risk and men whose disease progressed. RESULTS: Demographic, clinical and physical characteristics were similar between comparative groups and cohorts, with the exception that age at the time of diagnosis and questionnaire was increased among men whose disease progressed. Lifestyle scores among men who remained low- to intermediate-risk were higher than those whose risk progressed; however, scores were only significant in one cohort on univariable analysis. On multivariable analysis, the only predictor of progression was age at diagnosis. Physical activity was consistently higher in both low risk groups, although this difference was insignificant. Consistent differences in other lifestyle variables were not observed. CONCLUSIONS: Age remains an important predictor of PCa progression. Improving lifestyle characteristics among men initially managed with AS might help to reduce the risk of progression. Given the limitations of this study, more rigorous investigation is required to confirm whether lifestyle characteristics influence the progression of low- to intermediate-risk PCa.

Diagnostic prostate biopsy performed in a non-academic center increases the risk of re-classification at confirmatory biopsy for men considering active surveillance for prostate cancer.

BACKGROUND: To examine whether diagnostic biopsy (B1), for patients on active surveillance (AS) for prostate cancer, performed at an outside referral centre (external) compared with our in-house tertiary center (internal), increased the risk of re-classification on the second (confirmatory) biopsy (B2). METHODS: Patients on AS were identified from our tertiary center database (1997-2012) with PSA<10, Gleason sum (GS) ⩽6, clinical stage ⩽cT2, ⩽3 positive cores, <50% of single core involved, age ⩽75 years and having a B2. Patients who had <10 cores at B1 and delay in B2 >24 mo were excluded. Depending on center where B1 was performed, men were dichotomized to internal or external groups. All B2 were performed internally. Multivariate logistic regression examined if external B1 was a predictor of re-classification at B2. RESULTS: A total of 375 patients were divided into external (n=71, 18.9%) and internal groups (n=304, 81.1%). At B2, more men in the external group re-classified (26.8%) compared with the internal group (13.8%) (P=0.008). On multivariate analysis, external B1 predicted grade-related re-classification (odds ratio (OR) 4.14, confidence interval (CI) 2.01-8.54, P<0.001) and volume-related re-classification (OR 3.43, CI 1.87-6.25, P<0.001). Other significant predictors for grade-related re-classification were age (OR 2.13 per decade, CI 1.32-3.57, P<0.001), PSA density (OR 2.56 per unit, CI 1.44-4.73, P<0.001), maximum % core involvement (OR 1.04 per percentage point, CI 1.01-1.09, P=0.02) and time between B1 and B2 (OR 1.43 per 6 months, CI 1.21-1.71, P<0.001). CONCLUSION: At our institution, patients on AS who had their initial B1 performed externally were more likely to have adverse pathological features and re-classify on internal B2.

Pre-treatment neutrophil-to-lymphocyte ratio as predictor of adverse outcomes in patients undergoing radical cystectomy for urothelial carcinoma of the bladder.

BACKGROUND: An elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor outcome in various tumours. Its prognostic utility in patients with urothelial carcinoma of the bladder (UCB) undergoing radical cystectomy (RC) is yet to be fully elucidated. METHODS: A cohort of patients undergoing RC for UCB in a tertiary referral centre between 1992 and 2012 was analysed. Neutrophil-to-lymphocyte ratio was computed using complete blood counts performed pre-RC, or before neo-adjuvant chemotherapy where applicable. Time-dependent receiver operating characteristic curves were used to determine the optimal cutoff point for predicting recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The predictive ability of NLR was assessed using Kaplan-Meier analyses and multivariable Cox proportional hazards models. The likelihood-ratio test was used to determine whether multivariable models were improved by including NLR. RESULTS: The cohort included 424 patients followed for a median of 58.4 months. An NLR of 3 was determined as the optimal cutoff value. Patients with an NLR⩾3.0 had significantly worse survival outcomes (5y-RFS: 53% vs 64%, log-rank P=0.013; 5y-CSS: 57% vs 75%, log-rank P<0.001; 5y-OS: 43% vs 64%, log-rank P<0.001). After adjusting for disease-specific predictors, an NLR ⩾3.0 was significantly associated with worse RFS (HR=1.49; 95% CI=1.12-2.0, P=0.007), CSS (HR=1.88; 95% CI=1.39-2.54, P<0.001) and OS (average HR=1.67; 95% CI=1.17-2.39, P=0.005). The likelihood-ratio test confirmed that prognostic models were improved by including NLR. CONCLUSIONS: Neutrophil-to-lymphocyte ratio is an inexpensive prognostic biomarker for patients undergoing RC for UCB. It offers pre-treatment prognostic value in addition to established prognosticators and may be helpful in guiding treatment decisions.

