Larry Goldenberg

A Multi-Institutional Evaluation of Active Surveillance for Low Risk Prostate Cancer

PURPOSE For select men with low risk prostate cancer active surveillance is more often being considered a management strategy. In a multicenter retrospective study we evaluated the actuarial rates and predictors of remaining on active surveillance, the incidence of cancer progression and the pathological findings of delayed radical prostatectomy. MATERIALS AND METHODS A cohort of 262 men from 4 institutions met the inclusion criteria of age 75 years or younger, prostate specific antigen 10 ng/ml or less, clinical stage T1-T2a, biopsy Gleason sum 6 or less, 3 or less positive cores at diagnostic biopsy, repeat biopsy before active surveillance and no treatment for 6 months following the repeat biopsy. Active surveillance started on the date of the second biopsy. Actuarial rates of remaining on active surveillance were calculated and univariate Cox regression was used to assess predictors of discontinuing active surveillance. RESULTS With a median followup of 29 months 43 patients ultimately received active treatment. The 2 and 5-year probabilities of remaining on active surveillance were 91% and 75%, respectively. Patients with cancer on the second biopsy (HR 2.23, 95% CI 1.23-4.06, p = 0.007) and a higher number of cancerous cores from the 2 biopsies combined (p = 0.002) were more likely to undergo treatment. Age, prostate specific antigen, clinical stage, prostate volume and number of total biopsy cores sampled were not predictive of outcome. Skeletal metastases developed in 1 patient 38 months after starting active surveillance. Of the 43 patients undergoing delayed treatment 41 (95%) are without disease progression at a median of 23 months following treatment. CONCLUSIONS With a median followup of 29 months active surveillance for select patients appears to be safe and associated with a low risk of systemic progression. Cancer at restaging biopsy and a higher total number of cancerous cores are associated with a lower likelihood of remaining on active surveillance. A restaging biopsy should be strongly considered to finalize eligibility for active surveillance.

Transatlantic Consensus Group on active surveillance and focal therapy for prostate cancer

Whats known on the subject? and What does the study add?

A RANDOMIZED PHASE 3 STUDY OF INTRAOPERATIVE CAVERNOUS NERVE STIMULATION WITH PENILE TUMESCENCE MONITORING TO IMPROVE NERVE SPARING DURING RADICAL PROSTATECTOMY

PURPOSE We determine if mapping of the cavernous nerve during radical prostatectomy using intraoperative cavernous nerve stimulation with tumescence monitoring results in improved erectile potency compared to conventional nerve sparing. MATERIALS AND METHODS A prospective, randomized, single blinded study was performed on 61 patients at 6 centers. Patients had elected to undergo nerve sparing prostatectomy and had normal preoperative erectile function documented by the Sexual Function Inventory Questionnaire (SFIQ) and RigiScan parallel testing. Patients were randomized between conventional nerve sparing and nerve sparing assisted by the CaverMap Surgical Aid. paragraph sign In all patients neural continuity was assessed immediately after prostate removal by proximal cavernous nerve stimulation. All patients were blinded according to their allocation cohort. RESULTS At 1 year there was substantial improvement in erectile function in the CaverMap group as measured by RigiScan. This group had a mean of 15. 9 minutes of greater than 60% nocturnal tumescence compared to 2.1 minutes in the conventional nerve sparing group (p <0.024). By SFIQ there was a nonsignificant trend to improved potency in the CaverMap group (71% versus 62%, p = 0.17). Of patients who had bilateral, unilateral and no response to stimulation after resection erectile function assessed by SFIQ recovered in 68%, 27% and 0%, respectively (p = 0.016). CONCLUSIONS CaverMap assisted prostatectomy led to improved erectile function as assessed by RigiScan testing with no associated adverse events. A response to stimulation immediately after removal of the prostate accurately predicted return of erectile function.

