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.

Androgen Deprivation and Sleep Disturbance: A Mixed Methods Pilot Study of Remote Assessment and Intervention.

BACKGROUND: Men receiving androgen deprivation therapy (ADT) for prostate cancer (PC) are at risk for cardiovascular comorbidities and cognitive changes. Interventional research involves in-person assessment of physical fitness/activity and cognitive function, which has been negatively affected by the COVID-19 pandemic. Androgen deprivation therapy-related hot flashes and nocturia increase risk for insomnia. Insomnia is associated with fatigue and may exacerbate ADT-related cognitive changes. OBJECTIVES: The purpose of this mixed-methods pilot was to (1) determine feasibility/acceptability of remotely assessing physical fitness/activity, cognitive function, and sleep; (2) deliver telehealth cognitive behavioral training for insomnia (teleCBT-I) to improve sleep; and (3) garner qualitative feedback to refine remote procedures and teleCBT-I content. METHODS: Fifteen men with PC receiving ADT completed a 4-week teleCBT-I intervention. Videoconferencing was used to complete study assessments and deliver the weekly teleCBT-I intervention. RESULTS: Self-report of sleep quality improved ( P < .001) as did hot flash frequency ( P = .04) and bother ( P = .025). Minimal clinically important differences were detected for changes in insomnia severity and sleep quality. All sleep logs indicated improvement in sleep efficiency. Remote assessment of fitness/cognitive function was demonstrated for 100% of participants. Sufficient actigraph wear time allowed physical activity/sleep assessment for 80%. Sleep actigraphy did not demonstrate significant changes. CONCLUSIONS: Remote monitoring and teleCBT-I are feasible/acceptable to men with PC on ADT. Further research to confirm teleCBT-I efficacy is warranted in this population. IMPLICATIONS FOR PRACTICE: Preliminary efficacy for teleCBT-I interventions was demonstrated. Remote assessments of physical fitness/activity, sleep, and cognitive function may enhance clinical trial access for rural or economically disadvantaged PC survivors.

Radical prostatectomy readmissions: Causes, risk factors, national rates, & costs.

INTRODUCTION: Readmissions have substantial clinical and financial impacts on the healthcare system. Radical prostatectomy (RP) is considered a standard treatment in the management of clinically localized prostate cancer. Yet, there is a paucity of research evaluating readmissions for RP in a national dataset. PATIENTS AND METHODS: Patients with histologically confirmed prostate cancer managed with RP were identified within the 2016 to 2018 Nationwide Readmissions Database. Patient factors, facility factors, and surgical characteristics were evaluated for associations with readmission using univariable and multivariable analyses. RESULTS: A total of 133,727 patients receiving RP were identified. Early (30-day) and late (31-90-day) readmission rates were 4.2% and 1.8% respectively. The most common cause of early readmission was postoperative digestive system complication (10%) and the most common cause of late readmission was septicemia (13%). On multivariable logistic regression, factors associated with both early and late readmission include nonroutine discharge at index (early: OR 1.877, 95% CI 1.667-2.113; late: OR 1.801, 95% CI 1.490-2.183), and circulatory system comorbidity (early: OR 1.29, 95% CI 1.082-1.538); late: OR 1.515, 95% CI 1.157-1.984). CONCLUSIONS: Our findings regarding factors associated with readmission provide insight for RP counseling and may inform postoperative care pathways. Elucidation of readmission trends may allow the identification and proactive management of patients at higher risk for readmission.

Variations in Age-Adjusted Prostate Cancer Incidence Rates by Race and Ethnicity After Changes in Prostate-Specific Antigen Screening Recommendation.