A pilot 'window of opportunity' neoadjuvant study of metformin in localised prostate cancer.

BACKGROUND: Metformin is an inhibitor of complex 1 in the respiratory chain, and is widely used to reduce insulin resistance. It has also been described to have pleotropic effects including via AMPK on inhibiting the mTOR kinase. Pre-clinical and epidemiological studies suggest an ability to modulate disease evolution in prostate cancer. In this study, we aimed to (i) demonstrate safety and tolerability of neoadjuvant metformin administration and (ii) document changes in proliferative (Ki67) and AMPK-related signalling indices between matching biopsies and prostatectomies METHODS: Men were treated in a single-arm 'window of opportunity' study between their decision to undergo radical prostatectomy and the operation itself. Forty patients were planned but only 24 patients were enrolled owing to slow accrual. Twenty-one patients were evaluable for pathological outcomes and 22 for serum metabolic indices. Metformin was given at doses to 500 mg t.i.d. Ki67 index was calculated using the Aperio-positive pixel count algorithm, whereas immunohistochemical measurements were by consensus H-Score. Comparative statistics were analysed by students t-tests and/or Wilcoxon matched pairs signed rank test. RESULTS: Baseline characteristics included median PSA 6 ng ml(-1) (3.22-36.11 ng ml(-1)). Median duration of drug treatment was 41 days (18-81). Treatment was well tolerated with only three patients developing G3/4 toxicities. In a per patient and per tumour analyses, metformin reduced the Ki67 index by relative amounts of 29.5 and 28.6 % (P=0.0064 and P=0.0042) respectively. There was also a significant decrease in P-4EBP1 staining (P<0.001) but no change in P-AMPK or P-ACC. There were no correlations between any metabolic, morphometric or cancer-related serum indices. There was a trend towards PSA reduction (P=0.08). The study is limited by small patient numbers and tumour heterogeneity. CONCLUSIONS: Neoadjuvant metformin is well tolerated prior to radical prostatectomy. Data to date indicate promising effects on metabolic and tissue proliferation and signalling parameters.

Should follow-up biopsies for men on active surveillance for prostate cancer be restricted to limited templates?

OBJECTIVE: To investigate if prostate biopsy templates with fewer cores can be used during active surveillance (AS) for prostate cancer. METHODS: At present, we use an AS protocol template (ASPT) consisting of 13-17 cores. We hypothesize in the setting of known cancer, sextant (6 cores) or standard extended (10-12 cores) templates, could be used with similar effect. We identified patients in our referral institution database (1997-2009) with entry prostate-specific antigen <10 ng/mL, stage ≤cT2, Gleason sum ≤6, ≤3 cores positive for cancer, <50% of single core involved, and age ≤75 years (N = 272). Patients fulfilling standard criteria for pathologic reclassification (N = 94) at any follow-up biopsy were selected for evaluation. By mapping tumor location on the pathologic reclassification determining biopsy, hypothetical scenarios of sextant or standard extended templates (SET) were compared with our ASPT and examined for frequency of cancer detection and pathologic reclassification. RESULTS: For the 94 patients analyzed, the median number of cores taken was 9.7 (6-22) at baseline and 15 (14-17) for the reclassification biopsy. The median time between baseline and the pathologic reclassification determining biopsy was 15.4 months. Analysis of subgroupings showed that sextant template would identify 84% of cancers and 47.9% of the reclassification events, whereas SET detected 99% of cancers and 81.9% of patients who pathologically reclassified. When only considering Gleason sum ≥7 related progression events, SET found 16.2% less (n = 57) compared with ASPT (n = 68). CONCLUSION: When monitoring patients on AS, a 13-17 core template detects more pathologic reclassification than standard sextant (18.1%) or extended (52.1%) biopsy templates.

Changes in bone mineral density in men starting androgen deprivation therapy and the protective role of vitamin D.

