Impact of Weight Management on Obesity-Driven Biomarkers of Prostate Cancer Progression.

PURPOSE: Excess body and visceral fat increase the risk of death from prostate cancer (PCa). This phase II study aimed to test whether weight reduction by > 5% total body weight counteracts obesity-driven PCa biomarkers. MATERIALS AND METHODS: Forty men scheduled for prostatectomy were randomized into intervention (n = 20) or control (n = 20) arms. Intervention participants followed a weight management program for 4 to 16 weeks before and 6 months after surgery. Control participants received standardized educational materials. All participants attended visits at baseline, 1 week before surgery, and 6 months after surgery. Circulating immune cells, cytokines, and chemokines were evaluated. Weight loss, body composition/distribution, quality of life, and nutrition literacy were assessed. Prostate tissue samples obtained from biopsy and surgery were analyzed. RESULTS: From baseline to surgery (mean = 5 weeks), the intervention group achieved 5.5% of weight loss (95% CI, 4%-7%). Compared to the control, the intervention also reduced insulin, total cholesterol, LDL cholesterol, leptin, leptin:adiponectin ratio, and visceral adipose tissue. The intervention group had reduced c-peptide, plasminogen-activator-inhibitor-1, and T cell count from baseline to surgery. Myeloid-derived suppressor cells were not statistically different by group. Intervention group anthropometrics improved, including visceral and overall fat loss. No prostate tissue markers changed significantly. Quality of life measures of general and emotional health improved in the intervention group. The intervention group maintained or kept losing to a net loss of 11% initial body weight (95% CI, 8%-14%) at the study end. CONCLUSIONS: Our study demonstrated improvements in body composition, PCa biomarkers, and quality of life with a weight management intervention.

Expressions of glucose transporter genes are diversely attenuated and significantly associated with prostate cancer progression.

Prostate cancer is a health-threaten disease in men worldwide, however, lacking is the reliable biomarkers for patient management. Aberrant metabolic events including glucose metabolism are involved in prostate cancer progression. To examine the involvement of glucose metabolic pathways in prostate cancer, we analyzed the expression profiles of glucose transporter family genes using multiple RNA-seq datasets. Our results showed that three SLC2A family genes (SLC2A4/5/9) were significantly downregulated in primary prostate cancers compared to their benign compartments. These down-regulated expressions were inversely correlated with their gene promoter methylation and genome abnormalities. Among these three SLC2A genes, only SLC2A4 showed a significantly reverse correlation with all clinicopathological parameters, including TNM stage, disease relapse, Gleason score, disease-specific survival, and progression-free interval. In addition, the expression levels of these three genes were strongly correlated with anti-cancer immune cell filtration in primary prostate cancers. In a group of patients with early-onset prostate cancers, SLC2A4 also showed a strong negative correlation with multiple clinicopathological parameters, such as tumor mutation burden, biochemical relapse, pre-surgical PSA levels, and Gleason score but a positive correlation with progression-free interval after surgery. In metastatic castration-resistant prostate cancers (CRPC), SLC2A9 gene expression but not SLC2A4 or SLC2A5 genes showed a significant correlation with androgen receptor (AR) activity score and neuroendocrinal (NE) activity score. Meanwhile, SLC2A2/9/13 expression was significantly elevated in CRPC tumors with neuroendocrinal features compared to those without NE features. On the other hand, SLC2A10 and SlC2A12 gene expression were significantly reduced in NEPC tumors compared to CRPC tumors. Consistently, SLC2A10/12 expression levels were significantly reduced in castrated animals carrying the LuCaP35 xenograft models. Survival outcome analysis revealed that SLC2A4 expression in primary tumors is a favorable prognostic factor and SLC2A6 is a worse prognostic factor for disease-specific survival and progression-free survival in prostate cancer patients. In conclusion, our results suggest that SLC2A4/6 expressions are strong prognostic factors for prostate cancer progression and survival. The significance of SLC2A2/9/13 over-expression during NEPC progression needs more investigation.

Aberrant expression of multiple glycolytic enzyme genes is significantly associated with disease progression and survival outcomes in prostate cancers.