The Correlation of Multichannel Urodynamic Pressure-Flow Studies and American Urological Association Symptom Index in the Evaluation of Benign Prostatic Hyperplasia

PURPOSE We correlated multichannel pressure-flow urodynamics and the American Urological Association (AUA) symptom index in the evaluation of benign prostatic hyperplasia. MATERIALS AND METHODS We evaluated 121 consecutive, symptomatic patients older than 55 years with the AUA symptom score and multichannel pressure-flow urodynamic studies. Testing was performed during a single session and the data obtained from 103 patients were plotted on the Schäfer nomogram for assessment of outflow obstruction. Linear regression statistical analysis was used to determine correlations. RESULTS There was no significant correlation between uroflowmetry and Schäfer curves (r = 0.173 to 0.326), uroflowmetry and AUA symptom scores (r = 0.134 to 0.153) and, most importantly, AUA symptom scores and Schäfer curves (r = 0.025 to 0.137). CONCLUSIONS We conclude that these modalities measure independent variables, and should not be linked in the evaluation and treatment decision of the patient with prostatism.

Nadir Testosterone Within First Year of Androgen-Deprivation Therapy (ADT) Predicts for Time to Castration-Resistant Progression: A Secondary Analysis of the PR-7 Trial of Intermittent Versus Continuous ADT

PURPOSE Three small retrospective studies have suggested that patients undergoing continuous androgen deprivation (CAD) have superior survival and time to progression if lower castrate levels of testosterone (< 0.7 nmol/L) are achieved. Evidence from prospective large studies has been lacking. PATIENTS AND METHODS The PR-7 study randomly assigned patients experiencing biochemical failure after radiation therapy or surgery plus radiation therapy to CAD or intermittent androgen deprivation. The relationship between testosterone levels in the first year and cause-specific survival (CSS) and time to androgen-independent progression in men in the CAD arm was evaluated using Cox regression. RESULTS There was a significant difference in CSS (P = .015) and time to hormone resistance (P = .02) among those who had first-year minimum nadir testosterone ≤ 0.7, > 0.7 to ≤ 1.7, and ≥ 1.7 nmol/L. Patients with first-year nadir testosterone consistently > 0.7 nmol/L had significantly higher risks of dying as a result of disease (0.7 to 1.7 nmol/L: hazard ratio [HR], 2.08; 95% CI, 1.28 to 3.38; > 1.7 nmol/L: HR, 2.93; 95% CI, 0.70 to 12.30) and developing hormone resistance (0.7 to 1.7 nmol/L: HR, 1.62; 95% CI, 1.20 to 2.18; ≥ 1.7 nmol/L: HR, 1.90; 95% CI, 0.77 to 4.70). Maximum testosterone ≥ 1.7 nmol/L predicted for a higher risk of dying as a result of disease (P = .02). CONCLUSION Low nadir serum testosterone (ie, < 0.7 mmol/L) within the first year of androgen-deprivation therapy correlates with improved CSS and duration of response to androgen deprivation in men being treated for biochemical failure undergoing CAD.

The Significance of Prostatic Acid Phosphatase in Adenocarcinoma of the Prostate

Our radioimmunoassay for prostatic acid phosphatase was compared to commercial radioimmunoassay kits. A close correlation among all 3 assays was found in control groups, and in patients with benign prostatic hyperplasia and adenocarcinoma of the prostate. These results also were compared to recent reports from other centers using similar methodologies. In 7 to 15 per cent of the patients with bone metastasis normal levels of serum prostatic acid phosphatase were found. Variability in prostatic acid phosphatase production by the tumor may account for this finding. Elevated levels of prostatic acid phosphatase were associated more commonly with less differentiated primary tumors. A low percentage of prostatic acid phosphatase elevations in patients with early localized and incidental adenocarcinoma was found for the 3 assays evaluated. These factors, along with the falsely positive rates in patients with benign disease, limit severely the application of these assays to the screening of male patients at risk for adenocarcinoma of the prostate.

