Prostate Health Index Density Outperforms Prostate-specific Antigen Density in the Diagnosis of Clinically Significant Prostate Cancer in Equivocal Magnetic Resonance Imaging of the Prostate: A Multicenter Evaluation.

PURPOSE: We compare Prostate Health Index, Prostate Health Index density, and PSA density in predicting clinically significant prostate cancer in MRI-guided prostate biopsy. MATERIALS AND METHODS: This is a multicenter evaluation of prospectively maintained prostate biopsy databases at 10 urology centers. Men with Prostate Health Index and MRI-guided targeted and systematic prostate biopsy performed and without prior prostate cancer diagnosis were included. The additional value of PSA density, Prostate Health Index, and Prostate Health Index density to MRI PI-RADS (Prostate Imaging Reporting & Data System) score was evaluated with multivariable analyses, area under the curve, and decision curve analyses. The proportion of unnecessary biopsies that can be avoided are estimated for clinically significant prostate cancer (International Society of Urological Pathology group ≥2 prostate cancer). RESULTS: A total of 1,215 men were analyzed. Prostate cancer and clinically significant prostate cancer were diagnosed in 51% (617/1,215) and 35% (422/1,215) of men, respectively. Clinically significant prostate cancer was diagnosed in 4.4% (3/68), 15% (72/470), 39% (176/446), and 74% (171/231) of highest PI-RADS score of 2, 3, 4, and 5 lesions, respectively. In multivariable analyses, independent predictors for clinically significant prostate cancer detection included Prostate Health Index (OR 1.04), prostate volume (OR 0.97), and PI-RADS score 4 (OR 2.81) and 5 (OR 8.34). Area under the curve for clinically significant prostate cancer of PI-RADS + Prostate Health Index density (0.85) was superior to PI-RADS + PSA density (0.81), Prostate Health Index density (0.81), Prostate Health Index (0.78), PI-RADS (0.76), PSA density (0.72), and PSA (0.60) in the whole cohort, and the superiority of Prostate Health Index density was also observed in PI-RADS 3 lesions. Decision curve analysis showed Prostate Health Index density achieving the best net clinical benefit in PI-RADS 3 or 4 cases. Among PI-RADS 3 lesions, using cutoffs of PSA density 0.15, Prostate Health Index 38.0, and Prostate Health Index density 0.83 could reduce 58%, 67%, and 72% of unnecessary biopsies, respectively. CONCLUSIONS: Prostate Health Index density outperformed Prostate Health Index or PSA density in clinically significant prostate cancer detection in men with multiparametric MRI performed, and further reduced unnecessary biopsies in PI-RADS 3 lesions.

Can we omit systematic biopsies in patients undergoing MRI fusion-targeted prostate biopsies?

Magnetic resonance imaging (MRI)-targeted prostate biopsy is the recommended investigation in men with suspicious lesion(s) on MRI. The role of concurrent systematic in addition to targeted biopsies is currently unclear. Using our prospectively maintained database, we identified men with at least one Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesion who underwent targeted and/or systematic biopsies from May 2016 to May 2020. Clinically significant prostate cancer (csPCa) was defined as any Gleason grade group ≥2 cancer. Of 545 patients who underwent MRI fusion-targeted biopsy, 222 (40.7%) were biopsy naïve, 247 (45.3%) had previous prostate biopsy(s), and 76 (13.9%) had known prostate cancer undergoing active surveillance. Prostate cancer was more commonly found in biopsy-naïve men (63.5%) and those on active surveillance (68.4%) compared to those who had previous biopsies (35.2%; both P < 0.001). Systematic biopsies provided an incremental 10.4% detection of csPCa among biopsy-naïve patients, versus an incremental 2.4% among those who had prior negative biopsies. Multivariable regression found age (odds ratio [OR] = 1.03, P = 0.03), prostate-specific antigen (PSA) density ≥0.15 ng ml-2 (OR = 3.24, P < 0.001), prostate health index (PHI) ≥35 (OR = 2.43, P = 0.006), higher PI-RADS score (vs PI-RADS 3; OR = 4.59 for PI-RADS 4, and OR = 9.91 for PI-RADS 5; both P < 0.001) and target lesion volume-to-prostate volume ratio ≥0.10 (OR = 5.26, P = 0.013) were significantly associated with csPCa detection on targeted biopsy. In conclusion, for men undergoing MRI fusion-targeted prostate biopsies, systematic biopsies should not be omitted given its incremental value to targeted biopsies alone. The factors such as PSA density ≥0.15 ng ml-2, PHI ≥35, higher PI-RADS score, and target lesion volume-to-prostate volume ratio ≥0.10 can help identify men at higher risk of csPCa.