Prostate cancer is the leading cause of cancer death after lung cancer in men. Recent studies showed that aberrant metabolic pathways are involved in prostate cancer development and progression. In this study, we performed a systemic analysis of glycolytic enzyme gene expression using the TCGA-PRAD RNAseq dataset. Our analysis revealed that among 25 genes, only four genes (HK2/GPI/PFKL/PGAM5) were significantly upregulated while nine genes (HK1/GCK/PFKM/PFKP/ALDOC/PGK1/PGAM1/ENO2/PKM) were downregulated in primary prostate cancer tissues compared to benign compartments. Among these 13 altered genes, four genes (ENO2/ALDOC/GPI/GCK) exhibited strong diagnostic potential in distinguishing malignant and benign tissues. Meanwhile, GPI expression exerted as a prognostic factor of progression-free and disease-specific survival. PFKL and PGAM5 gene expressions were associated with AR signaling scores in castration-resistant patients, and AR-targeted therapy suppressed their expression. In LuCap35 xenograft tumors, PFKL and PGAM5 expression was significantly reduced after animal castration, confirming the AR dependency. Conversely, GCK/PKLR genes were significantly associated with neuroendocrinal progression, representing two novel neuroendocrinal biomarkers for prostate cancer. In conclusion, our results suggest that GPI expression is a strong prognostic factor for prostate cancer progression and survival while GCK/PKLR are two novel biomarkers of prostate cancer progression to neuroendocrinal status.

Preoperative Optimization of Promotility in Robotic Prostatectomy and Minimally Invasive Kidney Surgery.

INTRODUCTION: Patients are routinely discharged postoperative day 1 following minimally invasive surgery (MIS) for prostate cancer and kidney cancer. Delays in discharge are often related to gastrointestinal symptoms such as nausea, abdominal pain and vomiting; however, the role of baseline constipation in these symptoms and resultant delays in discharge is unclear. We conducted a prospective observational study to describe the incidence of baseline constipation among patients undergoing MIS prostate and kidney surgery, and its relationship to length of stay (LOS). METHODS: Consenting adult patients undergoing MIS procedures for kidney and prostate cancer completed constipation symptom questionnaires perioperatively. Clinicopathological data were collected prospectively. Delay in discharge, defined as LOS >2 days, was the primary outcome. Patients were stratified by the primary outcome and preoperative Patient Assessment of Constipation Symptoms (PAC-SYM) scores were compared. RESULTS: A total of 97 patients enrolled, of whom 29 underwent radical nephrectomy, 34 underwent robotic partial nephrectomy and 34 underwent robotic prostatectomy. Constipation symptoms were reported in 67/97 patients (69%). A total of 17/97 patients (18%) had a delay in discharge. Patients who discharged on time had a median PAC-SYM score of 2 (IQR 2-9) compared to 4 (IQR 0-7.5) for those with a delay (p=0.021). Patients who had a delay with gastrointestinal symptoms had a median PAC-SYM score of 5 (IQR 1.5-11.5, p=0.032). CONCLUSIONS: Seven out of 10 patients undergoing routine MIS procedures report constipation symptoms, which may represent a target for preoperative interventions to reduce LOS after surgery.

Cost Implications of Routine Preoperative Blood Typing and Crossmatching Prior to Robot-Assisted Laparoscopic Partial Nephrectomy.

INTRODUCTION: The surgical treatment of small renal masses has shifted from open to minimally invasive approaches. Preoperative blood typing and product orders often mirror the practices of the open era. We aim to define the rate of transfusion after robot-assisted partial laparoscopic nephrectomy (RAPN) at an academic medical center and the costs associated with current practice. METHODS: A retrospective review of an institutional database was utilized to identify patients who underwent RAPN and transfusion of blood products. Patient, tumor and operative variables were identified. RESULTS: From 2008 to 2021, 804 patients underwent RAPN, with 9 (1.1%) patients requiring a transfusion. Comparison of the transfused group with nontransfused patients yielded a significant difference in mean operative blood loss (527.8 ml vs 162.5 ml, p <0.0001), R.E.N.A.L. (for radius, exophytic/endophytic, nearness of tumor to collecting system, anterior/posterior, location relative to polar line) nephrometry score (7.1 vs 5.9, p <0.05), hemoglobin (11.3 gm/dl vs 13.9 gm/dl, p <0.05) and hematocrit (34.2% vs 41.4%, p <0.05). The variables associated with transfusion on univariate analysis were examined for predictive capacity using logistic regression. Operative blood loss (p <0.05), nephrometry score (p=0.05), hemoglobin (p <0.05) and hematocrit (p <0.05) remained associated with a transfusion. The hospital charge for blood typing and crossmatching was $1,320 USD per patient. CONCLUSIONS: With the maturity of RAPN techniques and outcomes, the extent of preoperative testing related to blood products should evolve to better reflect current procedural risks. Prioritizing testing resources for patients at increased complication risk can be based on predictive factors.