Importance: After publication of US Preventive Task Force Prostate-Specific Antigen (PSA) screening guidelines in 2008 and 2012, there have been documented associations with incidence and stage distributions of prostate cancer. It is unclear if these changes were temporary or differed by age or race and ethnicity. Objective: To assess the association of 2008 and 2012 PSA guidelines with prostate cancer incidence by age and race and ethnicity in the US. Design, Setting, and Participants: This cross-sectional study evaluated prostate cancer incidence from 2005 to 2018 in the US using data from the US Cancer Statistics public use database. Data were analyzed from August 2020 through June 2022. Main Outcomes and Measures: The primary outcome was the year when rates of prostate cancer incidence changed directionality by age and race and ethnicity. Age-adjusted incidence rates of prostate cancer and corresponding 95% CIs were created, followed by join point regression analysis to evaluate trends of age-adjusted incidence rates of prostate cancer by age, race, Hispanic ethnicity, and stage of diagnosis. Results: Among 2 944 387 men with prostate cancer, 2 869 943 (97.5%) men were aged 50 years and older. Men aged 50 years and older accounted for 185 476 of 191 533 Hispanic individuals (96.8%) and 2 684 467 of 2 752 854 non-Hispanic individuals (97.5%). Men aged 50 years and older accounted for 427 016 of 447 847 African American individuals (95.4%), 12 141 of 12 470 American Indian or Alaska Native individuals (97.4%), 61 126 of 62 159 Asian or Pacific Islander individuals (98.3%), and 2 294 171 of 2 344 392 White individuals (97.9%). Men with unknown race (77 519 men) were excluded from the analysis. A decrease in age-adjusted rate of prostate cancer after the 2008 guideline change was observed in all age groups by race and ethnicity. For example, among African American men ages 65 to 74 years, 10 784 of 807 080 men (1.34%) had a prostate cancer diagnosis in 2007 vs 10 714 of 835 548 men in 2008 (1.28%). The mean annual age-adjusted incidence rates of prostate cancer per 100 000 men were 157.7 men (95% CI, 157.4-158.0 men) in 2005 to 2008 and 131.9 men (95% CI, 131.6-132.2 men) in 2009 to 2012. The number of inflections and annual percent changes (APCs) for segments separated by inflections varied by age, race, and Hispanic ethnicity. For men ages 65 to 74 years, the APC was -6.53 (95% CI, -9.28 to -3.69) for 2009 to 2014 among African American men (2 join points), -5.96 (95% CI, -6.84 to -5.07) for 2007 to 2018 among American Indian or Alaska Native men (1 join point), -6.52 (95% CI, -9.22 to -3.74) for 2007 to 2014 among Asian or Pacific Islander men (2 join points), -7.92 (95% CI, -11.36 to -4.35) for 2009 to 2014 among Hispanic men (2 join points), and -7.02 (95% CI, -9.41 to -4.57) for 2007 to 2014 among White men (2 join points).‬‬‬‬‬‬‬‬. Conclusions and Relevance: In this study, men in different age, race, and ethnicity groups had different APC patterns after 2008 and 2012 PSA screening guideline changes. These findings may provide important data on the timing and durations of changes in cancer diagnoses that are associated with changes in PSA screening recommendations and may be valuable for targeted strategies to reduce regional- and distant-staged cancers.

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.

Durable Treatment of Refractory Vesicourethral Anastomotic Stenosis via Robotic-assisted Reconstruction: A Trauma and Urologic Reconstructive Network of Surgeons Study.

