Long-Term Outcomes of Whole Gland Salvage Cryotherapy for Locally Recurrent Prostate Cancer following Radiation Therapy: A Combined Analysis of Two Centers.

PURPOSE: Radiation refractory prostate cancer (RRPCa) is common and salvage cryotherapy for RRPCa is emerging as a viable local treatment option. However, there is a paucity of long-term data. The purpose of this study is to determine long-term outcomes following salvage cryotherapy for RRPca. MATERIALS AND METHODS: Patients undergoing salvage cryotherapy for biopsy-proven, localized RRPCa from 1992 through 2004 were prospectively accrued at two centers. Preoperative characteristics, perioperative morbidity and postoperative data were reviewed from our database. The primary outcomes were overall survival (OS) and disease-specific survival (DSS). The secondary outcomes were freedom from castration-resistant prostate cancer (CRPC) and freedom from androgen deprivation therapy (ADT). RESULTS: A total of 268 patients were identified with a median followup of 10.3 years. A total of 223 complication events were recorded; of them, 168 were Clavien I-II events and 55 Clavien III events. At 10 years, 69% had freedom from ADT and 76% had freedom from CRPC. The 10-year DSS rate was 81%, and the 10-year OS rate was 77%. A pre-salvage prostate specific antigen level of >10 ng/ml was associated with an increased risk of developing CRPC and initiation of ADT but was not associated with DSS or OS. The use of neoadjuvant ADT was associated with improved OS and DSS but did not affect freedom from CRPC or adjuvant ADT. CONCLUSIONS: Salvage cryotherapy for RRPCa provides excellent long-term freedom from ADT, CRPC and DSS with acceptable morbidity. OS at 10 years was 77%. Prospective trials are required for validation.

[PROSTATE CANCER EARLY DETECTION USING PSA - CURRENT TRENDS AND RECENT UPDATES].

INTRODUCTION: Prostate cancer (Pca) is the most common malignancy in men and the second cause of death from cancer. The prostate specific antigen (PSA) assay has been used for Pca screening since the beginning of the 1990's and has brought a 40% reduction in mortality. Since Pca is a diverse disease, early detection can lead to overdetection and overtreatment. Pca treatment has significant adverse effects, namely incontinence and erectile dysfunction. How is it then that a simple and inexpensive test that probably caused the most significant reduction in mortality from cancer ever, is regarded to be "not recommended" by some health organizations? Why did the use of PSA testing fall drastically in the US in the last couple of years, while, at the same time, the tendency for diagnosis of higher risk diseases is noticed through large controlled studies, showing the efficacy of PSA testing in mortality reduction? Will PSA serve as a milestone for early detection and mass population screening in general? This review will deal with aspects of PSA screening and will bring the latest updates and dilemmas concerning this evolving topic. We will review the evolution of PSA testing and the different aspects of its application and effects on mortality reduction, overdiagnosis and overtreatment. Finally, we will bring the latest innovations in Pca screening and offer practical ways to deal with early detection and treatment of Pca in order to balance overdetection and overtreatment on the one hand and the need for early detection and treatment of aggressive Pca on the other.

Performance of standard systematic biopsy versus MRI/TRUS fusion biopsy using the Navigo® system in contemporary cohort.