Intensive preoperative ostomy education for the radical cystectomy patient.

OBJECTIVES: Patients undergoing radical cystectomy with ileal conduit formation usually receive training on the use of their stoma during their initial hospitalization - while actively recovering from surgery - often with little follow-up or reinforcement. Many of these patients are not equipped to deal with these significant body changes, which can lead to additional clinic visits, stoma-related complications, and decreased patient satisfaction/health-related quality of life (HRQOL). In an effort to improve patient education, we sought to evaluate the feasibility of implementing a preoperative comprehensive stoma education session termed the "stoma bootcamp" for patients scheduled for a radical cystectomy and ileal conduit (RCIC). We tracked patient related outcomes to determine its impact. METHODS: We performed a longitudinal, quality-improvement feasibility study at the University of Kansas Health System. All patients who were scheduled to undergo a RCIC for bladder cancer were offered enrollment into the study at their preoperative clinic visit. The "stoma boot camp" consisted of a 3-hour group session within 2 weeks of the surgery date. Patients were given a short presentation by residents and advanced practice providers regarding the operation, recovery, and expectations for their post-operative care. Ostomy nurses then demonstrated basic urostomy care - pouching, sizing, emptying - along with trouble-shooting tips for common ostomy problems. Measurements of HRQOL questionnaires were completed at the initial visit, after "boot camp," and at defined time points after surgery for 12 weeks. This included using an ostomy adjustment score. Length of stay, unplanned stoma-related interventions, and re-admissions within 30 days were also tracked. RESULTS: In this initial pilot program, 51 patients participated in the stoma bootcamp. The patients had an average ostomy adjustment score (OAS) of 150.4 (95% CI 142.0, 158.8) at discharge from the hospital, and these high OAS levels persisted throughout the 12 weeks of follow-up data without any significant decline. Short-form 36 (SF-36) scores demonstrated numerical improvements in each individual category at the 6-week mark above baseline. These improvements persisted at the 12-week mark. CONCLUSIONS: In this study we were able to establish the feasibility of implementing a preoperative comprehensive stoma education session for patients scheduled for a RCIC. Additionally, we were able to document favorable HRQOL data and improved ostomy adjustment scores surrounding the education session.

When virtual becomes reality: short term impressions of a two-week virtual urology sub-internship program.

INTRODUCTION: The COVID-19 pandemic disrupted medical student education and posed a unique challenge for educators, especially for surgical clerkships. In response to COVID-19 rotation restrictions, we implemented a virtual urologic surgery sub-internship program and evaluated medical student impressions of the experience. MATERIALS AND METHODS: A two-week urology curriculum was created with content delivered by interactive videoconferencing. The curriculum included synchronous and individual learning with live patient clinical experiences in the outpatient clinic and operating room, lectures, departmental conferences, a suture lab, self-reflective writing exercises, and an oral presentation. Student impressions were assessed with an exit survey. Descriptive statistics were utilized to evaluate the 5-point Likert scale responses. RESULTS: A total of 40 students applied, and 18 were selected for 1 of 5 two-week rotation blocks. All students successfully passed the rotation. Of the 18 students who participated, 16 (88.9%) completed the exit survey. The overall experience was rated as "strongly positive" by 14 of 16 (87.5%) students. The learning experience was rated as 4.75 (0.45) (average (SD)). The rotation positively impacted our virtual students' plan to apply to this residency program (mean 4.81 (0.54)). All students reported they would recommend this rotation to a fellow student, and feedback regarding the self-reflection activities was positive. CONCLUSIONS: We successfully implemented a two-week virtual urology sub-internship rotation with a wide variety of clinical and educational experiences. The rotation was well received by our medical students. This is a unique experience in urology that can easily be implemented by other surgical sub-specialty programs in the future.

