[Show abstract][Hide abstract] ABSTRACT: Background:
Extracellular vesicles released by prostate cancer present in seminal fluid, urine, and blood may represent a non-invasive means to identify and prioritize patients with intermediate risk and high risk of prostate cancer. We hypothesize that enumeration of circulating prostate microparticles (PMPs), a type of extracellular vesicle (EV), can identify patients with Gleason Score≥4+4 prostate cancer (PCa) in a manner independent of PSA.
Patients and methods:
Plasmas from healthy volunteers, benign prostatic hyperplasia patients, and PCa patients with various Gleason score patterns were analyzed for PMPs. We used nanoscale flow cytometry to enumerate PMPs which were defined as submicron events (100-1000nm) immunoreactive to anti-PSMA mAb when compared to isotype control labeled samples. Levels of PMPs (counts/µL of plasma) were also compared to CellSearch CTC Subclasses in various PCa metastatic disease subtypes (treatment naïve, castration resistant prostate cancer) and in serially collected plasma sets from patients undergoing radical prostatectomy.
PMP levels in plasma as enumerated by nanoscale flow cytometry are effective in distinguishing PCa patients with Gleason Score≥8 disease, a high-risk prognostic factor, from patients with Gleason Score≤7 PCa, which carries an intermediate risk of PCa recurrence. PMP levels were independent of PSA and significantly decreased after surgical resection of the prostate, demonstrating its prognostic potential for clinical follow-up. CTC subclasses did not decrease after prostatectomy and were not effective in distinguishing localized PCa patients from metastatic PCa patients.
PMP enumeration was able to identify patients with Gleason Score ≥8 PCa but not patients with Gleason Score 4+3 PCa, but offers greater confidence than CTC counts in identifying patients with metastatic prostate cancer. CTC Subclass analysis was also not effective for post-prostatectomy follow up and for distinguishing metastatic PCa and localized PCa patients. Nanoscale flow cytometry of PMPs presents an emerging biomarker platform for various stages of prostate cancer.
[Show abstract][Hide abstract] ABSTRACT: Magnetic resonance imaging–guided transurethral ultrasound ablation (MRI-TULSA) is a novel minimally invasive technology for ablating prostate tissue, potentially offering good disease control of localized cancer and low morbidity.
No preview · Article · Jan 2016 · European Urology
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Penile squamous cell carcinoma (SCC) is rare in North America; however, the morbidity can be devastating. This analysis represents the first reported penile cancer experience at a tertiary care centre in Canada.
We carried out a retrospective review of all patients who received care at our centre for penile SCC from 2005 until the present time. Epidemiological and clinical data were collected for all patients. Survival analysis was performed using Kaplan-Meier methods with log-rank test and Cox regression for univariate and multivariate analysis, respectively.
We identified 42 patients who were treated at our centre for penile SCC. Of these, 29% underwent excisional biopsy, 38% had partial penectomy, and 33% had total penectomy. Five patients with high-risk tumours underwent modified inguinal lymph node dissection (ILND), while 7 patients had radical ILND for clinically palpable disease. Overall, the median cancer specific survival (CSS) was undefined, with a 60% survival at 102 months. However CSS was significantly correlated to pT stage, pN stage, and tumour grade. The median follow-up was 25 months (interquartile range: 11-48).
These findings confirm the poor CSS of patients with positive lymph nodes in penile SCC. Patients with pN0 after ILND had a durable CSS. Risk factors for penile SCC were confirmed as elevated body mass index, positive smoking history, and lack of circumcision. This first epidemiologic report on penile SCC from a Canadian tertiary care centre should be expanded to other national centres.
Preview · Article · Oct 2015 · Canadian Urological Association journal = Journal de l'Association des urologues du Canada
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Bladder cancer represents 7% of all new cancers diagnosed in the USA in 2015. Furthermore, the mortality of metastatic bladder cancer has not decreased substantially in the last four decades. Angiogenesis is known to play a major role in the pathogenesis of bladder cancer.
The following article provides an overview of the first results of agents targeting the VEGF pathway in the treatment of metastatic bladder cancer.
Despite a few clinical trials providing preliminary encouraging results, the overall outcomes of the first published trials have been rather disappointing. In some instances, especially the case of trials which have investigated the use of new targeted agents as a single agent, no significant improvement in outcomes was seen, or was not sustained. In other cases, such as with combination trials, intolerable adverse effects have compromised the trials, due to overlapping toxicity between the targeted agent and chemotherapeutic agent(s). Further trials are warranted possibly combining different targeted agents or the use of sequential therapy. A better selection of the patient population may also be a key factor to improve patient outcomes, as many predictive factors of response seem to have already been identified.
No preview · Article · Jul 2015 · Expert Opinion on Investigational Drugs
[Show abstract][Hide abstract] ABSTRACT: Introduction:
We compared the morbidity of whole gland salvage ablation using cryotherapy (CRYO) and high-intensity focused ultrasound (HIFU) for radio recurrent prostate cancer at a single centre over a 17-year period.
Patients were divided in 3 cohorts. Group 1 included the first 65 patients treated with CRYO (1995-1998); Group 2 included the last 65 patients treated with CRYO (2002-2004), and Group 3 included 65 patients treated with HIFU (2006-2011). We analyzed the complications reported within at least 90 days of treatment or up to the last follow-up.
