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.

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.

A Rare Case of Prolapsed Ureterocele With Large Redundant Flap After Unroofing in Adult Female.

We present a case of 26-year female who presented with acute urinary retention and vulvar mass. She denies any urinary complaints in the past except for occasional straining for voiding. Imaging revealed a prolapsed ureterocele, it was successfully managed with incision and excising a flap of ureterocele due to the risk of postoperative protrusion of the redundant ureterocele. On follow-up at 6 months she was voiding well without any complaints.

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.

Combination Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-analysis.

INTRODUCTION: Randomized clinical trials have shown combination therapy to be superior in progression-free survival (PFS) rates when compared with sunitinib alone. However, there have been no direct comparisons among the combination strategies making it unclear as to which may be the preferred option. We performed a network meta-analysis of the combination therapy (immune checkpoint inhibitor plus axitinib or bevacizumab) used in metastatic renal cell carcinoma (mRCC) and provided a rank order preference based on PFS, and adverse events (AEs). MATERIALS AND METHODS: A systematic search on the treatment of mRCC using combination therapy till July 2019 was done. Studies reporting on combination therapies with immune checkpoint inhibitor plus axitinib or bevacizumab for mRCC were selected. Frequentist method was used for rank order generation. RESULTS: A total of 3 studies consisting of 2672 patients were selected. All combination therapies demonstrated improved PFS when compared with sunitinib alone. The rank order for PFS showed combination of pembrolizumab plus axitinib had the highest probability of favorability followed by avelumab plus axitinib and atezolizumab plus bevacizumab (surface under the cumulative ranking 0.9, 0.7, and 0.4, respectively). For AEs, pembrolizumab plus axitinib had the least AEs ≥grade 3, followed by avelumab plus axitinib and atezolizumab plus bevacizumab (surface under the cumulative ranking 0, 0.5, 1.0). CONCLUSIONS: This network meta-analysis demonstrates that combination of pembrolizumab plus axitinib may be the preferred option based on efficacy and side effect profile compared with avelumab plus axitinib or atezolizumab plus bevacizumab. However, all the 3 combination strategies were superior to sunitinib alone in improving PFS in patients with mRCC.

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.