INTRODUCTION: The introduction of multi parameter magnetic resonance imaging (mpMRI) of the prostate in combination with MRI/TRUS fusion and systematic biopsy resulted in improved detection of prostate cancer. The aim of the current study was to document the performance of MRI/TRUS fusion biopsy of the prostate using the Navigo™ software in a contemporary cohort of patients from nonreferral centers. MATERIAL AND METHODS: We performed a two centers prospective data collection (2014-2020) for men with clinically suspected Pca and patients on active surveillance for low-risk Pca that were referred for TRUS biopsy after performing mpMRI of the prostate with a visible lesion. The primary outcome was detection of clinically significant cancer (csPca) defined as ISUP grade group ≥2. Patients were stratified according to biopsy technique and PI-RADS category. RESULTS: The study group included 236 patients of whom 129 (54.9%) were diagnosed with Pca and 82 (34.7%) with csPca (GG ≥ 2) on combined biopsy. The overall detection of csPca was 31% for targeted vs. 25.4% for systematic biopsy with an absolute difference of 5.6% in favor of the fusion technique. No significant difference between the two techniques was observed for detection of benign prostate or GG1 disease. The improved performance of the targeted approach was noted only in patients with PI-RADS 4 and 5 lesions. Of the patients with csPca 10 (12%) were diagnosed only by the systematic biopsy while 20 (24%) were detected only in the fusion biopsy. Systematic biopsy of prostate lobe without MRI lesion detected only 2 cases (∼1%) with high grade disease. CONCLUSIONS: Detection of csPca by mpMRI/TRUS fusion biopsy using the 3D Navigo™ system is feasible. The targeted approach outperforms the systematic one, however the later technique also detects high risk disease and should be included in the biopsy procedure. The overall detection rate (34.9%) of clinically significant prostate cancer by both targeted and systematic sampling is relatively low.

Implications of a Novel Biopsy Downloading System on Prostate Cancer Detection Rate, Surveillance and Focal Therapy - A Prospective Study.

OBJECTIVE: To examine the SmartBx, a novel biopsy downloading system, allowing downloading of biopsy cores with maximal core preservation as prostate biopsy sampling lacks preservation of core configuration & orientation. METHODS: We prospectively collected cores from TRUS biopsy patients. Half were collected using the SmartBx & half using standard downloading. We measured length of the first ∼3200 cores through various pathology steps and within core cancer length in 160 SmartBx cores. We compared core length, yield (% of core available for final analysis/ original core on needle) and cancer detection rate between SmartBx and standard cores. T-test or chi-square were used for analysis. RESULTS: 6014 cores were collected from 429 patients. Core length (12.3mm vs. 10mm; P<.01) and core yield (77.5% vs. 62.2%; P<.01) were significantly higher using the SmartBx compared to standard method, respectively. Cancer detection rate was significantly higher using the SmartBx for patients with PSA<10 (10.1% vs. 7.96%; n=2080 & n=2073, respectively; P<.016). Other subgroups showed non-significant higher detection rate for SmartBx cores. We noticed higher detection rate of clinically significant prostate cancer. Within core cancer length in 160 SmartBx cores was significantly lower compared to standard positive whole cores (4.45mm vs. 10.9mm; P<.001). Assuming cancer site a perfect sphere, disease volume was 11-fold lower for within core compared to entire core (46.1mm vs. 679.9mm; P<.0001). CONCLUSIONS: SmartBx results in significant higher core length, yield and cancer detection rate. Precise localization of within core tumor foci allows significant reduction in tumor volume.

Prostatic dystrophic calcification following salvage cryotherapy for prostate cancer - an under-reported entity?

BACKGROUND: Salvage cryoablation (SCA) is an accepted treatment for radio-recurrent prostate cancer with well-established oncological and functional outcomes. Based on one of the longest reported prospective follow-ups in the literature (median 12 years) on 187 patients, this study reports what appears to be an under-appreciated finding in eight patients with dystrophic calcifications (DC) of the prostate following SCA, causing severe bladder outlet obstruction. MATERIALS AND METHODS: Between 1995 and 2004, 187 patients underwent SCA, with a median follow-up of 12 years. This database was reviewed for functional and oncological outcomes and DC were evaluated. RESULTS: Functional data was available in 85 patients, amongst whom eight patients were found to develop DC (9.4%) proven when the patients presented with urinary difficulties and attempted transurethral resection was undertaken for bladder outlet obstruction. Mean time for emergence of significant symptoms of bladder outlet obstruction was 8.6 years from SCA (standard deviation (SD) = 6 years). All eightpatients required permanent drainage (seven suprapubic catheters, one nephrostomy). All patients with DC experienced biochemical recurrence (BCR), compared to 57.1% of the patients with no DC (p = 0.01). CONCLUSION: DC following SCA appears to be an under-reported late adverse effect which may only become evident with long follow-up, and should be included in preoperative counselling.

