Optimum threshold of the 4Kscore for biopsy in men with negative or indeterminate multiparametric magnetic resonance imaging.

Objective: The study aims to identify the optimal 4Kscore thresholds to determine the need for a prostate biopsy when multiparametric magnetic resonance imaging (MRI) (mpMRI) is negative or indeterminate. Materials and methods: We analysed retrospective data from men in eight different institutions who underwent an mpMRI, 4Kscore and prostate biopsy for evaluation of prostate cancer. We selected men with a negative (PIRADS ≤2) or indeterminate (PIRADS 3) mpMRI. 4Kscore values were categorized into ranges of 1-7, 8-19, 20-32 and greater than 32. We evaluated the proportion of men with grade group 2 or higher (GG2+) cancer in groups defined by PIRADS and 4Kscore. We also evaluated the number of biopsies avoided and GG2+ cancer missed in each group reported depend on 4Kscore cutoff points. Results: Among 1111 men who had an mpMRI, 4Kscore and biopsy, 625 of them had PIRADS ≤3 on mpMRI: 374 negative (PIRADS ≤2) and 251 indeterminate (PIRADS 3). In men with a negative mpMRI, we found a 4Kscore cut-point of 33 resulted in an increased risk of GG2+ cancer on biopsy. In patients with an equivocal lesion on mpMRI, men with a 4Kscore cutoff ≥8 had a greater risk of GG2+ cancer on biopsy. Decision curve analysis supported the proposed cut-points in each mpMRI group. Conclusions: In men with negative and indeterminate mpMRI, we found the best 4Kscore threshold to determine the need for biopsy to be 33 and 8 respectively. Future prospective studies in independent populations are needed to confirm these findings.

The Evolution of Systemic Therapy in Metastatic Renal Cell Carcinoma.

The treatment landscape for renal cell carcinoma (RCC) is a dynamic process that has seen considerable change in recent years. We have seen a rebirth of original breakthroughs with immune checkpoint inhibitors showing promise in patients with treatment-refractory disease. The optimal sequencing of treatments and incorporation of novel therapeutics are actively being investigated and have yet to be determined. The clinical challenges of this evolving treatment paradigm can be attributed to cost considerations, toxicity, and defining endpoints in the management of advanced RCC. As novel therapeutics emerge, finding the optimal treatment regimen for patients will have an increasing focus on patient-centered outcomes and improvement in quality of life in addition to improving survival.

Predicting Renal Parenchymal Loss after Nephron Sparing Surgery.

PURPOSE: We analyze the relationship among various patient, operative and tumor characteristics to determine which factors correlate with renal parenchymal volume loss after nephron sparing surgery using a novel 3-dimensional volume assessment. MATERIALS AND METHODS: We conducted a retrospective review of an institutional database of patients who underwent nephron sparing surgery from 1992 to 2014 for a localized renal mass. Tumors were classified according to the R.E.N.A.L. nephrometry system. Using 3-dimensional reconstruction imaging software, preoperative and postoperative renal parenchymal volume was calculated for the ipsilateral and contralateral kidney. RESULTS: A total of 158 patients were analyzed. Mean patient age was 58.7 years and mean followup was 40.1 months. Mean preoperative tumor volume was 34.0 cc and mean tumor dimension was 3.4 cm. Mean R.E.N.A.L. nephrometry score was 6.2, with 60.1%, 34.2% and 5.7% of tumors classified as low, medium and high complexity, respectively. Mean change in renal parenchymal volume after nephron sparing surgery was -15.3% for the ipsilateral kidney and -6.8% for total kidney volume. On univariate analysis ischemia time, tumor size, R.E.N.A.L. nephrometry score, complexity grouping and the individual nephrometry components of tumor size, percent exophytic, anterior/posterior, depth and tumor proximity to the renal artery or vein were associated with greater renal parenchymal volume loss. On multivariate analysis only ischemia time, tumor size, posterior location and percent exophytic were independently associated with more renal parenchymal volume loss. CONCLUSIONS: Using precise 3-dimensional volumetric analysis we found that ischemia time, tumor size and endophytic/exophytic properties of a localized renal mass are the most important determinants of renal parenchymal volume loss.

Does Pressure Regulating Balloon Location Make a Difference in Functional Outcomes of Artificial Urinary Sphincter?

PURPOSE: We compared functional outcomes in patients who received an artificial urinary sphincter in the space of Retzius vs the same device placed at a high submuscular location. MATERIALS AND METHODS: We reviewed a prospectively maintained database of patients who received an artificial urinary sphincter between July 2007 and December 2014. After cuff placement was completed via a perineal incision, a 61 to 70 cm H2O pressure regulating balloon was placed through a separate high scrotal incision in the space of Retzius or in a high submuscular tunnel. Demographics, perioperative comorbidities and functional outcomes were compared between the groups. RESULTS: A total of 294 consecutive patients underwent artificial urinary sphincter placement. Mean followup was 23 months. Space of Retzius and high submuscular placement was performed in 140 (48%) and 154 patients (52%), respectively. Functional outcomes were similar between the groups, including the continence rate (defined as 0 or 1 pad daily) in 81% vs 88% (p = 0.11), the erosion rate in 9% vs 8% (p = 0.66) and the explantation rate in 10% vs 11% (p = 0.62). Artificial urinary sphincter revision for persistent incontinence was required in a similar proportion of the 2 groups (13% vs 8%, p = 0.16) with a comparable mean followup (24 vs 23 months, p = 0.30). Kaplan-Meier analysis revealed no difference between the groups in the rate of explantation (p = 0.70) or revision (p = 0.06). CONCLUSIONS: High submuscular placement of a pressure regulating balloon at artificial urinary sphincter surgery is a safe, effective alternative with functional outcomes equivalent to those of traditional placement in the space of Retzius.