SUMMARY: Androgen deprivation therapy in 80 men was associated with declines in bone mineral density (BMD), which were greatest in the first year, and in the lumbar spine compared to controls. Vitamin D use was associated with improved BMD in the lumbar spine and in the first year. INTRODUCTION: Decreased BMD is a common side effect of androgen deprivation therapy (ADT), leading to increased risk of fractures. Although loss of BMD appears to be greatest within the first year of starting ADT, there are few long-term studies of change in BMD, and risk factors for bone loss are not well-characterized. METHODS: Men aged 50+ with nonmetastatic prostate cancer starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual-energy x-ray absorptiometry at baseline and yearly for 3 years. Matched controls were men with prostate cancer not receiving ADT. Multivariable regression analysis examined predictors of BMD loss. RESULTS: Eighty ADT users and 80 controls were enrolled (mean age 69 years); 52.5 % had osteopenia and 8.1 % had osteoporosis at baseline. After 1 year, in adjusted models, ADT was associated with significant losses in lumbar spine BMD compared to controls (-2.57 %, p = 0.006), with a trend towards greater declines at the total hip (p = 0.09). BMD changes in years 2 and 3 were much smaller and not statistically different from controls. Use of vitamin D but not calcium was associated with improved BMD in the lumbar spine in year 1 (+6.19 %, p < 0.001) with smaller nonsignificant increases at other sites (+0.86 % femoral neck, +0.86 % total hip, p > 0.10) primarily in the first year. CONCLUSIONS: Loss of BMD associated with ADT is greatest at the lumbar spine and in the first year. Vitamin D but not calcium may be protective particularly in the first year of ADT use.

Plasma osteopontin as a biomarker of prostate cancer aggression: relationship to risk category and treatment response.

BACKGROUND: High plasma osteopontin (OPN) has been linked to tumour hypoxia, metastasis, and poor prognosis. This study aims to assess whether plasma osteopontin was a biomarker of increasing progression within prostate cancer (PCa) prognostic groups and whether it reflected treatment response to local and systemic therapies. METHODS: Baseline OPN was determined in men with localised (n=199), locally recurrent (n=9) and castrate-resistant, metastatic PCa (CRPC-MET; n=37). Receiver-operating curves (ROC) were generated to describe the accuracy of OPN for distinguishing between localised risk groups or localised vs metastatic disease. We also measured OPN pre- and posttreatment, following radical prostatectomy, external beam radiotherapy (EBRT), androgen deprivation (AD) or taxane-based chemotherapy. RESULTS: The CRPC-MET patients had increased baseline values (mean 219; 56-513 ng ml(-1); P<0.0001) compared with the localised, non-metastatic group (mean 72; 12-438 ng ml(-1)). The area under the ROC to differentiate localised vs metastatic disease was improved when OPN was added to prostate-specific antigen (PSA) (0.943-0.969). Osteopontin neither distinguished high-risk PCa from other localised PCa nor correlated with serum PSA at baseline. Osteopontin levels reduced in low-risk patients after radical prostatectomy (P=0.005) and in CRPC-MET patients after chemotherapy (P=0.027), but not after EBRT or AD. CONCLUSION: Plasma OPN is as good as PSA at predicting treatment response in CRPC-MET patients after chemotherapy. Our data do not support the use of plasma OPN as a biomarker of increasing tumour burden within localised PCa.

Metformin enhances the antiproliferative and apoptotic effect of bicalutamide in prostate cancer.