A systematic review and meta-analysis on delaying surgery for urothelial carcinoma of bladder and upper tract urothelial carcinoma: Implications for the COVID19 pandemic and beyond.

Purpose: The COVID-19 pandemic has led to competing strains on hospital resources and healthcare personnel. Patients with newly diagnosed invasive urothelial carcinomas of bladder (UCB) upper tract (UTUC) may experience delays to definitive radical cystectomy (RC) or radical nephro-ureterectomy (RNU) respectively. We evaluate the impact of delaying definitive surgery on survival outcomes for invasive UCB and UTUC. Methods: We searched for all studies investigating delayed urologic cancer surgery in Medline and Embase up to June 2020. A systematic review and meta-analysis was performed. Results: We identified a total of 30 studies with 32,591 patients. Across 13 studies (n = 12,201), a delay from diagnosis of bladder cancer/TURBT to RC was associated with poorer overall survival (HR 1.25, 95% CI: 1.09-1.45, p = 0.002). For patients who underwent neoadjuvant chemotherapy before RC, across the 5 studies (n = 4,316 patients), a delay between neoadjuvant chemotherapy and radical cystectomy was not found to be significantly associated with overall survival (pooled HR 1.37, 95% CI: 0.96-1.94, p = 0.08). For UTUC, 6 studies (n = 4,629) found that delay between diagnosis of UTUC to RNU was associated with poorer overall survival (pooled HR 1.55, 95% CI: 1.19-2.02, p = 0.001) and cancer-specific survival (pooled HR of 2.56, 95% CI: 1.50-4.37, p = 0.001). Limitations included between-study heterogeneity, particularly in the definitions of delay cut-off periods between diagnosis to surgery. Conclusions: A delay from diagnosis of UCB or UTUC to definitive RC or RNU was associated with poorer survival outcomes. This was not the case for patients who received neoadjuvant chemotherapy.

Contemporary management of inguinal lymph nodes in squamous cell carcinoma of the scrotum: A case report and literature review.

Due to the rarity of scrotal squamous cell carcinoma (SCC), management of inguinal lymph nodes in scrotal SCC is largely extrapolated from management guidelines for penile SCC. This case report aims to enhance clarity on the management of inguinal lymph nodes in scrotal SCC. We recommend that for clinically node-negative patients, invasive techniques for lymph node sampling should be strongly considered and followed up with a radical inguinal lymph node dissection (ILND) where positive for lymph node metastasis. In the setting of clinically palpable lymph nodes which appear suspicious for metastasis on imaging, upfront radical ILND should be considered.

Cost-effectiveness of MRI targeted biopsy strategies for diagnosing prostate cancer in Singapore.

BACKGROUND: To evaluate the cost-effectiveness of six diagnostic strategies involving magnetic resonance imaging (MRI) targeted biopsy for diagnosing prostate cancer in initial and repeat biopsy settings from the Singapore healthcare system perspective. METHODS: A combined decision tree and Markov model was developed. The starting model population was men with mean age of 65 years referred for a first prostate biopsy due to clinical suspicion of prostate cancer. The six diagnostic strategies were selected for their relevance to local clinical practice. They comprised MRI targeted biopsy following a positive pre-biopsy multiparametric MRI (mpMRI) [Prostate Imaging - Reporting and Data System (PI-RADS) score ≥ 3], systematic biopsy, or saturation biopsy employed in different testing combinations and sequences. Deterministic base case analyses with sensitivity analyses were performed using costs from the healthcare system perspective and quality-adjusted life years (QALY) gained as the outcome measure to yield incremental cost-effectiveness ratios (ICERs). RESULTS: Deterministic base case analyses showed that Strategy 1 (MRI targeted biopsy alone), Strategy 2 (MRI targeted biopsy ➔ systematic biopsy), and Strategy 4 (MRI targeted biopsy ➔ systematic biopsy ➔ saturation biopsy) were cost-effective options at a willingness-to-pay (WTP) threshold of US$20,000, with ICERs ranging from US$18,975 to US$19,458. Strategies involving MRI targeted biopsy in the repeat biopsy setting were dominated. Sensitivity analyses found the ICERs were affected mostly by changes to the annual discounting rate and prevalence of prostate cancer in men referred for first biopsy, ranging between US$15,755 to US$23,022. Probabilistic sensitivity analyses confirmed Strategy 1 to be the least costly, and Strategies 2 and 4 being the preferred strategies when WTP thresholds were US$20,000 and US$30,000, respectively. LIMITATIONS AND CONCLUSIONS: This study found MRI targeted biopsy to be cost-effective in diagnosing prostate cancer in the biopsy-naïve setting in Singapore.

