Surgical management and post-operative functional outcomes of patients with a penile fracture-a single centre experience over 10 years.

BACKGROUND: Penile fractures are uncommon urological emergencies which occur when there has been a breach in the tunica albuginea of the corpora cavernosum that may be unilateral and bilateral and can extend to involve the urethra. AIM: To assess the management and outcomes of penile fractures in a single institution in Ireland. METHODS: A retrospective review of the emergency theatre logbooks was performed between 2011 and 2021 to identify patients who had undergone an exploration for a suspected penile fracture. OUTCOMES: Seventeen patients were initially identified on review of theatre logbooks as having an exploration for a suspected penile fracture. Two patients were excluded from the study due to a lack of clinical notes being available. A further 4 patients on chart review were found to not have a penile fracture at exploration. RESULTS: Eleven patients had a confirmed penile fracture intra-operatively, four of whom had an associated urethral injury. Nine (9/11) patients had preserved normal erections post-operatively documented on follow-up; two, however, reported erectile dysfunction requiring phosphodiesterase inhibitors. CLINICAL IMPLICATIONS: Our study supports urgent surgical exploration for penile fractures to ensure good functional outcomes. STRENGTHS AND LIMITATIONS: This is a retrospective review of theatre logbooks to identify patients with a suspected penile fracture. CONCLUSION: The results of our cohort show a good outcome of erectile function following surgical repair of a penile fracture (9/11; 82%). Four patients (4/11; 36%) had a urethral injury diagnosed intra-operatively, one of whom required a formal urethroplasty.

Biospecimen Qualification in a Clinical Biobank of Urological Diseases.

Development of novel biomarkers for diagnosis of disease and assessment of treatment efficacy utilizes a wide range of biospecimens for discovery research. The fitness of biospecimens for the purpose of biomarker development depends on the clinical characteristics of the donor and on a number of critical and potentially uncontrolled pre-analytical variables. Pre-analytical factors influence the reliability of the biomarkers to be analyzed and can seriously impact analytic outcomes. Sample quality stratification assays and tools can be utilized by biorepositories to minimize bias resulting from samples' inconsistent quality. In this study, we evaluated the quality of biobanked specimens by comparing analytical outcomes at 1, 5, and 10 years after collection. Our results demonstrate that currently available assays and tools can be used by biobank laboratories to support objective biospecimen qualification. We have established a workflow to monitor the quality of different types of biospecimens and, in this study, present the results of a qualification exercise applied to fluid samples and their derivatives in the context of urological diseases.

Mesorectal nodal metastasis with seminal vesicle invasion in biochemically recurrent prostate cancer.

OBJECTIVES: To determine the prevalence and predictors of mesorectal lymph node (MLN) metastases on prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) in patients with biochemically recurrent prostate cancer (PCa) following radical therapy. MATERIALS AND METHODS: This was a cross-sectional analysis of all PCa patients with biochemical failure following radical prostatectomy or radiotherapy who underwent an 18 F-DCFPyL-PSMA-PET/CT at the Princess Margaret Cancer Centre between December 2018 and February 2021. Lesions with PSMA scores ≥2 were considered positive for PCa involvement (PROMISE classification). Predictors of MLN metastasis were evaluated using univariable and multivariable logistic regression analyses. RESULTS: Our cohort consisted of 686 patients. The primary treatment method was radical prostatectomy and radiotherapy in 528 (77.0%) and 158 patients (23.0%), respectively. The median serum PSA level was 1.15 ng/mL. Overall, 384 patients (56.0%) had a positive scan. Seventy-eight patients (11.3%) had MLN metastasis, with 48/78 (61.5%) having MLN involvement as the only site of metastasis. On multivariable analysis, presence of pT3b disease (odds ratio 4.31, 95% confidence interval 1.44-14.2; P = 0.011) was significantly associated with increased odds of MLN metastasis, whereas surgical factors (radical prostatectomy vs radiotherapy; performance/extent of pelvic nodal dissection), surgical margin positivity, and Gleason Grade were not. CONCLUSIONS: In this study, 11.3% of PCa patients with biochemical failure had MLN metastasis on 18 F-DCFPyL-PET/CT. pT3b disease was associated with 4.31-fold significantly increased odds of MLN metastasis. These findings suggest alternate drainage routes for PCa cells, either via alternate lymphatic drainage from the seminal vesicles themselves or secondary to direct extension from posteriorly located tumours invading the seminal vesicles.