A qualitative evaluation of a nurse-led pre-operative stoma education program for bladder cancer patients.

INTRODUCTION: Radical cystectomy remains the standard of care for muscle-invasive bladder cancer and high-risk non-muscle-invasive bladder cancer. Postoperative ostomy education is common, but patients struggle to maintain self-management practices. A preoperative ostomy education program was developed to meet this need, and we conducted a qualitative study with participating patient-caregiver dyads to evaluate the educational and psychosocial impacts of the program and examine alignment with program objectives. MATERIALS AND METHODS: A qualitative descriptive study was conducted utilizing a thematic analysis approach. Sixteen patients, eighteen caregivers, and three program educators completed semi-structured interviews from 3 to 18 months post the program. Interviews were audio-recorded and transcribed. Thirteen end-of-course surveys from the initial educational program cohort were transcribed, coded, analyzed; this data was triangulated with patient, caregiver, and educator interviews. RESULTS: Analysis uncovered three themes: (1) Patient and caregiver motivation to attend the program, (2) attitudes toward this life-changing event, and (3) education. For theme 1, patients and caregivers cited lack of knowledge, fear, and concern about ostomy surgery and care as motivation. For theme 2, there were a variety of attitudes toward the ostomy, ranging from avoidance to acceptance, and a similar breadth of attitudes toward caregiving, with some patients and caregivers describing ongoing dependence and other patients seeking complete independence. For theme 3, the interactive curriculum was determined to be effective, and the patient advocate was cited as the most memorable program component. CONCLUSIONS: A formal preoperative ostomy education program employing an interactive educational approach and featuring a patient advocate can prepare bladder cancer patients and caregivers for ostomy self-management and post-ostomy life.

Feasibility of a Weight Management Program Tailored for Overweight Men with Localized Prostate Cancer - A Pilot Study.

BACKGROUND: Overweight men with prostate cancer are more likely to suffer from recurrence and death following prostatectomy compared with healthy weight men. This study tested the feasibility of delivering a comprehensive program to foster weight loss before and weight maintenance after surgery in overweight men with localized prostate cancer. METHODS: Twenty overweight men scheduled for prostatectomy elected either the intervention (n = 15) or the nonintervention (n = 5). Anthropometrics, biomarkers, diet quality, nutrition literacy, quality of life, and long-term follow-up were assessed in both groups. RESULTS: The intervention led to 5.55 kg of weight loss including 3.88 kg of fat loss from baseline to surgery (mean = 8.3 weeks). The intervention significantly increased fiber, protein, fruit, nut, and vegetable intake; and decreased trans fats intake during weight loss. The intervention significantly reduced insulin, C-peptide, systolic blood pressure, leptin:adiponectin ratio, and visceral adiposity compared to the nonintervention. Post-surgically, weight loss was maintained. Changes in lipid profiles, nutrition literacy, and follow-up were not statistically significant in either group. CONCLUSION: Significant weight loss (≥5%) is feasible with a coaching intervention in overweight men preparing for prostatectomy and is associated with favorable cardiometabolic effects. This study is registered under NCT02252484 (www.clinicaltrials.gov).

Effect of COVID-19 on Urology Residency Training: A Nationwide Survey of Program Directors by the Society of Academic Urologists.