Does adding local salvage ablation therapy provide survival advantage for patients with locally recurrent prostate cancer following radiotherapy? Whole gland salvage ablation post-radiation failure in prostate cancer.

INTRODUCTION: Some men who experience prostate cancer recurrence post-radiotherapy may be candidates for local salvage therapy, avoiding and delaying systemic treatments. Our aim was to assess the impact of clinical outcomes of adding salvage local treatment in prostate cancer patients who have failed radiation therapy. METHODS: Following radiation biochemical failure, salvage transperineal cryotherapy (sCT, n=186), transrectal high intensity focused ultrasound ablation (sHIFU, n=113), or no salvage treatment (NST, identified from the pan-Canadian Prostate Cancer Risk Stratification [ProCaRS] database, n=982) were compared with propensity-score matching. Primary endpoints were cancer-specific survival (CSS) and overall survival (OS). RESULTS: Median followup was 11.6, 25.1, and 14.3 years following NST, sCT, and sHIFU, respectively. Two propensity score-matched analyses were performed: 1) 196 NST vs. 98 sCT; and 2) 177 NST vs. 59 sHIFU. In the first comparison, there were 78 deaths and 49 prostate cancer deaths for NST vs. 80 deaths and 24 prostate cancer deaths for sCT. There were significant benefits in CSS (p<0.001) and OS (p<0.001) favoring sCT. In the second comparison, there were 52 deaths (31 from prostate cancer) for NST vs. 18 deaths (nine from prostate cancer) for sHIFU. There were no significant differences in CSS or OS possibility attributed to reduced sample size and shorter followup of sHIFU cohort. CONCLUSIONS: In select men with recurrent prostate cancer post-radiation, further local treatment may lead to benefits in CSS. These hypothesis-generating findings should ideally be validated in a prospective clinical trial setting.

A Randomized Controlled Trial of a Modified Cystoscopy Technique using the Peak-End Rule in order to Improve Pain and Anxiety.

OBJECTIVE: To determine if a modified cystoscopy technique utilizing the peak-end rule cognitive bias decreases pain and anxiety during flexible cystoscopy in patients who undergo cystoscopy. METHODS: A total of 85 participants undergoing their first diagnostic cystoscopy were enrolled in a blinded single-center, prospective, randomized controlled trial. Patients with lower urinary tract abnormalities, prior radiation and chronic pelvic pain were excluded. Participants were randomized to a standard cystoscopy (arm A) or a modified cystoscopy (arm B) where a two-minute period at the end of the procedure was completed during which the cystoscope was left in the bladder without being manipulated. Following the cystoscopy, participants completed a standard pain and anxiety questionnaire. Differences in mean pain and anxiety score between arms were evaluated using a Mann-Whitney test with a two-sided alpha of 0.05. RESULTS: Eighty-five patients were randomized and underwent flexible cystoscopy. Three participants were ineligible, one required secondary procedures, and two did not complete the questionnaires. Among the 82 eligible patients, 45 were randomized to standard cystoscopy (arm A) and 37 to the modified cystoscopy (arm B) with mean pain scores of 23.20 and 11.97, respectively (P = .039). Mean anxiety scores were 2.09 and 0.88 for arm A and B, respectively (P = .013). CONCLUSION: This study demonstrated a clinically meaningful decrease in pain and anxiety for patients undergoing flexible cystoscopy when employing the modified cystoscopy technique versus the standard practice. This free and straightforward method to improve patient comfort and decrease stress during first time flexible cystoscopy should be considered by clinicians.

Long-term outcomes of two ablation techniques for treatment of radio-recurrent prostate cancer.