Multiparametric MRI in Active Surveillance of Prostate Cancer: An Overview and a Practical Approach.

MRI has become important for the detection of prostate cancer. MRI-guided biopsy is superior to conventional systematic biopsy in patients suspected with prostate cancer. MRI is also increasingly used for monitoring patients with low-risk prostate cancer during active surveillance. It improves patient selection for active surveillance at diagnosis, although its role during follow-up is unclear. We aim to review existing evidence and propose a practical approach for incorporating MRI into active surveillance protocols.

A systematic review and meta-analysis of magnetic resonance imaging and ultrasound guided fusion biopsy of prostate for cancer detection-Comparing transrectal with transperineal approaches.

Targeted biopsy using multiparametric magnetic resonance imaging increases the detection rate of clinically significant prostate cancer (csCaP). In this meta-analysis, we compare the diagnostic accuracy of transrectal (TR) vs transperineal (TP) approaches for MRI-guided software fusion biopsy (FB) in the detection of csCaP. A literature search was performed in PubMed, Cochrane and Embase electronic databases up until July 2019 following the preferred reporting items for systematic review and meta-analysis system. The pooled sensitivity and specificity of either approach was evaluated using radical prostatectomy or systematic biopsies with ≥24 biopsy cores to be the reference standard. Fourteen papers with a total of 2002 patients were selected. Seven hundred and sixty-five patients underwent TR FB, while 1,387 underwent TP FB. One hundred and fifty of the patients underwent both TR and TP approaches. Both approaches were similar in terms of sensitivity (TR vs. TP: 0.81 vs 0.80) and specificity (TR vs. TP: 0.99 vs 0.95). In terms of likelihood ratios and diagnostic odds ratio, TR performed better than TP approach. The area under the receiving operator curve for both approaches was similar (0.91 vs 0.88 respectively). However, there was substantial heterogeneity across the studies for both approaches. TP and TR approaches to software-based FB yield similar diagnostic performance for the detection of csCaP. When deciding on the approach, physicians should consider other inherent features of either technique that suit their practice.

Optimal Management of Upper Tract Urothelial Carcinoma: Current Perspectives.

INTRODUCTION: Upper tract urothelial carcinoma (UTUC) is a relatively uncommon urologic malignancy for which there has not been significant improvement in survival over the past few decades, highlighting the need for optimal multi-modality management. METHODS: A non-systematic review of the latest literature was performed to include relevant articles up to June 2019. It summarizes the epidemiologic risk factors associated with UTUC, including smoking, carcinogenic aromatic amines, arsenic, aristolochic acid, and Lynch syndrome. Molecular pathways underlying UTUC and potential druggable targets are outlined. RESULTS: Surgical management for UTUC includes kidney-sparing surgery (KSS) for low-risk disease and radical nephroureterectomy (RNU) for high-risk disease. Endoscopic management of UTUC may include ureteroscopic or percutaneous resection. Topical instillation therapy post-KSS aims to reduce recurrence, progression and to treat carcinoma-in-situ; this may be achieved retrogradely (via ureteric catheterization), antegradely (via percutaneous nephrostomy) or via reflux through double-J stent. RNU, which may be performed via open, laparoscopic or robot-assisted approaches, is the gold standard treatment for high-risk UTUC. The distal cuff may be dealt with extravesical, transvesical or endoscopic techniques. Peri-operative chemotherapy and immunotherapy are increasingly utilized; level 1 evidence exists for adjuvant chemotherapy, but neoadjuvant chemotherapy is favored as kidney function is better prior to RNU. Immunotherapy is primarily reserved for metastatic UTUC but is currently being investigated in the perioperative setting. CONCLUSION: The optimal management of UTUC includes a firm understanding of the epidemiological factors and molecular pathways. Surgical management includes KSS for low-risk disease and RNU for high-risk disease. Peri-operative immunotherapy and chemotherapy may be considered as evidence mounts.

Safe transition from extracorporeal to intracorporeal urinary diversion following robot-assisted cystectomy: a recipe for reducing operative time, blood loss and complication rates.