PURPOSE: Coronavirus disease (COVID-19) has profoundly impacted residency training and education. To date, there has not been any broad assessment of urological surgery residency changes and concerns during the COVID-19 pandemic. MATERIALS AND METHODS: The Society of Academic Urologists distributed a questionnaire to urology residency program directors on March 30, 2020 exploring residency program changes related to the COVID-19 pandemic. Descriptive statistics are presented. A qualitative analysis of free response questions was undertaken. A post hoc analysis of differences related to local COVID-19 incidence is described. RESULTS: The survey was distributed to 144 residency programs with 65 responses for a 45% response rate. Reserve staffing had started in 80% of programs. Patient contact time had decreased significantly from 4.7 to 2.1 days per week (p <0.001). Redeployment was reported by 26% of programs. Sixty percent of programs reported concern that residents will not meet case minimums due to COVID-19. Wellness activities centered on increased communication. All programs had begun to use videoconferencing and the majority planned to continue. Programs in states with a higher incidence of COVID-19 were more likely to report resident redeployment (48% vs 11%, p=0.002) and exposure to COVID-19 positive patients (70% vs 40%, p=0.03), and were less likely to report concerns regarding exposure (78% vs 97%, p=0.02) and personal protective equipment availability (62% vs 89%, p=0.02). CONCLUSIONS: As of April 1, 2020 the COVID-19 pandemic had resulted in significant changes in urology residency programs. These findings inform a rapidly changing landscape and aid in the development of best practices.

The Limited Usefulness of Ultrasound Surveillance after Radical and Partial Nephrectomy for Renal Cell Carcinoma.

INTRODUCTION: We determined the usefulness of ultrasound compared to cross-sectional imaging in the detection of intra-abdominal recurrences after radical or partial nephrectomy for localized renal cell carcinoma. METHODS: We performed a retrospective review of 800 patients with clinically localized renal cell carcinoma who had undergone radical or partial nephrectomy between 2008 and 2015. Patients had at minimum 1 year of followup at our institution, at least 1 ultrasound during surveillance and no metastases at time of surgery. Our primary outcome was the rate of diagnosis of abdominal recurrence based on modality of surveillance. RESULTS: Median followup for the entire cohort was 37.5 months (range 12 to 166). Overall 396 and 404 patients underwent radical and partial nephrectomy, respectively, for localized renal cell carcinoma. There were 224 (57%) and 234 (58%) patients in the radical and partial nephrectomy cohorts, respectively, who had 2 or more ultrasounds performed during surveillance. In the radical and partial nephrectomy cohorts a total of 149 (19%) abdominal recurrences were detected, with only 8 (19%) initially detected by ultrasound. On the other hand, 15 (10%) recurrences were missed by a prior negative ultrasound. Furthermore, there were 8 false-positive ultrasound studies that cross-sectional imaging later ruled out. CONCLUSIONS: The low yield of ultrasound in the detection of abdominal recurrences after radical or partial nephrectomy for renal cell carcinoma raises questions as to its usefulness in routine surveillance.

Eighteen-Year Review of Resident Performance on the American Urological Association In-Service Examination.

OBJECTIVE: To analyze national performance trends of urology residents on the American Urological Association In-Service Examination (ISE) over the last 18 years. METHODS: Trends in the national averages on the in-service examination for each year of residency training were collected and analyzed between the years 2000 and 2017. Mean and standard error were calculated for examination performance for each year of residency. Subject-specific performance was also determined for each given year of residency. Regression analysis was used to model trends in performance as a function of residency year. RESULTS: There was no significant difference in examination performance over 18 years with respect to each specific residency year. While there was an overall improvement in total scores with each advancing training year, year-over-year improvement in total examination performance began to plateau after Uro-2. Largest absolute performance improvement from Pre-Uro to Uro-4 were in subjects of "Urinary Diversion," "Obstructive Uropathy" and "Neoplasm." Scores in "Sexual Dysfunction, Endocrinopathy, Fertility Problems", and "Congenital Anomalies, Embryology, Anatomy" were consistently the lowest regardless of year of training. CONCLUSION: No significant change in performance was seen in each given year of residency over the 18-year period. There was improvement in overall scores as residents progressed through training, but scores plateaued after Uro-2 with minimal improvement between Uro-3 and Uro-4 years. Difference in subject scores suggests a disparity in educational focus in residency curricula and a potential need to improve the teaching strategies for subjects that tested less well throughout residency training.

The Feasibility of a Health Care Application in the Treatment of Patients Undergoing Radical Cystectomy.