We tallied Clavien grade complications. For Groups 1, 2 and 3, we recorded the following Clavien I-II complications: 78, 49 and 13, respectively. For Clavien grade IIIa, 2, 5 and 4 for Groups 1, 2 and 3, respectively. For Clavien grade IIIb, 8, 2 and 3 for Groups 1, 2 and 3, respectively. Clavien grade II complications were statistically higher in Group 1 versus Group 2 (p = 0.005) and in Group 2 versus Group 3 (p = 0.0001). The rate of mild-moderate incontinence was significantly higher in the CRYO group compared to the HIFU cohort (p ≤ 0.05). The rate of urinary retention was significantly higher in Group 2 compared to Group 3 (p = 0.0005). The rates of severe incontinence (range: 1.5%-5%), need for surgical intervention (uniform at 1.5%), and recto-urethral fistulae (range: 1.5%-3%) were not statistically different.
CRYO was associated with higher overall morbidity. The morbidity during the early experience with HIFU was lower than both subgroups of CRYO. This may reflect the advancement of technology or cumulative learning experience.
Full-text · Article · Apr 2015 · The Journal of Urology
[Show abstract][Hide abstract] ABSTRACT: Radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) must include some form of distal ureter management to avoid high rates of tumour recurrence. It is uncertain which distal ureter management technique has the best oncologic outcomes. To determine which distal ureter management technique resulted in the lowest tumour recurrence rate, we analyzed a multi-institutional Canadian radical nephroureterectomy database.
We retrospectively analyzed patients who underwent radical nephroureterectomy with distal ureter management for UTUC between January 1990 and June 2010 at 10 Canadian tertiary hospitals. Distal ureter management approaches were divided into 3 categories: (1) extravesical tenting for ureteric excision without cystotomy (EXTRAVESICAL); (2) open cystotomy with intravesical bladder cuff excision (INTRAVESICAL); and (3) extravesical excision with endoscopic management of ureteric orifice (ENDOSCOPIC). Data available for each patient included demographic details, distal ureter management approach, pathology and operative details, as well as the presence and location of local or distant recurrence. Clinical outcomes included overall recurrence-free survival and intravesical recurrence-free survival. Survival analysis was performed with the Kaplan-Meier method. Multivariable Cox regression analysis was also performed.
A total of 820 patients underwent radical nephroureterectomy with a specified distal ureter management approach at 10 Canadian academic institutions. The mean patient age was 69.6 years and the median follow-up was 24.6 months. Of the 820 patients, 406 (49.5%) underwent INTRAVESICAL, 316 (38.5%) underwent EXTRAVESICAL, and 98 (11.9%) underwent ENDOSOPIC distal ureter management. Groups differed significantly in their proportion of females, proportion of laparoscopic cases, presence of carcinoma in situ and pathological tumour stage (p < 0.05). Recurrence-free survival at 5 years was 46.3%, 35.6%, and 30.1% for INTRAVESICAL, EXTRAVESICAL and ENDOSCOPIC, respectively (p < 0.05). Multivariable Cox regression analysis confirmed that INTRAVESICAL resulted in a lower hazard of recurrence compared to EXTRAVESICAL and ENDOSCOPIC. When looking only at intravesical recurrence-free survival (iRFS), a similar trend held up with INTRAVESICAL having the highest iRFS, followed by ENDOSCOPIC and then EXTRAVESICAL management (p < 0.05). At last follow-up, 406 (49.5%) patients were alive and free of disease.
Open intravesical excision of the distal ureter (INTRAVESICAL) during radical nephroureterectomy was associated with improved overall and intravesical recurrence-free survival compared with extravesical and endoscopic approaches. These findings suggest that INTRAVESICAL should be considered the gold standard oncologic approach to distal ureter management during radical nephroureterectomy. Limitations of this study include its retrospective design, heterogeneous cohort, and limited follow-up.
[Show abstract][Hide abstract] ABSTRACT: We studied the effect of dutasteride on the length of the off-treatment period in prostate cancer patients on intermittent androgen deprivation (IAD) therapy.
We conducted a randomized, placebo-controlled Phase II trial in men with localized prostate cancer and a rising prostate-specific antigen (PSA) level post-primary treatment. Patients were randomized to dutasteride (0.5 mg/day) or placebo. All patients received androgen deprivation therapy (ADT), which was stopped at month 9 if the PSA level was <1.0 ng/mL. ADT was resumed when PSA increased to ≥5.0 ng/mL. End points included time off treatment, PSA nadir after 9 months of ADT, serum testosterone and dihydrotestosterone levels, and time to castrate-resistant prostate cancer (rising PSA while testosterone levels remain <50 ng/mL).
There were 87 evaluable patients: 49 dutasteride, 38 placebo. In total, 80 patients completed one treatment cycle: 45 dutasteride, 35 placebo. The median time off treatment for patients reaching ≥5 ng/mL was 18.6 and 16.7 months for dutasteride and placebo, respectively (p = 0.7600). The median PSA nadir at 9 months was 0.1 and 0.075 ng/mL, respectively (p = 0.4486). There were no cases of androgen-independent prostate cancer. Our study limitations include its short duration with only one treatment cycle evaluated.
This small-scale Phase II randomized controlled trial showed no benefit to the addition of dutasteride to an IAD regimen.