Marc Zanaty

A prospective clinical trial of HIFU hemiablation for clinically localized prostate cancer

Background:Focal therapy is an emerging mini-invasive treatment modality for localized prostate cancer aimed to reduce the morbidity associated with radical therapy while maintaining optimal cancer control. We report the mid-term oncological and functional results of primary hemiablation high-intensity focused ultrasound (HIFU) in a prospective cohort of patients.Methods:Over 8 years, hemiablation HIFU was primarily performed in 50 selected patients with biopsy-proven clinically localized unilateral, low–intermediate risk prostate cancer in complete concordance with the prostate cancer lesions identified by magnetic resonance imaging with precise loci matching on multimodal approach. Post-treatment follow-up included regular serial PSA measurements. Biochemical recurrence was reported using Stuttgart and Phoenix criteria. The latter was used as a threshold to offer whole-gland biopsies.Results:Complete follow-up was available for all patients and the median follow-up was 39.5 months (range: 6–94). Mean nadir PSA value was 1.6 ng ml−1, which represents 72% reduction compared with initial PSA pre-treatment value (P<0.001). Median time to achieve PSA nadir was 3 months. Biochemical recurrence, according to Phoenix and Stuttgart definition, occurred in 28 and 36% of patients, respectively. The 5-year actuarial metastases-free survival, cancer-specific survival and overall survival rates were 93, 100 and 87%, respectively. Out of the eight patients undergoing biopsy, six patients had a positive biopsy for cancer occurring in the untreated contralateral (n=3) or treated ipsilateral lobe (n=1) or bilaterally (n=2). A Clavien–Dindo grade 3b complication occurred in two patients. Complete continence (no pads) and erection sufficient for intercourse were documented in 94 or 80% of patients, respectively.Conclusion:Hemiablation HIFU therapy, delivered with intention to treat, for carefully selected patients affords mid-term promising functional and oncological outcomes. The effectiveness of this technique should be now compared with whole-gland radical therapy.

In Search for a Common Pathway for Health Issues in Men--the Sign of a Holmesian Deduction.

The evidence for the existence of a common pathway for health issues in men is presented in this review. Several epidemiological studies have shown that conditions like cardiovascular diseases (CVD), metabolic syndrome, diabetes, lower urinary tract symptom (LUTS), erectile dysfunction (ED), prostate cancer, hypogonadism, depression and suicide can be associated as risk factors for each other. Thus, the risk of CVD is significantly increased in men with metabolic syndrome, ED, hypogonadism, prostate cancer and/or LUTS. In addition, the above mentioned conditions are more prevalent in atherosclerotic patients. In addition, growing evidence indicates that low androgen levels can cause metabolic syndrome. In addition, obesity, dyslipidaemia and diabetes can further reduce androgen levels potentiating their adverse effect. Low testosterone levels are also associated with a higher incidence of aggressive prostate cancer on biopsy and on definitive pathology, and lower probability of abiraterone response in the metastatic setting. Several recent studies point towards diffuse endothelial dysfunction and dysregulated pro-inflammatory state as the biological link between all these disorders. Our current hypothesis is that oxidative stress caused by these dysfunctions explains the pathogenesis of each of these conditions.

Contemporary Incidence and Cancer Control Outcomes of Primary Neuroendocrine Prostate Cancer: A SEER Database Analysis

Micro‐Abstract Reports on neuroendocrine prostate cancer (NEPC) are scarce and mostly based on historical series or case reports. Importantly, incidence rates and survival figures of NEPC in contemporary patients are unknown. A retrospective analysis from a large administrative database was used to answer this question. NEPC is rare and mostly diagnosed at metastatic stage. Prognosis is poor regardless of histologic subtype. Introduction: Neuroendocrine carcinoma of the prostate (NEPC) is a rare entity. We aimed at providing contemporary data on incidence and survival figures of de‐novo NEPC. Materials and Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database, we identified 309 individuals with de‐novo NEPC diagnosed between 2004 and 2013. We evaluated age‐adjusted incidence rates over the study. Kaplan‐Meier analyses assessed overall survival (OS) after stratification according to histologic subtype, metastatic status, and treatment. Cox regression analyses tested the predictors of overall mortality, after adjusting for confounders. Results: A total of 309 cases of NEPC were identified from 510,913 cases of prostate cancer. Metastatic disease was identified in 198 (64.1%) cases. The most common histologic subtype (n = 186; 60.2%) was small‐cell carcinoma (SCC). The age‐adjusted incidence of NEPC significantly increased over the study span. However, this increase only affected SCC (from 0.13/1,000,000 person‐years in 2004 to 0.30/1,000,000 person‐years in 2013; P = .001). Median survival for NEPC was 10 months. After stratification by metastatic status, no difference was observed according to SCC versus non‐SCC. Treatment with radical prostatectomy improved OS only among individuals with non‐metastatic disease, whereas radiation therapy did not affect OS rates. In multivariable Cox regression analyses predicting overall mortality, metastatic stage (hazard ratio, 1.52; 95% confidence interval, 1.12‐2.06; P < .01) and radical prostatectomy (hazard ratio, 0.38; 95% confidence interval, 0.20‐0.74; P < .01) achieved independent predictor status. Conclusion: De‐novo NEPC is extremely rare and will be encountered in clinical practice by few urologists. Most cases are metastatic at diagnosis. Prognosis is poor regardless of histologic type, especially in metastatic stage.