PURPOSE: Patients who undergo radical cystectomy of bladder cancer are at high risk for complications and hospital readmissions. Studies indicate insufficient preoperative education and perioperative monitoring. The aim of this study was to demonstrate the feasibility of implementing a health care application to provide more patient education and more thorough monitoring perioperatively. MATERIALS AND METHODS: Participants with home Wi-Fi access who were undergoing radical cystectomy were recruited for this pilot trial. Each subject was provided a tablet preloaded with the m.Care (LifeScience Technologies, Leawood, Kansas) health care application, an accelerometer and vital sign equipment. Participants were asked to watch educational videos, use the provided accelerometer and perform vital sign monitoring. RESULTS: In 1 year 20 participants enrolled in the study and 15 completed it. The most frequently viewed videos were "Ileal Conduit versus Neobladder" and "Comprehensive Care Pathway." All participants used the accelerometer and 60% kept up with syncing the data regularly. The average step count preoperatively was 5,679 reflecting a sedentary population. Step counts decreased during the inpatient stay (1,351 steps) and trended toward baseline during the postoperative period (3,156 steps). Vital signs were recorded on 85% of assigned days and generated 33 triggers for intervention. While most triggers led to repeat assessment, education and encouragement, 4 participants underwent outpatient treatment, including cultures, intravenous fluids, antibiotics or dronabinol prescription, without the need for hospital readmission. CONCLUSIONS: Providing more education and monitoring perioperatively is feasible using a health care application. Testing is warranted to determine the extent to which implementation will improve patient triaging and reduce readmissions.

Perioperative Immunonutrition Modulates Inflammatory Response after Radical Cystectomy: Results of a Pilot Randomized Controlled Clinical Trial.

PURPOSE: Poor preoperative nutritional status is associated with a higher complication rate after radical cystectomy in patients with bladder cancer. Given the short interval between diagnosis and radical cystectomy, we compared the effect of short-term specialized immunonutrition to that of a standard oral nutritional supplement on the acute inflammatory response and arginine status in patients treated with radical cystectomy. MATERIALS AND METHODS: In this prospective, randomized study in 29 men 14 received specialized immunonutrition and 15 received oral nutritional supplement. Each group drank 3 cartons per day for 5 days before and 5 days after radical cystectomy. The Th1-Th2 balance, plasma interleukin-6 and plasma amino acids were measured at baseline, intraoperatively and on postoperative days 2, 14 and 30. Body composition was measured by dual energy x-ray absorptiometry at baseline and on postoperative days 14 and 30. Differences in outcomes were assessed using the generalized linear mixed model. RESULTS: In the specialized immunonutrition group there was a 54.3% average increase in the Th1-Th2 balance according to the tumor necrosis factor-α-to-interleukin-13 ratio from baseline to intraoperative day, representing a shift toward a Th1 response. In the oral nutritional supplement group the Th1-Th2 balance decreased 4.8%. The change in the Th1-Th2 balance between the specialized immunonutrition and oral nutritional supplement groups significantly differed (p <0.027). Plasma interleukin-6 was 42.8% lower in the specialized immunonutrition group compared to the oral nutritional supplement group on postoperative day 2 (p = 0.020). In the specialized immunonutrition group plasma arginine was maintained from baseline to postoperative day 2 and yet the oral nutritional supplement group showed a 26.3% reduction from baseline to postoperative day 2 (p = 0.0003). The change in appendicular muscle loss between the groups was not statistically significant. CONCLUSIONS: Th1-to-Th2 ratios, peak interleukin-6 levels and plasma arginine suggest that consuming specialized immunonutrition counteracts the disrupted T-helper balance, lowers the inflammatory response and prevents arginine depletion due to radical cystectomy.

Metastatic prostate cancer in the modern era of PSA screening

ABSTRACT Introduction To characterize initial presentation and PSA screening status in a contemporary cohort of men treated for metastatic prostate cancer at our institution. Materials and methods We reviewed records of 160 men treated for metastatic prostate cancer between 2008-2014 and assessed initial presentation, categorizing patients into four groups. Groups 1 and 2 presented with localized disease and received treatment. These men suffered biochemical recurrence late (>1 year) or earlier (<1 year), respectively, and developed metastases. Groups 3 and 4 had asymptomatic and symptomatic metastases at the outset of their diagnosis. Patients with a first PSA at age 55 or younger were considered to have guideline-directed screening. Results Complete records were available on 157 men for initial presentation and 155 men for PSA screening. Groups 1, 2, 3 and 4 included 27 (17%), 7 (5%), 69 (44%) and 54 (34%) patients, respectively. Twenty (13%) patients received guideline-directed PSA screening, 5/155 (3%) patients presented with metastases prior to age 55 with their first PSA, and 130/155 (84%) had their first PSA after age 55, of which 122/130 (94%) had metastasis at the time of diagnosis. Conclusion Despite widespread screening, most men treated for metastatic prostate cancer at our institution presented with metastases rather than progressed after definitive treatment. Furthermore, 25 (16%) patients received guideline-directed PSA screening at or before age 55. These data highlight that, despite mass screening efforts, patients treated for incurable disease at our institution may not have been a result of a failed screening test, but a failure to be screened.

