Benjamin T. Ristau

Upper Tract Urothelial Carcinoma: Current Treatment and Outcomes

The reference standard treatment of upper tract urothelial carcinoma is open radical nephroureterectomy. Many centers have advocated less-invasive treatment modalities. We reviewed contemporary treatments of upper tract urothelial carcinoma and their outcomes. A MEDLINE search was conducted for all relevant published data during the past 15 years. Endoscopic management is feasible for low-grade disease with strict surveillance protocols. Radical nephroureterectomy remains the reference standard for upper tract urothelial carcinoma. The intermediate-term oncologic outcomes are similar between the laparoscopic and open approaches. Controversies still exist regarding the optimal management of the distal ureter, the utility of topical therapy, and the role of lymphadenectomy.

Obesity Is Not Associated With Aggressive Pathologic Features or Biochemical Recurrence After Radical Prostatectomy

OBJECTIVE To determine whether obesity is associated with adverse pathologic characteristics, positive surgical margins, greater biochemical recurrence rates, and interval to death after primary treatment with radical prostatectomy (RP). MATERIALS AND METHODS A 12-year, retrospective, single-institution analysis of patients treated with RP was performed. Patients were categorized by their body mass index (BMI) as normal weight (n = 533), overweight (n = 1342), obese (n = 603), and morbidly obese (n = 22). The associations among the BMI, clinicopathologic characteristics, and biochemical recurrence rates were assessed. RESULTS After adjusting for multiple clinical preoperative characteristics, the BMI category was not associated with positive surgical margins (P = .66), organ-confined disease (P = .10), Gleason score (P = .22), extracapsular extension (P = .09), seminal vesicle invasion (P = .15), percentage of cancer in the prostate gland (P = .67), largest tumor nodule (P = .13), or lymph node metastasis (P = .39). Gleason score 4+3 (P <.001), Gleason score 9 and 10 (P <.001), and an increasing prostate-specific antigen level (P <.001) were associated with biochemical recurrence. At a mean overall follow-up of 55.6 months, 276 patients (11.0%) had developed biochemical recurrence (normal weight 11.3%, overweight 10.5%, obese 12.3%, and morbid obesity 4.5%). After multivariate adjustment for age, ethnicity, risk group, clinical stage, Gleason score, preoperative prostate-specific antigen level, and year of surgery, no association was found between the BMI and biochemical recurrence (P = .87). CONCLUSION In men undergoing RP for clinically localized prostate adenocarcinoma, obesity was not associated with adverse pathologic features, positive surgical margins, or biochemical recurrence. These data provide evidence that obese men undergoing RP are not more likely to have aggressive prostate cancer.

Botulinum Toxin Therapy for Neurogenic Detrusor Overactivity

Detrusor injection of botulinum toxin (BTX) has shown great promise in the treatment of neurogenic detrusor overactivity (NDO) refractory to conservative therapy. Despite a paucity of prospective evidence, there exists a growing consensus that BTX injection therapy is a well-tolerated, low-risk therapy. Injections result in substantial subjective improvement in continence and quality of life. Moreover, assessment of urodynamic parameters demonstrates objective changes: (1) an increase in maximum cystometric capacity; (2) when applicable, a reduction in maximal detrusor voiding pressures; and (3) an increase in bladder compliance in cases where baseline bladder compliance measures were abnormal. While BTX bladder injection offers both objective and subjective measures of incontinence control, treatment duration is limited by the gradual reinnervation of injected tissue over an approximately 6- to 9-month interval. However, repeat injection cycles do appear to achieve similar levels of efficacy. The objective of this review is to provide a focused summary of the current body of literature, investigating the safety and efficacy of bladder BTX injection in patients with NDO.

Contemporary use trends and survival outcomes in patients undergoing radical cystectomy or bladder‐preservation therapy for muscle‐invasive bladder cancer

The current study was performed to examine temporal trends and compare overall survival (OS) in patients undergoing radical cystectomy (RC) or bladder‐preservation therapy (BPT) for muscle‐invasive urothelial carcinoma of the bladder.

Prognostic implications of lymph node involvement in bladder cancer: are we understaging using current methods?