Rh2 Synergistically Enhances Paclitaxel or Mitoxantrone in Prostate Cancer Models

PURPOSE We explored the efficacy of the ginsenoside Rh2 and examined its impact on the effective dose of paclitaxel and mitoxantrone in the LNCaP prostate tumor model. MATERIALS AND METHODS Cultured LNCaP cell viability was assessed following treatment (48 hours) with Rh2 (0 to 40 microM) alone or in combination with paclitaxel and mitoxantrone. Synergism or antagonism observed when combining treatment was calculated using CalcuSyn software (Biosoft). In addition, the inhibition of LNCaP human xenograft tumor growth was examined in vivo when Rh2 treatment was combined with chemotherapy. Harvested tumors were immunohistochemical stained with p27kip and Ki67. RESULTS Rh2 and paclitaxel act synergistically in cultured LNCaP cells to lower ED50 and ED75 values. Rh2 and mitoxantrone are also synergistic. However, when combined as ED95, an antagonistic effect was observed in this cell line. Treatment of LNCaP tumors by Rh2 plus paclitaxel produced a significant decrease in tumor growth and serum prostate specific antigen. Immunohistochemical analysis revealed an apparent but nonsignificant effect on proliferation markers in LNCaP tumors. When Rh2 and mitoxantrone were combined in vivo, there was no significant benefit observed. CONCLUSIONS These results indicate that the combination of Rh2 and paclitaxel has an effect on growth inhibition that is greater and synergistic, as demonstrated in a cultured LNCaP cell line. Conversely combining Rh2 with mitoxantrone appears to elicit no benefit. Therefore, combination therapy using chemotherapy and Rh2 requires further investigation.

Diagnosis and management of testosterone deficiency syndrome in men: clinical practice guideline

See also page [1342][1] and [www.cmaj.ca/lookup/doi/10.1503/cmaj.151208][2] Testosterone deficiency syndrome, also known as late-onset hypogonadism, is a clinical and biochemical syndrome that can occur in men in association with advancing age. The condition is characterized by deficient testicular

Statistical Biomechanical Surface Registration: Application to MR-TRUS Fusion for Prostate Interventions

A common challenge when performing surface-based registration of images is ensuring that the surfaces accurately represent consistent anatomical boundaries. Image segmentation may be difficult in some regions due to either poor contrast, low slice resolution, or tissue ambiguities. To address this, we present a novel non-rigid surface registration method designed to register two partial surfaces, capable of ignoring regions where the anatomical boundary is unclear. Our probabilistic approach incorporates prior geometric information in the form of a statistical shape model (SSM), and physical knowledge in the form of a finite element model (FEM). We validate results in the context of prostate interventions by registering pre-operative magnetic resonance imaging (MRI) to 3D transrectal ultrasound (TRUS). We show that both the geometric and physical priors significantly decrease net target registration error (TRE), leading to TREs of 2.35 ± 0.81 mm and 2.81 ± 0.66 mm when applied to full and partial surfaces, respectively. We investigate robustness in response to errors in segmentation, varying levels of missing data, and adjusting the tunable parameters. Results demonstrate that the proposed surface registration method is an efficient, robust, and effective solution for fusing data from multiple modalities.

Comparison of open and robotic-assisted prostatectomy: The University of British Columbia experience

INTRODUCTION We assessed outcomes and costs of open prostatectomy (OP) versus robotic-assisted prostatectomy (RAP) at a single tertiary care university hospital. METHODS We retrospectively analyzed 200 consecutive OP by 1 experienced open surgeon (MG) and 200 consecutive RAP by an experienced open surgeon (SLG), after allowing for a short learning curve of 70 cases. RESULTS The 2 groups had similar demographics, including mean age (64.7 vs. 64.2) and mean body mass index (27.2 vs. 27.2). The OP group had a higher proportion of higher risk cancers compared to the RAP group (32.5% vs. 8.5%). Mean skin-to-skin operative room time was less for the OP (114.2 vs. 234.1 minutes). Transfusion rates were similar at 1.5% with OP compared to 3.5% with RAP. The mean length of stay was 1.78 days for OP compared to 1.76 days for RAP, for the last 100 patients in each group. The OP group had more high-grade disease in the prostatectomy specimen, with Gleason ≥8 in 23.5% compared to 3.5% in the RAP group. Positive surgical margin rates were comparable at 31% for OP and 24.6% for RAP, and remained similar after stratification for pT2 and pT3 disease. The grade I and II perioperative complication rate (Clavien-Dindo classification) was lower in the OP group (8.5% vs. 20%). Postoperative stress urinary incontinence rates (4.8% for OP and 4.6% for RAP) and biochemical-free status (91.8% for OP and 96% for RAP) did not differ at 12 months post-surgery. The additional cost of RAP was calculated as