BACKGROUND: Refractory vesicourethral anastomotic stenosis (VUAS) after radical prostatectomy poses challenges distinct from bladder neck contracture, due to close proximity to the sphincter mechanism. Open reconstruction is technically demanding, risking de novo stress urinary incontinence (SUI) or recurrence. OBJECTIVE: To demonstrate patency and continence outcomes of robotic-assisted VUAS repair. DESIGN, SETTING AND PARTICIPANTS: Patients with VUAS underwent robotic-assisted reconstruction from 2015 to 2020 in the Trauma and Urologic Reconstructive Network of Surgeons (TURNS) consortium of institutions. The minimum postoperative follow-up was 3 mo. SURGICAL PROCEDURE: The space of Retzius is dissected and fibrotic tissue at the vesicourethral anastomosis is excised. Reconstruction is performed with either a primary anastomotic or an anterior bladder flap-based technique. MEASUREMENTS: Patency was defined as either the passage of a 17 French flexible cystoscope or a peak flow on uroflowmetry of >15 ml/s. De novo SUI was defined as either more than one pad per day or need for operative intervention. RESULTS AND LIMITATIONS: A total of 32 patients met the criteria, of whom 16 (50%) had a history of pelvic radiation. Intraoperatively, 15 (47%) patients had obliterative VUAS. The median length of hospital stay was 1 d. At a median follow-up of 12 mo, 24 (75%) patients had patent repairs and 26 (81%) were voiding per urethra. Of five men with 30-d complications, four were resolved conservatively (catheter obstruction and ileus). In eight patients, recurrent stenoses were managed with redo robotic reconstruction (in two), endoscopically (in four), or catheterization (in two). Of 13 patients without preexisting SUI, 11 (85%) remained continent at last follow-up. No patients underwent urinary diversion. CONCLUSIONS: Robotic-assisted VUAS reconstruction is a viable and successful management option for refractory anastomotic stenosis following radical prostatectomy. The robotic transabdominal approach demonstrates high patency and continence rates. PATIENT SUMMARY: We studied the outcomes of robotic-assisted repair for vesicourethral anastomotic stenosis. Most patients, after the procedure, were able to void per urethra and preserve existing continence.

Factors associated with utilization of neoadjuvant chemotherapy in charlson comorbidity zero non-metastatic muscle-invasive bladder cancer patients

ABSTRACT Background: Guideline-based best practice treatment for muscle invasive bladder cancer (MIBC) involves neoadjuvant chemotherapy followed by radical cystectomy (NACRC). Prior studies have shown that a minority of patients receive NACRC and older age and renal function are drivers of non-receipt of NACRC. This study investigates treatment rates and factors associated with not receiving NACRC in MIBC patients with lower comorbidity status most likely to be candidates for NACRC. Materials and Methods: Retrospective United States National Cancer Database analysis from 2006 to 2015 of MIBC patients with Charlson comorbidity index (CCI) of zero. Analysis of NACRC treatment trends in higher CCI patients was also performed. Results: 15.561 MIBC patients met inclusion criteria. 1.507 (9.7%) received NACRC within 9 months of diagnosis. NACRC increased over time (15.0% in 2015 compared to 3.6% in 2006). Higher NACRC was noted in females, cT3 or cT4 cancer, later year of diagnosis, and academic facility treatment. Lower utilization was noted for blacks and NACRC decreased with increasing age and CCI. Only 16.9% of patients aged 23-62 in the lowest age quartile with muscle invasive bladder cancer and CCI of 0 received NACRC. Conclusions: Although utilization is increasing, receipt of NACRC remains low even in populations most likely to be candidates. Further study should continue to elucidate barriers to utilization of NACRC.

Factors associated with utilization of neoadjuvant chemotherapy in charlson comorbidity zero non-metastatic muscle-invasive bladder cancer patients.

BACKGROUND: Guideline-based best practice treatment for muscle invasive bladder cancer (MIBC) involves neoadjuvant chemotherapy followed by radical cystectomy (NACRC). Prior studies have shown that a minority of patients receive NACRC and older age and renal function are drivers of non-receipt of NACRC. This study investigates treatment rates and factors associated with not receiving NACRC in MIBC patients with lower comorbidity status most likely to be candidates for NACRC. MATERIALS AND METHODS: Retrospective United States National Cancer Database analysis from 2006 to 2015 of MIBC patients with Charlson comorbidity index (CCI) of zero. Analysis of NACRC treatment trends in higher CCI patients was also performed. RESULTS: 15.561 MIBC patients met inclusion criteria. 1.507 (9.7%) received NACRC within 9 months of diagnosis. NACRC increased over time (15.0% in 2015 compared to 3.6% in 2006). Higher NACRC was noted in females, cT3 or cT4 cancer, later year of diagnosis, and academic facility treatment. Lower utilization was noted for blacks and NACRC decreased with increasing age and CCI. Only 16.9% of patients aged 23-62 in the lowest age quartile with muscle invasive bladder cancer and CCI of 0 received NACRC. CONCLUSIONS: Although utilization is increasing, receipt of NACRC remains low even in populations most likely to be candidates. Further study should continue to elucidate barriers to utilization of NACRC.