To review the current and newer, alternative methods for evaluating lymph nodes for tumor involvement in bladder cancer as relapse rates for organ‐confined disease remain high despite improvements in surgical technique, suggesting the possibility of understaging. To propose a research agenda based on these findings. A PubMed literature search was performed to identify studies examining the prognostic implications of and outcomes associated with lymph node involvement in bladder cancer as well as those that utilized newer methodologies to identify the possibility for metastatic disease. Lymph node involvement remains one of the strongest predictors of clinical outcome in bladder cancer. Histologic and molecular techniques for identification of lymph node metastasis provide a sensitivity and specificity equal to if not higher than standard pathologic evaluation. Further research into this field would help to elucidate the potential utility of these techniques with regard to proper staging and potential relevance to clinical outcomes.

Prospective Assessment of Radiation in Pediatric Urology: The Pediatric Urology Radiation Safety Evaluation Study

PURPOSE Pediatric tissues are exquisitely sensitive to ionizing radiation from diagnostic studies and therapies involving fluoroscopy. We prospectively monitored radiation exposure in our pediatric urology patients during fluoroscopy guided operative procedures with single point dosimeters to quantify radiation dose. MATERIALS AND METHODS Children undergoing fluoroscopy guided urological procedures were prospectively enrolled in the study from 2013 to 2015. Single point dosimeters were affixed to skin overlying the procedural site for the durations of the procedures to record dosimetry data. Patient demographics, procedural variables and fluoroscopic settings were recorded. RESULTS A total of 78 patients underwent 96 procedures, including retrograde pyelography, ureteral stent insertion, ureteroscopy and percutaneous nephrolithotomy. Median patient age was 12 years (range 0.3 to 17) and median body mass index percentile for age was 70.7 (1.0 to 99.1). Median skin entrance radiation dose for all procedures performed was 0.56 mGy. Median dosages associated with the 29 diagnostic procedures and 49 definitive interventions were 0.6 mGy (mean 0.8, range 0.1 to 2.2) and 0.7 mGy (1.1, 0.0 to 5.5), respectively. The dose associated with the 18 procedures of temporization was significantly higher by comparison (median 1.0 mGy, mean 2.6, range 0.1 to 10.7, p = 0.02). CONCLUSIONS Pediatric radiation exposure is not insignificant during urological procedures. Further multi-institutional work would provide context for our findings. Protocols to optimize fluoroscopic settings and minimize patient exposure, and guidelines for radiation based imaging should have a key role in all pediatric radiation safety initiatives.

The role of radical prostatectomy in high-risk localized, node-positive and metastatic prostate cancer

A lack of quality evidence comparing management strategies confounds complex treatment decisions for patients with high-risk prostate cancers. No randomized trial comparing surgery to radiation has been successfully completed. Despite inherent selection biases, however, observational and registry data suggest improved outcomes for patients initially managed with prostatectomy. As consensus shifts away from aggressive treatment for low-risk disease and toward multimodal treatment of locally advanced and metastatic disease, there is renewed interest in surgery for local control in patients presenting with high-risk localized, node-positive and minimally metastatic disease. The objective of this review is to examine the evidence evaluating clinical outcomes of patients with high-risk clinically localized, node-positive and metastatic prostate cancer treated with radical prostatectomy.

Retroperitoneal Lymphadenectomy for High Risk, Nonmetastatic Renal Cell Carcinoma: An Analysis of the ASSURE (ECOG-ACRIN 2805) Adjuvant Trial