Comparative evaluation of urolithiasis management options in patients with horseshoe kidney: A systematic review and meta-analysis.

Background: Horseshoe kidney is a rare congenital anomaly commonly complicated by urolithiasis. Extracorporeal shockwave lithotripsy (ESWL), ureteroscopy (URS), and percutaneous nephrolithotomy (PCNL) are treatment options for horseshoe kidney stones. The aim of this systematic review is to compare the benefits and risks of these management options. Methods: MEDLINE, EMBASE, and Cochrane Library databases were searched from inception to February 2022. A total of 516 nonduplicate studies were screened against the inclusion and exclusion criteria. Studies comparing at least 2 interventions with ≥10 patients per intervention were included. Results: Nine retrospective observational studies published from 2007 to 2021 with a total of 565 patients were included. Reported mean ± SD or mean (range) stone sizes ranged between 17.90 ± 2.43 mm and 27.9 ± 8.6 mm for PCNL, 8.4 (2-25) mm and 22.3 ± 9.1 mm for URS, and 11.9 ± 2.0 mm and 16.8 ± 4.4 mm for ESWL. There was no difference in single-session and overall stone-free rate (SFR) between PCNL and URS, with a risk ratio of 1.04 (95% confidence interval, 0.95-1.13; I2 = 20.63%). Ureteroscopy had better stone clearance than ESWL, with an overall SFR risk ratio of 1.38 (95% confidence interval, 1.04-1.82; I2 = 0%). There was no statistically significant difference in overall SFR between PCNL and ESWL. Most patients who underwent URS and ESWL experienced Clavien-Dindo (CD) grade I-II complications. Percutaneous nephrolithotomy was associated with the highest complication rates, including 5 CD grade III and 3 CD grade IV complications and a mean postoperative hemoglobin drop of 0.47 to 1.83 g/dL. There were no CD grade V complications across all studies. Conclusions: There was no difference in SFR between PCNL and URS. Ureteroscopy was associated with a smaller stone burden and fewer and less severe complications. Ureteroscopy was found to be more effective than ESWL with a higher SFR and comparable safety profile. Further large-scale randomized controlled trials are needed to confirm these findings.

Lymphotropic Pattern of Prostate-specific Membrane Antigen-detected Metastases Among Biochemically Recurrent Radical Prostatectomy Patients with Cribriform Disease.

BACKGROUND: Cribriform morphology portends worse oncologic outcomes, and has unique cellular intrinsic pathway alterations and tumor microenvironments that may impact metastatic spread patterns. OBJECTIVE: To determine whether the presence of cribriform morphology in prostatectomy specimens of patients with biochemical recurrence after radical prostatectomy (RP) is associated with the presence of metastasis on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and a distinct pattern of spread. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional analysis was conducted of all prostate cancer patients with biochemical recurrence after RP undergoing 18F-DCFPyL-PET/CT between December 2018 and February 2021 at the Princess Margaret Cancer Centre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were presence of any metastasis in the overall cohort and lymphatic versus bone/visceral metastases among patients with metastatic disease. The associations between the presence of intraductal (IDC) and/or invasive cribriform (ICC) carcinoma on the RP specimen and study outcomes were evaluated using logistic regression analyses. RESULTS AND LIMITATIONS: The cohort included 176 patients. IDC and ICC were observed in 77 (43.8%) and 80 (45.5%) RP specimens, respectively. The median time from RP to PSMA-PET/CT was 5.0 yr. The median serum prostate-specific antigen level at PSMA-PET/CT was 1.12 ng/ml. Overall, metastasis was observed in 77 patients, of whom 58 were had lymphatic-only metastasis. On a multivariable analysis, presence of IDC on RP was associated with increased odds of overall metastasis (odds ratio [OR]: 2.17; 95% confidence interval [CI]: 1.07-4.45; p = 0.033). Presence of ICC on RP was associated with significantly increased odds of lymphatic versus bone/visceral metastases (OR: 3.13; 95% CI: 1.09-21.7; p = 0.004). CONCLUSIONS: Presence of cribriform morphology on RP specimens of patients with biochemical failure after RP is associated with increased odds of PSMA-PET/CT-detected metastases with a lymphatic predominant pattern of spread. These findings have implications for the design and evaluation of post-RP salvage therapies. PATIENT SUMMARY: We found that microscopic cribriform appearance correlates with disease spread on imaging in prostate cancer patients with recurrence and has a predilection for spread to lymph nodes, as opposed to bone or visceral organs.