PURPOSE: We report the perioperative outcomes and complications after transition from extracorporeal urinary diversion (ECUD) to intracorporeal urinary diversion (ICUD) following robot-assisted radical cystectomy (RARC). METHODS: Analysis of data from a prospectively maintained institutional review board-approved database of 180 patients treated with cystectomy at our institution from April 2015 to October 2017 was performed. 127 patients underwent RARC and received an ileal conduit. Only five patients received a neobladder after RARC and were excluded from analysis. RESULTS: 68 patients had extracorporeal and 59 intracorporeal ileal conduit after RARC. There were no significant differences in patient demographics and oncological characteristics between the two groups. Of note, intracorporeal ileal conduit was associated with significantly reduced median total operative times (330 vs 375 min, p = 0.019), reduced median estimated blood loss (300 vs 425 ml, p < 0.035) and lower 30-day overall complication rates (48.4 vs 71.4%, p = 0.008) when compared to extracorporeal diversion. However, the median length of stay, 30-90-day complication rates, mortality rates and ureteroileal anastomotic stricture rates were similar in both groups. The median operative time for RARC and intracorporeal ileal conduit was significantly shorter in the second cohort of 29 cases compared to the first 30 cases (300 vs 360 min, p = 0.004). Other outcomes were similar in both cohorts. CONCLUSION: In our experience, transition from extracorporeal to intracorporeal diversion after RARC is safe, technically feasible and benefits from shorter operative times, reduced estimated blood loss, and lower 30-day overall complication rates.

Management of penile cancer in a Singapore tertiary hospital.

OBJECTIVES: To present our experience of managing penile squamous cell carcinoma (SCC) in a tertiary hospital in Singapore and to evaluate the prognostic value of the inflammatory markers neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR). PATIENTS AND METHODS: We reviewed our prospectively maintained Institutional Review Board-approved urological cancer database to identify men treated for penile SCC at our centre between January 2007 and December 2015. For all the patients identified, we collected epidemiological and clinical data. RESULTS: In all, 39 patients were identified who were treated for penile SCC in our centre. The median [interquartile range (IQR)] follow-up was 34 (16.5-66) months. Although very few (23%) of our patients with high-risk clinical node-negative underwent prophylactic inguinal lymph node dissection (ILND), they still had excellent 5-year recurrence-free survival (RFS; 90%) and cancer-specific survival (CSS; 90%). At multivariate analysis, higher N stage was significantly associated with worse RFS and CSS. Patients with a high NLR (≥2.8) had significantly higher T-stage (P = 0.006) and worse CSS (P < 0.001) than those with a low NLR. Patients with a low LMR (<3.3) had significantly higher T-stage (P = 0.013) and worse RFS (P = 0.009) and CSS (P < 0.022) than those with a high LMR. CONCLUSIONS: Although very few of our patients with intermediate- and high-risk clinical node-negative SCC underwent prophylactic ILND, they still had excellent 5-year RFS and CSS. However, survival was poor in patients with node-positive disease. The pre-treatment NLR and LMR could serve as biomarkers to predict the prognosis of patients with penile cancer.

MRI Fusion-Targeted Transrectal Prostate Biopsy and the Role of Prostate-Specific Antigen Density and Prostate Health Index for the Detection of Clinically Significant Prostate Cancer in Southeast Asian Men.

OBJECTIVE: To test the hypothesis that targeted biopsy has a higher detection rate for clinically significant prostate cancer (csPCa) than systematic biopsy. We defined csPCa as any Gleason sum ≥7 cancer. In patients with Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, to determine if factors, such as prostate-specific antigen density (PSAD) and prostate health index (PHI), can predict csPCa and help select patients for biopsy. MATERIALS AND METHODS: We report the first series of targeted biopsies in Southeast Asian men, with comparison against systematic biopsy. Consecutive patients were registered into a prospective institutional review board-approved database in our institution. We reviewed patients who underwent biopsy from May 2016 to June 2017. Inclusion criteria for our study were patients with at least one PI-RADS ≥3, and who underwent both targeted and systematic biopsies in the same sitting. RESULTS: There were 115 patients in the study, of whom 74 (64.3%) had a previous negative systematic biopsy. Targeted biopsies detected significantly less Gleason 6 cancers than systematic biopsies (p < 0.01), and demonstrated significantly higher sensitivity, specificity, positive predictive value, and negative predictive value (NPV) for the detection of csPCa. For patients with PI-RADS 3 lesions, PHI and PSAD were found to be the best predictors for csPCa. PSAD <0.10 ng/mL/mL had an NPV of 93% and sensitivity of 92%, while allowing 20% of patients to avoid biopsy. PHI cutoff of <27 would allow 34% of patients to avoid biopsy, with both sensitivity and NPV of 100%. CONCLUSIONS: Targeted prostate biopsies were found to be significantly superior to systematic biopsies for the detection of csPCa, while detecting less Gleason 6 cancer. Usage of PSAD and PHI cutoff levels in patients with PI-RADS 3 lesions may enable a number of patients to avoid unnecessary biopsy.