Exploration of biomarkers from a pilot weight management study for men undergoing radical prostatectomy.

BACKGROUND: Several biologic mechanisms, including inflammation and immune changes, have been proposed to explain the role of obesity in prostate cancer (CaP) progression. Compared to men of a healthy weight, overweight and obese men are more likely to have CaP recurrence post-prostatectomy. Obesity is related to inflammation and immune dysregulation; thus, weight loss may be an avenue to reduce inflammation and reverse these immune processes. OBJECTIVES: This study explores the reversibility of the biological mechanisms through intentional weight loss using a comprehensive weight management program in men undergoing prostatectomy. Outcomes include blood and tissue biomarkers, microtumor environment gene expression, inflammation markers and Dietary Inflammatory Index (DII) scores. METHODS: Twenty overweight men undergoing prostatectomy participated in this study. Fifteen men chose the intervention and 5 men chose the nonintervention group. The intervention consisted of a comprehensive weight loss program prior to prostatectomy and a weight maintenance program following surgery. Prostate tissue samples were obtained from diagnostic biopsies before the intervention and prostatectomy samples after weight loss. Blood samples and diet records were collected at baseline, pre-surgery after weight loss and at study end after weight maintenance. Immunohistochemistry and NanoString analysis were used to analyze the tissue samples. Flow cytometry was used to assess circulating immune markers. Inflammation markers were measured using Luminex panels. RESULTS: The intervention group lost >5% body weight prior to surgery. DII scores improved during the weight loss intervention from baseline to pre-surgery (P = 0.002); and between group differences were significant (P = 0.02). DII scores were not associated with IL-6 nor hsCRP. In the intervention, CXCL12, CXCR7, and CXCR4 (C-X-C motif chemokine ligand/receptor) and Ki67 expression decreased in the prostate tissue from biopsy to surgery (P = 0.06), yet plasma CXCL12 increased during the same timeframe (P = 0.009). The downregulation of several genes (FDR<0.001) was observed in the intervention compared to the non-intervention. Changes in immune cells were not significant in either group. CONCLUSION: This feasibility study demonstrates that in overweight men with localized CaP, weight loss alters blood, and tissue biomarkers, as well as tumor gene expression. More research is needed to determine the biological and clinical significance of these findings.

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).

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.

More Extensive Lymph Node Dissection at Radical Prostatectomy is Associated with Improved Outcomes with Salvage Radiotherapy for Rising Prostate-specific Antigen After Surgery: A Long-term, Multi-institutional Analysis.

Up to 50% of patients recur after salvage radiation therapy (sRT) for prostate-specific antigen (PSA) rise following radical prostatectomy (RP). Notably, the importance of lymph node dissection (LND) at the time of RP with regard to recurrence risk following sRT has not been previously determined. Therefore, we evaluated the association between nodal yield at RP and recurrence after sRT. We performed a multi-institutional review of men with a rising PSA after RP treated with sRT. Clinicopathologic variables were abstracted, and the associations between lymph node yield and biochemical (BCR) as well as clinical recurrence (CR) after sRT were assessed using multivariable Cox proportional hazards regression models. In total, 728 patients were identified; of these, 221 and 116 were diagnosed with BCR and CR, respectively, during a median follow-up of 8.4 (interquartile range: 4.2-11.2) yr. On multivariable analysis, the risk of BCR after sRT was inversely associated with the number of nodes resected at RP (hazards ratio [HR]: 0.98; 95% confidence interval [CI]: 0.96-0.99; p=0.049). Increased extent of dissection was also independently associated with a decreased risk of CR after sRT (HR: 0.97; 95%CI: 0.94-0.99; p=0.042). These data support the importance of an extensive LND at surgery and may be used in prognosis assessment when sRT is being considered. PATIENT SUMMARY: We found that patients who had increased number of lymph nodes resected at surgery had improved outcomes after the receipt of salvage radiation therapy. These findings support the use of the extended lymph node dissection at initial surgery and should serve to improve counseling among patients who require salvage radiation therapy.