Age related differences in primary testicular lymphoma: A population based cohort study.

INTRODUCTION: Primary testicular non-Hodgkin's lymphoma (PTL) is a very rare disease, comprising 1% of all non-Hodgkin's lymphoma and <5% of all cases of testicular tumors. With a median age at diagnosis of 67 years, PTL is the most common testicular malignancy in men aged >60 years. There is limited published data on PTL incidence and outcomes in younger patients. The aim of this study is to compare the clinical parameters and survival outcomes between the patients older and younger than 50. METHODS: The SEER database was queried for all patients diagnosed with PTL between 1983 and 2017. Data collected consisted of demographic, and clinical parameters, including staging, pathological assessments, and survival data. Patients were stratified according to their age and compared. RESULTS: There was a total of 1,581 patients diagnosed with PTL between the year 2000 and 2017, of whom 215 (13.6%) were younger than 50 years old. The median age at diagnosis was 41 (interquartile range [IQR] 1-50), and 72 (IQR 51-95) years old for patients ≤50 and patients > 50 years of age, respectively. Comparison of younger and older patients detected similarities in disease laterality (92% vs. 94%, P = 0.38) and Ann Arbor stage I to II at diagnosis (76% vs. 75%, P = 0.59). The most common diffuse large B-cell lymphoma (DLBCL) subtype was more common in older patients (61% vs. 87%, P < 0.001). Radical orchiectomy (71% vs. 79%, P = 0.004) and radiation treatment (40% vs. 37%, P = 0.49) rates were comparable between both groups. However, a higher proportion of younger patients underwent chemotherapy (83% vs. 72%, P < 0.001). Patients ≤50 and >50 years old had a hazard ratio (HR) of 0.63 (95% CI: 0.57-0.71) and 0.34 (95% CI: 0.31-0.37), respectively, for 10-year OS with a median survival time for patients >50 of 5.75 years (95% CI: 5.25-6.33), P < 0.001. Patients ≤50 years old had a HR of 0.33 (95% CI: 0.26-0.40) compared to HR of 0.40 (95% CI: 0.37-0.43) in patients >50 years old for cumulative disease-specific mortality (DSM, P = 0.0204). Age >50 years was associated with worse DSM with a HR of 1.39 (95% CI: 1.05- 1.86, P = 0.024). Ann Arbor stage II and higher was also associated with worse DSM, while undergoing surgery, radiotherapy, and chemotherapy were associated with improved DSM. CONCLUSIONS: PTL is the most common testicular malignancy in men older than 60 years of age, but more than a quarter of the patients are younger than 60 and more than 13% are ≤50 years. Younger patients are more likely to receive chemotherapy and radiation, and overall do better in terms of DSM. Being younger, having a lower Ann Arbor stage and being treated with chemotherapy and radiotherapy increase the chances of survival.

Salvage partial gland ablation for recurrent prostate cancer following primary partial gland ablation: Functional and oncological outcomes.