BACKGROUND: In men with recurrence of prostate cancer post radiation therapy, further treatment remains a challenge. The default salvage option of androgen-deprivation therapy (ADT) has adverse effects. Alternatively, selected men may be offered salvage therapy to the prostate. Herein, we present long-term oncological outcomes of two whole-gland ablation techniques, cryotherapy (sCT) and high-intensity-focused ultrasound (sHIFU). METHODS: Men undergoing sCT (1995-2004) and sHIFU (2006-2018) at Western University were identified. Oncological endpoints included biochemical recurrence (BCR), ADT initiation, metastases, castration resistance (CRPC), and prostate cancer-specific mortality (PCSM). Survival analysis with competing risks of mortality was performed. Multivariable analysis was performed using Fine and Gray regression. RESULTS: A total of 187 men underwent sCT and 113 sHIFU. Mean (SD) age of the entire cohort was 69.9 (5.9 years), median pre-radiation PSA 9.6 ng/ml (IQR 6.1-15.2), and pre-salvage PSA 4.5 ng/ml (IQR 2.8-7.0). Median total follow-up was 116 months (IQR 67.5-173.8). A total of 170 (57.6%) developed BCR, 68 (23.4%) metastases, 143 (49.3%) were started on ADT, 58 (20.1%) developed CRPC, and 162 (56%) patients died of which 59 (36.4%) were of prostate cancer. On multivariable analysis, sHIFU (HR 1.65, 95% CI 1.15-2.36, p = 0.006) and pre-salvage PSA (HR 1.09, 95% CI 1.06-1.13, p < 0.0001) were associated with a higher risk of BCR. Similarly, sHIFU patients had a higher risk of CRPC (HR 2.31, 95% CI 1.23-4.35, p = 0.009). The cumulative incidence (for both treatments) of PCSM was 16.5% (95% CI 12.2-21.4%) at 10 years and 28.4% (95% CI 22.1-34.9%) at 20 years, with no difference between treatment modalities. Pre-salvage PSA was a common predictor for the measured oncological outcomes. CONCLUSIONS: Although sHIFU had higher BCR and CRPC rates, there were no differences in PCSM when compared with sCT. The long-term oncological data on two ablation techniques highlighted that only 50% of patients started ADT after 10-year follow-up.

Adrenalectomy During Radical Nephrectomy- Incidence and Oncologic Outcomes From the Canadian Kidney Cancer Information System (CKCis) -A Modern Era, Nationwide, Multicenter Cohort.

OBJECTIVE: To characterize proportion of patients receiving adrenalectomy, adrenal involvement prevalence and oncologic outcomes of routine adrenalectomy in contemporary practice. Ipsilateral adrenalectomy was once standard during radical nephrectomy. However, benefit of routine adrenalectomy has been questioned because adrenal involvement of renal cell carcinoma (RCC) is low. METHODS: All patients receiving radical nephrectomy in the Canadian Kidney Cancer information system, a collaborative prospective cohort populated by 14 major Canadian centers, between January 2011 to February 2020 were included. Patients were excluded if they had non-RCC histology, multiple tumors, contralateral tumors, metastatic disease or previous history of RCC. Patient demographic, clinical, and surgical information were summarized and compared. Cox-proportional hazards was used for multivariable analysis. RESULTS: During study period, 2759 patients received radical nephrectomy, of these, 831(30.1%) had concomitant adrenalectomy. Pathological adrenal involvement was identified in 102 (3.7%overall; 12.3%of adrenalectomy). Median follow-up was 21.6months (Interquartile range 7.0-46.5). Patients with adrenalectomy had higher venous tumor thrombus (30.3% vs 9.6%; P <.0001), higher T stage (71.1% vs 43.4% pT3/4; P <.0001), lymph node metastases (17.6% vs 10.7%; P = .0035), Fuhrman grades (71.4% of Fuhrman grades 3/4 vs 56.2%; P <.0001) and increased proportion of clear cell histology (79.3% vs 74.5%; P = .0074) compared to the no adrenalectomy group. Adrenalectomy patients had higher risk of recurrence (HR 1.23; 95% CI 1.04-1.47; P = .019) and no difference in survival (HR 1.09, 95% CI 0.86-1.38, P = .48). CONCLUSION: Adrenalectomy is not associated with better oncological outcome of recurrence/survival. Adrenalectomy should be reserved for patients with radiographic adrenal involvement and/or intra-operative adrenal involvement.