Postoperative Outcomes After Radical Cystectomy in Patients With Prior Pelvic Radiation.

OBJECTIVE: To compare complication rates, perioperative outcomes, and survival after radical cystectomy (RC) in patients with prior abdominal or pelvic radiation therapy (RT) vs those without an RT history. MATERIALS AND METHODS: We retrospectively reviewed patients undergoing RC for urothelial carcinoma between January 2008 and January 2016. Patients were stratified by receipt of RT, and differences in complications (any, minor, and major) at 30 and 90 days, as well as estimated blood loss, length of surgery, length of hospital stay, and pathologic stage, were compared. Recurrence-free, cancer-specific, and overall survival were compared using the Kaplan-Meier method and log-rank test. RESULTS: We identified 518 patients who underwent RC between 2008 and 2016. Of these patients, 55 (11%) had a history of RT. There were no significant differences in complication rates (66% vs 69%, P= .80) between patients who did not and patients who did have a history of RT. Similarly, there were no differences in any perioperative or pathologic outcome by receipt of prior RT (all P>.05). Meanwhile, at a median follow-up of 26 (interquartile range 13-46) months among patients alive at last follow-up, no differences in survival were observed by prior RT (P= .08). CONCLUSION: Among patients with a history of prior abdominal or pelvic RT treated at a tertiary referral center, there was no difference in complication rates, perioperative, or pathologic outcomes. Importantly, no differences in survival were noted by prior RT receipt. Therefore, our data support the use of RC, when indicated, in patients with a prior history of abdominal or pelvic RT.

Predicting Oncologic Outcomes in Renal Cell Carcinoma After Surgery.

BACKGROUND: Predicting oncologic outcomes is important for patient counseling, clinical trial design, and biomarker study testing. OBJECTIVE: To develop prognostic models for progression-free (PFS) and cancer-specific survival (CSS) in patients with clear cell renal cell carcinoma (ccRCC), papillary RCC (papRCC), and chromophobe RCC (chrRCC). DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort review of the Mayo Clinic Nephrectomy registry from 1980 to 2010, for patients with nonmetastatic ccRCC, papRCC, and chrRCC. INTERVENTION: Partial or radical nephrectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PFS and CSS from date of surgery. Multivariable Cox proportional hazards regression was used to develop parsimonious models based on clinicopathologic features to predict oncologic outcomes and were evaluated with c-indexes. Models were converted into risk scores/groupings and used to predict PFS and CSS rates after accounting for competing risks. RESULTS AND LIMITATIONS: A total of 3633 patients were identified, of whom 2726 (75%) had ccRCC, 607 (17%) had papRCC, and 222 (6%) had chrRCC. Models were generated for each histologic subtype and a risk score/grouping was developed for each subtype and outcome (PFS/CSS). For PFS, the c-indexes were 0.83, 0.77, and 0.78 for ccRCC, papRCC, and chrRCC, respectively. For CSS, c-indexes were 0.86 and 0.83 for ccRCC and papRCC. Due to only 22 deaths from RCC, we did not assess a multivariable model for chrRCC. Limitations include the single institution study, lack of external validation, and its retrospective nature. CONCLUSIONS: Using a large institutional experience, we generated specific prognostic models for oncologic outcomes in ccRCC, papRCC, and chrRCC that rely on features previously shown-and validated-to be associated with survival. These updated models should inform patient prognosis, biomarker design, and clinical trial enrollment. PATIENT SUMMARY: We identified routinely available clinical and pathologic features that can accurately predict progression and death from renal cell carcinoma following surgery. These updated models should inform patient prognosis, biomarker design, and clinical trial enrollment.