The Role of High Dose Interleukin-2 in the Era of Targeted Therapy.

PURPOSE: We assessed survival outcomes following high dose interleukin-2 in a contemporary cohort of patients during the era of targeted agents. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with metastatic renal cell carcinoma treated with high dose interleukin-2 between July 2007 and September 2014. Clinicopathological data were abstracted and patient response to therapy was based on RECIST (Response Evaluation Criteria In Solid Tumors), version 1.1 criteria. The Kaplan-Meier method was used to estimate progression-free and overall survival in the entire cohort, the response to high dose interleukin-2 in regard to previous targeted agent therapy and the response to the targeted agent in relation to the response to high dose interleukin-2. RESULTS: We identified 92 patients, of whom 87 had documentation of a response to high dose interleukin-2. Median overall survival was 34.4 months from the initiation of high dose interleukin-2 therapy in the entire cohort. Patients who received targeted therapy before high dose interleukin-2 had overall survival (median 34.4 and 30.0 months, p = 0.88) and progression-free survival (median 1.5 and 1.7 months, p = 0.8) similar to those in patients who received no prior therapy, respectively. Additionally, patients with a complete or partial response to high dose interleukin-2 had similar outcomes for subsequent targeted agents compared to patients whose best response was stable or progressive disease (median overall survival 30.1 vs 25.4 months, p = 0.4). CONCLUSIONS: Our data demonstrate that patient responses to high dose interleukin-2 and to targeted agents before and after receiving high dose interleukin-2 are independent. As such, carefully selected patients should be offered high dose interleukin-2 for the possibility of a complete and durable response without the fear of limiting the treatment benefit of targeted agents.

Metastatic prostate cancer in the modern era of PSA screening.

INTRODUCTION: To characterize initial presentation and PSA screening status in a contemporary cohort of men treated for metastatic prostate cancer at our institution. MATERIALS AND METHODS: We reviewed records of 160 men treated for metastatic prostate cancer between 2008-2014 and assessed initial presentation, categorizing patients into four groups. Groups 1 and 2 presented with localized disease and received treatment. These men suffered biochemical recurrence late (>1 year) or earlier (<1 year), respectively, and developed metastases. Groups 3 and 4 had asymptomatic and symptomatic metastases at the outset of their diagnosis. Patients with a first PSA at age 55 or younger were considered to have guideline-directed screening. RESULTS: Complete records were available on 157 men for initial presentation and 155 men for PSA screening. Groups 1, 2, 3 and 4 included 27 (17%), 7 (5%), 69 (44%) and 54 (34%) patients, respectively. Twenty (13%) patients received guideline-directed PSA screening, 5/155 (3%) patients presented with metastases prior to age 55 with their first PSA, and 130/155 (84%) had their first PSA after age 55, of which 122/130 (94%) had metastasis at the time of diagnosis. CONCLUSION: Despite widespread screening, most men treated for metastatic prostate cancer at our institution presented with metastases rather than progressed after definitive treatment. Furthermore, 25 (16%) patients received guideline-directed PSA screening at or before age 55. These data highlight that, despite mass screening efforts, patients treated for incurable disease at our institution may not have been a result of a failed screening test, but a failure to be screened.

Findings and Impact of Early Imaging After Partial Nephrectomy.