The history of cryosurgery in Canada: A tale of two cities.

Although not commonly available in Canada, cryosurgery (cryoablation) for prostate cancer has been practiced in many countries. The field of cryoablation has evolved significantly over the past 30 years. Two prostate cryoablation programs were started in Canada in the early 1990s, in London, ON and Calgary, AB, focusing, respectively, on salvage therapy following radiation failure and primary local treatment. This article chronicles the development of the two programs and outlines the scientific and clinical contributions by investigators at the two centers.

Long-term Testis Cancer Survivors in Canada-Mortality Risks in a Large Population-based Cohort.

BACKGROUND: Testis cancer (TC) patients are young with excellent cancer prognosis. Hence, the risk of late-onset treatment-related morbidity and mortality is of concern due to longer survival after treatment. OBJECTIVE: We set to characterize long-term survival of TC patients through a Canadian population dataset. DESIGN SETTING AND PARTICIPANTS: We used a population-based dataset, the Canadian Census Health and Environment Cohort (CanCHEC), to identify individuals diagnosed with TC between 1991 and 2010. We compared them with all other male individuals without TC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was mortality due to cardiovascular disease (CVD) or nontesticular malignancy. Mann-Whitney or chi-square test was used where applicable. Data were analyzed using a Cox proportional hazard model with and without matching. RESULTS AND LIMITATIONS: We identified 1950 individuals with TC. We compared them with 1 300 295 men with no TC. There were 335 deaths in the study group during the study period (17.2%) with a mean follow-up of 19.6 yr. TC patients were at increased risk of death from secondary malignancies (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.39-1.91; p < 0.0001) with specific risks for hematologic neoplasms (HR 3.86, 95% CI 2.78-5.37; p < 0.001) and other malignancies (HR 2.41, 95% CI 1.76-3.29; p < 0.001). Gastrointestinal, hematologic, and respiratory toxicities were the most common secondary malignancies leading to death. When stratified according to histology, nonseminoma (NS) patients were at significantly increased risk of death from CVD (HR 2.03, 95% CI 1.27-3.25; p = 0.0032). Individuals with seminoma were at increased risk of death from other nontestis neoplasms (HR 1.46, 95% CI 1.17-1.82; p = 0.0007), specifically hematologic neoplasms (HR 2.09, 95% CI 1.18-3.72; p = 0.0118). CONCLUSIONS: NS patients are at increased risk of CVD-related death, whereas seminoma patients are at increased risk of death from non-testis-related malignancies. PATIENT SUMMARY: We report long-term mortality following diagnosis of testis cancer. Nonseminoma patients have an increased risk of death from cardiovascular disease, while seminoma patients have an increased risk of death from secondary malignancies.

Primary Mediastinal Germ Cell Tumors-The University of Western Ontario Experience.