Malakoplakia of the Prostate as a Mimicker of Prostate Cancer on Prostate Health Index and Magnetic Resonance Imaging-Fusion Prostate Biopsy: A Case Report.

Background: Isolated malakoplakia of the prostate is a rare inflammatory condition that has been clinically mistaken for prostatic malignancies. The development of Prostate Imaging Reporting and Data System (PI-RADS) classifications, and Prostate Health Index (PHI) has led to more accurate diagnosis of clinically significant disease and stratification of patients that may be at risk of prostate cancer. Case Presentation: We present a case of a 75-year-old male who was on follow-up with our hospital for elevated prostate specific antigen (PSA). He was admitted for an episode of urosepsis, which was treated with antibiotics and subsequently underwent further workup and was found to have a raised PHI, as well as a high PI-RADS classification and was later found to have malakoplakia based on histology of prostate tissue obtained during targeted magnetic resonance imaging (MRI)-guided fusion prostate biopsy. Conclusion: To our understanding, this is the first case where a prostate lesion has been labeled as a PI-RADS 5 lesion, with elevated PHI that has subsequently been proven histologically to be malakoplakia. An important possible confounder is the interval between the MRI and the episode of urosepsis and it is well known that urosepsis can affect the PSA and MRI result. We present this case to highlight the potential for a false diagnosis of prostate cancer, in spite of laboratory and radiological findings.

Successful removal of a penoscrotal constricting ring in a 49-year-old male.

Placement of constricting devices around the penis and scrotum for autoerotic purposes or increasing sexual performance represents a well-known challenge for urologists and can result in serious complications. The removal of the constricting devices can be challenging and often requires resourcefulness and multidisciplinary approach. We report one case of successful removal of a penoscrotal constricting metal ring in a 49-year-old male using a hand-held orthopaedic saw under ketamine and midazolam sedation in the emergency department.

Cerebral arterial gas embolism in a diver using closed circuit rebreather diving apparatus.

A Singaporean naval diver suffered symptoms and signs of cerebral arterial gas embolism (CAGE) following a panicked ascent from a depth of 5-6 metres' sea water while using a Dräger LAR V closed-circuit oxygen rebreather system. He presented with altered mental status and paresis. CAGE due to gas mixtures with high oxygen content has seldom been reported. The diver had no sequelae following prompt recompression therapy. This positive clinical outcome may be attributable to the high oxygen content in the diver's inspired gas and/or the promptness of recompression.

Changes in lung function in Republic of Singapore Navy divers.

BACKGROUND: It is recognized that diving may result in long-term adverse effects on the lungs, In the Republic of Singapore Navy (RSN), divers undergo an annual examination, which includes spirometry to detect early any deterioration in lung function, to ensure that personnel are fit to continue their duties. There are a few Asian studies on lung function, and none on Asian divers. OBJECTIVES: To analyze the lung function of a group of RSN divers over a five-year period. METHODOLOGY: This was a retrospective study based on the spirometric results of RSN divers during their annual recertification in 2001 and in 2006. There were 116 subjects who underwent the spirometry at the same centre in both 2001 and 2006. RESULTS: The divers showed a statistically significant increase in mean forced vital capacity (FVC) from 86.1% to 89.5% of predicted (P < 0.01) over the five-year period. In addition, the mean forced expiratory volume in one second (FEV1) improved significantly from 87.2% to 90.2% of predicted (P < 0.01). However, there was a statistically significant decrease in FEV1/FVC ratio from 87.0% to 85.0% of predicted (P < 0.01). Mean peak expiratory flow rose from 100.1% to 111.00% of predicted (P < 0.01). We did not find any statistically significant relationship between years of service or smoking history and changes in lung function for the divers. CONCLUSION: Despite being statistically significant, these findings are probably of minimal clinical significance, but do demonstrate that there is no decline in lung function in these divers over this period of time.