Natural history, and impact of surgery and radiation on survival outcomes of men diagnosed with low-grade prostate cancer at ≤ 55 years of age: a 25-year follow-up of > 60,000 men.

PURPOSE: Low-grade prostate cancer has low mortality rates at 10 years; however, it is unclear if the response is sustained for up to 25 years of follow-up. METHODS: Using Surveillance, Epidemiology, and End Results database, the overall and cancer-specific mortality rates were compared among men ≤ 55 years of age diagnosed with low-grade prostate cancer that either had radical prostatectomy, radiotherapy, or no known treatment. RESULTS: Of the 62,772 men diagnosed with low-grade prostate cancer between 1975 and 2016, about 60%, 20% and 20% of men underwent radical prostatectomy, radiotherapy, and no known treatment, respectively. At a median follow-up of 10 years, almost 2% and 7% of men died of prostate cancer and other causes, respectively. The overall mortality was significantly better in radical prostatectomy group compared to no known treatment group (HR 1.99, CI 1.84-2.15, P value < 0.001), but not between the radiotherapy and no known treatment groups. Moreover, the overall and cancer-specific mortality rates in the radiotherapy group were almost two and three times compared to the radical prostatectomy group, respectively (HR 2.15, CI 2.01-2.29, P value < 0.001 for overall mortality and HR 2.87, CI 2.5-3.29, P value < 0.001 for cancer-specific mortality). CONCLUSIONS: The study confirms low mortality rates in men diagnosed with low-grade prostate cancer for over 25 years' follow-up. While radical prostatectomy improves survival significantly compared to no known treatment, radiotherapy is associated with an increase in overall and cancer-specific mortality, which may be related to long-term toxicities.

Combination therapy in metastatic castration sensitive prostate cancer: A Systematic review and network meta-analysis.

Introduction: Studies directly comparing the different combination therapies offered to men with metastatic castration sensitive prostate cancer (mCSPC), are not available yet. This study was designed using the network meta-analysis (NMA) framework to provide a comparison of the different available options for the treatment of men with mCSPC. Methods: A systematic search was performed and the prospective randomized controlled trials reporting the overall survival (OS) or failure-free survival (FFS) were selected for review. A total of 14 studies were included in the NMA. Results: The addition of abiraterone, apalutamide, docetaxel, and docetaxel with zoledronic acid to the androgen deprivation therapy (ADT) demonstrated a significant improvement in the OS. In indirect comparison, abiraterone had a higher impact on the OS as compared to docetaxel (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.0-1.46) and docetaxel with zoledronic acid (HR: 1.31, 95% CI: 1.05-1.63) but not apalutamide. Furthermore, apalutamide was not different than docetaxel or docetaxel with zoledronic acid. There was a significant improvement in the FFS with the combination of abiraterone, apalutamide, docetaxel (HR: 0.61, 95% CI: 0.46-0.81), docetaxel with zoledronic acid (HR: 0.62, 95% CI: 0.43-0.9), and enzalutamide (HR: 0.39, 95% CI: 0.25-0.61) as compared to the ADT alone. Similar to the indirect comparison of OS, abiraterone outperformed docetaxel (HR: 1.66, 95% CI: 1.12-2.47), docetaxel with zoledronic acid (HR: 1.69, 95% CI: 1.06-2.68), and enzalutamide (HR: 1.06, 95% CI: 0.63-1.80), but not apalutamide in terms of impact on the FFS. Conclusion: Overall, abiraterone demonstrated better OS and FFS outcomes as compared to all the other combination strategies in this NMA.

Diagnostic accuracy of vesical imaging-reporting and data system (VI-RADS) in suspected muscle invasive bladder cancer: A systematic review and diagnostic meta-analysis.

OBJECTIVE: To investigate the accuracy of Vesical Imaging-Reporting and Data System (VI-RADS) in detection of muscle-invasive bladder cancer (MIBC) we performed a systematic review and meta-analysis of the available literature. MATERIALS AND METHODS: Scopus, Web of Science, PubMed, and EMBASE were searched up to 8 March 2021 for the studies evaluating the diagnostic performance of VI-RADS for the detection of MIBC. Inclusion criteria were patients with bladder cancer; index test of VI-RADS based on multiparametric MRI; reference test of histopathological findings from TURBT, re-TURBT, or cystectomy and study design of cohort. Case reports, review articles, and editorials were eliminated, as well as studies with insufficient knowledge to acquire TP, FP, FN, and TN values of VI-RADS. The MIDAS module of STATA was for statistical analysis. The heterogeneity was explored using subgroup analysis and meta-regression analysis. RESULTS: Overall, 22 eligible studies, consisting of 2,576 participants and 5,414 MRI reports, were included in this meta-analysis. The area under curve (AUC) of VI-RADS at cut-point values of 3 and 4 were 0.93 (95%CI: 0.91, 0.95), 0.93 (95%CI: 0.90, 0.95), respectively. Based on Youden's J statistic, the optimal VI-RADS cutoff value for predicting MIBC was determined as 3 which granted a pooled sensitivity of 89% (95%CI: 87%, 91%; I2=48%) and a specificity of 84% (95%CI: 80%, 87%; I2=90%). Based on meta-regression, the sources of inter-study heterogeneity for VI-RADS ≥ 3 were the sample size > 70, study design, single-center vs multi-center, patient population characteristics (i.e., gender, age), reference standard, histology, magnetic strength, T2WI slice thickness, and the number of radiologists reporting the MRI results (P value ≤ 0.01). CONCLUSION: The VI-RADS demonstrates consistently high diagnostic accuracy to predict MIBC. This scoring system could be applied in standard staging MRI reports of bladder cancer and can be incorporated into future MIBC work up guidelines.