INTRODUCTION: American Urological Association guidelines for surveillance of renal-cell carcinoma after partial nephrectomy recommend imaging within 3-12 months of surgery. Imaging following partial nephrectomy may be difficult to interpret due to the surgical defect, the use of surgical material, and normal postoperative fluid collections. Our primary objective was to evaluate the frequency of indeterminate postoperative imaging results and how those radiographic findings altered patient management. METHODS: Retrospective chart review from 2006 to 2013 of patients who had undergone open, laparoscopic, and robotic partial nephrectomy at our institution was completed. There was a minimum of 2 years of follow-up imaging. Radiology reports were reviewed from follow-up imaging and were categorized as "normal" or "abnormal." RESULTS: We identified 180 patients with 127 (70.5%) considered to have normal findings on initial follow-up imaging, and 53 (29.5%) with abnormal findings. Median time to initial postoperative imaging for normal findings was 6.8 months compared with 4.4 months for patients with abnormal postoperative scans (p = 0.02). On subsequent imaging, 60% of abnormal studies were downgraded to normal. The median time to receive a second postoperative image from surgery in the normal and abnormal groups was 13.2 and 10.2 months, respectively. The median time interval to the second imaging study was 6.3 months for normal initial scans compared with 5.2 months for initially abnormal scans (p ≤ 0.01). CONCLUSIONS: Early postoperative imaging after partial nephrectomy frequently results in "abnormal" findings and more subsequent radiology exams even though the findings rarely represent cancer recurrences. Based on our results, and pending further validation from other centers, we believe postoperative CT or MRI surveillance after partial nephrectomy can be safely deferred until 1 year after surgery.

Venous thromboembolism after radical cystectomy: Experience with screening ultrasonography.

OBJECTIVES: To detect the incidence of immediate postoperative deep vein thrombosis (DVT) using screening lower extremity ultrasonography (US) in patients undergoing radical cystectomy (RC) and to determine the rate of symptomatic pulmonary embolism (PE) after RC and identify risk factors for venous thromboembolic (VTE) events in a RC population. PATIENTS AND METHODS: We performed a retrospective review of prospective data collected on patients who underwent RC between July 2008 and January 2012. These patients underwent screening US at 2/3 days after RC to determine the rate of asymptomatic DVT. A chart review was completed to identify those who had a symptomatic PE. Univariate and multivariable analysis was used to identify risk factors associated with DVT, PE and total VTE events. RESULTS: In all, 221 patients underwent RC and asymptomatic DVT was identified in 21 (9.5%) on screening US. Nine (4.5%) developed symptomatic PE at a median of 9 days, of which no patients had positive lower extremity US postoperatively. Increased length of hospital stay, increased estimated blood loss, and lower body mass index were linked to risk of PE, and only a previous history of DVT was associated with postoperative DVT. CONCLUSION: Patients who undergo RC are at high-risk for thromboembolic events and multimodal prophylaxis should be administered. Clinicians should be especially vigilant in those who demonstrate factors associated with higher risk for VTE events.

Effects of Immunonutrition for Cystectomy on Immune Response and Infection Rates: A Pilot Randomized Controlled Clinical Trial.

UNLABELLED: After radical cystectomy (RC), patients are at risk for complications including infections. The expansion of myeloid-derived suppressor cells (MDSCs) after surgery may contribute to the lower resistance to infection. Immune response and postoperative complications were compared in men consuming either specialized immunonutrition (SIM; n=14) or an oral nutrition supplement (ONS; n=15) before and after RC. MDSC count (Lin- CD11b+ CD33+) was significantly different between the groups over time (p=0.005) and significantly lower in SIM 2 d after RC (p<0.001). MDSC count expansion from surgery to 2 d after RC showed a weak association with an increase in infection rate 90 d after surgery (p=0.061). Neutrophil:lymphocyte ratio was significantly lower in SIM compared with ONS 3h after the first incision (p=0.039). Participants receiving SIM had a 33% reduction in postoperative complication rate (95% confidence interval [CI], 1-64; p=0.060) and a 39% reduction in infection rate (95% CI, 8-70; p=0.027) during late-phase recovery. The small sample size limits the study findings. PATIENT SUMMARY: Results show that the immune response to surgery and late infection rates differ between radical cystectomy patients receiving specialized immunonutrition versus oral nutrition supplement in the perioperative period. TRIAL REGISTRATION: ClinicalTrials.gov NCT01868087.