High Intensity Focused Ultrasound versus Brachytherapy for the Treatment of Localized Prostate Cancer: A Matched-Pair Analysis.

Purpose. To evaluate postoperative morbidity and long term oncologic and functional outcomes of high intensity focused ultrasound (HIFU) compared to brachytherapy for the treatment of localized prostate cancer. Material and Methods. Patients treated by brachytherapy were matched 1 : 1 with patients who underwent HIFU. Differences in postoperative complications across the two groups were assessed using Wilcoxons rank-sum or χ 2 test. Kaplan-Meier curves, log-rank tests, and Cox regression models were constructed to assess differences in survival rates between the two groups. Results. Brachytherapy was significantly associated with lower voiding LUTS and less frequent acute urinary retention (p < 0.05). Median oncologic follow-up was 83 months (13–123 months) in the HIFU cohort and 44 months (13–89 months) in the brachytherapy cohort. Median time to achieve PSA nadir was statistically shorter in the HIFU. Biochemical recurrence-free survival rate was significantly higher in the brachytherapy cohort compared to HIFU cohort (68.5% versus 53%, p < 0.05). No statistically significant difference in metastasis-free, cancer specific, and overall survivals was observed between the two groups. Conclusion. HIFU and brachytherapy are safe with no significant difference in cancer specific survival on long term oncologic follow-up. Nonetheless, a randomized controlled trial is needed to confirm these results.

Standardized 4-step technique of bladder neck dissection during robot-assisted radical prostatectomy

Bladder neck (BN) dissection is considered one of the most challenging steps during robot-assisted radical prostatectomy. Better understanding of the BN anatomy, coupled with a standardized approach may facilitate dissection while minimizing complications. We describe in this article the 4 anatomic spaces during standardized BN dissection, as well other technical maneuvers of managing difficult scenarios including treatment of a large median lobe or patients with previous transurethral resection of the prostate. The first step involves the proper identification of the BN followed by slow horizontal dissection of the first layer (the dorsal venous complex and perivesicle fat). The second step proceeds with reconfirming the location of the BN followed by midline dissection of the second anatomical layer (the anterior bladder muscle and mucosa) using the tip of the monopolar scissor until the catheter is identified. The deflated catheter is then grasped by the assistant to apply upward traction on the prostate from 2 directions along with downward traction on the posterior bladder wall by the tip of the suction instrument. This triangulation allows easier, and safer visual, layer by layer, dissection of the third BN layer (the posterior bladder mucosa and muscle wall). The forth step is next performed by blunt puncture of the fourth layer (the retrotrigonal fascia) aiming to enter into the previously dissected seminal vesical space. Finally, both vas deferens and seminal vesicles are pulled through the open BN and handed to the assistant for upper traction to initiate Denovilliers dissection and prostate pedicle/neurovascular bundle control.