Extragonadal germ cell tumors account for 2-5.7% of germ cell tumors (GCTs). Of these, primary mediastinal GCTs (PMGCTs) are responsible for 16-36% of cases. Given the rarity of these tumors, specific treatment strategies have not been well defined. We report our experience in treating these complex patients. In total, 318 men treated at our institution with chemotherapy for GCTs between 1980 and 2016 were reviewed. PMGCT was defined as clinically diagnosed mediastinal GCT with no evidence of testicular GCT (physical exam/ultrasound). We identified nine patients diagnosed with PMGCT. All patients presented with an anterior mediastinal mass and no gonadal lesion; four patients also had metastatic disease. Median age at diagnosis was 30 years (range, 14-56) and median mass size at diagnosis was 9 cm (range, 3.4-19). Eight patients had non-seminoma and one had pure seminoma. All patients received cisplatin-based chemotherapy initially. Surgical resection was performed in four patients; three patients had a complete resection and one patient was found to have an unresectable tumor. At a median follow-up of 2 years (range, 3 months-28 years) six patients had progressed. Progression-free survival was short with a median of 4.1 months from diagnosis (range 1.5-122.2 months). Five patients died at a median of 4.4 months from diagnosis. One and 5-year overall survivals were 50% and 38%, respectively. PMGCT are rare and aggressive. Our real-life Canadian experience is consistent with current literature suggesting that non-seminoma PMGCT has a poor prognosis despite prompt cisplatin-based chemotherapy followed by aggressive thoracic surgery.

The Urology Residency Program in Israel-Results of a Residents Survey and Insights for the Future.

OBJECTIVE: Urology practice has undergone several changes in recent years mainly related to novel technologies introduced. We aimed to get the residents' perspective on the current residency program in Israel and propose changes in it. METHODS: A web-based survey was distributed among urology residents. RESULTS: 61 residents completed the survey out of 95 to whom it was sent (64% compliance). A total of 30% replied that the 9 months of mandatory general surgery rotation contributed to their training, 48% replied it should be shortened/canceled, and 43% replied that the Step A exam (a mandatory written certifying exam) in general surgery was relevant to their training. A total of 37% thought that surgical exposure during the residency was adequate, and 28% considered their training "hands-on." Most non-junior residents (post-graduate year 3 and beyond) reported being able to perform simple procedures such as circumcision and transurethral resections but not complex procedures such as radical and laparoscopic procedures. A total of 41% of non-junior residents practice at a urology clinic. A total of 62% of residents from centers with no robotics replied its absence harmed their training, and 85% replied they would benefit from a robotics rotation. A total of 61% of residents from centers with robotics replied its presence harmed their training, and 72% replied they would benefit from an open surgery rotation. A total of 82% of the residents participated in post-graduate courses, and 81% replied they would engage in a clinical fellowship. CONCLUSION: Given the survey results we propose some changes to be considered in the residency program. These include changes in the general surgery rotation and exam, better surgical training, possible exchange rotations to expose residents to robotic and open surgery (depending on the availability of robotics in their center), greater out-patient urology clinic exposure, and possible changes in the basic science period.

A urologic stethoscope? Urologist performed sonography using a pocket-size ultrasound device in the point-of-care setting.

PURPOSE: Ultrasound is commonly used in urology. Technical advances with reduced size and cost led to diffusion of small ultrasound devices to many clinical settings. Even so, most ultrasound studies are performed by non-urologists. We aimed to evaluate the utility of a pocket-size ultrasound device (Vscan™ GE Healthcare) and the quality of urologist performed study. METHODS: Three consecutive studies were performed: (1) a urologist using the pocket ultrasound, (2) a sonographist using the pocket ultrasound, and (3) a sonographist using a standard ultrasound device. Thirty-six patients were evaluated with a basic urologic ultrasound study. An excepted deviation between studies was preset for numeric parameters and t test performed. Ordinal parameters were analyzed using Cohen's kappa coefficient. RESULTS: Kidney length, renal pelvis length, renal cyst diameter, post-void residual and prostate volume (transabdominal) differences were found to be insignificant when comparing a urologist pocket ultrasound study to a sonographist standard ultrasound study (P = 0.15; P = 0.21; P = 0.81; P = 0.32; P = 0.07, respectively). Hydronpehrosis evaluation (none, mild, moderate and severe) and the presence of ureteral jet signs conferred a high inter-observer agreement when comparing the above studies using the Cohen's kappa coefficient (K = 0.63; K = 0.62, respectively). CONCLUSIONS: Urologist performed pocket ultrasound study is valid in evaluating the upper and lower urinary tract and is practical in many clinical scenarios. The urologic stethoscope is now becoming a reality within reach.