Purpose Lymphadenectomy is a well established practice for many urological malignancies but its role in renal cell carcinoma is less clear. Our primary objective was to determine whether lymphadenectomy impacted survival in patients with fully resected, high risk renal cell carcinoma. Materials and Methods Patients with fully resected, high risk, nonmetastatic renal cell carcinoma were randomized to adjuvant sorafenib, sunitinib or placebo in the ASSURE (Adjuvant Sorafenib and Sunitinib for Unfavorable Renal Carcinoma) trial. Lymphadenectomy was performed for cN+ disease or at surgeon discretion. Patients treated with lymphadenectomy were compared to patients in the trial who did not undergo lymphadenectomy. The primary outcome was overall survival associated with lymphadenectomy. Secondary outcomes were disease free survival, factors associated with performing lymphadenectomy and surgical complications. Results Of the 1,943 patients in ASSURE 701 (36.1%) underwent lymphadenectomy, including all resectable patients with cN+ and 30.1% of those with cN0 disease. A median of 3 lymph nodes (IQR 1–8) were removed and the rate of pN+ disease in the lymphadenectomy group was 23.4%. There was no overall survival benefit for lymphadenectomy relative to no lymphadenectomy (HR 1.14, 95% CI 0.93–1.39, p = 0.20). In patients with pN+ disease who underwent lymphadenectomy no improvement in overall or disease‐free survival was observed for adjuvant therapy relative to placebo. Lymphadenectomy did not confer an increased risk of surgical complications (14.2% vs 13.4%, p = 0.63). Conclusions The benefit of lymphadenectomy in patients undergoing surgery for high risk renal cell carcinoma remains uncertain. Future strategies to answer this question should include a prospective trial in which patients with high risk renal cell carcinoma are randomized to specific lymphadenectomy templates.

Active Surveillance for Localized Renal Masses: Tumor Growth, Delayed Intervention Rates, and >5-yr Clinical Outcomes

BACKGROUND Active surveillance (AS) has gained acceptance as a management strategy for localized renal masses. OBJECTIVE To review our large single-center experience with AS. DESIGN, SETTING, AND PARTICIPANTS From 2000 to 2016, we identified 457 patients with 544 lesions managed with AS from our prospectively maintained kidney cancer database. A subset analysis was performed for patients with ≥5-yr follow-up without delayed intervention (DI). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Linear growth rates (LGRs) were estimated using linear regression for the initial LGR (iLGR) AS interval and the entire AS period. Overall survival (OS) and cumulative incidence of DI were estimated with Kaplan-Meier methods utilizing iLGR groups, adjusting for covariates. DI was evaluated for association with OS in Cox models. RESULTS AND LIMITATIONS Median follow-up was 67 mo (interquartile range [IQR] 41-94 mo) for surviving patients. Cumulative incidence of DI (n=153) after 1, 2, 3, 4, and 5 yr was 9%, 22%, 29%, 35%, and 42%, respectively. Median initial maximum tumor dimension was 2.1cm (IQR 1.5-3.1cm). Median iLGR and overall LGR were 1.9 (IQR 0-7) and 1.9 (IQR 0.3-4.2) mm/yr, respectively. Compared with the no growth group, low iLGR (hazard ratio [HR] 1.25, 95% cumulative incidence [CI] 0.82-1.91), moderate iLGR (HR 2.1, 95% CI 1.31-3.36), and high iLGR (HR 1.87, 95% CI 1.23-2.84) were associated with DI (p=0.003). The iLGR was not associated with OS (p=0.8). DI was not associated with OS (HR 1.34, 95% CI 0.79-2.29, p=0.3). Five-year cancer-specific mortality (CSM) was 1.2% (95% CI 0.4-2.8%). Of 99 patients on AS without DI for >5 yr, one patient metastasized. CONCLUSIONS At >5 yr, AS±DI is a successful strategy in carefully managed patients. DI often occurs in the first 2-3 yr, becoming less likely over time. Rare metastasis and low CSM rates should reassure physicians that AS is safe in the intermediate to long term. PATIENT SUMMARY In this report, we looked at the outcomes of patients with kidney masses who elected to enroll in active surveillance rather than immediate surgery. We found that patients who need surgery are often identified early and those who remain on active surveillance become less likely to need surgery over time. We concluded that active surveillance with or without delayed surgery is a safe practice and that, when properly managed and followed, patients are unlikely to metastasize or die from kidney cancer.

Active Surveillance for the Small Renal Mass: Growth Kinetics and Oncologic Outcomes

Active surveillance for small renal masses (SRMs) is an accepted management strategy for patients with prohibitive surgical risk. Emerging prospectively collected data support the concept that a period of initial active surveillance in an adherent patient population with well-defined criteria for delayed intervention is safe. This article summarizes the literature describing growth kinetics of SRMs managed initially with observation and oncologic outcomes for patients managed with active surveillance. Existing clinical tools to determine and contextualize competing risks to mortality are explored. Finally, current prospective clinical trials with defined eligibility criteria, surveillance schema, and triggers for delayed intervention are highlighted.