Monopolar Transurethral Enucleo-Resection of the Prostate (TUERP) versus HoLEP: A Canadian Novel Experience

OBJECTIVE To study the functional outcome of patients undergoing transurethral enucleation and resection of the prostate (TUERP) vs patients undergoing holmium laser enucleation of the prostate (HoLEP) in men with bladder outlet obstruction. MATERIALS AND METHODS We retrospectively analyzed our prospectively collected database of two groups of patients. Twenty-four patients underwent TUERP (group 1), and 27 underwent HoLEP (group 2). Preoperative characteristics, intervention parameters, postoperative functional outcomes, uroflowmetry, and complications were collected. RESULTS Mean prostate size in groups 1 and 2 were 87.2 and 93.5 cc, respectively. The mean duration of surgery was 110 minutes in group 1 and 136 minutes in group 2. In group 1, prostate-specific antigen (PSA) dropped from 4.4 to 1.2 ng/cc after 12 months. International Prostate Symptom Score (IPSS) was 3.75 at 12 months with a preoperative value of 20.9. With respect to maximum urinary flow rate (Qmax), it increased to 21.8 mL/s from a preoperative value of 6.4 mL/s. In group 2, the PSA dropped from 7.6 to 1.3 ng/cc. IPSS dropped from 22.3 to 3.8, Qmax increased from 7.7 to 22.5 mL/s. Hemoglobin, complications, and all studied parameters were not statistically significant between both groups. CONCLUSION In this study, TUERP was safe and efficacious in benign prostatic hyperplasia patients with large glands. Modifications can be implemented on the standard transurethral resection of the prostate technique to treat patients with prostate sizes >70 cc.

Monopolar Transurethral Enucleo-Resection of the Prostate Versus Holmium Laser Enucleation of the Prostate: A Canadian Novel Experience

OBJECTIVE To study the functional outcome of patients undergoing transurethral enucleation and resection of the prostate (TUERP) vs patients undergoing holmium laser enucleation of the prostate (HoLEP) in men with bladder outlet obstruction. MATERIALS AND METHODS We retrospectively analyzed our prospectively collected database of two groups of patients. Twenty-four patients underwent TUERP (group 1), and 27 underwent HoLEP (group 2). Preoperative characteristics, intervention parameters, postoperative functional outcomes, uroflowmetry, and complications were collected. RESULTS Mean prostate size in groups 1 and 2 were 87.2 and 93.5 cc, respectively. The mean duration of surgery was 110 minutes in group 1 and 136 minutes in group 2. In group 1, prostate-specific antigen (PSA) dropped from 4.4 to 1.2 ng/cc after 12 months. International Prostate Symptom Score (IPSS) was 3.75 at 12 months with a preoperative value of 20.9. With respect to maximum urinary flow rate (Qmax), it increased to 21.8 mL/s from a preoperative value of 6.4 mL/s. In group 2, the PSA dropped from 7.6 to 1.3 ng/cc. IPSS dropped from 22.3 to 3.8, Qmax increased from 7.7 to 22.5 mL/s. Hemoglobin, complications, and all studied parameters were not statistically significant between both groups. CONCLUSION In this study, TUERP was safe and efficacious in benign prostatic hyperplasia patients with large glands. Modifications can be implemented on the standard transurethral resection of the prostate technique to treat patients with prostate sizes >70 cc.

External validation of the novel International Society of Urological Pathology (ISUP) Gleason grading groups in a large contemporary Canadian cohort

INTRODUCTION We sought to test the discriminatory ability of the 2014 International Society of Urological Pathology (ISUP) Gleason grading groups (GGG) for predicting biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP) in a large, contemporary, Canadian cohort. METHODS A total of 621 patients who underwent RARP in two major Canadian centres were identified in a prospectively maintained Canadian database between 2006 and 2016. Followup endpoint was BCR. Log-rank test, univariable, and multivariable Cox regression analyses were used. RESULTS Mean followup was 27.9 months. All five ISUP GGG independently predicted BCR. Statistically significant differences in BCR rates were found between GGG 2 and GGG 3 strata (p<0.001). No statistically significant differences in BCR rates were found between GGG 4 and GGG 5 strata (p=0.3). Relative to GGG 1, the GGG 2, GGG 3, GGG 4, and GGG 5 yielded a 1.10-, 3.44-, 4.18-, and 4.74-fold hazard ratio (HR) increment in BCR, respectively. CONCLUSIONS This population-based Canadian cohort study confirms the added discriminatory property of the novel ISUP grading, specifically for GGG 2 and GGG 3 strata. No difference, however, was observed between GGG 4 and GGG 5, likely due to the lower number of patients in these groups. As such, after external validation, the 2014 ISUP GGG appears to retain clinical prognostic significance in a Canadian population.