BACKGROUND: Prostate cancer incidence and mortality vary dramatically by geographical location. Both are higher in developed countries. Some attribute this to westernized lifestyles of high-energy diets and limited physical activity with consequent obesity. Obesity and obesity-related diseases like diabetes cause hyperinsulinaemia, which upregulates pro-survival cell signalling. Previous work revealed diet-induced hyperinsulinaemia enhances prostate cancer xenograft growth in vivo. Metformin, an antidiabetic medication, reduces hyperinsulinaemia and also exhibits antineoplastic properties. Herein, we assess the potential additive benefit of combining bicalutamide antiandrogen therapy with metformin, in vitro and in vivo. METHODS: Using clonogenic assays, we assessed the effect of bicalutamide and/or metformin on clonogenicity in prostate cancer cell lines. Western blot and cell cycle analyses were used to elucidate mechanisms of interaction between the drugs in androgen receptor (AR)-positive (LNCaP) and AR-negative (PC3) cell lines. The combination treatment regimen was assessed in vivo using an LNCaP murine xenograft model. RESULTS: Micromolar bicalutamide or millimolar metformin caused a significant dose-dependent reduction in clonogenicity (P<0.001). Combination treatment further significantly reduced clonogenicity (P<0.005) with greater effects in AR-positive cells. Western blot and cell cycle analyses suggested differing mechanisms of interaction in AR-positive and -negative cell lines. Following combination treatment, LNCaP cells exhibited an altered cell proliferation (decreased phospho mammalian target of rapamycin expression) and perturbed cell cycle kinetics (G1/S cell cycle arrest). PC3 cells showed evidence of enhanced apoptosis (increased Bcl-2-associated X protein and decreased total caspase 3 expression). Markedly diminished tumour growth occurred following combination treatment in vivo (P<0.001). CONCLUSIONS: Combining bicalutamide and metformin significantly reduces prostate cancer cell growth further than either monotherapy. In AR-positive cells, this effect appeared to be mediated by reducing proliferation rates, whereas in AR-negative cells the combination treatment appeared to promote apoptosis. This combination drug regimen may improve prostate-cancer-specific survival by the direct antineoplastic properties outlined.

Salvage radical prostatectomy following primary high intensity focused ultrasound for treatment of prostate cancer.

PURPOSE: High intensity focused ultrasound for the treatment of primary prostate cancer is increasing in a subset of men seeking definitive treatment with reduced morbidity. We review outcomes in men undergoing salvage radical prostatectomy after failed whole gland high intensity focused ultrasound. MATERIALS AND METHODS: Prospective data were collected for men presenting with an increasing prostate specific antigen and biopsy proven prostate cancer after high intensity focused ultrasound from 2007 to 2010 who underwent salvage open radical prostatectomy with a 22-month median followup, including prostate specific antigen, prostate volume, pathology results, continence and erectile function. RESULTS: Data for 15 men were available, including median age 64 years (IQR 55-69), Gleason score before high intensity focused ultrasound of 6 (8), Gleason score 7 (7), median cores positive 39% (IQR 17%-63%) and median prostate specific antigen 7 ng/ml (IQR 5-8). Whole gland high intensity focused ultrasound achieved median nadir prostate specific antigen 1.1 ng/ml (IQR 0.5-3.1). Biopsy after high intensity focused ultrasound demonstrated Gleason score 6 (in 3 patients), 7 (9) and 8/9 (3), and 42% (IQR 25%-50%) cores positive and a median time from high intensity focused ultrasound to radical prostatectomy of 22 months (IQR 7-26). Perioperative morbidity was limited to 1 transfusion in a patient with a rectal injury. Pathologically extensive periprostatic fibrosis was found with persistent prostate cancer, as pT3 disease (in 9 of 14), Gleason scores 6 (2), 7 (9) and 8 of 9 (4), with focally positive margins in 3 of 11 (pT3a). Postoperative prostate specific antigen was unrecordable in 14 of 15 patients with further treatment in 2. Postoperative continence (more than 12 months of followup) yielded no pad use in 6 of 10 men with universally poor erectile function. CONCLUSIONS: Radical prostatectomy as salvage is feasible for men in whom high intensity focused ultrasound failed, but with a higher morbidity than for primary surgery. Pathology results are alarming given the number of cases with extraprostatic extension yet early followup data suggest acceptable oncologic control. These results should be factored in when counseling men who wish to undergo primary high intensity focused ultrasound.

Prevention strategies in prostate cancer.

Prostate cancer (PCa) prevention has been an exciting and controversial topic since the results of the Prostate Cancer Prevention Trial (PCPT) were published. With the recently published results of the reduce (Reduction by Dutasteride of Prostate Cancer Events) trial, interest in this topic is at a peak. Primary pca prevention will be unlikely to affect mortality significantly, but the reduction in overtreatment and the effect on quality of life from the avoidance of a cancer diagnosis are important factors to consider.This review provides a comparative update on the REDUCE and PCPT trials and some clinical recommendations. Other potential primary preventive strategies with statins, selective estrogen response modulators, and nutraceutical compounds-including current evidence for these agents and their roles in clinical practice-are discussed. Many substances that have been examined in the primary prevention of pca and for which clinical data are either negative or particularly weak are not covered.The future of PCa prevention continues to expand, with several ongoing clinical trials and much interest in tertiary prostate cancer prevention.