Pathology grade influences competing mortality risks in elderly men with prostate cancer.

BACKGROUND: Recent guidelines recommend active management of prostate cancer (CaP), especially high-risk disease, in elderly men. However, descriptive data from a large cohort with extended follow up on the risk of death from CaP in men diagnosed over 70 years of age and its relationship to Gleason score (GS) and serum prostate specific antigen (PSA) level is lacking. Using the Surveillance, Epidemiology, and End Results database, we evaluated the influence of GS and serum PSA levels on the risks of mortality from PC (PCM) and mortality from other causes in localized (LPC) and metastatic (MPC) disease in elderly population. METHODS: Men diagnosed with PC over 70 years of age between 2004 and 2016 were divided into LPC and MPC groups, categorized by age: 70-74, 75-79, 80-84, 85-89, and ≥90 years and stratified by GS <7, 7, and >7, and serum PSA level <4, 4-10, 10-20, 20-50, and >50 ng/mL. Competing risk estimates for PCM and mortality from other causes were generated for both groups. RESULTS: Of the 85,649 men, 85.5 % were LPC at diagnosis. Overall, at a median follow up of 4 years, 15% of the men had died including a third from PC. While <15% of men with GS ≤7 died from PC, the PCM was >30% in men with GS >7 in LPC group, which accounted for almost half of total deaths for age 70-84 years. The GS >7 was also significantly associated with PCM in men with MPC. Furthermore, PCM directly correlated with serum PSA levels, with mortality rates reaching up to 50% and 70% for PSA >50 ng/dl for LPC and MPC, respectively. CONCLUSIONS: There is a substantial risk of dying in men diagnosed with LPC over 70 years of age with GS >7 or a serum PSA >20 ng/mL. Furthermore, the risk for death for MPC directly correlated with GS with PCM increasing from 10%-30% for GS ≤7 to >50% for GS >7. The data, in conjunction with other clinical parameters such as comorbidities could be used to counsel elderly men on management options of PC for both localized and metastatic PC.

An Indirect Comparison of Newer Minimally Invasive Treatments for Benign Prostatic Hyperplasia: A Network Meta-Analysis Model.

Objective: This study was designed to provide an indirect comparison of the urinary and sexual domain outcomes and complications after newer minimally invasive surgical therapy (MIST) of Aquablation, Rezum, and UroLift for benign prostatic hyperplasia (BPH) for transurethral resection of prostate (TURP). Methods: We searched Embase, Medline, and Cochrane in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, in December 2019. Only randomized clinical trials (RCTs) that reported outcomes after treatment of BPH for prostate less than 80 g with Aquablation, Rezum, or UroLift were included in the analysis. Results: A total of four RCTs reporting the outcomes after treatment with newer MIST for BPH were identified. Patients undergoing the resective procedures, that is, TURP and Aquablation, had greater improvement in urinary domain outcomes: International Prostate Symptom Score, quality of life, peak flow rate, and postvoiding residual compared to patients undergoing nonresective procedures: UroLift and Rezum. Patients in UroLift group maintained a higher sexual function domain score compared to TURP, but not Aquablation. Our multiple comparison analysis did not reveal a significant difference in urinary and sexual domain scores between patients undergoing UroLift and Rezum at 24 months of follow-up. Conclusions: Aquablation and TURP necessitate general or regional anesthesia and both produced significantly better urinary domain scores compared to Rezum and UroLift. On the other hand, UroLift demonstrated better sexual function domain scores compared to TURP, but not Aquablation. There was no significant difference in urinary domain scores between UroLift and Rezum at 24 months of follow-up.

Intracorporeal versus extracorporeal urinary diversion following robot-assisted radical cystectomy: a meta-analysis, cumulative analysis, and systematic review.