Perioperative predictors for post-prostatectomy urinary incontinence in prostate cancer patients following robotic-assisted radical prostatectomy: Long-term results of a Canadian prospective cohort

INTRODUCTION We aimed to report the impact of perioperative factors that have not been well-studied on continence recovery following robotic-assisted radical prostatectomy (RARP). METHODS We analyzed data of 322 men with localized prostate cancer who underwent RARP between October 2006 and May 2015 in a single Canadian centre. All patients were assessed at one, three, six, 12, and 24 months after surgery. We evaluated risk factors for post-prostatectomy urinary incontinence from a prospectively collected database in multivariate Cox regression analysis. The primary endpoint was continence, defined as 0 pad usage per day. RESULTS 0-pad continence rates were 126/322 (39%), 187/321 (58%), 222/312 (71%), 238/294 (80%), and 233/257 (91%) at one, three, six, 12, and 24 months, respectively. Bladder neck preservation (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.5-0.99; p=0.04), and prostate size (HR 0.99; 95% CI 0.98-0.99; p=0.02) were independent predictors of continence recovery after RARP. Smoking at time of surgery predicted delayed continence recovery on multivariate analysis (HR 1.42; 95% CI 1.01-1.99; p=0.04). Neurovascular bundles preservation was associated with continence recovery after 24 months. No statistically significant correlation was found with other variables, such as age, body mass index, Charlson comorbidity index, preoperative oncological baseline parameters, presence of median lobe, or thermal energy use. CONCLUSIONS Our results confirmed known predictors of postprostatectomy incontinence (PPI), namely bladder neck resection and large prostate volume. Noteworthy, cigarette smoking at the time of RARP was found to be a possible independent risk factor for PPI. This study is hypothesis-generating.

Photoselective vaporization of the prostate with the 180-W XPSGreenlight laser: Five-year experience of safety, efficiency, and functional outcomes

INTRODUCTION Transurethral resection of the prostate (TURP) is still considered the gold standard surgical treatment for symptomatic benign prostatic hyperplasia (BPH). However, photoselective vaporization of the prostate (PVP) has gained widespread global acceptance in national guidelines as a safe and effective alternative option. Nevertheless, further evidence is required to assess the durability of Greenlight PVP. Herein, we report our five years of PVP experience with the Greenlight 180W XPS laser system. METHODS A retrospective analysis was conducted on a prospectively gathered database of 370 consecutively included patients who underwent PVP using Greenlight XPS-180 W laser system (Boston Scientific, Boston, MA, U.S.) performed by a single experienced laser surgeon between 2011 and 2016. Preoperative characteristics, intervention parameters, postoperative functional, uroflowmetry outcomes, and complications were collected. Outcomes are reported over a period of five years. RESULTS Mean age was 68 years, with a mean prostate volume of 78.8 cc (95% confidence interval [CI] 70.9-78.7]). The mean followup was 59.4 months (55.4-63.5). Mean energy, operative time, and energy/cc were 270.2 kJ (255.2-285.2), 62.7 minutes (59.6-65.7), and 3.7 kJ/cc (3.6-3.9), respectively. Compared to preoperative values, International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), and post-void residual (PVR) parameters were significantly improved and sustained over the five postoperative years. Of note, only 66 patients (out of 370) had a complete five-year followup. Prostate-specific antigen (PSA) reached nadir at one year, with a drop of 67% from the mean preoperative value of 6.2 ng/mL. Mean IPSS nadir was reached at three years, with a drop of 80.4% (-21.1 points). Similarly, mean quality of life (QoL) score dropped by 82.8% after three years (preoperative mean of 4.7). With respect to mean Qmax, there was an increase by 72.7% (+14.7 mL/s) at one year, reaching the value of 19.9 mL/s. Moreover, mean PVR was 32.8 mL at four years compared to 345 mL preoperatively. At five years followup, PSA, IPSS, QoL, and PVR dropped by 59.7% (3.7 ng/mL), 75.2% (19.7 points), 78.72% (3.7 points), and 84.4% (291.3 mL), respectively. Qmax increased by 12.9 mL/s. Clavien complication rates were low, with bladder neck stenosis observed in seven (1.6%) men. During the five-year followup, only four patients (1%) required BPH surgical re-intervention. CONCLUSIONS This is the first long-term reporting of Greenlight XPS-180W laser system. In experienced hands, the observed outcomes appear to demonstrate that Greenlight XPS-180 W laser system is safe, efficacious, and durable for the treatment of bladder outlet obstruction (BOO) secondary to BPH.