Comparison of Renal Parenchymal Volume Preservation Between Partial Nephrectomy, Cryoablation, and Radiofrequency Ablation Using 3D Volume Measurements.

PURPOSE: Small renal masses (SRM) can be managed via a variety of nephron-sparing procedures (NSPs), but the association between choice of NSP and renal parenchymal volume (RPV) preservation is not well understood. We sought to examine RPV preservation after partial nephrectomy (PN) performed via open, robotic, or laparoscopic approaches and thermal ablation (TA) performed via cryoablation (CA) or radiofrequency ablation (RFA). PATIENTS AND METHODS: The study was a retrospective review of three institutional databases of patients with a SRM <4 cm treated via one of the five NSPs (open PN, laparoscopic PN, robotic PN, percutaneous CA, or percutaneous RFA). The 30 most recent consecutive cases treated via each NSP were selected to obtain a total of 150 cases for analysis. Patient characteristics were obtained via manual chart review, and tumor characteristics were assessed via the R.E.N.A.L. nephrometry score. Using three-dimensional rendering software, preoperative and postoperative RPV was calculated for the tumor-bearing kidney, excluding the tumor itself (for preoperative images) or the postsurgical/ablative defect (for postoperative images). The percent change in RPV was compared between the procedure types. RESULTS: One hundred fifty cases were included in the final analysis, with 30 cases from each NSP category. While preoperative tumors were larger in the PN group, there was no difference in the mean nephrometry score between groups. The TA group was found to have a lower mean RPV loss (-8.1% vs -16.5%, p<0.005). There was no difference in the RPV loss between modalities of TA (CA vs RFA) or between approaches to PN (open, laparoscopic, robotic). Matched-pair analysis based on the tumor size and multivariate analysis indicated TA vs PN was independently associated with less RPV loss. CONCLUSIONS: TA is associated with less RPV loss than PN in the management of SRM, but there is no difference between modalities of TA (CA vs RFA) or between approaches to PN.

Emerging therapies in castration resistant prostate cancer.

INTRODUCTION: Prostate cancer continues to be the second leading cause of cancer related mortality in men within the United States. Despite a consistent decline in prostate cancer mortality over the past two decades, the prognosis for men with metastatic prostate cancer remains poor with no curative therapies. In this article, we review the recently approved and emerging therapeutics for patients with castrate resistant prostate cancer. MATERIALS AND METHODS: An advanced search was conducted on the clinicaltrials.gov database, using search terms "metastatic prostate cancer", and limiting results to phase II-IV clinical trials. Clinically relevant emerging therapeutics were selected and a Medline search for supporting documents was performed. An emphasis was placed on newly approved and promising new therapeutics. RESULTS: A total of four Food and Drug Administration approved medications and eight investigational agents were chosen for review. The background and role of these therapeutics in the treatment of prostate cancer treatment is discussed. CONCLUSIONS: The past few years have yielded a near exponential increase in treatments for metastatic prostate cancer, many of which have a unique mechanism of action. The estimated median survival for patients with metastatic prostate cancer remains dynamic as we begin to integrate these therapeutics into clinical practice and determine the optimal sequence and timing of treatment.

Emerging drugs for prostate cancer.

INTRODUCTION: Androgen deprivation therapy is the mainstay treatment for patients with prostate cancer who are not candidates for definitive treatment, are diagnosed with advanced disease on initial presentation or progress after primary treatment. Patients who stop responding to androgen deprivation therapy develop castration resistant prostate cancer (CRPC). Emerging drugs undergoing clinical evaluation and drugs that have recently received FDA approval for the treatment of CRPC are reviewed. AREAS COVERED: As the natural history and signaling pathways of prostate cancer are better understood, new treatments and targeted therapies will be developed. The FDA recently approved 5 medications that increase survival in patients with CRPC. Additional medications and drug classes are being explored that may eventually lead to new treatment options. Articles were identified using a PubMed database search. EXPERT OPINION: Recent FDA medication approvals and the development of emerging treatments are promising for the future of patients with prostate cancer. The addition of new medications challenges physicians to identify the optimal sequence and/or combination in which newer and older medications should be administered. Physicians treating patients with prostate cancer have a growing responsibility to keep pace with these new medications so that they may counsel and treat patients appropriately.

The role of systemic chemotherapy in management of upper tract urothelial cancer.

Upper tract urothelial cancer (UTUC) accounts for roughly 5 % of all urothelial cancers. At presentation, 30 % of patients demonstrate invasive and/or locally advanced disease, 30-40 % have regional lymph node involvement, and 20 % harbor metastatic disease. Systemic recurrence and progression rates after surgery for patients with advanced disease range between 45-60 %. Five-year cancer specific survival rates for pT2 and pT3 tumors are 73 % and 40 %, respectively. Median survival for patients with pT4 disease is approximately 6 months. Nonetheless, there is a lack of improvement in the rates of systemic recurrence and progression in patients with advanced UTUC. Extrapolating evidence obtained from experience with multi-modal therapy of patients with urothelial bladder cancer, additional improvements in oncological outcomes for patients with UTUC can be achieved through integration of effective systemic chemotherapy with local tumor control. We provide an overview of the rationale and utilization strategies of peri-operative systemic chemotherapy in patients with UTUC.