INTRODUCTION AND OBJECTIVE: Partial gland ablation (PGA) for localised prostate cancer (CaP) aims to eradicate clinically significant tumours while preserving healthy tissue, thereby decreasing the likelihood of side effects compared to whole-gland approaches. Although salvage radical prostatectomy (sRP) is a well-described salvage option in cases of PGA failure, the evidence supporting salvage PGA (sPGA) is limited. We hereby report the oncologic and functional outcomes of patients treated with sPGA following initial treatment with primary PGA (pPGA). METHODS: We describe the findings of a retrospective review of patients who had a CaP recurrence after pPGA and then underwent sPGA, at 3 medical centers in Ontario, Canada, between 2005 and 2017. Oncological outcomes following sPGA were assessed for biochemical recurrence (BCR) and biopsy-proven recurrence (BPR). Functional outcomes were described using the international prostate symptom score (IPSS), international index of erectile function (IIEF), and rates of urinary incontinence (use of >1 pad/day). RESULTS: We identified 25 patients who underwent sPGA following pPGA (hemiablation in 48% and zonal ablation in 52% of the patients). The median length of time was 16.8 months (interquartile range [IQR] 14.0-19.1) from pPGA to sPGA and 47.06 months (IQR 19.9-171.3) from pPGA to date of last follow up. High intensity focused ultrasound (HIFU) was the only modality used in all patients. At baseline, the median age was 65 years (IQR 52-77) and median prostate specific antigen (PSA) level was 7.46 ng/mL (IQR 1-25). The median time from pPGA to BPR was 12.7 months (IQR 5.19-36). At BPR following pPGA, 4 patients (17%) had CaP grade group (GG) 1, 10 patients (42%) had GG2, 6 patients (25%) had GG3, and 4 patients (17%) had GG4 disease, with a median PSA of 3.58 ng/mL (IQR 0.67-19). The median length of follow up after sPGA was 27.3 months (IQR 14.5-86.3). Following sPGA, 13/25 patients (52%) had BCR with median time to recurrence of 14 months (IQR 2.5-82.15), with a recurrence-free survival of 24.5 months (95% confidence interval: 15.3-not reached). Of those 13 patients, 4 were managed with sRP, 4 were managed with salvage radiotherapy, 3 were managed with androgen-deprivation therapy, 1 had a third PGA with HIFU, and 1 was managed with active surveillance. The mean change from baseline to last follow up in IPSS and IIEF scores was +1.3 (P = 0.66) and -2.3 (P = 0.32), respectively. Urinary incontinence was reported by 9% of patients at baseline, with only one additional patient developing incontinence following sPGA. CONCLUSION: Our present study demonstrates that after a median follow-up of 27 months, sPGA for recurrent CaP following pPGA provides disease control in up to 50% of patients with nonsignificant detrimental effects on functional outcomes. Appropriate patient selection and adequate staging are important to consider before offering PGA to patients.

Variability in testosterone measurement between radioimmunoassay (RIA), chemiluminescence assay (CLIA) and liquid chromatography-tandem mass spectrometry (MS) among prostate cancer patients on androgen deprivation therapy (ADT).

INTRODUCTION & AIMS: Monitoring testosterone (T) levels is recommended to assess the effectiveness of androgen deprivation therapy (ADT) in advanced prostate cancer. T levels below 20 ng/dL have been associated with better outcomes. Three main measures for T exist including radioimmunoassay (RIA), chemiluminescence assay (CLIA) and mass spectrometry (MS). While CLIA and RIA are ubiquitous, MS is regarded as the reference standard. We set out to determine the discordance of T measurements amongst men on ADT. METHODS: A retrospective review of men with prostate cancer on ADT for ≥3 months was conducted. Serum samples were split in triplicate. Observational data was reported and T measurements were compared analyzing for variability looking for categorical concordance. Over and under-estimation rates were calculated. RESULTS: Ninety-five patients were included with a mean age of 70 (50-92) years. Mean ADT duration was 24.1 (3-144) months. Ninety-five percent of patients had T ≤20ng/dL by MS and CLIA as compared to only 80% by RIA. After subdividing into T categories of ≤20, 20 to 50 and ≥50 ng/dL concordance analysis showed that 4.3% and 18.9% of T measured by MS would have a different category result when remeasured by CLIA (Kappa 0.84) or RIA (Kappa 0.50) respectively. CLIA and RIA overestimated T in 66.7% of patients with T <20 ng/dL measured by MS. Conversely CLIA and RIA underestimated T in only 4.4% of cases with T >20 ng/dL measured by MS. CONCLUSIONS: There is significant variability in T measured with RIA, CLIA and MS. CLIA and RIA overestimated T levels in majority of patients leaving a concern of misdiagnosing truly castrate patients as being inadequately treated.

Defining oligometastatic hormone sensitive prostate cancer and clinically significant outcomes: Implications on clinical trials?