Identification of Recurrence Sites Following Post-Prostatectomy Treatment for Prostate Cancer Using 11C-Choline Positron Emission Tomography and Multiparametric Pelvic Magnetic Resonance Imaging.

PURPOSE: We describe anatomical sites of recurrence in patients with prostate cancer who had biochemical recurrence following radical prostatectomy and who received radiotherapy and/or androgen deprivation therapy postoperatively. We performed 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging. MATERIALS AND METHODS: After radiotherapy and/or androgen deprivation therapy patients who underwent radical prostatectomy were evaluated by 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging to determine recurrence patterns and clinicopathological features. Recurrent sites were described as local only (seminal vesicle bed/prostate fossa, vesicourethral anastomosis and bladder neck) or distant metastatic disease. Features associated with the identification of any distant metastatic disease were evaluated by multivariable logistic regression. RESULTS: A total of 550 patients were identified. Treatment included androgen deprivation therapy in 108, radiotherapy in 201, and androgen deprivation therapy and radiotherapy in 241. Median prostate specific antigen at evaluation was 3.9, 3.6 and 2.8 ng/ml in patients treated with androgen deprivation therapy, radiotherapy and a combination, respectively. Recurrence developed locally in 77 patients (14%), as distant metastasis only in 411 (75%), and as local and distant metastatic disease in 62 (11%). On multivariable analysis treatment with radiotherapy (OR 7.18, 95% CI 2.92-17.65), and radiotherapy and hormonal therapy (OR 9.23, 95% CI 3.90-21.87, all p <0.01) was associated with increased odds of distant failure at evaluation. CONCLUSIONS: The combination of 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging successfully identified patterns of recurrence after postoperative radiotherapy and/or androgen deprivation therapy at a median prostate specific antigen of less than 4 ng/ml. Half of this cohort had local only recurrence and/or a low disease burden limited to pelvic lymph nodes. These patients may benefit from additional local therapy. These data and this analysis may facilitate the evaluation of such patients with biochemically recurrent prostate cancer.

Adverse Pathology After Neoadjuvant Chemotherapy and Radical Cystectomy: The Role of Adjuvant Chemotherapy.

BACKGROUND: The current guidelines do not recommend adjuvant chemotherapy (AC) for patients with adverse pathologic findings after neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for bladder cancer. We sought to evaluate the association of AC with overall survival (OS) in these patients. MATERIALS AND METHODS: The National Cancer Database was used to identify patients with adverse pathologic findings (ypT3N0, ypT4N0, or ypTanyN1-N3) after NAC and RC for bladder cancer from 2006 to 2012. The clinicopathologic variables were abstracted, and the patients were stratified according to the receipt of AC. OS was estimated using the Kaplan-Meier method and log-rank test. Associations between AC and OS were evaluated in multivariable Cox proportional hazards regression models among all patients and stratified by pathologic classification. RESULTS: A total of 1361 patients were identified: 444 (32.6%) with ypT3N0, 162 (11.9%) with ypT4N0, and 755 (55.5%) with ypTanyN1-N3. The median OS for the entire cohort was 22.9 months, which differed by pathologic classification: 34.6 months with ypT3N0, 21.4 months with ypT4N0, and 19.3 months with ypTanyN1-N3 (P < .01). AC was used in 328 patients (24.1%), and no difference in OS was observed by receipt of AC (24.6 months with AC vs. 22.0 months without; P = .18). On multivariable analysis, AC was not independently associated with OS (hazard ratio, 0.86; 95% confidence interval, 0.74-1.01; P = .06). CONCLUSION: Patients with adverse pathologic findings at RC after previous NAC have a median OS of approximately 2 years, which was not significantly improved with AC. Clinical trials with newer systemic agents are warranted for patients in this setting to guide future therapy.