Over the last decade, the increased utilization of robot-assisted radical cystectomy (RARC) in the surgical treatment of muscle-invasive bladder cancer has led to an uptrend in intracorporeal urinary diversions (ICUD). However, the operative results comparing ICUD to extracorporeal urinary diversion (ECUD) have varied widely. We performed a meta-analysis to analyze perioperative outcomes and complications of ICUD compared to ECUD following RARC. This study is registered at International Prospective Register of Systematic Reviews (PROSPERO) CRD42020164074. A systematic literature review was conducted using PubMed, EMBASE, and Cochrane databases in August 2019. A total of six studies comparing ICUD vs ECUD were identified and meta-analysis was conducted on these studies. In addition, a cumulative analysis was also performed on 83 studies that reported perioperative outcomes after RARC and ICUD or ECUD. The Weighed Mean Difference of operative time and blood loss between ICUD and ECUD group was (16; 95% confidence interval - 34 to 66) and (- 86; 95% confidence interval - 124 to - 48), respectively. ICUD and ECUD had comparable early (30-day) and mid-term (30-90-day) complication rate (RR 1.19; 95% confidence interval 0.71-2.0; p = 0.5) and (RR 0.91; 95% confidence interval 0.71-1.15 p = 0.4) respectively. In the 83 studies that were included in the cumulative analysis, the mean operative time for ileal conduit and neobladders by ICUD were 307 and 428 min, respectively, compared to ECUD 428 and 426 min, respectively. ICUD and ECUD have comparable short- and mid-term complication rate. The ICUD group has lower blood loss and lower rate of blood transfusion compared to ECUD.

Comparative efficacy of apalutamide darolutamide and enzalutamide for treatment of non-metastatic castrate-resistant prostate cancer: A systematic review and network meta-analysis.

INTRODUCTION: Studies using apalutamide, enzalutamide, or darolutamide have shown improved metastasis free survival (MFS) rates, leaving clinicians with a dilemma of choosing one over the other, for nonmetastatic castration recurrent prostate cancer (nmCRPC). We performed a network meta-analysis to provide an indirect comparison of oncologic outcomes and adverse events (AEs) of these medications. MATERIAL AND METHODS: We searched PubMed, MEDLINE, and SCOPUS databases, for studies reporting apalutamide, enzalutamide, or darolutamide until January 25, 2020. Results were input into an EndNote library, and data were extracted into a predefined template. Progression free survival (PFS) was defined as radiologic progression or death. Network meta-analysis was done using R and meta-analysis was performed with RevMan v. 5. Surface under the cumulative ranking (SUCRA) value was used to provide rank probabilities. RESULTS: We found 3 studies reporting results for apalutamide, enzalutamide, and darolutamide. MFS was significantly lower in patients receiving darolutamide compared to both apalutamide (hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.55-0.97) and enzalutamide (HR: 0.71, 95% CI: 0.54-0.93). MFS was similar for enzalutamide and apalutamide (HR: 0.97, 95% CI: 0.73-1.28). In PFS, apalutamide showed a slightly higher rate compared to darolutamide (HR: 0.76, 95% CI: 0.59-0.99). There was no difference in overall survival (OS) between any of the medications. There was no statistically significant difference in AEs profile of the 3 medications. However, darolutamide had the highest SUCRA value and probability of being the most preferred medication based on AEs profile. CONCLUSION: Enzalutamide and apalutamide had similar and higher MFS rate in indirect comparison with darolutamide. In cases where AEs are concerning, darolutamide might be the preferred agent.

A Systematic Review and Meta-Analysis of Methods Used to Reduce Infectious Complications Following Transrectal Prostate Biopsy.

We reviewed and analyzed the most effective methods to reduce infectious complications (IC) after transrectal prostate biopsy (TRPB). We included only prospective randomized-controlled trials in the analysis. The analysis neither demonstrated any superiority of fluoroquinolones over other antibiotic classes nor of targeted antibiotics over empiric regimens in men undergoing TRPB. However, longer course antibiotics (3 days or more) compared to single dose or day regimens, combination of fluoroquinolones with aminoglycosides compared to fluoroquinolones alone and povidone-iodine rectal cleansing compared to control significantly reduced IC following TRPB. A combination of addition of aminoglycosides to oral antibiotics for 3 days along with povidone-iodine rectal cleansing may be an optimum strategy to minimize the risk of IC after TRPB.

Meta-analysis and systematic review of intermediate-term follow-up of prostatic urethral lift for benign prostatic hyperplasia.