PURPOSE: With the current movement toward treating oligometastatic hormone sensitive prostate cancer (OMPC), we design a study with the objective of gathering opinions regarding what would be considered a clinically significant benefit from such treatments. METHODS: Data was collected from physicians of the Society of Urologic Oncology using a self-administered questionnaire using SurveyMonkey. The questionnaire was designed to obtain characteristics on clinical practice of the respondents, definitions used for OMPC and also what would be considered a clinically significant benefit according to the respondents. We present a descriptive analysis of the responses obtained. RESULTS: We obtained 119 responses (response rate of 12.6%) after sending the questionnaire twice with one month apart. Most of them being staff/faculty (89%) practicing in the United States of America (84.87%). Most of the responders referred that a significant proportion of their practice comes from PC patients. Most defined OMPC <3 bone/lymph node metastasis seen with conventional imaging, only 26.9% of the responders used positron emission tomography. Regarding the clinical benefit of metastasis-oriented treatment, a curing rate >10% or an increase in 1 year of androgen deprivation therapy-free survival would make the treatment worthwhile. We present examples of sample size calculations for future clinical trials using these parameters as an expected "clinically-significant" benefit. CONCLUSION: This study shows that most clinicians still support the use of conventional imaging to define OMPC. Our findings show that a curing rate of a minimum of 11% and an androgen deprivation therapy-free survival at 1 year are considered clinically significant and this should be used for estimating the sample size in future clinical trials.

A Prospective Randomized Controlled Trial of Irrigation "Bag Squeeze" to Manage Pain for Patients Undergoing Flexible Cystoscopy.

PURPOSE: We determined if the "bag squeeze" technique decreases pain during flexible cystoscopy in men. MATERIALS AND METHODS: This single center, prospective, double-blind, randomized controlled trial recruited 200 consenting participants who were ambulatory, outpatient males who had undergone prior cystoscopy and were not expected to require any secondary procedures. Men with prior urethral stricture or bladder neck contracture were excluded from study. Once eligibility was assessed and consent obtained, participants were randomized to undergo cystoscopy with the bag squeeze (group A) or the sham bag squeeze procedure (group B). Following cystoscopy, participants completed a pain questionnaire (visual analogue scale). Differences in mean pain score between groups were evaluated using Students' t-test with a 2-sided alpha of 0.05. RESULTS: A total of 200 patients were randomized and underwent flexible cystoscopy. Ten participants were ineligible because they required secondary procedures. Among the 190 eligible patients 97 were randomized to bag squeeze (group A) and 93 to sham bag squeeze (group B) with mean pain scores of 1.91 and 3.39, respectively (p <0.005). CONCLUSIONS: This study demonstrated a clinically meaningful decrease in pain for men undergoing flexible cystoscopy when the irrigation bag squeeze technique was used vs placebo bag squeeze. Accordingly, this useful, simple and free method to improve patient comfort during flexible cystoscopy should be adopted by clinicians.

The oncologic impact of hormone replacement therapy in premenopausal breast cancer survivors: A systematic review.

SYNOPSIS: This is the first systematic review to investigate the risk of recurrence in breast cancer survivors <50 years old who have used hormone replacement therapy (HRT). BACKGROUND: The risk of HRT in premenopausal breast cancer survivors is unclear. Due to the higher incidence of estrogen receptor negative tumours in women <50, the potential for HRT to promote breast cancer recurrence may differ from older age groups. METHODS: We performed a search of Medline, EMBASE and CINAHL through June 2016. For the observational studies relative risk (RR) and 95% confidence interval (CI) were calculated for the recurrence rate among HRT users and nonusers. A random effects model was used to estimate the combined RR using the Mantel-Haenszel method. RESULTS: Four papers satisfied our inclusion criteria. 3477 subjects were analyzed. On pooled meta-analysis of breast cancer recurrence in the observational studies, no significant association was found between HRT and risk of recurrence (RR 1.04 [95% CI 0.45, 2.41]). The randomized controlled trial (RCT) included found an increased risk of recurrence with HRT among women <50 (HR 1.56 [95% CI 1.1-2.2]). However, among women of all ages with an estrogen receptor negative tumour there was no significant difference in recurrence when compared to hormone receptor positive tumours (HR 1.15 [95% CI 0.7-1.8, p = 0.55]). DISCUSSION: This review on HRT in breast cancer survivors <50 revealed conflicting results between randomized and observational study data. Further studies are warranted to investigate the association between HRT and recurrence rates in younger breast cancer survivors.