Utilization and Outcomes of Radical Cystectomy for High-grade Non-muscle-invasive Bladder Cancer in Elderly Patients.

BACKGROUND: Radical cystectomy (RC) represents a treatment option for patients with high-grade non-muscle-invasive bladder cancer (HG-NMIBC); however, perioperative morbidity is not insignificant, particularly in elderly patients. We sought to evaluate the associations of age with utilization and outcomes of RC for HG-NMIBC. PATIENTS AND METHODS: Patients with HG-NMIBC diagnosed between 2004 and 2013 were identified in the National Cancer Database and stratified by age: ≤ 60, 61-70, 71-80, and > 80 years. Association between age and treatment with RC was assessed by multivariable logistic regression. Associations between age and overall survival were assessed using the Kaplan-Meier method. A multi-institutional analysis was performed to evaluate the associations of age with perioperative outcomes and survival among patients managed with RC for HG-NMIBC. RESULTS: On multivariable analysis, age was associated with RC utilization, with the lowest usage in patients > 80 years (2.1%; P < .01). Upstaging at RC occurred in 40% of patients with HG-NMIBC, and no association of age with upstaging risk was noted. Significantly inferior overall survival was observed in the patients who were upstaged across age strata (all P < .01). In the multi-institutional cohort, age was not associated with risks of upstaging, receipt of transfusion, 30-/90-day complications, or recurrence-free or cancer-specific survival (all P > .05), whereas upstaging was associated with inferior recurrence-free and cancer-specific survival regardless of age. CONCLUSION: RC for HG-NMIBC is used less frequently in older adults, despite similar risks of pathologic upstaging. As upstaging is associated with inferior survival regardless of age, these data suggest that elderly patients with HG-NMIBC may be at risk for undertreatment.

Impact of Postoperative Radiotherapy in Men with Persistently Elevated Prostate-specific Antigen After Radical Prostatectomy for Prostate Cancer: A Long-term Survival Analysis.

BACKGROUND: Prostate cancer (PCa) patients with prostate-specific antigen (PSA) persistence after radical prostatectomy (RP) are at increased risk of mortality, although the natural history of these men is heterogeneous and the optimal management has not been established. OBJECTIVE: To develop a model to predict cancer-specific mortality (CSM) and to test the impact of radiotherapy (RT) on survival in this setting. DESIGN, SETTING, AND PARTICIPANTS: We identified 496 patients treated with RP and lymph node dissection at two referral centers between 1994 and 2014 who had PSA persistence, defined as a PSA level between 0.1 and 2 ng/ml at 6-8 wk after RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: A multivariable model predicting CSM was developed. We assessed whether the impact of postoperative PSA levels on survival differed according to baseline CSM risk. The nonparametric curve fitting method was then used to explore the relationship between baseline CSM risk and 10-yr CSM rates according to postoperative RT. RESULTS AND LIMITATIONS: Median follow-up for survivors was 110 mo. Overall, 49 patients experienced CSM. The 10-yr CSM-free survival was 88%. Pathologic grade group and pathologic stage were independent predictors of CSM (all p=0.01). The association between CSM-free survival and PSA at 6-8 wk differed by the baseline CSM risk, whereby the effect of increasing PSA was evident only in patients with a CSM risk of ≥10%. Postoperative RT was beneficial when the predicted risk of CSM was ≥30% (p=0.001 by an interaction test). Our study is limited by its retrospective design. CONCLUSIONS: Increasing PSA levels should be considered as predictors of mortality exclusively in men with worse pathologic characteristics. Postoperative RT in this setting was associated with a survival benefit in patients with a CSM risk of ≥30%. Conversely, individuals with a CSM risk of <30% should be initially managed expectantly. PATIENT SUMMARY: Not all patients with prostate-specific antigen persistence have a poor prognosis. Pathologic characteristics should be used to estimate the risk of cancer-specific mortality in these individuals and to identify patients who could benefit from postoperative radiotherapy.