BACKGROUND: Prostatic urethral lift (PUL), is a relatively new minimally invasive procedure for treatment of benign prostatic hyperplasia (BPH).This article is a systematic review and meta-analysis of all the articles published including follow-up of at least 24 months to analyze sustainability of results. METHODS: We performed a critical review in according to the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. From a total 768 published articles that matched our search terms, 5 studies with minimum follow-up of 24 months were selected for comparison and data analyzed in terms of baseline characteristics, functional, and sexual health outcomes. RESULTS: Included in the analyses are five studies with a minimum follow-up of 24 months. A total of 386 patients underwent PUL and 322 patients (83.4%) are available for follow-up at 24 months. The randomized studies are grouped as group A and non-randomized studies as group B. At 24 months, the mean reduction in International Prostate Symptom Score (IPSS) from baseline was 9.1 in group A and 10.4 in group B. The mean improvement in peak flow rate (Qmax) was 3.7 mL/s in group A and 3 mL/s in group B, and quality of life (QoL) improved by 2.2 in both groups. CONCLUSION: PUL is a well-tolerated, minimally invasive therapy for BPH that provides favorable and durable symptomatic, sexual health, and functional outcomes up to 24 months. Longer follow-up and randomized studies comparing to current standards are required to further confirm the long-term sustainability of PUL.

Comparison of Outcome of Percutaneous Nephrolithotomy in Adult Versus Paediatric Patients.

OBJECTIVE: To compare the outcome of percutaneous nephrolithotomy (PCNL) in terms of operative time, hospital stay, stone clearance, and postoperative complications in adult versus paediatric patients. STUDY DESIGN: Descriptive case series. PLACE AND DURATION OF STUDY: Shifa International Hospital, Islamabad, from January 2010 to December 2013. METHODOLOGY: Aretrospective analysis of 155 patients who underwent PCNL from January 2010 to December 2013. The patients were divided into 2 groups: patients aged ≤12 years were included in paedriatic group (A) while patients aged > 12 years were included in adult group (B). The patients were analyzed for age, gender, stone size, operative time, stone clearance, hospital stay, and peroperative and postoperative complications. Data was collected by chart review on specified proforma. RESULTS: One hundred and twenty-nine (129) patients including 44 (34.10%) females and 85 (65.89%) males with a mean age of 45.00 ±1.44 years were adults. Twenty-six palrents with mean age of 9.21 ±5.70 years, 17 (65.4%) males and 9 (34.6%) females, were included in the paedriatic group. Mean stone size was 2.12 ±1.01 cm in paedriatic group compared to 2.52 ±0.77 cm in adult group (p = 0.023). Mean operative time in paedriatic group was 158.8 ±39.63 minutes compared to 119.34 ±37.06 minutes in adult group (p < 0.001). Mean hospital stay in paedriatic group was 2.76 ±1.14 days compared to 3.12 ±1.27 days in adult group (p=0.1881). Peroperative stone clearance was in paedriatic group was 93.28 ±9.23% compared to 90.81 ±12.23% in adult groups (p = 0.331). One patient in the adult group developed urosepsis. CONCLUSION: There was no significant difference in outcome of percutaneous nephrolithotomy in terms of hospital stay, stone clearance, and postoperative complications in adult versus paediatric patients. Operative time was significantly shorter in adult cases compared to paedriatic cases.

Effect of body mass index on operative time, hospital stay, stone clearance, postoperative complications, and postoperative analgesic requirement in patients undergoing percutaneous nephrolithotomy.

OBJECTIVE: To compare the effect of body mass index (BMI) on operative time, hospital stay, stone clearance, postoperative complications, and postoperative analgesic requirement in patients undergoing percutaneous nephrolithotomy (PCNL) by comparing three BMI groups. MATERIAL AND METHODS: This is a retrospective analysis of 129 patients who underwent PCNL from January 2010 to August 2013. All the patients underwent PCNL by a standard technique. The patients were divided into three groups: patients having a BMI ≤24 kg/m(2) were included in the normal group, those having a BMI of 24.1-30.0 kg/m(2) were included in the overweight group, and those having a BMI >30 kg/m(2) were included in the obese group. Three groups were compared for operative time, hospital stay, stone clearance, postoperative complications, and postoperative analgesic requirement. RESULTS: A total of 129 patients including 44 females and 85 males were included with a mean age of 45.00±1.44 years. The mean age in the normal group was 43.29±1.69 years, 47.08±1.29 years in the overweight group, and 43.61±1.25 years in the obese group. The mean stone size in the normal group was 25.46±8.92 mm, 28.01±8.40 mm in the overweight group, and 26.84±7.41 mm in the obese group. Our results showed no statistically significant difference with respect to mean operative time, mean hospital stay, and stone clearance in the normal, obese, and overweight patients undergoing PCNL. Postoperative complications and analgesia requirement were also similar in all the three groups. CONCLUSION: There was no effect of BMI on operative time, hospital stay, stone clearance, postoperative complications, and postoperative analgesic requirement in patients undergoing PCNL. PCNL is a safe and effective procedure for the removal of renal stones in obese patients.